Alexandras Bachelorprojekt NY

aa10s313 TheNutritionalManagementofDialysisPatientswithConstipation 26thofMay2014
TheNutritionalManagement
ofDialysisPatients
withConstipation

byAlexandraD.S.Prokisch,aa10s313
Supervisor:LineBakJosephsen
No.ofcharacters:84,000(35pages)

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Abstract
Background: The quality of life (QoL) in dialysis patients with End Stage Renal Disease (ESRD) is
wellbelowthethresholdofhealthycontrols.SinceQoLisassociatedwithahighermortalityinthis
patient population, developing treatment options aimed at enhancing the QoL in patients with
ESRDisanimportantpartoftheoveralltreatment.Onefactorloweringthesepatient'sQoListhe
high prevalence of constipation, ranging from 21% to 63%. Despite these high values, no clear
guidelines on the treatment of constipation in this patient group currently exist. Since the
registered dietician plays an important part in the nutritional management of both constipation
andESRD,itmakesonlysensetocombinethesetwoareasofexpertise.
Aim:Theaimofthisstudyistodetermineif,andifso,howtheregistereddieticianmayassistthe
populationofESRDpatientsondialysissufferingfromconstipationinalleviatingthisconditionin
ordertoenhancetheirqualityoflifebydrawingonevidencebaseddieteticknowledge.
Methods:Aliteraturereviewhasbeenconductedonthesubject,drawingonbothcoursebooks,
personalnotesandarticlesfoundviaathoroughdatabaseandmanualreferencelistsearch.173
articles were chosen for thorough reading and relevant information was extracted and
incorporatedinthisthesis.
Conclusion: Once it has been established that the ESRDpatient's constipated state is rooted in
nutritional causes, remedying malnutrition and/or dehydration represents the first step in the
nutritional treatment; however, an excessive fluid intake is neither helpful nor recommended.
Next, omitting phosphate binders might prove to be an effective step as well. Since 50% of the
diet's phosphorus intake stems from processed foods, it might be possible to prevent
hyperphosphatemianaturallybycounselingthepatienttoavoidadditivescontainingphosphates.
In the case of a dietary fiber deficiency, ensuring a sufficient intake of fiber without having to
resort to bulking agents is possible. Adding pro and prebiotics to improve the composition of
colonicmicrobiotamightpresentachallengeduetothehighphosphorusandpotassiumcontent
ofdairyproductsandthesatiatingeffectofcertainprebiotics,butisstillcompatiblewithanESRD
diet and should be attempted if other options show no effect. Physical activity, often
recommendedastreatmentagainstconstipation,maybeadded,thoughonlytoimproveQoL.
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Resum
Baggrund: Dialysepatienters livskvalitet er nedsat markant i forhold til raske kontrolgrupper.

Samtidigterlivskvalitetttforbundetmedmortalitetsratenidennepatientgruppe.Afdennersag
erdetvigtigtatudarbejdebehandlingsregimer,derkanvremedtilatforbedredialysepatienters
livskvalitet. Med en prvalens p 21% til 63% udgr forstoppelse en af de faktorer, der pvirker
patienterslivskvalitetinegativretning,menptrodsafdetteeksistereringenklareretningslinjer
for behandling. Da den kliniske ditist arbejder bde med den ditetiske behandling af
forstoppelseognyresygdom,giverdetgodmeningatkombinerebeggefagomrder.
Forml:Formletmeddetteprojekteratundersgeomogigivetfaldhvordandenkliniskeditist
vha.evidensbaseretditetiskbehandlingkanafhjlpedialysepatientersforstoppelseogdermed
vremedtilatforbedredereslivskvalitet.
Metode:Derblevgennemfrtengrundiglitteratursgningifaglitteratur,noterfraundervisningen,
i flere relevante databaser samt ved manuel referencesgning. 173 artikler blev valgt til grundig
gennemlsningogrelevanteinformationerblevherefterinkorporeretidetteprojekt.
Konklusion: Nr det er sikkert, at forstoppelsen i dialysepatienten skyldes en ditetisk

problemstilling,erdetfrsteskridtatbehandleeneventuelunderernringog/ellerdehydrering;
et overdrevent vskeindtag kan dog ikke anbefales. At seponere phosphatbindere fra
behandlingen kan vre et effektivt skridt. 50% af kostens phosphorindtag stammer fra
forarbejdede fdevarer, hvorfor det i teorien er muligt at forhindre hyperphosphatmi naturligt
ved at vejlede patienten i at undg fdevarer tilsat phosphater. Foreligger der et for lavt
kostfiberindtag burde dette behandles gennem vejledning om muligt. Eksisterer forstoppelsen
stadigvk efter disse tiltag, kan det forsges at tilfje pro og prbiotika til patients kost for at
forbedre tarmens mikroflora, dog under hensyntagen til disse produkters hje phosphat og
kaliumindholdsamtdenmttendeeffektafnogleprbiotika.Fysiskaktivitetkanvremedtilat
forbedrepatienterslivskvalitet,menkanikkestaleneibehandlingenafforstoppelse.
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TableofContents
1.Introduction....................................................................................................................................................5
2.Aim,ResearchQuestions,ResearchField,PurposeandStructureofthisThesis...........................................7
2.1AimandResearchQuestions...................................................................................................................7
2.2ResearchFieldandPurposeofthisStudy...............................................................................................7
2.3TheStructureofthisThesis.....................................................................................................................8
3.ThePhilosophyofSciencebehindthisThesis................................................................................................9
4.MethodologicalandEthicalConsiderations.................................................................................................12
5.ThePathophysiologyofESRD.......................................................................................................................14
5.1.RenalFunctions....................................................................................................................................14
5.2TheCausesofCKDandtheProgressiontoESRD..................................................................................15
5.3TheEffectofImpairedKidneyFunctionontheHumanBody...............................................................16
5.3.1TheDevelopmentofPEW.............................................................................................................16
5.3.2.MineralDisordersandtheUseofBinders....................................................................................17
6.TheNutritionalManagementofESRDpatientsonDialysis.........................................................................19
6.1EnergyIntakeandMacronutrients........................................................................................................19
6.2PhosphateManagement.......................................................................................................................20
6.3PotassiumManagement........................................................................................................................20
6.4FluidandSodiumManagement............................................................................................................20
7.ThePathophysiologyofConstipation...........................................................................................................22
7.1Epidemiology.........................................................................................................................................22
7.2CausesofConstipation..........................................................................................................................23
7.3CausesSpecifictoDialysisPatients.......................................................................................................24
7.4TheAdverseEffectsofConstipationinGeneralandinESRD................................................................26
8.TheNutritionalManagementofConstipation.............................................................................................29
8.1EnsuringanAdequateDietaryIntake....................................................................................................29
8.2DietaryFiber..........................................................................................................................................30
8.3TheRoleofHydration............................................................................................................................31
8.4ProbioticsandPrebiotics.......................................................................................................................31
8.5Prunes....................................................................................................................................................32
8.6TheRoleofPhysicalActivity..................................................................................................................33
9.TheNutritionalManagementofConstipationinESRDPatientsonDialysis................................................34
9.1EvaluatingtheNeedforNutritionalIntervention..................................................................................34
9.2EnsuringanAdequateDietaryandFluidIntake....................................................................................34
9.3ChallengingtheNeedforPhosphateBinders........................................................................................35
9.4TheChallengesofFiberIntake..............................................................................................................37
9.5TheChallengesoftheUseofProandPrebiotics..................................................................................39
9.6Prunes....................................................................................................................................................40
9.7PhysicalActivity.....................................................................................................................................41
9.8OliveOil.................................................................................................................................................41
9.9PossibleGuidelinesfortheRD..............................................................................................................42
10.Conclusion..................................................................................................................................................44
11.FurtherThoughts:TheLackofLargeScaleRCTs........................................................................................46
12.ReferenceList.............................................................................................................................................47
Appendix1:Studyoverview.............................................................................................................................59
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1.Introduction
Thekidneysperformseveralimportantfunctionsinthehumanbody,excretingwastesubstances
and maintaining the body's fluid balance being some of them. Should the kidneys begin to fail,
externalinterventionbecomesnecessaryduringEndStageRenalDisease(ESRD),eitherbyfinding
asuitabledonorkidneyorbyusinghemodialysis(HD)orperitonealdialysis(PD)tocarryoutthe
mostimportanttasksofthekidney.InDenmark,approx.2300patientsarecurrentlyemployingthe
latteroption(1).Thoughtheirlifeexpectancydoesrisesteeplyduetodialysiswithoutmedical
intervention, death would supervene within weeks if not days (2) this treatment does not
perform all of the kidneys' functions, nor does it come without adverse effects. Considering the
varietyoftasksdemandedofthisspecificorganaswellastheinvasivenatureofthisintervention,
symptomssuchaspain,fatigueandnauseaare,notsurprisingly,widespread(3)andexertsevere
negative influence on the quality of life (QoL) of dialysis patients. Since QoL has become an
importantfactorintheoveralltreatmentofpatientsbecause,amongstothers,thereseemstoexist
a correlation between QoL and mortality during ESRD (4), means by which to alleviate these
symptomsaremuchsoughtafter.
OnesymptomaddingtotheburdenoflifewithESRDisconstipation.Thoughnotoneofthemost
addressedones(5,6),itsprevalenceisreportedtobemuchhigherthantheestimatednumberof
15%inwesterncountries(7),rangingfrom21%(5)to63%inHDpatients(8).Sincepatientswith
chronickidneydisease(CKD),especiallyduringthemoreadvancedstages,alreadysufferfroman
impaired QoL well below the threshold of healthy controls (9) and since constipation influences
heavily on QoL it is thus, according to the authors of a systematic review on the subject, a
conditionnot[to]bedismissedas[...]trivial(10).Apartfromthisreason,otheradverseeffectsof
constipationhavebeennotedindialysispatientsthatrequireattention,spanningfromissuessuch
asthedevelopmentofmalnutrition(11,12)andnonadherencetotheprescribedtherapy(13,14)
tomoresuddenbutnolesslifethreateningoccurrencessuchasperitonitisinPDpatients(15,11,
16) and the development of hyperkalemia (17). Yet, as a gastrointestinal (GI) disorder, it is a
condition frequently underrecognized and, consequently, undertreated in nephrology care
settings (18, 19). According to Licensed Master Social Worker Steven Iacono, Constipation [and
other gastrointestinal symptoms] are so common that there may be a tendency by clinicians to
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disregardorminimizetheirimportance(14).Thetruthofthisstatementisunderlinedbythefact
that Danish and international guidelines for the nutritional treatment of ESRDpatients are quite
thoroughintheirdescriptionofthecomplexinteractionofkidneyfailureandnutrition,yetneglect
theoccurrenceofconstipationasasideeffectofthedisease:Onlyoneoffivemajorcoursebooks
withinthefieldofclinicalnutritionusedasareferencebytheauthor(20,21,22,23,24,cf.also25)
mentions constipation as an important part of the clinical symptoms (26), and none of them
presentguidelinesforthetreatmentofthiscondition.LookingatsomeoftheDanishguidelinesfor
thetreatmentofconstipationinpatientsingeneral(27,28)revealsthatseveralofthetraditional
treatment options might be of no use to ESRDpatients due to the impairment of the kidney. In
lightofthesevereconsequencesconstipationmayholdforaffecteddialysispatients,thisvoidof
usefulinformationseemsdistressing.
Onepossiblereasonforthelackofguidelinesmightbethebroadarrayofsymptomsmorepressing
than GI disorders in dialysis patients; in comparison, one comprehensive study showed that
symptomssuchasfatigue,pruritusandbone/jointpainaremorecommon(69%,54%,50%)and
haveagreaterimpactinmeanseveritythanconstipation(21%)(5).Yeteventhoughmeanseverity
mightbelowerthanforothersymptoms,those21%sufferingfromtheconditionstilldescribeitas
beingbothersome,whichmeansthatitaffectstheirQoLnegatively.Unfortunatelythetreatment
ofpatientsdependentondialysisiscomplicatedandtimeconsumingsincemajorissuessuchas
dialysisaccessandthemanagementofbonemetabolismandanemia(18)requiretheattentionof
the attending physician, which may downplay the emphasis placed on minor symptom
management. In this connection, the importance of a multidisciplinary approach to symptom
management in hemodialysis patients is stressed. Since [registered dieticians] practicing in
nephrologycareareanintegralpartoftheinterdisciplinaryteamthatprovides[this]care(29)and
since lifestyle modifications often are used as firstline treatment against constipation, it seems
onlyreasonabletoexaminethepossibilitiesandlimitationsoftheregistereddietician(RD)inthe
managementofconstipationindialysisdependentpatients.
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2.Aim,ResearchQuestions,ResearchField,PurposeandStructureofthisThesis
2.1AimandResearchQuestions
Basedontheabovetheaimofthisstudyistodetermineif,andifso,howtheregistereddietician
mayassistthepopulationofESRDpatientsondialysissufferingfromconstipationinalleviatingthis
condition in order to enhance their QoL by drawing on evidencebased dietetic knowledge. To
complywiththisaim,thefollowingresearchquestionswillbeanswered:
WhatisthepathophysiologyofESRDandhowisthisconditiontreatedvianutrition?
Whatisthepathophysiologyofconstipationandhowisthisconditiontreatedvianutrition?
WhichdiscrepanciesexistinthenutritionaltreatmentofESRDandconstipation?
Whichnutritionalmeasuresoftreatmentmayprovethemselvesusefulinthetreatmentof
constipationinESRDpatients?
2.2ResearchFieldandPurposeofthisStudy
The field of research derived from both aim and research questions is the dietetic approach to
treatingconstipationinHDandPDpatients;hereby,patientswithchronicoracuterenaldisease
or patients suffering from constipation without the inclusioncriteria of dialysis treatment are
excluded,asaretreatmentstrategiesnotbaseduponnutrition.However,sincecertainsimilarities
do exist in the research literature concerning CKD and ESRDpatients, some articles covering a
widerfieldareusedasreferenceswhererelevant.
Usually, the field of nutrition also covers the therapeutic approach of enteral and parenteral
nutrition(thoughthelatterismainlytheresponsibilityoftheattendingphysician);thesetwoareas
ofexpertisewillnotbeincludedinthisstudyduetoalackofresearchconcerningbothfieldsas
wellastheatrophiceffectthatparenteralnutritionhasontheGItractwhichbringswithititsown
challenges.
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The main players within this field are RDs within a nephrology care setting and their patients.
Otherhealthcareprovidersmaybeaffectedbytheresultsofthisstudy,butarenotincludedasitis
assumedthatthemainresponsibilityforthenutritionalcareofnephrologicpatientsrestswiththe
RD. Important institutional structures such as the hospital or the health care system are not
addressedeitherduetotheaimofthisstudy;structuressuchasthehospitalmayplayapartinthe
successfultreatmentofconstipationinESRDpatientsonceitistobecarriedoutinclinicalpractice,
yet they are of little import to the systematic evaluation of existing literature within the field of
research.
The purpose of this study is to further develop the field of clinical nutrition by adding relevant
information to the existing knowledge about nutritionbased nephrology care. Furthermore, it is
thehopeoftheauthorthatthisthesiswillinspirefurtherresearchaimedatimprovingtheQoLof
dialysispatientswithconstipation.
2.3TheStructureofthisThesis
Afteraninitialconsiderationofthephilosophybehindthescientificapproachofthisstudyanda
short review of the methods applied in accumulating knowledge on the subjects at hand, the
structure of this thesis corresponds to the order of research questions (cf. ill. 1), resulting in an
attemptatformulatingpossibleguidelinesinpart9.Aconclusionandthoughtsonfurtherresearch
concludethisproject.
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Illustration1:Thestructureofthisthesis.
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3.ThePhilosophyofSciencebehindthisThesis
Theissueofwhattoresearchisinextricablylinkedtothehow,which,inturn,beckonsthequestion
of which scientific approach to adopt. Launs et al (30, p. 44 pp.) differentiate between three
scientific paradigms that influence the way the researcher thinks and acts and determine the
methods applicable to a given research project as well as the validity of the project's results.
Within the empiricalanalytical paradigm, the researcher is occupied with extracting and
systematizing causal explanations from an objective reality by accumulating knowledge through
empirical findings. In order to be valid, results must be precise, reliable, and generalizable. The
interpretiveparadigm,ontheotherhand,ismoreconcernedwithdeterminingthemeaningthat
thepopulationtoberesearchedascribestoagivenphenomenon,whichmeansthatthedesireto
operatewithinanobjectiverealitybecomesnaught;realitywithintheinterpretiveparadigm,after
all, is constructed by social interactions. Results must still be valid, but the criteria for validity
changeintheinterpretiveparadigm:Mostimportantly,themethodusedmustbeconsistentwith
theresearchfield(31,p.231).Last,Launsetaldescribethecriticalparadigmwhichdoesbelieve
in an objective reality, but claims that this reality is shrouded by underlying, oppressive power
relationsthatneedtobeidentified.Resultsarevalidiftheresearchmethodappliedsucceedsin
initiatingalearningprocessandinelicitingchange.
In order to answer the research questions posed in this thesis, it has been chosen to operate
mainly within the empiricalanalytical paradigm and, more specifically, to adopt a biomedical
approach. The biomedical paradigm regards the human body as a machine and disease as an
obstruction that prevents the machine from operating fully (32, p. 17, see also 33, p. 37). The
context e.g. the patient's current situation or opinion upon the matter of the disease is not
given much, if any, weight. Treating a patient means removing the obstruction by applying the
correcttreatment;inthecaseoftheRDthismeanstofindthecorrectdieteticapproachthatwill
remedy the disease or adverse effect. In clinical practice, however, the tasks required of an RD
extendfartherthanmerelyacquiringandapplyingscientificknowledgeoftheroleofnutritionto
curing and treating various diseases. Though the biomedical approach is warranted, it cannot,
reductionisticasitis,standaloneinthetreatmentofapatientsincethepatientis,infact,aperson
and not a machine. In order to be able to provide comprehensive treatment, the health care
providerwouldneedtoincludethepersonbehindthediseaseaswellasstructuresinfluencingon
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the wellbeing of this person. He or she would therefore have to assume an interparadigmatic
pointofviewthatcombinesbiomedicalresearchattainedwithintheempiricalanalyticalparadigm,
psychologicallyandsociallyorientatedknowledgegatheredwithintheinterpretiveparadigmanda
morestructuralapproachasitisadoptedwithinthecriticalparadigm.Theauthoriswellawareof
the fact that, by choosing to operate almost solely within the empiricalanalytical paradigm, a
majorpartoftheRD'sworkisbeingneglectedandthatthisthesisthereforecannotstandalonein
thenutritionaltreatmentofESRDpatientssufferingfromconstipation.Theviabilityofguidelines
emergingfromthisstudywillnotonlybedeterminedbytheiractualeffectonthepatientandhis
orhersymptoms,butalsobythehealthcaresystem'sflexibilityinallowingnewtreatmentoptions
to be implemented in the current treatment of this patient population, the RD's skills in
communicatingthemandmotivatingthepatienttoconcurwiththemand,lastbutnotleast,the
patient's ability to adhere to these guidelines (which incidentally is impaired in dialysis patients
withconstipation(14)).Thereadershouldbearthislimitationinmind.
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4.MethodologicalandEthicalConsiderations
Theaimofagivenresearchprojectandtheparadigmaticapproachdeterminethemethodsthat
willbeappliedinordertoanswertheposedresearchquestions.Inthiscaseadescriptiveresearch
typewillbeadopted(30,p.13)asthistypeisinaccordancewiththeempiricalanalyticalparadigm
andsincetheonlydatausedconsistofresearchprojectsthathavealreadybeencarriedout.
Initially it had been planned to conduct a systematic literature review by searching in relevant
databasesforlarge,or,ifthosewerenotavailable,smallscalerandomizedcontrolledtrials(RCTs)
aimedatalleviatingconstipationinESRDpatientsindialysistreatment.Itquicklybecameevident,
however,thatsuchstudieshadnotbeenconducted.Thechallengeoftreatingconstipationinthis
patient population had been addressed in several articles and various remedies had been putto
thetest,yetfewofthesestudieswereRCTsandonlyfewofthemencompassedalargepartofthe
patientpopulation.Furthermore,thenumberoftestsubjects,themethodsusedandthedefinition
of what constituted constipation varied greatly between studies, which made it impossible to
determinedistinctinclusioncriteriaforaproperliteraturereview.Anotherapproachhastherefore
been adopted which takes on the shape of a patchwork, pointing out trends and making
suggestionsforfurtherresearchareas.
The following databases and journals have been subjected to a thorough search: Pubmed,
Cochrane, ScienceDirect, Forskningsdatabasen, American Journal of Clinical Nutrition, American
Dietetic Association, Web of Science, Embase and Google Scholar; though this ensures a broad
coverage,itisnoguaranteethatallrelevantworkwithinthisfieldhasbeenfound,especiallysince
theauthorwasunawareofgrayliteratureanddatanotaccessibleinpublicdomain(34).
The following search terms have been applied in various combinations: Kidney, kidney
insufficiency, renal insufficiency, renal, chronic kidney disease, CKD, dialysis, HD, CAPD, PD,
hemodialysis, haemodialysis, peritoneal dialysis, ESRD, end stage renal disease, obstipation,
constipation,nutrition,qualityoflife,QoL,nutritionaltreatment.
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All articles listed were scanned: First, the title was evaluated in respect of relevance. Next, the
abstractsofallarticlesdeemedrelevantwereexamined.Atthispointitbecameevidentthatnot
enough studies existed to conduct the planned review. The search was therefore expanded to
include articles that made a manual comparison of nutritional guidelines for ESRDpatients and
constipated patientspossible.Thisbroadersearchyieldedwellovera hundredarticles.Thenext
stepconsistedofamanualsearchofreferencelistsfromrelevantarticlestoensurethatnostudies
hadbeenmissed.Finally,173articleswerechosenforfurtherreading.Furthermore,coursebooks
onclinicalnutritionaswellaspersonalnotesfromclasswereconsulted.
Aspreviouslymentionedmoststudiesonthemaintopicofthisthesishadnotbeensubjectedto
the gold standard within biomedical research, the RCT (35), which impairs their validity. Most of
the data used here is based on reviews, overviews, cohort and crosssectional studies as well as
casereports.Furthermore,manyoftheresultshavenotbeenreproducedinfurthertrials,which
makesitdifficulttogeneralizeontheefficacyofthetestedtreatment.Whereguidelinesbasedon
studiesaregiven,theevidenceonwhichthesearebasedissummedup.Forotherstudiesused,a
quick overview of their design and rank is given in appendix 1 (books and official guidelines not
included).
Sincenoexternalpartnerswereinvolvedinthedevelopmentofthisthesis,ethicalconsiderations
willnotbedescribed.However,duetothelackofconsultationwithe.g.RDsorphysiciansworking
in the field of nephrology care, possible guidelines presented in this thesis are of a strictly
theoreticalnatureandthusrequirevalidationbyexternalsourcesorthroughpracticalapplication
withintheresearchfield.
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5.ThePathophysiologyofESRD
Thekidneysarethefocalpointofthispartandtheirfunctions,thedevelopmentofCKDaswellas
thesymptomsofESRDarebrieflydescribedhere.
5.1.RenalFunctions
Inshort,themainfunctionofthekidneysistokeepthelevelofseveralsubstanceswithinanarrow
homeostatic range by measuring the current content and regulating the excretion, reabsorption
and secretion of these substances accordingly during the process of filtration (36, 37). Most
importantly,thekidneysregulatethecontentofbodywaterandinorganicions(suchasphosphate
and potassium) as well as the acidbase balance. They also assist in removing metabolic waste
products such as urea and creatinine and foreign chemicals derived from e.g. drugs from the
blood. Impairment of these functions without intervention results in the accumulation of toxic
substances,leadingtoafataloutcomewithinashortspanoftime.Moreover,thekidneysplayan
importantpartintheprocessofgluconeogenesisduringfastingandtakeonanendocrineroleas
well by secreting hormones and enzymes involved in the regulation of erythrocyte, sodium and
calciumbalance.
About 1.3 liters of blood pass through the functioning units of the kidneys, the nephrons, each
minute, where it is filtrated by a large number of capillary loops called glomeruli. In healthy
kidneys the glomerular filtration rate (GFR) is approx. 125 ml pr. minute, yet various conditions
suchasdiabeticnephropathymaycauseittodeclineuntilnofiltrationoccurs.AGFRlowerthan90
mlpr.minutemarksthebeginningofstages2to5ofCKD(ill.2);itisnotbeforetheGFRhasfallen
below15mlpr.minute(stage5)thatexternalinterventionisparamounttoensuresurvival.
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Stages GFR Kidneyfunction
1 Morethan90mlpr.minute Indications of kidney damage, though still normal or

increasedkidneyfunction
2 Between6089mlpr.minute Kidneydamagewithmildlyreducedkidneyfunction
3 Between3059mlpr.minute Moderatelyreducedkidneyfunction
4 Between1529mlpr.minute Severelyreducedkidneyfunction
5 Lessthan15mlpr.minute EndStageRenalDisease
Illustration2:The5stagesofCKD.
5.2TheCausesofCKDandtheProgressiontoESRD
ThoughtheGFRdoesdecreasewithage,adeclinesevereenoughtoleadtoESRDdoesnotoccur
naturally, but requires a condition that actively damages the kidneys. The two most common
reasons are dysregulated diabetes (27.8% of patients in Denmark in 2012 (1)) and high blood
pressure(10.6%),sincebothastateofcontinuoushyperglycemiaandhypertensionputstoomuch
of a strain on the kidneys. The results are glomerular hyperfiltratrion, intraglomerular
hypertension1 and vascular complications (such as a higher degree of vascular permeability and
abnormalities of the membrane in short called glomerulosclerosis), all of which damage the
glomeruli. After an initial period of hypertrophy to compensate for the reduced function of the
damagedunits,thefiltrationratedecreases,markingtheonsetofCKD.Ifleftuntreated,theGFR
will diminish further until, eventually, the rate of filtration reaches almost nil. At that point the
patienthasdevelopedESRD.
1 Notethathypertensionmaybothbecauseandeffectinthiscase.
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5.3TheEffectofImpairedKidneyFunctionontheHumanBody
Sincethefunctionsofthekidneysareratherdiverse,soarethesymptomsofCKD.Initsentirety,
thestateofmetabolicabnormalitiesandelectrolyte,fluidandhormonalimbalanceswhichemerge
with ESRD is often referred to as uremia and presents with syndromes and symptoms such as
proteinenergywasting(PEW),bonemineraldisorder,nausea,anorexia,vomiting,fatigue,pruritus
and psychological disorders. Since the focal point of the author is the nutritional treatment of
constipationinESRDpatients,acompleteoverviewofthedisorderspresentinuremialiesbeyond
the scope of this thesis. Therefore, only areas of interest concerning the development and
treatmentofconstipationinthispatientpopulationaredescribed.
5.3.1TheDevelopmentofPEW
WithkidneyfunctiondecliningtoaGFRbelow1020ml/min,thedevelopmentofPEWbecomes
more prominent (38). PEW has recently been defined as a state of decreased body stores of
proteinandenergyfuels(bodyproteinandfatmasses)(39),anditspathogenesisismultifactorial,
with undernutrition only constituting one of many causes. In ESRD, an inadequate nutritional
intake is a common side effect related to symptoms such as nausea, vomiting and other GI
problems(40,41),tasteabnormalities(42),anorexia,hyperleptinemiaanddietaryrestrictions(38)
and emotional stress (43). At the same time nutrients are often lost with the dialysate.
Furthermore,ESRDpatientsoftenshowsignsofinflammation,whichisnotonlyassociatedwithan
increasedenergyexpenditureandanorexia,butalsowithacytokineinducedcatabolicstateand
insulinresistancewhichleadstoanincreasedlossofmusclemassandareducedabilitytorebuild
the mass lost (44, 38). Other factors often associated with ESRD such as comorbidities (e.g.
diabetes and cardiovascular disease (CVD)), metabolic acidosis (due to reduced acid excretion
throughtheurine),hormonalabnormalities(suchaselevatedglucagonandparathyroidhormone
levels) and a decreased protein synthesis add to this hypercatabolic state. Since PEW is a strong
predictorformortalityinESRDpatients,nutritionalandmedicalinterventionisoftenindicated.
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5.3.2.MineralDisordersandtheUseofBinders
Sincethekidneysplayanimportantfunctioninmineralhomeostasis,animpairedrenalfunction
oftenleadstomineraldisorders,specificallyinrelationtocalciumandphosphorus(mostlyinthe
formofphosphate2),bothusedfor,amongstothers,themaintenanceofbonemassandtheproper
functioning of nerves and muscles. Usually the serum levels of calcium and phosphate are kept
within a homeostatic range by kidneyinduced excretion and reabsorption of calcium and
phosphate and the activation of vitamin D required for the absorption of dietary calcium and
phosphorus. Once the GFR declines, however, the kidneys are no longer capable of excreting
excessmineralswithhyperphosphatemiaasoneofseveralresults.Atthesametimethefailureto
activatevitaminDmayleadtohypocalcemia.Whenphosphatelevelsarehighandcalciumlevels
arelow,theparathyroidglandsarestimulatedtosecreteparathyroidhormone(PTH),whichhelps
in regulating calciumphosphatehomeostasis by drawing calcium from the bones. In prolonged
hyperphosphatemia, a state of PTHresistance followed by secondary hyperparathyroidism
develops, leading to osteodystrophy, increased vascular calcification and mortality; a syndrome
termedCKDboneandmineraldisorder(CKDMBD)(45).
In order to avoid these adverse outcomes of renal impairment, phosphate levels are monitored
closelyand,ifnecessary,treatedbothnutritionally(part6)andmedically,especiallythroughthe
useofphosphatebinders
Calciumandphosphatearenottheonlymineralsforwhichhomeostasisisimpairedwithdeclining
renal function. Potassium, also involved in nerve and muscle function, is excreted through the
kidneysaswell,andadecreaseinurinaryexcretionmaythereforeleadtoastateofhyperkalemia.
Furthermore,thehypercatabolicstateassociatedwithESRDreleaseslargeamountsofpotassium
fromthebrokendowncells,furthercontributingtothecondition.Ifleftuntreatedhyperkalemia
notonlypresentswithsymptomssuchasfatigueandweakness,butmaybecomelifethreatening
duetocardiacarrhytmias.Hyperkalemiamaybetreatedthroughnutrition(part6)and/ortheuse
ofpotassiumbinders.
2 ThetermphosphorusencompassestheelementP,whiletheinorganicionphosphateconsistsoffouroxygenatoms
bound to phosphorus; since most of the phosphorus content in the human body exists as phosphate, the latter
termistheonemostlyusedinamedicalcontext,whilethetermphosphorusisusedinrelationtoe.g.chemical
analyses.Sincethisprojectcombinesbothfields,bothtermswillbeusedaccordingtocontext.
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5.3.3.FluidandSodiumImbalances
The kidneys are involved in maintaining a proper fluid balance by adjusting the amount of fluid
excreted to the amount of fluid ingested. During the latter stages of CKD, the kidneys' ability to
diluteandconcentrateurinedecreasesand,consequently,sodoesurineoutput;duringESRDthe
osmolalityoftheurinereachesaconstantconcentrationofsolutessuchassodiumirrespectiveof
the patient's water and sodium intake (46). The resulting fluid retention (often evident by the
presenceofedemas)increasestheosmolalityofthebody'sfluidcompartmentsandleadstothe
development or worsening of hypertension and a state of dysnatremia; mainly hyponatremia,
though hypernatremia is possible due to the impaired renal ability to concentrate urine. Both
hypertensionanddysnatremiaarecloselyrelatedtosodiumintake,assodiumonlycanbeexcreted
viatheurineandanimpairedrenalfunctionthuswillretainsodiumwithinthebody.Sincesodium
isconsideredapotenturemictoxin(47),thisstateishighlyundesirable.
During dialysis, excess fluid (and sodium) is removed, which means that patients on PD seldom
experience fluid overload, while patients on HD with only 3 weekly dialysis days often are
restrictedintheirfluidandsodiumintake(part6)topreventahighinterdialyticweightgain.
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6.TheNutritionalManagementofESRDpatientsonDialysis
Due to the high impact of the kidneys on bodily functions, the nutritional management of this
conditionisquitecomprehensive,asisillustratedbelow.Medicalorothertreatmentoptionsnot
encompassedbyorofspecialimporttotheRDarenotcoveredinthisthesis.
6.1EnergyIntakeandMacronutrients
Asruleofthumb,patientsundergoingdialysishaveanenergyrequirementof150kJpr.kgbody
weight pr. day (24); that includes energy derived from the dialysate. However, since dialysis
patients often suffer from edemas, energy intake should be based on the patient's dry weight,
whichisnotalwayseasytodetermine.ThepresenceofPEWandtheabsorptionofglucosefrom
thedialysatefurthercomplicateanexactcalculationofthepatient'senergyrequirements,anditis
therefore recommended to monitor the patient's weight and nutritional status closely and to
adjustenergyintakeaccordingly.
Concerningtheintakeofcarbohydratesandfat,therecommendationsforthegeneralpopulation
(basedonNNR2004(48))apply(24),thoughtheincreasedriskofcardiovascularmortalitywithin
this patient population does warrant a close monitoring of the patient's serum lipid profile.
However, since cardiovascular calcification is one of the adverse effects of hyperphosphatemia,
treatmentofCVDcannotoccurwithfocusonfatintakealone.
Protein recommendations during dialysis differ markedly from those given to the general
population(48).Sinceproteinislostduringdialysis(1012gofproteinpr.dialysisdayinHDand5
15 g of protein pr. day in PD) and protein catabolism is increased in ESRD and during dialysis,
currently an intake of 1.2 g pr. kg pr. day is recommended (24) for both HD and PDpatients.
However,patientsonPDmightrequireupto1.5gpr.kgpr.dayduetoagreaterlossofprotein
throughthedialysate.
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6.2PhosphateManagement
To avoid the adverse effects of hyperphosphatemia on bone metabolism and pruritus (49) it is
recommended to keep the serum phosphate level below 1.8 mmol/l (26), though nutritional
therapyistypicallyinitiatedonceserumphosphaterisesabove1.5mmol/l(24).Thetherapymay
consist of medicated regulation of the secondary hyperparathyroidism sparked by the impaired
kidney function as well as regulation of dialysis dose, but of most interest to the RD is the
nutritional management of hyperphosphatemia and the use of phosphate binders. Phosphorus
intakeisrestrictedto8001000mgpr.day,andsincephosphorus/phosphateisfoundinavarietyof
foods,bothasfreephosphorusandasanadditiveusedduringfoodproduction(phosphate),itis
impossible for most ESRDpatients to continue their dietary habits while adhering to
recommended phosphorus restrictions; in comparison the typical Danish phosphorus intake is
1339 mg pr. day (24). Main sources of phosphorus constitute dairy products, cereals and grains,
nuts,meat,fishandpoultry(50)aswellasprocessedfoods.
6.3PotassiumManagement
As mentioned above, hyperkalemia can be avoided through nutrition as well, and dietetic
intervention takes place once serum potassium has reached 5 mmol/l, though values up to 5.5
mmol/lareacceptableinnephrologicpatients(24).SincetraditionalDanishdietscontainapprox.
3500mgofpotassiumanddietaryrestrictionsrecommendapotassiumcontentof20002500mg,
theimpactonthepatient'sdietisquitecomprehensive(24).Similartophosphorus,potassiumis
foundindairyproducts,grains,nuts,meat,fishandpoultry,butalsoinpotatoes,vegetablesand
fruits,andcontentmaybeloweredbyusingspecificpreparationmethodssuchasacombinationof
choppingandcooking(50).
6.4FluidandSodiumManagement
Due to fluid imbalances caused by ESRD, fluid intake is often restricted to 800 ml + the amount
excretedthroughurine.SinceHDpatients,especiallyduringthelatterstagesofESRD,mighthave
nourineoutputatall,thisisaburdensomerestriction.Inthisconnectionitisimportanttofocus
onsodiumaswell,sincesodiumplaysanimportantroleinthebody'sfluidbalance.Furthermore,a
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highsodiumintakemighttriggerthepatient'sthirstandcontributetotheproblemofhypertension
often already present in ESRDpatients. An intake of 20002400 mg of sodium (56 g of salt) is
thereforerecommended(24),whichissignificantlylowerthanthetypicalDanishintakeof3700mg
pr. day. Processed foods are the main source of salt (approx. 70% in Denmark (24)), and,
incidentally,alsooneofthemainsourcesofphosphorusintake(part9).
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7.ThePathophysiologyofConstipation
Afteraddressingthekidneys,focusnowshiftsontothesubjectofconstipationbydescribingthe
epidemiology of this condition, its pathogenesis and symptoms in the general population and
dialysispatients.
7.1Epidemiology
It is difficult to determine the exact prevalence of constipation in the general population, and
estimatessuchas15%inwesterncountries(7)coveroverquiteabroadrangeofvaryingvalues.A
largescalereviewconductedin2011(51)showedaprevalencebetween0.7%and79%worldwide,
while another systematic review carried out in 2004 (52) presented numbers between 1.9% and
27.2%inNorthAmerica.SeveralsmallerstudiescarriedoutwithinthefieldofESRDshowvalues
ranging from 8% and 57% (3), 21% (5), 40% (53) and even up to 63% in one study with the
incidenceconsistentlyhigherinHDpatients(8)thaninPDpatients(29%(8)).
These values do not come as a surprise when bearing in mind that, until quite recently,
constipationhadnotbeendefinedclearly.Acomprehensivestudyconductedin1996revealedthat
patientsanddoctorsrefertodifferententitieswhentheytalkof'constipation'(54).Whereasthe
medical definition of constipation back then was mainly based on time elapsed between stools,
patientsweremoreconcernedabouttheconsistencyoftheirstool;atendencythatisreflectedin
other studies as well: Often patients' complaints of constipation have little to do with the
frequency of bowel movements. When patients are questioned about their perception of
constipationtheyfrequentlyregardstraining,passageofhardstools,ordifficultypassingstoolsas
constipation (52). This discrepancy has led to a revision of the Rome Diagnostic Criteria for
FunctionalGastrointestinalDisorderstoencompassstraining,stoolconsistencyandsensationsof
e.g. incomplete evacuation (55, see ill. 3). Though the use of Rome III within clinical studies has
become more widespread, it does not form the basis of all research within the field of
constipation,especiallynotinstudiesconductedbefore2006inwhichthedifferencebetweenself
defined constipation and constipation based on stool frequency is quite marked. In light of the
severityofadverseeffects(seebelow),lowervalues,however,donotsuggestthatconstipationisa
conditiontobetakenlightly.
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Illustration3:Rome3DiagnosticCriteriaforFunctionalConstipation.
7.2CausesofConstipation
Constipation is multifactorial in its nature and, thus, in its treatment. Initially it is important to
differentiatebetweenprimaryandsecondarycauses(56). Primarycausesincludeaphysiological
impairmentofcolonicmotility,adysfunctionalinteractionbetweencolorectalmotorandsensory
functions, an unhealthy defecation behavior (withholding), a state of psychological distress and,
lastbutnotleast,aninexpedientdiet;thoughoftenthesefactorsmayoverlap.Thetermsecondary
causesreferstoalonglistofdiseasesand/ormedicationsassociatedwithconstipation.Otherrisk
factors often associated with constipation include age and gender, as the condition seems to be
moreprevalentintheelderlyandinwomen(51).Sincetheauthor'sfocusliesonthenutritional
treatment of dialysis patients with constipation, a thorough overview of each of these factors
extends beyond the scope of this thesis. Yet, in order to find the right treatment for a specific
patient, it is important to keep the broad range of possible causes of constipation in mind, as a
remedythathasproventobeeffectiveinonepatientmightworsentheconditioninanother(see
part8.2).
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Concerningpossibledietarycausesofconstipation,theimportoffiberandfluidintakeaswellas
adequate nutrition has to be highlighted. In a groundbreaking study from 1972, Burkitt et al
demonstratedthattheprevalenceofconstipationismuchhigherinpopulationsonalowfiberdiet
thaninpopulationsconsumingatraditionalhighfiberdiet(57),whichhasledtotheuseoffiber
supplementsasfirstlinetreatmentofconstipation.Inanotherstudytheimportoffluidintakeon
colonictransittimewasexaminedbyrestrictingthefluidintakeofeighthealthymalevolunteersto
lessthan500mlpr.day;theresultsshowedasignificantdecreaseinstoolfrequencycomparedtoa
fluid intake of more than 2500 ml (58). Moreover, several studies encompassing patients with
anorexianervosahaveshownthataninadequatecaloryintakedelayscolonictransittime,which
alsomayleadtoconstipation(56,59).
Whetheraconnectionexistsbetweenphysicalactivityandconstipationisyettobedetermined;
some studies show that physical activity does affect colonic transit time, but the amount and
intensityofphysicalactivityrequiredtoalleviateconstipationislesscertain(part8.6).Ithasbeen
shown,however,thatphysicalactivityplaysaroleinimprovingQoL(60,61).
7.3CausesSpecifictoDialysisPatients
Aspreviouslymentioned,theprevalenceofconstipationishigherindialysispatientsthaninthe
general population. Considering that CKD, age, diabetes and the use of phosphate binders all
constitutesecondarycausesforthedevelopmentofconstipation,thisdoesnotcomeasasurprise.
Since the prevalence of constipation is positively correlated with age (51) and since most ESRD
patientsareolderthan50years(1),agemightbeoneexplanationforthehighrateofconstipation
foundamongthesepatients.Itisbelievedthatwithage,neurodegenerativechangesintheenteric
nervoussystemleadtothedevelopmentofdelayedcolonictransittime(62),asdopsychological
disorders(12),whiletheanorexiaofaging(63),reducedmusclestrength(whichmakesitdifficult
to e.g. shop and prepare food) and morbidities such as dementia lead to a decreased fluid and
dietaryintake(cf.alsowith64onthesubject).
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ConsideringthatalmostonethirdofESRDpatientssufferfromdiabetes(1),thisconditionmight
be another cause, as it has been shown that hyperglycemia delays colonic motility (65).
Furthermore,ithasbeendemonstratedthatdisordersofGImotility,suchaspoorperistalsisand
delayedgastricemptying,areoftenfoundinpatientswithdiabetes(66)andarealsoknowntobe
common in ESRDpatients (67). In addition, two studies have demonstrated that colonic transit
timeisdelayedindialysispatients(68,69).This,aswellasthestateofuremiaitself,oftencauses
symptomssuchasnauseaandvomiting,whichreduceappetiteand,concomitantly,caloryintake;
symptoms which also are associated with renal insufficiency in general with 24% suffering from
vomiting(70),33%sufferingfromnauseaand38%fromanorexia(3).Dietaryrestrictionsaimedat
managinguremicsymptomsmightaddtothisproblematicsituationaspatientsinanattemptto
adheretoacomplicateddietaryregimenreducetheircaloryintakeinordertoavoidingestingthe
unrecommended food (38). Whatever the cause, this state of anorexia may play a role in the
development of constipation, both due to the inadequate intake in itself (consider that without
foodintake,noresponsetonutrientingestionsuchasperistalsisorsecretionofdigestiveenzymes
cantakeplace,cf.71),butalsoduetoareducedintakeoffibersandfluid.Atthesametimethe
developmentofPEWin ESRDmayplayaroleinthedevelopmentofconstipationasithasbeen
shown that the mucosal and muscular layers of the intestinal tract show signs of atrophy and
reduceddigestiveenzymeactivityinastateofproteincaloriemalnutrition(72).
Phosphate binders are often viewed as the most important treatment in the prevention of
hyperphosphatemia, yet their use is associated with the development of constipation (73). Even
thoughthemostconstipatingbindersonanaluminumbaseseldomareprescribedtodayduetoa
highriskoftoxicity,modernbindersonacalciumbase(14)andresinssuchasSevelamer(74)still
contributetothedevelopmentofconstipationinsomepatients3.
Asmentioned,psychologicalandbehavioralfactorsmightaddtothecomplexpathophysiologyof
constipation as well, maybe especially in dialysis patients due to the psychological distress
associated with ESRD: A review by Murtagh et al 2007 (3) shows that between 5% and 58% of
ESRDpatients suffer from depression. Since the close connection between depression and
3 Potassiumbindersmayplayaroleaswell(77),thoughinthestudiesfoundduringtheliteraturesearch,onlythree
wroteaboutthispossibleconnection(78,8,25),aswasthecasewiththeroleofironsupplements(onestudy,79).
Therefore,theywillnotbeaddressedanyfurtherhere.Thereadershouldbearinmind,however,thattheymight
constituteafurtherchallenge.
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constipationhasbeendemonstrated,thismightbeanotherpossiblecauseforconstipationinthis
patientpopulation(cf.75ontheassociationbetweenconstipationanddepressioninESRDand76
ontheroleofserotonininGIdisorders).
SpecificallyforpatientsonHD,behavioralfactorsmightplayarole,sinceithasbeenshownthat
severalofthesepatientssuppresstheurgetodefecateduringHDtherapy(8);abehaviorthatmay
causeconstipationaswell(56).
7.4TheAdverseEffectsofConstipationinGeneralandinESRD
Thoughconstipationisrarelyassociatedwithlifethreateningconditions,itisnotwithoutadverse
effects either. More wellknown complications include haemorrhoids and anal fissures, but the
condition may also have a major impact on social life (such as the inability to work (10)) and
psychological wellbeing and even lead to more severe complications, especially in dialysis
patients.
In two comprehensive reviews, the impact of chronic constipation on the patient's mental and
physical QoL has been found to be markedly lower in patients compared to healthy controls,
comparable to patients suffering from hypertension, diabetes and depression (7) and patients
suffering from chronic allergies, chronic rheumatological conditions and inflammatory bowel
disease(10).Acrosssectionalstudyexaminingtheimpactofconstipationondialysispatientsalso
showed that QoL was significantly lower in those sufferingfrom constipation than in the control
group(16),whileanotherstudyfoundthatdepressionwasmuchhigherinconstipatedthannon
constipateddialysispatients.Theseresultswereinconcordancewithotherstudiescomparingthe
prevalenceofdepressioninconstipatedpatients(75).ConsideringthatQoLisalreadyreducedin
dialysispatientsandthosesufferingfromCKD(80,9,81)thiscombinedeffectofdialysis/CKDand
constipation is not surprising. Furthermore, one study examining the impact of GI symptoms in
general on the psychological wellbeing of ESRDpatients speculates that a large number of GI
symptomssuchasconstipationmightcontributetothedevelopmentofmalnutritioninthispatient
population due to a decreased food intake (82). The fact that constipation seems to be closely
associated with depression and that depression may be the cause of malnutrition as well (26)
further strengthens this speculation, as does a study conducted on PDpatients that found a
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relationship between PEW and severe GI symptoms (11, cf. 12). In addition, untreated chronic
constipationmayleadtofecalimpaction(animmobilebulkoffeces)whichalsoisassociatedwith
anorexia(83).Malnutrition,therefore,mightnotonlybeonepossiblecauseofconstipation,but
alsoapossiblesymptom.
AreducedQoLmightbeoneofthereasonsforpatientswithconstipationandESRDtodisregard
thenutritionalrestrictionsimposedonthem:Apartfromdepressioninitselfbeingassociatedwith
nonadherence(84),thewishtoalleviateconstipationhereandnowmightbestrongerthanthe
longterm complications associated with e.g. fluid retention (14) or hyperphosphatemia (13).
Anothersymptomofconstipation,therefore,mightbealackofconcordance.
Asmentionedintheintroductionofthisthesis,theriskofdevelopingperitonitisismuchgreaterin
PDpatients with constipation than in nonconstipated patients (15, 11, 16). Furthermore,
constipation is associated with peritoneal catheter malfunction and may thus interfere with the
effectivenessofPD(25).
SpecifictoESRDpatientsingeneralistheriskofdevelopinghyperkalemiaduetoconstipation.Itis
wellknownthat,withdecreasingkidneyfunction,renalexcretionofpotassiumdecreasesaswell.
Incontrasttoe.g.sodium,however,whichaccumulatesinastageofrenalfailure,thebodyisable
to compensate for the decrease in renal excretion of potassium by enhancing absorption in the
colonandtherebyincreasingfecalexcretion(85,145,146).Testingthistheory,alargestudyof354
dialysis patients demonstrated that those suffering from constipation were at a higher risk of
developing hyperkalemia since serum potassium levels were already higher in this patient
population(17).However,tothebestknowledgeoftheauthor,thisstudyistheonlyoneofitskind
and, even though a highly significant correlation was found between high serum potassium and
constipation,thereadershouldbearinmindthatonly20ofthe354patientsweresufferingfrom
constipationandtheresultsthereforeshouldbeevaluatedwithcaution.
AnothercomplicationspecifictoESRDpatientsistheaccumulationofuremictoxinsproducedby
intestinalbacteria.AsmallstudyincludingninepatientsonHDdemonstratedthattheserumlevel
of the uremic toxin paraCresol was higher in constipated than in nonconstipated patients (86).
SinceparaCresolcannotbeeffectivelyremovedbyHD,thismightconstituteanotherunfortunate
adverse effect of constipation in dialysis patients; though it is important to note that this
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informationisbasedononlyoneminorstudy.
Asmentionedintheintroductionofthisthesis,apartfromperitonitisinPDpatients,otheracute
lifethreateningcomplications,thoughrare,dooccur:Bothcasesofperforationofthecolon(87,
88, 89, 90, 91, 92) and of ischemic bowel disease and necrosis (93, 94) have been reported.
Furthermore, a largescale cohort study suggests that constipation might play a role in the
developmentofcoloncancer(95).
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8.TheNutritionalManagementofConstipation
Followingthepathophysiologyofconstipation,nutritionaltreatmentoptions4arepresented,based
onvariousreviewsandstudiessincenosinglearticlecoveredallpossibleapproaches.
8.1EnsuringanAdequateDietaryIntake
It is wellknown that the small and large intestine are dependent on a sufficient supply of
nutrients. During states of malnutrition, the usual growth and turnover of the mucosal layer is
inhibited and the number of enzymes involved in digestion is reduced markedly, leading to a
reducedabsorptivecapacityoftheintestine,aprolongedcolonictransittimeand,ifleftuntreated,
even the risk of developing a state of bacterial translocation. While the most important trophic
factor of the small intestine is the nonessential amino acid glutamine5, the colon is heavily
dependent on short chain fatty acids derived from fermentation of dietary fiber (98, 72). It has
beenestimatedthatasmuchas70gofnondigestiblecarbohydrates(includingfibers)arerequired
pr.daytomaintainthecolonicflora(99),thoughinordertostrengthenthegrowthofbeneficial
bacteriathecompositionofthesearenotwithoutimport(part8.4).
If a state of malnutrition is present in the constipated patient, treating this condition should be
consideredasthefirststepinthenutritionalintervention(cf.100).
4 The RD is not the onlyhealth care professional involved in the treatment of nephrologic patients,yet treatment
options offered by other health care workers will not be addressed here. This means that pharmacological
measuressuchastheuseofosmoticlaxatives,bulkingagentsthatexceedthenaturalintakeofdietaryfiber(e.g.
psyllium) and stimulant laxatives will not be reviewed, neither will surgical solutions, biofeedback therapy or
psychologicaltreatment.Thereaderisreferredtothoroughoverviewsonthesubject(96,97).However,physical
activityandfluidintake,thoughnotdirectlytheareaofexpertiseoftheRD,arestillmentionedshortlyduetotheir
closerelationtothefieldofnutritionandhealth.
5 Glutaminissynthesizedbythebodyitself,butduringseverecatabolicstatesitseemstoberequiredintoogreata
quantityforthebodytomeetthedemand.SinceithasbeenshownthatdialysispatientssufferingfromPEWarein
a state of chronic catabolism and since dialysis itself removes a large amount of amino acids with the dialysate,
adding glutamin supplements to the patient's nutrition might aid in avoiding the atrophy of the small intestine
(101). However, treatment with amino acid supplements is part of the area of pharmaconutrition and will
thereforenotbereviewedhere.
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8.2DietaryFiber
ThoughBurkitt'sstudy(57)clearlydemonstratedthatadifferenceinbowelmovementsexistswith
a varying dietary fiber intake, it also brought into being the quite persistent myth that fiber
supplementationmustberegardedasthebesttreatmentofconstipation(102).TheNurses'Health
Study has indeed shown that those with a median fiber intake of 20 g pr. day had a lower
prevalence of constipation (97). Other studies have demonstrated that a diet rich in fiber does
increase stool weight and decrease colonic transit time due to fibers ability to bind water
(however, there seems to be disagreement whether soluble or insoluble fiber is most effective
(103, 102, 104, 97)). Though this has been shown to be true both in healthy and constipated
subjects, the effect is markedly higher in healthy controls than in patients and even less so in
patientssufferingfromdiagnoseddelayedcolonictransittime(102).Furthermore,sincepatients
seldom define constipation by regarding stool weight and transit time but rather by describing
perceivedexperienceofstrainingandincompleteemptyingduringdefecation(54),theperceived
effect of dietary fiber might be even less pronounced in this group despite measurable
improvements(102).Lastbutnotleast,especiallyinthosesufferingfromdelayedcolonictransit
timedietaryfibermightevenworsentheirconditionbyaddingotherGIsymptomssuchasbloating
totheirclinicalpicture,ascolonicbacteriaproducegasduringfermentation(56).
Therefore it should not be assumed that an increase in dietary fiber will always alleviate the
patient's symptoms, yet the treatment option should not be discarded either since it is the
simplest,mostphysiologic,andcheapestformoftreatment(105).Athoroughdietaryinterview,
focusingon currentfiberintakeandpreviousattemptstoincreasetheamountoffiberingested,
willdeterminewhetherafiberdeficiencymightindeedbethecauseofconstipation.Ifthisisthe
case, increasing the intake of dietary fiber naturally should be attempted. If fiber intake already
matches recommendations of 2535 g pr. day (48) or if an increase shows no effect, other
treatmentoptionsshouldbeconsidered.
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8.3TheRoleofHydration
Though one study demonstrated that a very low fluid intake (500 ml pr. day) does reduce stool
weight and frequency (58), thereby suggesting that dehydration may lead to constipation, no
evidence exists to determine whether a fluid intake above the current recommendations (102,
105)alleviatessymptomsofconstipation. Thereforeadietaryinterviewdirectedatpatientswith
constipationshouldalwaysexplorewhetherthepatientmightbeatriskofdehydration.Ifthisis
thecase,anincreasedfluidintakemightbeapossibletreatmentoption.
8.4ProbioticsandPrebiotics
It has been established that colonic motility and GI health is influenced by the composition of
bacteria in the colon (106). Based on this it has been hypothesized that adding these bacterial
strains as well as substrates known to be preferred by these strains to the diet of patient's with
adverse GI symptoms such as constipation might prove to be an effective treatment option.
Indeed, several studies have shown that the ingestion of probiotics such as Bifidobacterium
animalisandLactobacilluscaseiandprebioticssuchasfructooligosaccharides(FOS)andgalacto
oligosaccharides (GOS) does indeed alleviate symptoms of mild to moderate constipation (105)6.
However, the variety of bacterial strains and prebiotics used in these studies as well as an
inconsistentstudydesignhaveledtovaryingandsometimescontradictingresults,whichmakesit
difficult to recommend certain products and doses rather than others. Currently, the probiotics
Lactobacillus casei and Bifidobacterium animalis seem to produce the best results in reducing
colonictransittime(107,108,cf.also109),yetfurtherstudiesareneeded.Concerningprebiotics,
several studies reviewed by the author have shown an effect of their use against constipation.
Kleessenetaldemonstratedthatinulinwaseffectiveagainstconstipationinelderlysubjects(110,
6
Probioticsaredefinedasalivemicrobialfeedsupplementthatisbeneficialtohealth(107),whileaprebioticis
definedasaselectivelyfermentedingredientthatallowsspecificchanges,bothinthecompositionand/oractivity
in the gastrointestinal microflora that confers benefits upon host wellbeing and health (108); in other words,
prebioticsmustbeabletoactassubstratesforlacticacidbacteria,therebypromotingtheirgrowthandalteringthe
bacterialcompositionoftheintestinetotheadvantageofbeneficialbacteria.Basedonthesecriteriaandrecent
research,accordingtodeVrese&Schrezenmeirthetermprebioticsthereforeonlyencompassesbifidogenic,non
digestible oligosaccharides (particularly inulin), its hydrolysis product oligofructose, and
(trans)galactooligosaccharides (108). Oligosaccharides are nondigestible carbohydrates (except inulin), which
exhibit properties typical of dietary fibers (cannot be hydrolyzed by digestive enzymes, act as substrate to
bifidogeniccolonicbacteria,aremetabolizedtoshortchainfattyacids),andshouldthusbeclassedasfibers(115).
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10patients,nocontrolgroup),whileChowfoundthatFOSshortenGItransittime(111).Wangetal
showed an increase in the number of bowel movements in HDpatients treated with isomalto
oligosaccharides(IMO)(112,20patients,nocontrolgroup),whileTeuri&Korpela1998(113,14
patients, no control group) illustrated how GOS relieved constipation in elderly subjects (though
duringthisadmittedlysmallstudytheGOSwereingestedwithyoghurt,whichmighthaveplayeda
role as well due to its probiotic effect). Cockram et al demonstrated how medical nutrition
productscontainingFOSloweredtheprevalenceofconstipationintestsubjectswithrenaldisease
(114). In those studies measuring adverse effects such as bloating and cramping, only mild
symptomswererecorded.DespitethestudyofTeuri&Korpelashowinganeffectwithadoseas
lowas4.5gpr.day,moststudiesonlydemonstratedaneffectatadoseofmorethan8gpr.day
(108).
Sinceespeciallystudiesontheuseofprebioticsaresmall,conclusiverecommendationsconcerning
the therapeutic use of pro and prebiotics cannot be given. However, there does seem to be a
trendtowardsaneffectagainstconstipation.Therefore,asynbiotictreatment(combiningpreand
probiotics)mightbeconsideredinpatientsunresponsivetoothertreatments.
8.5Prunes
Prunes have a long history of claims for preventing constipation, reaching back to the 19th
century(116).Newerstudieshaveshownthatprunesandprunejuiceindeeddohavealaxative
effectbysofteningstools,increasingstoolfrequencyanddecreasingtheincidenceofdifficultyof
defecation (117). The mechanism is still unknown, yet it is believed that the content of sorbitol,
whichisknowntoactasanosmoticlaxative,mightplayarole,asmightthedietaryfibercontent
of prunes (118). Furthermore, certain phenolic compounds believed to increase GI motility are
found in prunes. Another possible explanation for the laxative effect of prunes might be their
prebiotic effect since especially sorbitol is a source for the growth of beneficial bacteria in the
colon; until further studies have been conducted, however, this is a mere theory. The
neurotransmitterserotonin,knownforitslaxativeeffectontheintestinaltract(76),ispresentin
freshplumsandmightbepartofprunes'effectivenessagainstconstipationaswell,thoughstudies
toconfirmserotonincontentinprunesare,tothebestknowledgeoftheauthor,stilllacking.
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ItisimportanttonotethatnolargescaleRCTshavebeenconductedinordertoestablishtheeffect
of prunes on constipation (most of the studies mentioned in the review used here (117) were
eithersmalland/ordidnotfocusonprunesalone).Yetsomeevidencedoesexisttorecommend
dried prunes in the treatment of constipation, which is why the RD should keep this simple,
inexpensivetreatmentinmindwhencounselingapatient.
8.6TheRoleofPhysicalActivity
Population studies indicate that the prevalence of constipation is lower in groups with an active
lifestyle(102,97),thoughnotallwereabletofindthesamerelationship(60).Thissuggeststhat
other factors not included in these studies might play a role. The same seems to be true for
interventions aimed at relieving constipation by increasing the patient's amount of physical
activity;somestudiesshowapositiveeffect,especiallyinelderlypatients(102),whileothersdo
not (119). Indeed, it has been shown that only vigorous amounts of physical activity, such as
runningamarathon,areabletoaffectcolonicactivitydramatically(105).Often,thiswillnotbea
viabletreatmentoption.
However, while evidence of the impact of physical activity on constipation is lacking, its positive
effect on QoL has been determined (60, 61). Since constipation negatively affects QoL and even
mightleadtodepression(part7.4),physicalactivity,eveninamildtomoderatedegree,mightstill
playanimportantroleandshouldtherefore,evenifnoeffectsonbowelmovementareobserved,
notbediscardedintreatingpatientswithadecreasedQoL.
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9.TheNutritionalManagementofConstipationinESRDPatientsonDialysis
In this section, parts 58 are combined, resulting in possible nutritional guidelines for the RD
treatingdialysispatientswithconstipation.
9.1EvaluatingtheNeedforNutritionalIntervention
Since constipation in dialysis patients often occurs due to secondary causes of ESRD and the
medications prescribed to dialysis patients, it might seem tempting to the attending physician
whomightbemoreconcernedwiththelifethreateningelementsofESRDthanwiththepatient's
QoL (18) simply to ascribe constipation to factors such as diabetic neuropathy or the use of
opiodsandeithertoignoretheconditionortoseektoremedyitbytheuseoflaxatives.Though
this might help some patients, it is striking that 50% of patients treated for constipation are
dissatisfiedwiththeresultsoftheirtreatment(118).Furthermore,laxativesonlyaddtothewide
variety of medications already prescribed for the treatment of ESRD. Considering that non
adherence is already a problem in this patient population (43), this might not be the most
desirable solution. Remembering that constipation is multifactorial and that no single treatment
existsthatpromisesrelieftoallpatientsisthereforeanimportantpartofthetreatmentandshould
bereflectedinathoroughmedical,psychological,socialandnutritionalanamnesis.First,itshould
beestablishedwhethertheconditionwaspresentbeforetheonsetofCKDandESRDinorderto
determinepossiblecauses.Ifthisisthecase,physiologicalreasonssuchaspelvicfloordysfunction
(97)orbehavioralfactorsshouldberuledoutorbetreatedwithoutsuccess.Iftheonsetofrenal
failure marked the incidence of constipation, a closer look should be taken at interchangeable
medications known to cause constipation and they should be substituted with less constipating
drugs without success. If the anamnesis clearly shows a need for dietary intervention (e.g. the
presenceofPEW)itistimetoconsulttheRD.
9.2EnsuringanAdequateDietaryandFluidIntake
IthasalreadybeenstatedthatESRDpatientsareatanincreasedriskofdevelopingPEW.Sincethis
conditionnotonlymayleadtothedevelopmentofconstipation(part7),butisalsodirectlyrelated
toahighermorbidityandmortality(2),thefirstlineofactionshouldbetorectifythissituationby
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ensuringanadequatedietaryintakeinaccordancewithexistingguidelinesofnutritionaltherapy
(100)inconsiderationofguidelinesspecifictoESRDpatients(24).Thepatient'scurrentnutritional
status should be assessed, a thorough dietary interview determining the causes of the
malnourishedstateshouldbeconductedand,lastly,indepthcounselingshouldtakeplaceinorder
to help the patient overcome whatever reasons might exist for the inadequate dietary intake.
Duringthistreatment,thepatient'shydrationstatusshouldbeevaluatedaswelltodetermineif
dehydration might be the cause of constipation, and, if so, the patient should be encouraged to
increase fluid intake to the allowed amount. If constipation persists after a good nutritional and
hydratedstatushasbeenrestored,thenextstepscanbetaken.
9.3ChallengingtheNeedforPhosphateBinders
Consideringthattherelationshipbetweenconstipationandtheuseofphosphatebindershasbeen
wellestablished,removingthesedrugsfromthepatient'sregimenmightbeapossiblesolutionin
thosewhodevelopedconstipationafterbeginningtreatmentwithbinders.However,thereseems
to be a disagreement in the therapeutic approach to hyperphosphatemia whether or not
treatment without binders is possible, since some articles and course books clearly state that
hyperphosphatemia cannot be prevented without binders (120, 26, 121), while others take the
viewthatitmightbenecessarytosupplywiththesedrugsifnutritionaltherapyinitselffails(38,2,
73).Othersagainleavethedecisionwhetherornottousethemtotheattendingphysician(24),
while some even state that the efficacy of binders is limited and a dietary approach therefore
always is necessary (122). In order to establish whether omitting binders is a viable approach, a
closerlookatcurrentknowledgeonthesubjectofphosphorusneedstobetaken.
Aspreviouslystated,phosphorusismainlyfoundindairyproducts,meat,fishandpoultry,andin
cereals,grainsandnuts.Duetothesehighproteinsources,thoseclaimingthatphosphatebinders
cannot be omitted argue that a dietary intake low in phosphorus would inevitably lead to the
developmentoforworseningofPEW.Twocounterargumentsmaybepresentedagainstthisview.
Firstly, hyperphosphatemia is often a problem in younger patients (123, 26) which might be
explainedbythefactthatthesepatientshaveahigherenergyintakeintotal(124).Constipationon
the other hand is often more widespread in older patients (8, cf. part 7) who, incidentally, also
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oftenarethosealreadyatnutritionalrisk(63).Althoughitisdifficulttogeneralizeinthismatter
andalthoughthedecisionwhetherornottousebindersinthispatientpopulationshouldalways
bebasedonindividualevaluations,thesefindingsmightsuggestthattheneedforbindersmaynot
be as pressing in this patient population. Of course, should severe PEW be the cause of
constipation,thisconditionshouldbetreatedfirst.
Secondly, the belief that it is impossible to lower serum phosphate levels through diet without
compromisingnutritionalstatusmightbeoutdated.Rufinoetal'sstudyfrom1998(121)concludes
thatitisimpossibletoguaranteeanadequateproteinintakewithoutriskinghyperphosphatemiaif
bindersarenotusedconcomitantly.Yetthisstudydoesnotfocusonthesourceofphosphorusand
states an absorption of 6080% for phosphorus derived from ingestion. Newer studies have
demonstrated quite clearly that this latter assumption is not correct. In an article published in
2012,Wingeretal(122)havescrutinizedthebioavailabilityofdifferentphosphorussourcesand
concluded that the absorption of phosphorus varies according to the source. In natural sources
suchasmeatandplants,phosphorusexistsmainlyasorganicallyboundphosphorus,whichisnot
readily absorbed by the human intestine: While 4060% of the phosphorus content of meat is
absorbed as inorganic phosphates, less than 50% of phosphorus in plants can be absorbed. In
contrast,duringtheprocessingoffood,phosphorusisaddedintheformofinorganicphosphate
saltssuchassodiumphosphatesandisthuseasilyandalmostcompletelyabsorbed.Considering
thelargeamountofprocessedfoodsingestedandthebynowwidespreaduseoffoodadditives,it
is not surprising that 50% of daily phosphorus intake are estimated to stem from food additives
(122). Furthermore, Rufino et al did not consider the option to prepare food in order to extract
phosphorusfromit,whichmayalsoreducethephosphoruscontentbyupto63%(125)without
compromisingproteincontent.
Based on an RCT conducted in 2009 (126), showing that serum phosphate declined markedly in
dialysispatientscounseledtoavoidfoodswithphosphatebasedadditives,Wingeretalconclude
that it is, indeed, possible to prevent hyperphosphatemia through nutritional education and
dietary counseling without compromising the patient's nutritional status (cf. 127 for a thorough
reviewandaDanishapproachonthematter).Consideringthehighamountofsodiumaddedto
processedfoods(128)andsodiumrestrictionsimposedonESRDpatients,restrictingtheintakeof
thesefoodswouldthereforehaveatwofoldeffectonthispatientpopulation.However,Wingeret
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aldocalltheapproachtosimplyaskdialysispatientstoavoidprocessedfoodsneitherpractical
norsensibleduetoadverseeffectsofESRDsuchasfatigue.Insteadtheycallonthefoodindustry
totakeontheresponsibilitytolabelthephosphatecontentoftheirproducts.
Still, in counseling the individual patient it should be remembered that this approach omitting
phosphatebinderstoalleviateconstipationaccordingtocurrentknowledgedoesexistandmight
constitute a possibility for some patients, especially considering that patients' knowledge of the
phosphoruscontentoffoodremainspoor(120).
9.4TheChallengesofFiberIntake
As shown, increasing the amount of dietary fiber in those suffering from a fiber deficiency may
alleviateconstipation.ThishasalsobeendemonstratedinpatientswithCKD(129,86,cf.also130).
Furthermore, an increased fiber intake might decrease the number of uremic molecules and
therebyalleviatesymptomsofuremia(129).Ifthenutritionalanamnesisthereforeshowssucha
deficiency in the patient with ESRD which, considering the often reduced intake observed in
thesepatients,mightindeedbethecaseIncreasingfiberintakemaybeconsidered.
Themainchallengesoftenassociatedwithanincreasedfiberintakeindialysispatientsare1)the
amount of fluid required when ingesting fibersupplements and 2) that fiber rich products often
also contain large amounts of phosphorus and potassium. Concerning the first challenge, it has
beenshowninastudywith11healthyvolunteersthatalmostnodifferencecouldbeobservedin
colonictransittimeandstoolweightwhenafibersupplement(wheatbran)wastakenwithand
withoutextrafluid(131).Theauthorsarguethatthehumanintestinehandlesbetween710liters
offluideachdayandthatthesmallamountusuallyrecommendedwhentakingfibersupplements
thereforemakesnodifference.Fluidrestrictionscommonindialysispatientsmightthusnotbean
obstacletoaddingdietaryfibertotheirdiet.However,thoughwelldesignedthestudywasquite
smallandpatientstakingfibersupplementswithoutaddedfluidshouldbemonitoredcloselyfor
tolerance. Furthermore, if fiber supplements were to be used it is important to remember that
supplements too may contain large amounts of potassium and phosphorus, as is the case with
wheatbran(1340mg/1055mgpr.100gresp.(FoodComp)).
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Thesecondchallengeincreasingfiberintakenaturallyisnotthiseasilymitigated.Fibercontent
is high in whole wheat and bran products, vegetables, fruit and potatoes, as is phosphorus and
potassium content. With proper counseling however, it isnot an impossible task. According to a
Danish nephrology RD (50), 2 slices of rye bread, 35 g of oats, 100 g of raw vegetables, and
potatoes(e.g.200g)andvegetables(e.g.200gbroccoli)preparedbychoppingandcookingmay
be included in the diet of a patient with ESRD. Using values extractedfrom the Danish database
FoodComp,thesefoodstuffscombinedwouldalmostyieldafibercontentof25g,whichisinthe
low end of NNR recommendations of 2535 g of dietary fiber pr. day, but still quite higher than
currentintakeof1718gfoundinastudyincluding43patients(123)andhigherthanthemedian
intakeof20gpr.dayassociatedwithalesserprevalenceofconstipation(97).Thiscombinationof
food stuffs contains approx. 1700 mg potassium and 550 mg of phosphorus (see ill. 4 for
equations),bothbeneathrecommendations;thoughadmittedlythisleavesonlyasmallmarginfor
other food stuffs each day and therefore requires thorough nutritional counseling as well as
motivationalsupport(e.g.byuseoftheMotivationalInterview(132)).
Food Potassium Phosporus Fiber
2 slices of rye bread ( 50 g) 273 156 8.6

1 dl of oats (35 g) 134.75 159.25 3.535
200 g cooked broccoli 586 134 6.6
200 g cooked potato 458 59 2.8
100 g raw carrot 257 29 2.7
1708.75 537.25 24.235
100 g probiotic yoghurt 146 99
1854.75 636.25

Illustration4:Equationsonpotassium,phosphorusandfiber.
Using fiber supplements such as psyllium as a laxative would be another possibility to increase
fiber intake in this patient population, but is not covered by this thesis since 1) it is viewed as
medicaltreatment,2)studiesofbulkingagentsaremostlyofsuboptimaldesign(133)and3)the
sameresultscouldbeobtainedbydietarymeans(105).However,Salmeanetaldemonstratedina
crossovertrialof15patientsthatfoodsuchascookiesenrichedwithfiberdidincreasefiberintake
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andhadapositiveeffectonstoolfrequency(129).Athirdoptionbetweenincreasingfiberintake
naturallyandresolvingtobulkingagentsthereforeexists.
Ifworriesariseconcerningtheborderlinepotassiumcontentofanaturalincreaseinfiberintake,
onestudy,comparingtheprevalenceofconstipationinPDandHDpatients,showedthatpatients
onPDnotonlyhadahigherfiberintake,butalsoalowerprevalenceofconstipationandalower
serumpotassiumlevelthanthoseonHD(8).SincePDremovespotassiummoreoftenthanHD,the
differencemightbeexplainedbythisfact,yet,consideringthatconstipationinitselfmightbearisk
factor for developing hyperkalemia (17), a connection is not impossible. Since it, in theory, is
possibletomaintainanadequatefiberintakeforESRDpatientsandsincehyperkalemiamightbe
prevented by ensuring regular bowel movements, increasing fiber intake in the diet of patients
withafiberdeficiencyisthereforerecommendedasonepossibletreatmentoption(underclose
monitoringofserumpotassiumandphosphatelevels).
9.5TheChallengesoftheUseofProandPrebiotics
Part 8.4 concluded that pro and prebiotics might be a treatment option (though the existing
evidenceisstillratherinconclusive).Yetasisthecasewithanincreasedfiberintake,implementing
thistreatmentinESRDpatientsmightnotbeeasy.
Though attempts have been made to add probiotics to other products than those derived from
fermented milk (such as cookies), only few are available on the market today and their actual
effecthasyettobedetermined(108).Forpatientsindialysisthismeansthatprobioticproducts
mainly consist of fermented dairy products such as yoghurt, which are restricted in their
consumption due to a high content of phosphorus and potassium. However, in those studies
conducted in an attempt to determine the effect of probiotics on constipation, the amount of
fermented dairy product consumed to elicit an effect was within the range of contemporary
recommendationsondairyproducts150mlgivenbyDanishRDs(134,50).InanRCTfrom2003
with70constipatedpatients,65mlpr.dayofaprobioticbeveragecontainingLactobacilluscasei
Shirota were given to the trial group (135), while another RCT conducted in 2008 with 135
constipated patients asked patients to consume 100 g of fermented milk with, amongst others,
strainsofBifidobacteriumlactis(136).Bothtrialsshowedsignificantimprovementsinthepatients'
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condition. Following up on the example in part 9.4, the potassium and phosphorus content of
yoghurtis146mgresp.99mgpr.100g(FoodComp)andthereforestillwithinanacceptablerange.
On the basis of this, probiotics in the form of fermented dairy products might be a possible
treatmentagainstconstipationinESRDpatients.
Concerning the use of prebiotics specific dietary fibers the same challenge as with dietary
fibersasawholeapplies,especiallysincefibersthathavebeenshowntohaveaprebioticeffect
(mostly inulin) are found mainly in fruits and vegetables with a high potassium content such as
bananas.Yet,accordingtostudiesusingprebioticsagainstconstipation,theamountneededtobe
effectiveissmall(4.5gofGOS(113),2040gofinulinorlactose(110),30gofIMO(112),more
than8gintotal(108)).Sinceitispossibletopurchasetheseprebioticsasisolatedproductswitha
negligiblepotassiumandphosphoruscontent(137),thechallengemaybeavoidedaltogether.
A recent study has shown that the intestinal microbiota is changed in patients with CKD with a
decreaseinbeneficialbacteriasuchasLactobacilliasaresult(138).Furthermore,adelayincolonic
motilityseemstoaffectintestinalmicrobiotaaswell(139,140).Basedontheabove,asynbiotic
treatmentisnotonlypossibleinESRDpatients,butshould,duetoitsallegedbifidogeniceffecton
analreadyimpairedmicrobiota,beconsideredifothertreatmentoptionsshownoeffect.TheRD
shouldnote,however,thatoligofructosehasbeenshowntoreduceappetitein31humansubjects
(141)andshouldthereforeonlybeusedifthepatientisnotatnutritionalrisk.
9.6Prunes
Asdescribedinpart8.5,prunesmightalleviateconstipationandarethereforeasimpleandcheap
treatmentoption.InESRD,however,theymightnotbeanoptimalsolution.Thepotassiumcontent
ofprunesisquitehighwithanaverageof416mgpr.100g(FoodComp)resp.732mgpr.100g(U.S.
DepartmentofAgriculture),withatypicalservingofprunejuicealmostashigh(117).Evenwhen
calculatingwiththelowervalue,thatwouldmeanthat100gofprunesthedoseusedeffectively
in two of the studies reviewed in 1177 would already contain around a fifth to a sixth of the
dietaryallowanceofdialysispatients.ConsideringthatthetraditionalDanishdietalreadycontains
7 Bearinmindthataneffectivedosehasnotyetbeenestablishedandaneffectwasalsonotedwhen12gofprunes
wherecombinedwithacupofyoghurtinonestudy(117).
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morethanrecommended,addingprunesasatreatmentforconstipationmightincreasetheriskof
developinghyperkalemia.
Furthermore, it has been shown that prunes have a satiating effect, which is desirable in other
patientgroupssuchasthosesufferingfromobesity.YetinESRDpatientsalreadyatnutritionalrisk
dueto,amongothers,reducedappetite,itcannotberecommendedtoingestfoodwhichincreases
satiety.Theuseofprunesagainstconstipation,therefore,shouldonlybeconsideredwithcaution
inthispatientpopulation.
9.7PhysicalActivity
Thoughevidenceconcerningtheeffectofphysicalactivityinthetreatmentofconstipationisnot
conclusive,somestudiesdid,afterall,findaconnectionbetweeninactivityandtheprevalenceof
constipation.Furthermore,areviewrecentlyfoundthatphysicalactivityhasapositiveimpacton
otherfactorsthatmayplayaroleinthedevelopmentofconstipationinthispatientpopulation,as
regular exercise increases energy intake, decreases patients' level of depression and improves
patients'QoL(61).ConsideringthatmalnutritionanddepressionarecommonsymptomsinESRD
patientsandthatQoLisalreadyheavilyimpairedinthispatientpopulation,thesefactorsalone(as
well as several other beneficial effects demonstrated in the review) are reason enough to
encouragedialysispatientstoengageinphysicalactivityifpossible.
However, implementing physical activity in the life of dialysis patients may prove quite the
challenge.SeveralstudiesshowthatprominentsymptomsaccompanyingESRDarealackofenergy
(69%,5)andfatigue,weaknessandalackofstrength(81%,6).Furthermore,dialysisisknownto
reduce physical capacity by 50% (142). Therefore, and due to the lack of conclusive evidence,
physicalactivitycannotstandaloneastreatmentoption.
9.8OliveOil
During the author's literature search, two minor studies were discovered that attempted to use
othernaturalremediesagainstconstipation.Duetotheirsizeandisolatednature,theywillnotbe
includedinthefollowingguidelines.However,thesedatamightbeimportantinrelationtofurther
research.
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Anunpublished,doubleblindedRCTtestingtheeffectofmineraloil(alaxative),flaxseedoiland
olive oil on 11, 11 and 14 HDpatients with constipation found that olive oil seems to alleviate
symptomsofconstipationsuchasstrainingandhardstools(143).AnothersmallRCTsuggeststhat
a chemically optimized version of olive oil not only works as treatment against constipation, but
also improves the nutritional status of patients with CKD (144). Since ESRDpatients are
encouragedtoingestmoreunsaturatedfattyacidsduetotheirincreasedriskofCVD,addingolive
oilmightprovetobeaninterestingapproachtotreatingconstipationinthispatientpopulation.
9.9PossibleGuidelinesfortheRD
According to the above, the following nutritional guidelines should be considered if no other
causesforconstipationinESRDpatientscouldbedeterminedortreatedsuccessfully:
1. Commencenutritionaltherapyand/orensureanadequatefluidintakeofmorethan500ml
pr.dayifthepatientismalnourishedand/ordehydrated.Ifconstipationpersists,attempt
oneormoreofthefollowingmeasures.
2. Attemptnutritionalcounselingaimedatpreventinghyperphosphatemiabydietarymeans
aloneifconstipationdevelopedafterinitiationofphosphatebindertreatment,e.g.educate
thepatientinthephosphoruscontentoffoods,inpreparingthesefoodscorrectlyandin
avoidingprocessedfoodswithphosphatebasedadditives.
3. Attempt nutritional counseling aimed at increasing the patient's fiber intake without
increasing the risk of developing hyperphosphatemia or hyperkalemia if a dietary fiber
deficiencyexists.
4. If steps 2 and 3 show no effect, consider initiating a pro and prebiotic treatment by
coercingthepatienttoeliminateothersourcesofphosphorusandpotassiumthanfoundin
fermented dairy products. Prebiotics are purchasable as potassium and phosphorusfree
extracts.
5. If nutritional therapy shows no effect, confer with the attending physician to initiate the
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use of laxatives. Physical activity may, if possible, be used to increase energy intake and
QoL,butcannotstandalone.
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10.Conclusion
ESRDpatientssufferfromabroadrangeofadverse,yetoftenundertreatedsymptomsassociated
with the development of renal failure, one of these being constipation. Since the first line of
treatmentofthisconditionusuallyislifestyleorientedandsincenoclearguidelinesexistonthe
nutritionaltreatmentofconstipationindialysispatients,theaimofthisstudywastodetermineif,
andifso,howtheRDmayassistthepopulationofdialysispatientssufferingfromconstipationin
alleviating this condition in order to enhance their QoL by drawing on evidencebased dietetic
knowledge.
A description of the pathophysiology of ESRD and constipation demonstrated that the causes of
constipationinrenalfailurearemultifactorialandthereforemustbetreatedassuchbymakinga
correct diagnosis before treatment is commenced. Since malnutrition, a deficient fiber and fluid
intake, the intake of phosphate binders to avoid hyperphosphatemia and a nonbeneficial
composition of colonic bacteria all might add to the nutritional component of the condition,
dieteticinterventionhasitsplaceinthetreatment.Theifoftheresearchaimcouldthereforebe
answeredintheaffirmative.
AreviewofcurrentnutritionaltreatmentoptionsforbothESRDandconstipationwasfollowedby
acombinationoftheseoptions,whichresultedinasetofguidelinesapplicableinclinicaldietetic
practice,answeringthehowpartoftheaimofthisthesis:Inthegeneralpopulation,studieshave
shownthatconstipationmaybetreatedbyincreasingthepatient'senergyordietaryfiberintakeif
adeficiencyexists,byachievingaproperlyhydratedstateandbyaddingproand/orprebioticsas
wellasprunestothepatient'scurrentdiet.Inpatientswithrenalfailure,remedyingmalnutrition
(which often presents as PEW) and/or dehydration must be the first step in the nutritional
treatment of constipation, since both have a negative impact on colonic motility; however, an
excessivefluidintakeisneitherhelpfulnorrecommended.Next,omittingphosphatebindersmight
provetobeaneffectivestepagainstconstipationinthispatientpopulation.Since50%ofthediet's
phosphorus intake stems from processed foods, it might be possible to prevent
hyperphosphatemianaturallybycounselingthepatienttoavoidadditivescontainingphosphates.
In the case of a dietary fiber deficiency, ensuring a sufficient intake of fiber without having to
resort to bulking agents is possible, yet it requires thorough counseling of the patient as well.
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Adding pro and prebiotics to improve the composition of colonic microbiota might present a
challengeduetothehighphosphorusandpotassiumcontentofdairyproductsandthesatiating
effect of certain prebiotics, but is still compatible with an ESRDdiet and should be attempted if
other options show no effect. As always, thorough counseling is required. Prunes, though
promising in the general population, cannot be recommended due to their very high potassium
content and their effect on satiety. Physical activity, often recommended as treatment against
constipation,maybeaddedifthepatientisabletodoso,thoughonlytoimprovequalityoflife.
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11.FurtherThoughts:TheLackofLargeScaleRCTs
In part 4 it was described how the original idea of this project had to be adjusted in order to
accommodate the lack of RCTs. Though the medical community is well aware of the fact that
constipation constitutes a problem for ESRDpatients, only small scale studies have been
conducted to determine which dietetic treatment options might be safe and effective on this
patientpopulation,yettheyoftenlackcontrolgroups,cleardefinitionsofconstipationandamore
systematic approach as it can be found in reviews on medical treatment of constipation.
Furthermore, to the best knowledge of the author, no attempts at compiling the various
fragmentedstudieshavebeenmade.Itisthehopeoftheauthorthatthisthesis,byalreadyhaving
conductedasystematicliteraturesearchandtherebylayingthegroundworkforfurtherresearch,
might inspire systematic largescale studies conducted by interprofessional teams of nephrology
health care workers who appreciate the broadness of this problematic condition by applying
severalrelevantangles.Areasthatshouldbeinvestigatedfurtherare:
the effect of synbiotic treatments in various combinations on ESRDpatients with

constipation,
the effect of different fibers (soluble and insoluble) in this patient population in order to
determinewhetheracertaincombinationoffoodstuffsholdsanadvantageagainstothers,
the effect of olive oil both on constipation and cardiovascular calcification in this patient
group,and
theimplementationoftheguidelinespresentedinthisthesisinordertovalidatethemand
to exceed the purely biomedical approach applied here, especially considering the
paradigmatic shift away from the use of phosphate binders. In this connection, a
cooperationwiththefoodindustryandfoodadministrations(suchasFdevarestyrelsenin
Denmark)mightprovetobeofuseinthefuturelabelingofphosphatebasedadditives.
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Appendix1:Studyoverview
Inthisoverview,thevariousstudiesusedinthisthesisare,wherepossible,gradedaccordingtothe
evidencehierarchypresentedbyGuyatt,G.H.,etal:Users'guidestothemedicalliterature.IX.A
method for grading health care recommendations, Journal of the American Medical Association
1995, 274, pp. 18001804, found on http://www.healthknowledge.org.uk/publichealth
textbook/researchmethods/1aepidemiology/hierarchyresearchevidence on 20. April 2014.
Course books, bachelor and module projects and official guidelines are not included, but the
referencesnumbersfromthereferencelisthavebeenkepttoeasethesearchforaspecificstudy.
Rank Studydesign
1 Systematicreviewsandmetaanalyses
Randomisedcontrolledtrials(RCT)withdefinitiveresults(confidenceintervalsthatdo
2
notoverlapthethresholdclinicallysignificanteffect)
Randomisedcontrolledtrialswithnondefinitiveresults(apointestimatethatsuggestsa
3 clinicallysignificanteffectbutwithconfidenceintervalsoverlappingthethresholdforthis
effect)
4 Cohortstudies
5 Casecontrolstudies
6 Crosssectionalsurveys
7 Casereports
Illustration5:EvidenceHierarchyaccordingtoGuyattetal1995.
59/86
3. Murtagh,F.E.,etal:Theprevalenceofsymptomsinendstagerenaldisease:asystematic
review,AdvancesinChronicKidneyDisease2007,14(1),pp.8299
AuthorisaphysicianandPhDinthefieldofpalliativecare
SystematicreviewtoestablishtheprevalenceofsymptomsinESRD
Basedon59studieswithdialysispatients,thoroughmethoddescription
Rank:1
4. Tsai,YiChin,etal:Qualityoflifepredictsrisksofendstagerenaldiseaseandmortalityin
patients with chronic kidney disease, Nephrology Dialysis Transplantation 2010, 25, pp.
16211626
a. AuthorsworkathospitalinTaiwan,divisionofnephrology
b. Cohort study (followup) of 423 patients with CKD, median of 410 days, based on
questionnaire
c. Rank:4
5. Weisbord,StevenD.,etal:Prevalence,Severity,andImportanceofPhysicalandEmotional
Symptoms in Chronic Hemodialysis Patients, Journal of the American Society of
a. Authorisassociateprofessorofmedicine
b. Crosssectional study (survey) of 162 patients from 3 dialysis units, based on
interviews
c. Rank:6
6. Hays,R.D.,etal:DevelopmentoftheKidneyDiseaseQualityofLife(KDQOLTM)Instrument,
QualityofLifeResearch1994,3,pp.329338
a. AuthorisprofessorofmedicineandhasaPhDinpsychology
b. Crosssectional study (survey) of 165 patients from 9 dialysis centers, based on
interviews
c. Rank:6
7. Wald, Arnold, & Sigurdsson, Luther: Quality of life in children and adults with
constipation,BestPractice&ResearchClinicalGastroenterology2011,25,pp.1927
a. Authorisprofessorofmedicine
60/86
b. Review, though number of included studies or inclusion and exclusion criteria are
notdescribedproperly;usesreviewsaswellasstudies
c. Rank:Difficulttoassessduetolackofthoroughmethoddescription
8. Yasuda, G., et al: Prevalence of constipation in continuous ambulatory peritoneal dialysis
patientsandcomparisonwithhemodialysispatients,AmericanJournalofKidneyDiseases
June2002,39(6),12921299
a. AuthorisMD,worksatYokohamaCityUniversityCenterHospital
b. Crosssectional study, 483 ESRDpatients, based on questionnaire, blood samples,
dietaryrecords
c. Rank:6
9. Gorodetskaya,Irina,etal:Healthrelatedqualityoflifeandestimatesofutilityinchronic
kidneydisease,KidneyInternational2005,68,pp.28012808
a. AuthorworksatUniversityofCalifornia,DepartmentofMedicine
b. Cohort study, 205 patients with CKD followed for 2 years, based on interviews
(questionnaire)
c. Rank:4
10. Belsey,J.,etal:Systematicreview:impactofconstipationonqualityoflifeinadultsand
children,AlimentaryPharmacologyandTherapeutics2010,31,pp.938949
a. Author has background in public health and primary care, works as consultant
withinhealthcare
b. Systematic review: Database search, manual search, distinct inclusion criteria,
thoughnomentioningofstudymethod.14studiesinall.
c. Rank:Difficulttoassess
11. Su,C.Y.,etal:GastrointestinalsymptomspredictperitonitisratesinCAPDpatients,Clinical
NephrologyApril2012,77(4),pp.267274
a. AuthorsworkatDepartmentofNephrologyatPekingUniversity,China
b. Combination of crosssectional and cohort study with 158 patients on CAPD,
followed for 2 years, based on questionnaire and incidence of peritonitis within
thesetwoyears
c. Rank:46
12. Eberhardie, Chris: Constipation: identifying the problem in Royal College of Nursing:
61/86
NursingOlderPeople2003/2004,15(9),pp.2226
a. Author is a nurse and holds MSc in Behavioural Biology and Healthcare, now
lecturer
b. Thisarticleisnotastudy,butpartofacoursebookaimedatprovidingnurseswith
knowledgeonhowtotreatolderpeople
c. Information in this article is consistent with information procured in other
articles/studies
d. Norank,sincenostudy
13. Maruyama, T., & Kadowaki, D.: To facilitate the compliance of phosphate binder for the
controlofhyperphosphatemiainchronickidneydiseasepatients,ClinicalCalciumFebruary
2009,19(2),pp.248252(Abstractonly)
a. Noinformationonauthor
b. Noinformationonstudydesign
c. Noinformationonrankofevidence
d. Reasonforinclusioninthisthesis:LogicalreflectionandconcurrencewithIacono's
article(seebelow)
14. Iacono, Steven A.: Medication Side Effects: Barriers to the Management of Fluid Intake,
Dialysis&TransplantationJune2008,pp.14
a. Author is Licensed Master Social Worker and has handson experience with CKD
patients
b. Articleisnostudyperse,butseemstobebasedontheauthor'sexperienceaswell
asalongreferencelist.ArticlehasbeenpublishedinDialysis&Transplantion,the
theoldestandlargestcirculationmultidisciplinaryrenalcarejournalwithaprimary
focus on clinical application
(http://www.scimagojr.com/journalsearch.php?q=19879&tip=sid)
c. Noinformationonrankofevidenceavailableduetothenatureofthisarticle
15. Singharetnam,W.,&Holley,J.L.:AcuteTreatmentofConstipationMayLeadtoTransmural
Migration of Bacteria Resulting in GramNegative, Polymicrobial, or Fungal Peritonitis,
PeritonealDialysisInternationalJulyAugust1996,16(4),pp.423425
a. Author works at Nephrology Unit of University of Rochester Medical Center,
physicianwithspecialtyinnephrology
62/86
b. Casereportwith5patients,basedonpatientcharts
c. Rank:7
16. Zhang,JiSheng,etal:Healthrelatedqualityoflifeindialysispatientswithconstipation:a
crosssectionalstudy,PatientPreferencesandAdherence2013,7,pp.589594
a. Author works at Division of Nephrology, School of Medicine, Ningbo Urology and
NephrologyHospitalinthePeople'sRepublicofChina
b. Crosssectional study with 605 dialysis patients from one hospital, based on
questionnaire
c. Rank:6
17. Khedr, Essam, et al: Prevalence of Hyperkalemia among Hemodialysis Patients in Egypt,
a. Author works at Department of Internal Medicine and Nephrology at Faculty of
MedicineatAinShamsUniversityinCairo,Egypt
b. Crosssectionalstudy,400patients,questionnaireandbiochemicalparameters
c. Rank:6
18. Claxton, Ren, et al: Undertreatment of Symptoms in Patients on Maintenance
Hemodialysis,JournalofPainandSymptomManagementFebruary2010,39,pp.211218
a. Author is Assistant Professor of Medicine in the Division of General Internal
Medicine,DepartmentofMedicineattheUniversityofPittsburgh,USA
b. Crosssectionalstudy,62patients,basedonquestionnairesandpatientcharts
c. Rank:6
19. Weisbord,StevenD.,etal:DevelopmentofaSymptomAssessmentInstrumentforChronic
Hemodialysis Patients: The Dialysis Symptom Index, Journal of Pain and Symptom
ManagementMarch2004,27,pp.226240
a. Authorisassociateprofessorofmedicine
b. Combination of review of existing assessment instruments, crosssectional study
basedonfocusgroupinterviews,expertopinionandanothercrosssectionalstudy
basedonquestionnairewith20dialysispatients
c. Rank:Difficulttoassessduetocombinationofmethods
25. Lee, Anna: Constipation in patients on peritoneal dialysis: a literature review, Renal
SocietyofAustralasiaJournalNovember2011,7(3),pp.122129
63/86
a. AuthorworksatDialysisHomeTherapies,RoyalPrinceAlfredHospitalinNewSouth
Wales,Australia
b. Reviewincluding5articlesbasedonthoroughdatabasesearch,someinclusionand
exclusioncriteria,overviewofarticlesusedgiven
c. Rank: Difficult to assess due to few included studies and varied nature of these
studies(interventions,cohort,crossover)
39. Jadeja, Yashpal P., & Kher, Vijay: Protein energy wasting in chronic kidney disease: An
update with focus on nutritional interventions to improve outcomes, Indian Journal of
EndocrinologyandMetabolism,MarchApril2012,16(2),pp.246251
a. AuthorismedicaladvisoratalargepharmaceuticalcompanyinIndia,andhedoes
favour the use of nutritional supplements; his results are in accordance with
textbooksonclinicalnutritionandkidneydisease,however,andheusesreferences
byexpertsinthisfield(Kopple,Beto,Kovesdy)
b. Notastudy,butanoverviewofnutritionalinterventionsinPEW
c. Norankingsincenotastudy
40. Chong, Vui Heng, & Tan, Jackson: Prevalence of gastrointestinal and psychosomatic
symptoms among Asian patients undergoing regular hemodialysis, Nephrology 2013, 18,
pp.97103
a. Authors work at Department of Medicine/Renal Medicine at RIPAS Hospital in
Brunei(Asia)
b. Casecontrol study with 123 ESRDpatients and 197 age and gender matched
controls,basedonquestionnaire
c. Rank:5
41. Silva,L.F.,etal:Gastrointestinalsymptomsandnutritionalstatusinwomenandmenon
maintenancehemodialysis,JournalofRenalNutritionMay2012,22(3),pp.32735
a. Author is an RD with a PhD degree, works at Hospital Professor Edgard Santos in
Brazil
b. Crosssectional study, 684 ESRDpatients, based on questionnaire, medical records
andnutritionalassessment
c. Rank:6
42. Bossola, M., et al: Appetite and gastrointestinal symptoms in chronic hemodialysis
64/86
patients,JournalofRenalNutritionNovember2011,21(6),pp.448454
a. AuthorisMD,worksatHemodialysisUnitatCatholicUniversityoftheSacredHeart
inItaly
b. Crosssectionalstudy,110patients,basedonquestionnaire
c. Rank:6
43. Krespi, Rita, et al: Hemodialysis patients' beliefs about renal failure and its treatment,
PatientEducationandCounseling,2004,53,pp.189196
a. Author has a PhD degree in psychology and works at the Department of Clinical
PsychologyattheUniversityofLiverpoolintheUK
b. Crosssectionalstudy,156ESRDpatients,basedonquestionnaire(whichisbasedon
qualitativeinterviewswith16ESRDpatients)
c. Rank:6
44. Han, SeungHyeok, & Han, DaeSuk: Nutrition in patients on peritoneal dialysis, Nature
ReviewsNephrology2012,8,pp.163175
a. AuthorsworkatDivisionofNephrology,DepartmentofInternalMedicineatYonsei
UniversityCollegeofMedicineinKorea
b. Review summarizing the nutritional issues regarding causes, assessment and
treatmentofPEWinPDpatients,butnothoroughintroductiontosearchstrategies
isgivenorwhicharticleshavebeenincluded(apartfromthoseshowingnutritional
intervention)orwhy.Atotalof159referencesislisted
c. Rank:Difficulttodetermineduetosuperficialmethoddescription
45. Bover,Jordi,&Cozzolino,Mario:Mineralandbonedisordersinchronickidneydiseaseand
endstage renal disease patients: new insights into vitamin D receptor activation, Kidney
InternationalSupplements2011,1,pp.122129
a. AuthorsworkathospitalnephrologydepartmentsinSpain/Italy
b. Articleisnotastudy,butathoroughoverviewofMBDCKDandrecentresearchinto
theeffectofvitaminD.108referenceshavebeenused,includingownresearch
c. Norank,sincenotastudy
46. Kovesdy, Csaba P.: Significance of hypo and hypernatremia in chronic kidney disease,
NephrologyDialysisTransplantation2012,27(3),pp.891898
a. AuthorisMD,researchinginCKD,works,amongstothers,atDivisonofNephrology
65/86
atSalemVeteransAffairsMedicalCenterintheUSA
b. Editorialreviewthatpresentsanoverviewofrecentresearchontheeffectofhypo
andhypernatremiaonCKDpatients,butnodescriptionofmethodsisgiven
c. Rank:Difficulttodetermineduetomissingmethoddescription
47. Ritz,Eberhard,etal:SaltAPotential'UremicToxin'?,BloodPurification2006,24,pp.63
66
a. Author is professor of medicine at Department of Internal Medicine at Ruperto
CarolaUniversityHeidelberg,Germany
b. Articleisnotastudy,butprovidesanoverviewofrecentresearchintotheeffectof
saltonthehumanbody,especiallyonthekidneys,presentingthehypothesisthat
saltexcesscausesorgandamage
c. Norank,sincenotastudy
49. Gatmiri,SeyedMansour,etal:UremicPruritusandSerumPhosphorusLevel,ActaMedica
Iranica2013,51(7),pp.477481
a. AuthorisMD,worksatNephrologyResearchCenteratTehranUniversityofMedical
SciencesinIran
b. Crosssectionalstudy,99ESRDpatients,basedonquestionnaireandbloodsamples
c. Rank:6
51. Mugie,SuzanneM.,etal:Epidemiologyofconstipationinchildrenandadults:Asystematic
review,BestPracticeandClinicalGastroenterology2011,25,pp.318
a. AuthorisMD,worksatDivisonofPediatricGastroenterology,NationwideChildrens
HospitalintheUSA
b. Review summarizing the prevalence and epidemiology of constipation. Methods
described thoroughly, including search strategies and in and exclusion criteria. 68
articleswereincluded
c. Rank:1
52. Higgins,PeterD.R.,&Johanson,JohnF.:EpidemiologyofConstipationinNorthAmerica:A
SystematicReview,AmericanJournalofGastroenterologyApril2004,99(4),pp.750759
a. Authors are MDs at Department of Internal Medicine, University of Michigan
DivisionofGastroenterology,USA
b. Review summarizing the prevalence and epidemiology of constipation in North
66/86
America. Methods described thoroughly, including search strategies and selection

criteria.30articleswereincluded
c. Rank:1
53. Hammer, J., et al: Chronic gastrointestinal symptoms in hemodialysis patients, Wiener
klinischeWochenschriftApril1998,110(8),pp.287291
a. Author is MD with a PhD degree, works at the Division for Gastroenterology and
HepatologyattheUniversittsklinikfrInnereMedizininVienna,Austria
b. Crosssectionalstudywith109ESRDpatients,basedonquestionnaire
c. Rank:6
54. Herz, Michael J., et al: Constipation: a different entity for patients and doctors, Family
Practice1996,13(2),pp.156159
a. Author is MD and works at Department of Family Medicine, Beilinson Medical
Center and Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University,
Isreal
b. Crosssectionalstudywith531randomizedpatientsand100randomizedspecialists
andresidentsinfamilymedicine,basedonquestionnaire
c. Rank:6
56. Basilisco,Guido,&Coletta,Marina:Chronicconstipation:Acriticalreview,Digestiveand
LiverDisease2013,45,pp.886893
a. AuthorsareMDs,workatgastroenterologydepartmentsinMilan,Italy
b. Review summarizing the current diagnostic and therapeutic options available for
adult patients with chronic constipation, but no method description included. 119
referenceslisted
c. Rank:Difficulttodetermineduetolackofmethoddescription
57. Burkitt, D. P., et al: Effect of dietary fibre on stools and transittimes, and its role in the
causationofdisease,TheLancetDecember30th1972,pp.14081411
a. AuthorisMDwithMedicalResearchCouncilExternalScientificStaff,London,UK
b. Largescale crosssectional study including patients from more than two hundred
hospitals in over twenty countries. Lack of matched control groups to support
conclusions
c. Rank:6
67/86
58. Klauser, A. G., et al: Low fluid intake lowers stool output in healthy male volunteers,
ZeitschriftfrGastroenterologieNovember1990,28(11),pp.606609
a. Author works at Department of Gastroenterology at Klinikum Innenstadt,
MedizinischeKlinik,UniversityofMunich,Germany
b. Controlled crossover trial with 8 healthy male volunteers. Two weeks of low fluid
intake,washoutweek,twoweeksofnormalfluidintake
c. Rank:2
60. Tuteja, Ashok K., et al: Is Constipation Associated with Decreased Physical Activity in
Normally Active Subjects?, American Journal of Gastroenterology January 2005, 100 (1),
pp.124129
a. AuthorisMDatVeteransAffairsMedicalCenterandUniversityofUtah,USA
b. Crosssectionalstudywith723employeesatVeteranAffairs,basedonquestionnaire
c. Rank:6
61. Heiwe, S., & Jacobson, S. H.: Exercise training for adults with chronic kidney disease
(Review),TheCochranedatabaseofsystematicreviewsOctober2011,5(10)
a. Authors work at Karolinska Institute, Department of Clinical Sciences, Danderyd
Hospital,Sweden
b. Review summarizing the effects of exercise training on adults with CKD. Thorough
methoddescription(Cochrane)
c. Rank:1
62. Rao,SatishS.C.,&Go,JorgeT.:Updateonthemanagementofconstipationintheelderly:
newtreatmentoptions,ClinicalInterventionsinAging2010,5,pp.163171
a. Authors are MDs, work at Department of Internal Medicine at University of Iowa,
CarverCollegeofMedicine,USA
b. Review summarizing the epidemiology and treatment options of elderly patients
withconstipation.Nomethoddescription,57referenceslisted
c. Rank:Difficulttoestablishwithoutmethoddescription
63. Malafarina, V., et al: The anorexia of ageing: Physiopathology, prevalence, associated
comorbidityandmortality.Asystematicreview,MaturitasApril2013,74(4),pp.293302
a. Author is MD at Department of Geriatrics, Hospital San Juan de Dios, Pamplona,
Spain
68/86
b. Review summarizing the causes for the development of anorexia of ageing in the
elderly.Methodsdescribedthoroughly,27studiesincluded
c. Rank:1
65. Bjrnsson,E.S.,etal:EffectsofHyperglycemiaonInterdigestiveGastrointestinalMotilityin
Humans,ScandinavianJournalofGastroenterology1994,29,pp.10961104
a. AuthorisMD,worksatDivisionsofGastroenterologyandDiabetology,Department
ofInternalMedicine,SahlgrenskaUniversityHospital,Gteborg,Sweden
b. Controlledcrossovertrialwith7healthysubjects,onedaywithhyperglycemia,one
daywitheuglycemia
c. Rank:2
66. Feldmann,Mark,&Schiller,LawrenceR.:DisordersofGastrointestinalMotilityAssociated
withDiabetesMellitus,AnnalsofInternalMedicine1983,98,pp.378384
a. Authors are MDs at the Department of Internal Medicine, Dallas Veteran Affairs
MedicalCenterandUniversityofTexasHealthScienceCenteratDallas,Texas,USA
b. Review explaining the pathophysiology of gastrointestinal disorders in diabetic
patientsbasedonrecentstudies.Nomethoddescription,52referenceslisted
c. Rank:Difficulttodeterminewithoutmethoddescription
67. Strid, Hans, et al: Delay in Gastric Emptying in Patients with Chronic Renal Failure,
ScandinavianJournalofGastroenterology2004,39,pp.516520
a. AuthorisresearcheratUniversityofGteborg,Sweden
b. Crosssectionalstudywithcontrolgroup:39ESRDpatientscomparedto131healthy
subjects,basedonquestionnaireandradioopaquemarkers
c. Rank:6
68. Wu, M. J., et al: Colonic transit time in longterm dialysis patients, American Journal of
KidneyDisease,August2004,44(2),pp.322327
a. Author is MD, works at Divisions of Nephrology and Gastroenterology, Taichung
VeteransGeneralHospital,Taiwan
b. Crosssectionalstudywithcontrolgroup,56HDpatients,63CAPDpatientsand25
healthycontrols,basedonradioopaquemarkers
c. Rank:6
69. Lee, Y. M., et al: Colonic Transit Time in Maintenance Hemodialysis Patients with
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Constipation,KoreanJournalofNephrologyMarch2006,25(2),pp.289294
a. Abstractonly
b. AuthorworksatDepartmentofInternalMedicine,WonkwangUniversitySchoolof
Medicine,Iksan,Korea
c. Crosssectionalstudy,10HDpatients,basedonradioopaquemarkers
d. Rank:6
70. Cano,AliciaE.,etal:GastrointestinalSymptomsinPatientswithEndStageRenalDisease
Undergoing Treatment by Hemodialysis or Peritoneal Dialysis, American Journal of
GastroenterologySeptember2007,102(9),pp.19901997
a. AuthorisMDatDepartmentofGastroenterology,St.GeorgesHospital,London,UK
c. Rank:6
71. Farr, Richard, & Tack, Jan: Food and symptom generation in functional gastrointestinal
disorders:physiologicalaspects,AmericanJournalofGastroenterologyMay2013,108(5),
pp.698706
a. Authors are part of the Rome Foundation Working Group, PhD/MD & PhD at
TranslationalResearchCenterforGastrointestinalDisorders(TARGID),Universityof
Leuven,Belgium
b. Articleisnotastudy,butanoverviewofthephysiologicalaspectsbehindfunctional
gastrointestinaldisorders.95referenceslisted
c. Norank,sincenostudy.
72. Ziegler, Thomas R., et al: Trophic and cytoprotective nutrition for intestinal adaptation,
mucosalrepair,andbarrierfunction,AnnualReviewofNutrition2003,23,pp.229261
a. Author is MD at Department of Medicine at Emory University School of Medicine,
Atlanta,Georgia,USA
b. Review summarizing the effect of nutrition on gut function, but no method
description
c. Rank:Difficulttodetermineduetolackofmethoddescription
73. Kazama,JunichiroJames:Oralphosphatebinders:Historyandprospects,Bone2009,45,
pp.S8S12
a. AuthorisAssociateProfessoratDivisionofNephrologyandIntensiveCareMedicine
70/86
atNiigataUniversityMedicalandDentalHospital,Niigata,Japan
b. Articleisnotastudy,butanoverviewoforalphosphatebinders
c. Norank,sincenostudy
74. Madan, Pankaj, et al: Lower gastrointestinal bleeding: Association with Sevelamer use,
WorldJournalofGastroenterologyApril2008,14(16),pp.26152616
a. Author is MD at Department of Medicine, Baylor College of Medicine, Houston,
Texas,USA
b. Articleisnotastudy,butalettertotheeditor,describinghowanoralphosphate
binder may lead to constipation and consequently to lower gastrointestinal
bleeding.Articleisbasedonacasereport,therefore:
c. Rank:7
75. Choi, So Yeon, et al: Constipation is Closely Associated with Depression in Patients with
EndStageRenalDiseaseUndergoingHemodialysisorPeritonealDialysis,KoreanJournalof
a. AuthorisMD,worksatDepartmentofMedicineatSeoulAdventistHospital,Korea
b. Crosssectionalstudywith91HDand55PDpatients,basedonquestionnaire
c. Rank:6
76. Kim,DoeYoung,&Camilleri,Michael:Serotonin:AMediatoroftheBrainGutConnection,
TheAmericanJournalofGastroenterology2000,95(10),pp.26982709
a. Authors are MDs at Gastroenterology Research Unit, Mayo Clinic and Mayo
Foundation,Rochester,Minnesota,USA
b. Article is not a study, but presents an overview of the role of serotonin on gut
function.138referenceslisted
78. Watson,Maura,etal:DamnedIfYouDo,DamnedIfYouDon't:PotassiumBindingResinsin
Hyperkalemia, Clinical Journal of the American Society of Nephrology 2010, 5, pp. 1723
1726
a. Author is MD at Nephrology Service, Department of Medicine, Walter Reed Army
MedicalCenter,WashingtonDC,USA
b. Article is not a study, but presents an overview of the role of potassium binding
resinsinhyperkalemia.24referenceslisted
71/86
79. Agarwal, Rajiv, et al: A Randomized Controlled Trial of Oral versus Intravenous Iron in
ChronicKidneyDisease,AmericanJournalofNephrology2006,26,pp.445454
a. Author is MD at Indiana University School of Medicine, Richard L. Roudebush
VeteranAffairsMedicalCenter,Indianapolis,Indiana,USA
b. RandomizedControlledTrial,thoroughmethoddescription,89patients
c. Rank:2
80. Birn,Henrik:Lngelevelivetogsidialyse?,UgeskriftforLgerJanuary2011,173(3)
a. AuthorisMD,PhD,atNyremedicinskAfdelingC,rhusUniversitetshospital,Skejby,
rhus,Denmark
b. Articleisnotastudy,butacommentonthequalityoflifeofESRDpatients,based
onexperienceand5references
81. Merkus,MaruschkaP.,etal:Physicalsymptomsandqualityoflifeinpatientsonchronic
dialysis:resultsofTheNetherlandsCooperativeStudyonAdequacyofDialysis(NECOSAD),
a. Author is PhD and researcher at Department of Clinical Epidemiology and
BiostatisticsatAcademicMedicalCenter,Amsterdam,TheNetherlands
b. Crosssectionalstudywith120HDand106PDpatients,basedonquestionnaire
c. Rank:6
82. Strid, Hans, et al: The prevalence of gastrointestinal symptoms in patients with chronic
renal failure is increased and associated with impaired psychological general wellbeing,
a. AuthorisresearcheratUniversityofGteborg,Sweden
b. Crosssectional study with 233 CKDpatients, based on medical records and
questionnaire,resultscomparedwithreferencevaluesfromgeneralpopulation
c. Rank:6
83. Hung,SzuChun,etal:Amalnourisheddialysispatientadiagnosticsurprise,Nephrology
DialysisTransplantation2000,15,pp.254256
a. Author is MD at Division of Nephrology, Department of Medicine, at Veterans
GeneralHospital,Taipei,Taiwan
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b. CasereportwithoneHDpatient
c. Rank:7
84. Garca,ValderramaF.W.,etal:Pooradherencetodietinhemodialysis:roleofanxietyand
depressionsymptoms,Nefrologia2002,22(3),pp.244252
a. Abstractonly
b. AuthorworksatUniversidadPeruanaCayetanoHeredia,Lima,Peru
c. Crosssectional study with 88 HDpatients, based on questionnaire and medical
records
d. Rank:6
85. Beto,Judith,etal:MedicalNutritionTherapyinChronicKidneyFailure:IntegratingClinical
PracticeGuidelines,JournaloftheAmericanDieteticAssociation2004,104,pp.404409
a. AuthorisPhDandRD,worksasresearchassociateintheDivisionofNephrologyand
Hypertension, Loyola University Medical Center, Maywood, Illinois, USA, and as
professorofnutritionsciencesatDominicanUniversity,RiverForest,Illinois,USA
b. Review which updates earlier published recommendations on nutritional care of
CKDpatients.Nomethoddescription.25referenceslisted
c. Rank:Difficulttoassesswithoutmethodsdescribed,yetpublishedbytheJournalof
theAmericanDieteticAssociationandthereforeacrediblesource
86. Nakabayashi, Iwao, et al: Effects of synbiotic treatment on serum level of pcresol in
haemodialysispatients:apreliminarystudy,NephrologyDialysisTransplantation2011,26,
pp.10941098
a. AuthorMDandPhD,worksatRenalUnitoftheDepartmentofInternalMedicine,
HachiojiMedicalCenterofTokyoMedicalUniversity,Hachioji,Tokyo,Japan
b. Crossover trial with 9 HDpatients, 2 weeks without treatment, 2 weeks with
treatment,basedonquestionnaireandmedicalrecords
c. Rank:2
87. Patel,V.G.,etal:Stercoralperforationofthesigmoidcolon:reportofararecaseandits
possible association with nonsteroidal antiinflammatory drugs, The American Surgeon,
January2002,68(1),pp.6264
a. AuthorisMDatGradyMemorialHospital,Georgia,USA
b. Casereportofa45yearoldwoman
73/86
c. Rank:7
88. Falidas,E.,etal:Stercoralperforationofthesigmoidcolon.Acasereportandbriefreview
oftheliterature,IlGiornalediChirurgiaAugustSeptember2011,32(89),pp.368371
a. AuthorworksatFirstDepartmentofGeneralSurgery,417NIMTS,VeteransHospital
ofAthens
b. Casereportofa82yearoldwomancombinedwithabriefreviewofsimilarcases
c. Rank:7
89. Nakamura, Hironori, et al: Stercoral Perforation of the Sigmoid Colon in a Patient
UndergoingCAPD:CaseReport,PeritonealDialysisInternationalJulyAugust2004,24(4),
pp.399404
a. AuthorworksatDepartmentofNephrology,ShowaUniversitySchoolofMedicine,
Tokyo,Japan
b. Casereportof72yearoldwoman
c. Rank:7
90. Adams, Patricia L., et al: Lower Gastrointestinal Tract Dysfunction in Patients Receiving
Longterm Hemodialysis, Journal of the American Medical Association Internal Medicine
February1982,142,pp.303306
a. AuthorisMDatDepartmentofMedicine,DivisionofNephrology,attheNephrology
ResearchandTrainingCenter,UniversityofAlabama,Birmingham,USA
b. Cohortstudyfollowing945patientsovertenyears
c. Rank:4
91. Lipschutz,DanielE.,etal:SpontaneousPerforationoftheColoninChronicRenalFailure,
Journal of the American Medical Association Internal Medicine November 1973, 132, pp.
758759
a. Author is MD with the Division of Nephrology, Department of Internal Medicine,
UniversityofMichiganMedicalCenter,AnnArbor,USA
b. Casereportof43yearoldman
c. Rank:7
92. Haldimann B., & Aeberhard, P.: Spontaneous perforation of the colon in patients in
hemodialysis, Schweizerische medizinische Wochenschrift December 1976, 106 (49), pp.
17431745
74/86
a. Abstractonly,noinformationonauthorsavailable
b. Casereportof5cases
c. Rank:7
93. Engel, A., et al: Nonocclusive ischaemic bowel disease in patients on chronic
haemodialysis, RFo (Fortschritte auf dem Gebiet der Rntgenstrahlen und
Nuklearmedizin)June1989,150(6),pp.704707
b. Casereportsof6cases
c. Rank:7
94. Charra, B., et al: Segmental necrosis of ascending colon in haemodialysis patients,
NephrologyDialysisTransplantationDecember1995,10(12),pp.22812285
b. Casereportsof13cases
c. Rank:7
95. Watabane, T., et al: Constipation, laxative use and risk of colorectal cancer: The Miyagi
CohortStudy,EuropeanJournalofCancer2004,40,pp.21092115
a. Author works at the Division of Epidemiology, Department of Public Health and
ForensicMedicine,TohokuUniversityGraduateSchoolofMedicine,Sendai,Japan
b. Cohort study following 41.670 subjects over 7 years, based on questionnaires and
medicalrecords
c. Rank:4
96. Selby, Warwick, & Corte, Crispin: Managing constipation in adults, The Australian
PrescriberAugust2010,33(4),pp.116119
a. AuthorsarebothMDsatRoyalPrinceAlfredHospital,Sydney,Australia
b. Article is not a study, but guidelines for physicians working with patients with
constipation, based on 13 references and, presumably, medical knowledge of the
author
97. FoxxOrenstein, Amy E., et al: Update on constipation: One treatment does not fit all,
ClevelandClinicJournalofMedicineNovember2008,75(11),pp.813824
a. Author is Associate Professor of Medicine at Division of Gastroenterology and
75/86
Hepatology at the Miles and Shirley FitermanCenter for Digestive Diseases, Mayo
ClinicCollegeofMedicine,Rochester,Minnesota,USA
b. Article is not a study, but guidelines for physicians working with patients with
constipation,basedon105referencesand,presumably,medicalknowledgeofthe
author
101. KalantarZadeh,Kamyar,etal:Dietsandenteralsupplementsforimprovingoutcomesin
chronickidneydisease,NatureReviewsNephrologyJuly2011,7,pp.369384
a. AuthorisProfessorofMedicine(specializedinresearchinnephrologyandnutrition)
withtheLosAngelesBiomedicalResearchInstituteatHarborUCLAMedicalCenter,
Torrance,California,USA
b. Review summarizing the effect of enteral nutrition on malnourished patients with
CKD,briefmethoddescription.185referenceslisted
c. Rank: Difficult to assess without a more thorough method description, but RCTs
seemtohavebeenthebasisofthisreview,so1or2
102. MllerLissner,StefanA.,etal:MythsandMisconceptionsAboutChronicConstipation,
AmericanJournalofGastroenterology2005,100,pp.232242
a. AuthorisMD,ProfessoratParkKlinikWeissensee,Berlin,Germany
b. Articleisnotastudy,butpresentsanoverviewofpossiblecausesofandtreatment
options for chronic constipation, based on 105 references, the authors own
researchandmedicalbackground
103. Suares,N.C.,&Ford,A.C.:Systematicreview:theeffectsoffibreinthemanagementof
chronicidiopathicconstipation,AlimentaryPharmacologyandTherapeutics2011,33,pp.
895901
a. Author is MD with specialty in gastroenterology, works at Leeds Gastroenterology
Institute,LeedsGeneralInfirmary,Leeds,UK
b. Review summarizing the effect of dietary fiber in the management of chronic
constipation, thorough method description, based on RCTs (though only 6 were
eligible)
c. Rank:1
76/86
104. MllerLissner, Stefan A.: Effect of wheat bran on weight of stool and gastrointestinal
transittime:ametaanalysis,BritishMedicalJournal(ClinicalResearchEdition)February
1988,296(6622),pp.615617
a. Author is MD, Professor at ParkKlinik Weissensee, Berlin, Germany (though at
MedizinischeKlinikInnenstadt,Munich,Germany,backthen)
b. Metaanalysis summarizing the effect of wheat bran on stool weight and
gastrointestinaltransittime,briefmethoddescription,20studiesincluded
c. Rank:Difficulttoassessduetobriefmethoddescription
105. FernndezBaares, Fernando: Nutritional care of the patient with constipation, Best
Practice&ResearchClinicalGastroenterology,200620(3),pp.575587
a. Authoris MD,PhD,atDepartmentofGastroenterology,HospitalUniversitariMutua
Terrassa,Barcelona,Spain
b. Article is not a study, but guidelines for those seeking to remedy constipation
through nutritional means, based on 53 references and, presumably, medical
knowledgeoftheauthor
106. Picard,C.,etal:Reviewarticle:bifidobacteriaasprobioticagentsphysiologicaleffects
andclinicalbenefits,AlimentaryPharmacology&Therapeutics2005,22,pp.495512
a. AuthorisPhD,worksatDanoneVitapole/Nutrivaleur,France
b. Review summarizing the effect of bifido bacteria as probiotics, no method
description.121referenceslisted
c. Rank:Difficulttoassesswithoutmethoddescription
107. Fooks,L.J.,&Gibson,G.R.:Probioticsasmodulatorsofthegutflora,BritishJournalof
Nutrition2002,88(suppl.1),pp.S39S49
a. Authors work at Food Microbial Sciences Unit, School of Food Biosciences, The
UniversityofReading,Whiteknights,Reading,UK
b. Notareviewperse,but116referenceshavebeenlistedandtheauthorsstatethat
50articleswerefoundduringasurveyoftheliterature
109. Adolfsson, Oskar, et al: Yoghurt and gut function, The American Journal of Clinical
Nutrition2004,80,pp.245256
77/86
a. Author is PhD, affiliated with the Jean Mayer USDA Human Nutrition Research
CenteronAgingatTuftsUniversity,Boston,USA
b. Reviewsummarizingcurrentevidenceofthehealthbenefitofyoghurtandspecific
lacticacidproducingstrains,yetnomethoddescription.144referenceslisted
110. Kleessen,Brigitta,etal:Effectsofinulinandlactoseonfecalmicroflora,microbialactivity,
and bowel habit in elderly constipated persons, American Journal of Clinical Nutrition
1997,65,pp.13971402
a. Authoris PhD,worksatGermanInstituteofHumanNutritionPotsdamRehbrcke,
Germany
b. Parallelgroup, doubleblinded RCT, 15 subjects with constipation in intervention
group1,10ininterventiongroup2,basedonquestionnaire
c. Rank:2
111. Chow,JoMay:Probioticsandprebiotics:Abriefoverview,JournalofRenalNutritionApril
2002,12(2),pp.7686
a. Author is PhD at StrategicDiscovery Research and Development, Ross Products
Division,AbbottLaboratories,Columbus,Ohio,USA
b. Review presenting an overview of the effect of pro and prebiotics, no method
description.123referenceslisted
c. Rank:Difficulttoassessduetolackofmethoddescription
112. Wang,H.F.,etal:Useofisomaltooligosaccharideinthetreatmentoflipidprofilesand
constipationinhemodialysispatients,JournalofRenalNutritionApril2001,11(2),pp.73
79
a. Author is MS at Department of Food and Nutrition, HungKuang Institute of
Technology,Shalu,Taichung,Taiwan
b. Crossovertrialwith20HDpatientswithconstipation,2weekswithouttreatment,4
weeks with treatment, 4 weeks without treatment, based on blood samples and
questionnaire
c. Rank:2
113. Teuri, Ulla, & Korpela, Riitta: GalactoOligosaccharides Relieve Constipation in Elderly
People,AnnalsofNutritionandMetabolism1998,42,pp.319327
78/86
a. Authors work at the Valio Ltd. R&D Centre in the Institute of Biomedicine,
DepartmentofPharmacologyandToxicology,UniversityofHelsinki,Finland
b. Crossover trial with 14 subjects with constipation, intervention was conducted
randomly,basedonquestionnaires
c. Rank:3(nondefinitiveresults)
114. Cockram,D.B.,etal:Safetyandtoleranceofmedicalnutritionalproductsassolesources
ofnutritioninpeopleonhemodialysis,JournalofRenalNutritionJanuary1998,8(1),pp.
2533
a. Author is MS, RD, at Medical Nutrition Research and Development, Ross Products
Division,AbbottLaboratories,Columbus,Ohio,USA
b. Singleblindedcrossovertrialwith79ESRDpatients,1weektoprovidebaseline,2
weeks of intervention (3 different kinds), based on medical records and
questionnaire
c. Rank:2
115. Niness,KathyR.:InulinandOligofructose:WhatAreThey?,TheJournalofNutritionJuly
1999,129(suppl.7),pp.1402S1406S
a. Author is VP Sales & Marketing at Orafti Active Food Ingredients, Malvern,
Pennsylvania,USA
b. Articleisnotastudy,butanoverviewofinulinandoligofructose,76references
c. No rank, since no study. Risk for bias due to authors position at company selling
theseprebiotics
116. StacewiczSapuntzakis, M., et al: Chemical composition and potential health effect of
prunes: A functional food?, Critical Reviews in Food Science and Nutrition 2001, 41, pp.
251286
a. Author is researcher at the Department of Human Nutrition and
Dietetics/Kinesiology and Nutrition at the University of Illinois in Chicago, Illinois,
USA
b. Article is not a study, but an overview of the composition and potential health
benefitsofprunes.157referenceslisted
117. StacewiczSapuntzakis, M.: Dried Plums and Their Products: Composition and Health
79/86
EffectsAnUpdatedReview,CriticalReviewsinFoodScienceandNutrition2013,53,pp.
12771302
a. Author is researcher at the Department of Human Nutrition and
Dietetics/Kinesiology and Nutrition at the University of Illinois in Chicago, Illinois,
USA
b. Review following up on the authors article from 2001 on the effect of prunes,
reviewingstudiesfrom20002010,butnomethoddescription,177referenceslisted
118. Attaluri, A., et al: Randomised clinical trial: dried plums (prunes) vs. psyllium for
constipation,AlimentaryPharmacologyandTherapeutics2011,33,pp.822828
a. Author is MD at Division of Gastroenterology/Hepatology at the Department of
Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa,
USA
b. Singleblindcrossovertrial,40subjectswithconstipation,14weekperiod(1week
runin,3weekstreatment,1weekwashout,3weekstreatment,6weeksfollowup)
c. Rank:2
119. Meshkinpour,H.,etal:EffectsofRegularExerciseinManagementofChronicIdiopathic
Constipation,DigestiveDiseasesandSciencesNovember1998,43(11),pp.23792383
a. AuthorisMDatDivisionofGastroenterology,DepartmentofMedicine,UCIMedical
Center,Orange,California,USA
b. Crossover trial, 8 patients with constipation, based on 1week recall test and
exercise test, then a rest period of 2 weeks, then an exercise period of 4 weeks,
resultsbasedonpedometerandlogofbowelmovements
c. Rank:3
120. Pollock, Judson B., & Jaffery, Jonathan B.: Knowledge of Phosphorus Compared with
Other Nutrients in Maintenance Dialysis Patients, Journal of Renal Nutrition September
2007,17(5),pp.323328
a. Authors are MDs, Pollock a nephrologist in Cincinnati, Ohio, USA, Jaffery Assistant
ProfessorofMedicineattheUniversityofWisconsin,Madison,Wisconsin,USA
c. Rank:6
80/86
121. Rufino,M.,etal:Isitpossibletocontrolhyperphosphatemiawithdiet,withoutinducing
malnutrition?,NephrologyDialysisTransplantation1998,13(suppl.3),pp.6557
a. AuthorworksatNephrologyService,HospitalUniversitarioCanarias,Spain
b. Crosssectionalstudywith60HDpatients,basedonrecordofdietaryintake
c. Rank:6
122. Winger, Ray J., et al: Phosphoruscontaining food additives: An insidious danger for
peoplewithchronickidneydisease,TrendsinFoodScience&Technology2012,24,pp.92
102
a. AuthorworksatInsideFoodsLimited,Pangbourne,UK
b. Articleisnotastudy,butanoverviewoftherisksfoodwithphosphoruscontaining
additivesposestopatientswithCKD
123. Cupisti, A., et al: Dietary Habits and Counseling Focused on Phosphate Intake in
HemodialysisPatientsWithHyperphosphatemia,JournalofRenalNutritionOctober2004,
14(4),pp.220225
a. Author is MD and researcher at Department of Internal Medicine, Nephrology,
UniversityofPisa,Pisa,Italy
b. Controlledtrial(notrandom,sincebasedonthesphosphoruslevelofpatients),43
patients with ESRD, based on dietary recall and blood samples, intervention
consisted of dietary counselling for patients with sphosphorus higher than 5.5
mg/dl
c. Rank:2
124. Cupisti, A., et al: Food Intake and Nutritional Status in Stable Hemodialysis Patients,
b. Crosssectional study with 94 ESRDpatients, based on nutritional assessment and
dietaryrecall
c. Rank:6
125. Cupisti,A.,etal:Effectofboilingondietaryphosphateandnitrogenintake,Journalof
RenalNutritionJanuary2006,16(1),pp.3640
81/86

b. Not a human study, but a biochemical analysis of the content of phosphate and
nitrogeninmeatafterboiling
c. Norank,sincenotahumanstudy
126. Sullivan, C., et al: Effect of food additives on hyperphosphatemia among patients with
endstage renal disease. A randomized controlled trial, Journal of the American Medical
Association2009,301(6),pp.629635
a. Author is MS, RD at Division of Nephrology at MetroHealth Medical Center for
ReducingHealthDisparitiesandDepartmentofMedicineatCaseWesternReserve
University,Cleveland,Ohio,USA
b. ClusterRCTat14HDfacilitiesinOhio,279ESRDpatientswithsphosphorushigher
than 5.5 mg/dl (145 intervention, 134 control), based on dietary counseling and
visualaidsconcerningphosphatecontainingadditives
c. Rank:2
128. Webster, Jacqueline L., et al: A systematic survey of the sodium contents of processed
foods,AmericanJournalofClinicalNutritionFebruary2010,91(2),pp.413420
a. AuthorisresearcheratGeorgeInstituteforInternationalHealth,Sydney,Australia
b. Not a human study, but a survey of Australian processed foods, based on review,
sodiumcontentwasmeasured
c. Norank,sincenotahumanstudy
129. Salmean,YounisA.,etal:Foodswithaddedfiberimprovestoolfrequencyinindividuals
withchronickidneydiseasewithnoimpactonappetiteoroverallqualityoflife,BioMed
CentralResearchNotes2013,6(510)
a. Author is researcher at Food Science and Human Nutrition, University pf Florida,
Florida,USA
b. Crossovertrial,15patientswithCKDandconstipation,basedonquestionnaireand
bloodsamples,twoweekswithoutaddedfiber,fourweekswithaddedfiber
c. Rank:2
130. Younes, H., et al: Role of dietary fibers in the nutritional management of chronic renal
failure,Nephrologie2004,25(7),pp.283285
82/86
a. Abstractonly
b. Seemstobeanoverview,butarticlewouldbeneededtodetermineexactnatureof
articleandrank
131. Ziegenhagen,D.J.,etal:Addingmorefluidtowheatbranhasnosignificanteffectson
intestinalfunctionsofhealthysubjects,JournalofClinicalGastroenterologyOctober1991,
13(5),pp.525530
a. AuthorisMDattheGastroenterologyUnit,ClinicIofInternalMedicine,University
ofCologne,Cologne,Germany
b. Crossovertrial,11healthysubjects,2studyperiods2weekswithwashoutperiod
in between, based on medical techniques (ultrasonography, hydrogen breath
exhalation test, radio opaque markers), stool samples, body weight and blood
samples
c. Rank:2
133. Brandt, Lawrence J., et al: Systematic Review on the Management of Chronic
ConstipationinNorthAmerica,AmericanJournalofGastroenterology2005,100(S1),pp.
S5S22
a. Author is MD at Division of Gastroenterology, Montefiore Medical Center/Albert

EinsteinCollegeofMedicine,Bronx,NewYork,USA
b. Review summarizing current recommendations on the treatment of chronic

constipationinNorthAmerica,thoroughmethoddescriptions
c. Rank:1
135. Koebnick, C., et al: Probiotic beverage containing Lactobacillus casei Shirota improves
gastrointestinal symptoms in patients with chronic constipation, Canadian Journal of
GastroenterologyNovember2003,17(11),pp.655659
a. Author is PhD at the German Institute of Human Nutrition, Department of

InterventionStudies,BergholzRehbrcke,Germany
b. Doubleblinded, placebocontrolled RCT, 70 patients with constipation, based on

questionnaire,2weeksofrunin,4weeksofintervention,evaluation1weeklater
c. Rank:2
83/86
136. Yang, YueXin, et al: Effect of a fermented milk containing Bifidobacterium lactis DN
173010onChineseconstipatedwomen,WorldJournalofGastroenterologyOctober2008,
14(40),pp.62376243
a. AuthorisprofessorofnutritionwithNationalInstituteofNutritionandFoodSafety
ChinaCenterforDiseaseControl,Beijing,China
b. ParallelgroupRCT,135patientswithconstipation,2weekswitheitherintervention
orcontrol,basedonquestionnaire,dietaryrecallandstoolsamples
c. Rank:2
138. Vaziri,NosratolaD.,etal:Chronickidneydiseasealtersintestinalmicrobialflora,Kidney
International2013,83,pp.308315
a. Author is Professor of Medicine, Physiology and Biophysics School of Medicine at

UniversityofCalifornia,Irvine,Orange,California,USA
b. Crosssectional study with 24 ESRDpatients and 12 healthy subjects, based on

analysisofstoolsamples
c. Rank:6
139. Quigley, Eamonn M. M.: Microflora Modulation of Motility, Journal of

NeurogastroenterologyandMotilityApril2011,17(2),pp.140147
a. AuthorisProfessorofMedicineandHumanPhysiologyattheNationalUniversityof
Ireland,Cork,Ireland
b. Notastudy,butanoverviewoftheeffectofmicrofloraongastrointestinalmotility.
95referenceslisted
140. Stephen,AlisonM.,etal:Effectofchangingtransittimeoncolonicmicrobialmetabolism
inman,Gut1987,28,pp.601609
a. AuthorisPhDwiththeMRCDunnClinicalNutritionCentre,Cambridge,UK
b. Crossover trial with 7 healthy subjects, diet was constant throughout study, but
medicationwasgiventospeeduporslowdowntransit,basedonfeacalanalysis,3
84/86
weeks with diet only, 3 weeks with speeding up medication, 3 weeks with slowing
downmedication
c. Rank:2
141. Verhoef, Sanne P. M., et al: Effects of oligofructose on appetite profile, glucagonlike
peptide 1 and peptide YY336 concentrations and energy intake, British Journal of
Nutrition2011,106,pp.17571762
a. AuthorisPhDstudentattheDepartmentofHumanBiology,NutritionandToxicology
ResearchInstituteMaastricht,MaastrichtUniversity,Maastricht,TheNetherlands
b. Crossover trial with 29 healthy subjects, 13 days of intervention with 2 weeks of

washoutinbetween,basedonbodyweightandbloodsamples
c. Rank:2
142. D Hra, Nette Solskov, et al: Fysisk aktivitet og trning til patienter i
hmodialysebehandling:entvrfagligrehabiliteringsindsats,InstitutforKliniskMedicin,
rhusUniversitetshospital,presentedasaposteronMarch8th2013
a. Abstractonly,basedonaconferenceposter
b. Authorisanurse,projectwasdoneincooperationwithInstitutforFolkesundhed
Epidemiologi and Institut for Klinisk Medicin Nyremedicinsk Afdeling C, rhus
Universitetshospital
c. Studyandresultshadnotbeenpublishedyet,thereforenorank
143. Ramos,ChristianeI.,etal:Adoubleblindedrandomizedcontrolledtrialontheeffectof
flax seed and olive oils on constipation of hemodialysis patients: Preliminary results,
KidneyResearchandClinicalPractice2012,31,pp.A88
a. Abstractonly
b. AuthorworksatDivisionofNephrology,FederalUniversityofSaoPaulo,SaoPaulo,
Brazil
c. Preliminarystudy,thereforenorank
144. Prez, Baasco V., et al: Preliminary study on efficacy and tolerance of a "coupage" of
olive oil in patients with chronic kidney disease. Nutritional evaluation, Nefrologia 2007,
85/86
27(4),pp.472481
a. Abstractonly
b. AuthorworksatNephrologyDepartment,HospitalComplexofJan,Jan,Spain
c. RCT,butsinceonlyabstract,norank
145. Mathialahan, T., et al: Enhanced large intestinal potassium permeability in endstage
renaldisease,JournalofPathology2005,206,pp.4651
a. Author is MD, PhD, at Molecular Medicine Unit, St. Jamess University Hospital,
Leeds,UK
b. Crosssectional study with 8/9 ESRDpatients, and 10/9 agematched subjects using
medicaltechniques(rectaldialysistechnique,rectalbiopsies)
c. Rank:6
146. Sandle, G. I., et al: Evidence for large intestinal control of potassium homeostasis in
uraemicpatientsundergoinglongtermdialysis,ClinicalScience1987,73,pp.247252
a. Author is MD at the Department of Medicine, Clinical Sciences Building, Hope
Hospital,Salford,UK
b. Crosssectionalstudywith14healthysubjects,10CAPDpatiensand7HDpatients,
basedonrectaldialysistechniqueanddietaryassessment
c. Rank:6
86/86

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aa10s313 TheNutritionalManagementofDialysisPatientswithConstipation 26thofMay2014

Baggrund: Dialysepatienters livskvalitet er nedsat markant i forhold til raske kontrolgrupper.

Konklusion: Nr det er sikkert, at forstoppelsen i dialysepatienten skyldes en ditetisk

Stages GFR Kidneyfunction

1 Morethan90mlpr.minute Indications of kidney damage, though still normal or

Food Potassium Phosporus Fiber

2 slices of rye bread ( 50 g) 273 156 8.6

100 g probiotic yoghurt 146 99

the effect of synbiotic treatments in various combinations on ESRDpatients with

137. Beneo: Product sheet OraftiGR, found at

139. Quigley, Eamonn M. M.: Microflora Modulation of Motility, Journal of

America. Methods described thoroughly, including search strategies and selection

a. Author is MD and researcher at Department of Internal Medicine, Nephrology,

a. Author is MD at Division of Gastroenterology, Montefiore Medical Center/Albert

b. Review summarizing current recommendations on the treatment of chronic

a. Author is PhD at the German Institute of Human Nutrition, Department of

b. Doubleblinded, placebocontrolled RCT, 70 patients with constipation, based on

a. Author is Professor of Medicine, Physiology and Biophysics School of Medicine at

b. Crosssectional study with 24 ESRDpatients and 12 healthy subjects, based on

139. Quigley, Eamonn M. M.: Microflora Modulation of Motility, Journal of

b. Crossover trial with 29 healthy subjects, 13 days of intervention with 2 weeks of

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