English Case Report

Nephrology Division
Chronic Kidney Disease Stage IV and Vesicoureteral Reflux Grade IV - V
in Spina Bifida
Raedy Ruwanda Susanto
Departemen Ilmu Kesehatan Anak FK UNHAS/
RSUP dr Wahidin Sudirohusodo Makassar

INTRODUCTION
Chronic kidney disease, defined as abnormality of the renal function (known from the
serum creatinine), urinanalysis, and imaging (known from the USG ) at least 3 months, and
classified as 5 grade. This decreasing function make toxic metabolic accumulate in serum,
and imparment of water, electrolyte and acid-base imbalance.
In Indonesia, between 1984 1988 in 7 central hospital incidence of CKD is 2 %
from 2889 children hospitalized with all kidney disease. In Cipto Mangunkusomo Hospital,
incidence of CKD significantly increasing, from 4, 9 % in 1991 became 13,3 % in 1996
2000 period. Whereas in Europe, prevalence of the terminal kidney disease between 1997
1999 in children below 18 years old is 7,4 per million children, with comparison between
male and female are 1,76 : 1. The most common cause of CKD in children < 5 years old is
most commonly a result of congenital abnormalities such as renal hypoplasia, dysplasia or
obstructive uropathy, like in ureter obstruction in spina bifida patient. After 5 year of age,
acquired diseases (various form of Glomerulonephritis including lupus nephritis, and
nephrotic syndrome) and inherited disorders are predominate. 1
Neural tube defects (NTDs) account for the largest proportion of congenital
anomalies of the CNS and result from failure of the neural tube to close spontaneously
between the 3rd and 4th week of in utero developement. The precise cause of NTDs
remains unknown, evidence suggests that many factors, including hyperthermia, drugs (such
as valproic acid), malnutrition, chemicals, maternal obesity or diabetes, nutritional deficiency
such as folic acid, and genetic factors ( cytoplasmic factors, polygenic inheritance, and
chromosomal abberations) can affect normal development of the time of conception
1

(nelson). There are many NTDs include spina bifida, and its classified as

spina bifida

occulta, meningochele, myelomeningochele. Myelomeningocele is the most involved type of

spina bifida and as such entails the greatest nerve damage. Current estimates suggest an
incidence rate of 1, 9 per 10.000 live births 2
Neuropathic or neurogenic bladder cause by spina bifida remains an important cause
of chronic renal disease in developing countries, in contrast in western countries, children
born with spina bifida can avoid such complication if they are provided adequate urological
intervention.Cause of renal disease in neurogenic bladder is associated in risk of recurrent
urinary tract infection. A study in saudi arabia demonstrate that spina bifida children
developed a renal damage at an early age , in this study 36 % of child had scared kidneys at
5 years of age. The cause of higher incidence of renal damage in developing countries can
be explained by the delay in proper management and lack of access to good medical facility
especially in patient at the peripheral area. 3
The urinary tract is the second most common site of infection in infants and children
after the respiratory tract infection. Approximately 5 % of 10 % children have at least 1
episode of urinary tract infection (UTI) of whom 30 50 % have at least 1 episode of urinary
tract infection. Of children with febrile UTI, 50 90% are found to have scintigraphic renal
scintigraphic renal cortical defects, indicating acute pyelonephritis, and among them, 40 to
60 % will develop permanent renal scarring that may cause long term complication such as
hypertension, decreased renal function and end stage renal disease in later life.

Vesicoureteral reflux (VUR) refers to the retrograde flow of urine from the bladder to
the ureter and kidney, this reflux occurs when the submucosal tunnel between the mucosa
and detrusor muscle is short or absent, this condition is often congenital and affects
approximately 1 % of children. VUR is the most frequent predisposing factors for UTI, and 30
% - 50 % of children with UTI have VUR, furthermore VUR is precipitating factor for acute
pyelonephritis and risk factor for renal scar formation. In conjuction with spina bifida, VUR is
present at birth in 25 % of children with neuropathic bladder, as occurs in
myelomeningocele, sacral agenesis, and many cases of high anal atresia. 4
This paper will report the chronic kidney disease and vesicouretral reflux in 6 years
old myelomeningocele patient.

CASE REPORT
2

A boy, Refly Meyzar,

6 years and 1 month, refer from bau-bau hospital on

September 20th, 2015 with diagnosis chronic kidney disease and hidronephrosis bilateral.
Chief complaint : since he was 1 years old, often accompanied by disuria.
Additional complaint : There were flank pain since 4 day before admission, swollen in the
lower waist since he was born, no pain. There was shortness of breath but no cough, no
fever no seizure. There was decrease of appetite. Defecation within normal limit.
There was history of urinary incontinence since 3 years before admission
History of Pregnancy : Not routinely control to midwife, not taking any medication or
traditional

medicine,

not

routinely

consuming

the

vitamin,

folic

acid

and

iron

supplementation, never got any diseases in her pregnancy.

Figure 1 The patient, Refly

Figure 2 Mass on lumbar suggest to

spina bifida

Figure 3 Turbid Urine

PHYSICAL EXAMINATION
General condition : Severe Illness Blood pressure 110/70 mmHg, Pulse rate 110
times/ min, Respiratory rate 60 times/min, Body temperature 37,2 C. Body weight 11 kg,
Body Length 95 cm (BW/LW =

78 % (Moderate Malnutrition), LW/Age = 61 % (Short

stature). He was conscious child with GCS 15 (E4M6V5), No Pale neither cyanosis and no
jaundice. Symetrical but no oldman face. Ear, Nose and throat within normal limit. Chest
was symmetric,and we found piano chest, breath sound vesicular, no rales and wheezing
over both lungs, but we found subcostal retraction. Heart we found the first and second heart
sound were reguler with no murmur, Abdomen was concave, follow breathing pattern,
normal peristaltic sound, liver was palpable 2 cm on right lobe 2 cm left lobe, soft
consistency, plain surface, lien not palpable, we found ascites with shifting dullness type.
Normal genitalia. From extremities there are wasting. Vertebral column no gibbus nor
scoliosis. We found mass in lumbal region size 8 x 7 x 1,5 cm, soft consistency, flat surface,
bluish colour, temperature same with the other surface. From neurological state 2nd nerve
pupil are both round, diameter 2,5 mm/2,5 mm, light reflex was normal, other cranial nerve
within normal limit. Meningeal sign was negative. Motoric muscle strength and tonus within

normal limit, physiological reflex was normal, patological reflex were not found. Sensibility
normal, Autonomical nerve we found urinary incontinence.
From the laboratory findings was found Hb 7,3 gr/dl, WBC : 18.400/uL, HCT 22 %,
PLT 516.000, MCV 82 fl, MCH 27 pg, MCHC 33 g/dl, Neutrofil 63,7 %, Eosinofil 0,1 %,
Basophyl 0,3 %, Monocyte 9,8 %, BUN 186 mg/dl, Creatinine 3 mg/dl, Natrium 142 mmol/L,
Kalium 3,4 mmol/L, Chlorida 120 mmol/L, GOT 23 mg/dl, GPT 7 mg/dl, Ferritine 291,27.
Urinalysis colour yellow, protein +3, blood +3, Wbc +2, Sediment : Wbc 50, Rbc 50.
Estimated Glomerular filtration rate 17,41 ml/min/1,73 m2. Blood gas analysis pH 7,364,
pCO2 9,7, pO2 158,7, SO2 96,3, HCO3 5,6, ctO2 11,7, result : Fully compensated Metabolic
acidosis
From the radiological examination, Abdominal sonography showed bilateral
hydronephrosis (picture 4), BNO plain chest X-Ray found no abnormality (picture 5), Lumbar
CT scan found Spina Bifida at level V.C L5 S1 accompanied with meningocystochele,
Bilateral hydronephrosis, Overdistended urinary vesicle suspected neurogenic bladder amd
cystitis (picture 6).
The working diagnosis was Chronic kidney disease stage IV, Hypertension Grade II,
Nutritional marasmus, Anemia by chronic disease, Suspected Spina bifida, Urinary
incontince cause by suspected Neurogenic bladder, Short stature.
Treatment was Oxygen nasal 2 lt/min, IVFD Kaen 3B, Antibiotics with renal
adjusment Cefotaxime 100 mg/12 hr/IV, Amikasin 40 mg/12 hr/IV, Nifedipine 5
mg/sublingual,place the urinary catheter Strictly fluid balance, Low salt diet with protein
1g/kg/day. Consult to Hematology and Metabolic Nutrition division.

Picture 4 Ultrasonograph
Liver : form, size and echoparenchym within
normal limit. No vascular or bile dilatation in
intra or extrahepatic. No echo mass
Pancreas : form, size and echoparenchym
within normal limit, no dilatation in pancreatic
duct, no echo mass/cyst
Spleen : form, size and echoparenchym within
normal limit, no echo mass/cyst
Both kidney : Increasing size but echo cortex
within normal limit, dilatation in both PCS, no
stone/mass/cyst echo
Bladder : Wall not thickened, no stone/mass
echo
No free fluid in peritoneum and both pleural cavity
Result : Bilateral Hydronephrosis
Suggestion : MSCT- Scan Urography

Picture 5 Chest X- Ray

Asymetric position, good film condition, enough
inspiration
Normal Bronchovascular pattern
No hilar enlargement
Heart Size and shape within normal limit
Both sinus and diaphragma normal
Intact bones
Result : No abnormalities in this Chest X- Ray

Picture 6 Lumbar CT-Scan

Axial
CT

Change in thoracolumbal vertebrae alignment

Defect in Processus Spinous at L5 S2 level, with the

widest diameter is 2,3 cm

accompanied by meninges and CSF

No destruction or fracture Discus
Incidental Finding :
Both Kidney : kidney enlargement, PCS dilatation, no stone/cyst/mass echo
Bladder : Overdistention, thickened wall, reguler mucosa, no Space occupying lesion
Result :
Spina bifida at level L5 S1 accompanied by meningocystochele
Bilateral hydronephrosis
Overdistention of bladder suspec neurogenic bladder
Cystitis.

Follow Up
Day :
1 (21/9/2015) : Still dyspnoe and urinary incontinence, but no fever. General condition still
weak,BP 140/90 mmHg, Temperature 37

C, CNS, lung, and heart examination normal,

abdominal peristaltic normal, liver 2 cm below costal margin, flat surface, soft consistency,
sharp edge, no tenderness, spleen not palpable, there was ascites with shifting dullnes type,
mass in lumbal region size 8 x 7 x 1,5 cm, soft consistency, flat surface, bluish colour,
temperature same with the other surface. Therapy oxygen nasal 2 L/min, IVFD Kaen 3B 14
7

drops/min, Continue the antibiotics cefotaxime and amikacin, nifedipine 5 mg/SL, and
addition of captopril 5mg/8 hr/NGT, furosemide 10 mg/12 hr/NGT for antihypertensive drugs,
and Natrium bicarbonat for treat acidosis 2 tablet/24 hr/oral.

Stop oral intake and give

parenteral nutrition.
3 (23/9/2015) : Dyspnoe was decrease,lower abdominal pain, micturition via urinary
catheter. Physical exam General condition weak, BP 120/90 mmHg, Pulse rate 100
times/min, RR 30 times/min. CNS, Lung, and Heart exam normal. Abdominal peristaltic
normal, liver 2 cm below costal margin, flat surface, soft consistency, sharp edge, no
tenderness, spleen not palpable, there was ascites with shifting dullnes type, mass in lumbal
region size 8 x 7 x 1,5 cm, soft consistency, flat surface, bluish colour, temperature same
with the other surface. Urin production 2,2 ml/kg/hr. Lab : BUN 119 mg/dl, Creatinine 2,74
mg/dl. Therapy oxygen nasal 2 L/min, IVFD Kaen 3B 14 drops/min, Continue the antibiotics
cefotaxime and amikacin, nifedipine 5 mg/SL, captopril 5mg/8 hr/NGT, furosemide 10 mg/12
hr/NGT, and Natrium bicarbonat for treat acidosis 2 tablet/24 hr/oral, Hematology give the
blood transfusion 180 ml, consult to neurology division, and plan to consult to endocrinology
division, repeating the blood gas analysis, and consult to neurosurgery.
5 (25/9/2015) :Minimal dyspnoe, lower abdominal pain was decrease, micturition via urinary
catheter. Physical exam General condition weak, BP 110/90 mmHg, Pulse rate 98 times/min,
RR 30 times/min. CNS, Lung, and Heart exam normal. Abdominal peristaltic normal, liver 2
cm below costal margin, flat surface, soft consistency, sharp edge, no tenderness, spleen
not palpable, there was ascites with shifting dullnes type, mass in lumbal region size 8 x 7 x
1,5 cm, soft consistency, flat surface, bluish colour, temperature same with the other surface.
Urin production 2,8 ml/kg/hr. BGA pH 7,52, pCO2 15,6, sO2 97,4 , pO2 137,0, HCO3 12,9,
BE -10 (Result Respiratory Alkalosis). Therapy oxygen nasal 2 L/min, IVFD Kaen 3B 14
drops/min, Continue the antibiotics cefotaxime and amikacin, nifedipine 5 mg/SL, captopril
5mg/8 hr/NGT, furosemide 10 mg/12 hr/NGT, and Natrium bicarbonat for treating the
acidosis was stop, from neurosurgery do the conservative treatment.
8 (28/9/2015) :No dyspnoe , micturition via urinary

catheter. Physical exam General

condition still weak, BP 100/60 mmHg, Pulse rate 98 times/min, RR 30 times/min. CNS,
Lung, and Heart exam normal. Abdominal peristaltic normal, liver 2 cm below costal margin,
flat surface, soft consistency, sharp edge, no tenderness, spleen not palpable, there was
ascites with shifting dullnes type, mass in lumbal region size 8 x 7 x 1,5 cm, soft consistency,
flat surface, bluish colour, temperature same with the other surface. Urin production 4,1
ml/kg/hr. We perform the mictiocystouretrogram and the result was suspecter diverticulosis
bladder + vesicoureteral reflux grade IV V + Cystitis. (Picture 4). Laboratory Hb 9,3 (after
8

transfusion), WBC 13.570, PLT 302.000, Hct 29,6, BUN 88, Creatinine 1,67 , Albumin 2,9
Sodium 151, Pottasium 5,5, Chlorida 122 mmol/L Therapy : oxygen nasal 2 L/min, IVFD
Kaen 3B 14 drops/min, Continue the antibiotics cefotaxime and amikacin, nifedipine 5
mg/SL, captopril 5mg/8 hr/NGT, furosemide 10 mg/12 hr/NGT.

Picture 7
35 ml Iodium inserted to the
urinary

catheter,

with

fluoroskop contrast filled the

bladder and left ureter, with
tortous ureter.
Multiple additional shadow on
bladder, with irreguler mucosa,
filling defect was not shown.
After catheter was pulled off,
contrast pass out the urethra.
Result :
-

Suspecter bladder diverticulosis

Vesicoureteral reflux grade IV-V
Cystitis

9 (29/9/2015) :No dyspnoe , micturition via urinary

catheter. Physical exam General

condition still weak, BP 120/80 mmHg, Pulse rate 98 times/min, RR 24 times/min. CNS,
Lung, and Heart exam normal. Abdominal peristaltic normal, liver 2 cm below costal margin,
flat surface, soft consistency, sharp edge, no tenderness, spleen not palpable, there was
ascites with shifting dullnes type, mass in lumbal region size 8 x 7 x 1,5 cm, soft consistency,
flat surface, bluish colour, temperature same with the other surface. Urin production 3,5
ml/kg/hr. Therapy :

stop the antibiotics cefotaxime and amikacin,and change to

9

cotrimoxazole 240 mg/24 jam/orally, stop the IVFD,

nifedipine 5 mg/SL, captopril 5mg/8

hr/NGT, and stop furosemide 10 mg/12 hr/NGT

14 (4/10/2015) : No dyspnoe , micturition via urinary

catheter. Physical exam General

condition still weak, BP 100/60 mmHg, Pulse rate 98 times/min, RR 30 times/min. CNS,
Lung, and Heart exam normal. Abdominal peristaltic normal, liver 2 cm below costal margin,
flat surface, soft consistency, sharp edge, no tenderness, spleen not palpable, there was
ascites with shifting dullnes type, mass in lumbal region size 8 x 7 x 1,5 cm, soft consistency,
flat surface, bluish colour, temperature same with the other surface. Urin production 3,2
ml/kg/hr. Laboratory result Hb 9,3 WBC 9.000 sel/uL, PLT 446.000. HT 27,6 %. BUN 74,
Creatinine 1,18 mg/dl (markedly decrease) , Electrolyte Sodium 141 mg/dl, Potassium 3,9
mg/dl, Chlorida 112 mg/dl. Therapy : 5th day cotrimoxazole, nifedipine 5 mg/SL, captopril
5mg/8 hr/NGT, diet with nefrisol 8 x 200 ml, plan to do bladder training 2-3 hour/day. From
the neurosurgeon just do the conservative therapy and later consult from outpatient
departement because no sign of emergency for this patient.
16 (6/10/2015) : No dyspnoe , urinary catheter was pulled off. Physical exam General
condition still weak, BP 100/60 mmHg, Pulse rate 98 times/min, RR 30 times/min. Abdominal
peristaltic normal, liver 2 cm below costal margin, flat surface, soft consistency, sharp edge,
no tenderness, spleen not palpable, there was ascites with shifting dullnes type, mass in
lumbal region size 8 x 7 x 1,5 cm, soft consistency, flat surface, bluish colour, temperature
same with the other surface. Urin production 3,2 ml/kg/hr. Therapy : cotrimoxazole, captopril
5mg/8 hr/NGT, diet with nefrisol 8 x 200 ml,. EPO 100 IU/kgBW was started to gave for this
patient.
23 (13/10/2015) No dyspnoe , Physical exam General condition still weak, vital sign normal.
Abdominal peristaltic normal, liver 2 cm below costal margin, flat surface, soft consistency,
sharp edge, no tenderness, spleen not palpable, there was ascites with shifting dullnes type,
mass in lumbal region size 8 x 7 x 1,5 cm, soft consistency, flat surface, bluish colour,
temperature same with the other surface. Urin production 3,2 ml/kg/hr. Lab Hb 8,6 plt
444.000, BUN 77, creatinine 1,4 mg/dl Therapy : cotrimoxazole stop change to continue the
ab with cefixime , captopril 5mg/8 hr/NGT, diet with nefrisol 8 x 200 ml, continue the EPO 3
times a week.
30 (20/10/2015) No dyspnoe , Physical exam General condition good, vital sign normal.
Abdominal peristaltic normal, liver 2 cm below costal margin, flat surface, soft consistency,
sharp edge, no tenderness, spleen not palpable, there was ascites with shifting dullnes type,
mass in lumbal region size 8 x 7 x 1,5 cm, soft consistency, flat surface, bluish colour,
temperature same with the other surface. Urin production 2,8 ml/kg/hr. BUN 56, creatinine
10

1,15 mg/dl .cefixime 2 x cth, captopril 5mg/8 hr/NGT, diet with nefrisol 8 x 200 ml, patient
allowed to go home and return to outpatient departement.

Definitive Diagnosis
-

Chronic Kidney Disease Stage IV

Vesicoureteral Reflux Grade IV V
Neurogenic Bladder
Meningocystocele
Cystitis
Anemia by Chronic Disease
Nutritional Marasmus
Short Stature

Discussion
Spina bifida is a general name for neural tube defects. It classified as many diseases
including meningocystocele or meningomyelocele. Myelomeningocele represents the most
severe forms of spina bifida, involving the vertebral column and spinal cord, which occurs
with an incidence of 1 /4000 live birth. Myelomeningocele produces dysfunction of many
organs and structure, including the skeleton, skin, and gastrointestinal ,genitourinary tracts,
and also the peripheral nervous system and the CNS. This condition may be located
anywhere along the neuraxis, but the lumbosacral region account for at least 75 % of the
cases. Central urinary control is located in level S2 S4 in spinal cord an innervated the
bladder, in myelomeningocele that located in low sacral region, causes bladder and bowel
incontinence associated with anesthesia in the perianal area but with no impairment of motor
function. This patient manifest as urinary incontince because the defect in spinal cord of
myelomeningocele is located in L 5 S 2 level. 4
Spina bifida is associated with various spinal cord and central nervous system
impairment,

the tye

and

severity of

which

are

related

to the

lesion

level.In

myelomeningocele, typical impairments include hydrocephalus, Chiari II malformation,

neurogenic blower and or bladder resulting in incontinence, muscle weakness and lack of
sensation in lower extremities and cognitive dysfunction that can significantly impair daily
activitiy 2,4
11

Folate is involved in the prevention and etiology of NTDs. Folate functions in single
carbon transfer reactions and exist in many chemical forms. Folic acid, which is the most
oxidizied and stable form of folate,occurs rarely in food but is the form used in vitamin
supplements and in fortified food products, particulary flour. Folate coenzymes are involved
in DNA synthesis, purine synthesis, generation of formate into the formate pool, and
aminoacid interconversion. Mutations in genes encoding the enzymes involved in
homocystein metabolism inculde 5, 10 methylenetetrahydrofolate reductase (MTHFR),
cystathionine B-synthase, and methionine synthase. Maternal periconceptional use of folic
acid supplementation reduces the incidences of NTD in pregnancies at risk by at least 50 %,
and to be effective, folic acid supplementation should be initiated before conception and
continued until at least the 12th week of gestation, when neurulation is complete. From the
history of this patient, the mother not routinely consume the vitamin or folic acid in her
pregnancy and not routinely control to the midwife. 5
Spina bifida, especially meningomyelocele, need multidisciplinary treatment. The
best time to treated the myelomeningcele in immediately after birth. It include surgical
closure of the defect, shunting for ventricular enlargement (which is often occured in
myelomeningocele, and prophylaxis for antibiotics. Optimally, the back lesion should be
closed within 72 hr following birth. In doing so, this further decreases the risk of CNS
infection, and possibly improves neurological outcome. In a retrospective review of a cohort,
the children who underwent back closure within 72 hr of birth have significantly better
bladder status on urodynamic testing as opposed to those children closed after 72 hr. (Grade
III Recommendation A). In this patient, even the myelomeningocele occured when his age
less than 1 years, but because of parental the lack of knowledge and location in very rural
area that far from the health facility, result in delayed treatment and poor outcome.6
Chronic Kidney Disease (CKD) may be result of congenital, acquired, inherited or
metabolic renal disease, and correlates closely with the age of the patient at the time when
CKD is first detected. In < 5 years old, most commonly cause of congenital abnormalities
such as renal hypoplasia, dysplasia, or obstructive uropathy such as neurogenic bladder in
spina bifida. This patient known to have spina bifida since he was < 1 years old and not
treated properly 5,6
The clinical presentation of CKD is varied and depends on the underlying renal
disease, infants and children with congenital disorders such as renal dysplasia and
obstructive uropathy can present as failure to thrive, recurrent urinary tract infection, or overt
renal insufficiency. From the physical examination , patients with CKD can reveal pallor and
chronic fatigue due to anemia, hypertension patients with long standing untreated CKD can
12

have short stature and the bony abnormalities of renal osteodystrophy.

5,6

Patient with

Hypertension in CKD, pharmacological treatment should be given in all stages of CKD.

Approximately 75 % children with CKD stage 2 4 blood pressure control below 95th % can
be achieved by monotherapy but 50 60% need polytherapy if intensified BP control (<50 th
percentile), but in children with ESRD, NAPRCS database and polish nationwide survey
found only 57 % children with ESRD adequately controlled with Antihipertensive even it use
the polytherapy. In this patient, we confirmed that this patient have hypertension grade II, so
we give the antihypertensive such as nifedipine, captopril and furosemide.
The objectives of CKD management are to decrease the progression of CKD and to
prevent cardiovascular events and lifestyle related disease. In advanced stage of CKD
(stage 4 5), multidisciplinary treatment should be considered, and preparations for renal
replacement therapy (RRT) should be made for children with CKD stage 4, but
commencement of RRT is recommended for children with CKD stage 5 or in stage 4 who
have retarded growth and developement, malnutrition, and uremia that is not well controlled
by conservative therapy (Grade 4 A Recommendation), and selection of RRT whether it is
hemodialysis, peritoneal dialysis, and renal transplantation can be performed in children,
however renal transplantation should be the ultimate goal in terms of patients survival. 7
As maintenance dialysis, peritoneal dialysis is the first line of treatment for children.
Peritoneal dialysis is superior to hemodialysis with respect to vascular access and fluid and
nutritional management, particularly in very young children (Grade IV Recommendation B).
There is no difference in the prognosis for survival between HD and PD for at least a few
years following the initiation of the procedure. In a cohort study for dialysis in children,
among children in this study, 70 % were started on PD and the remaining 30 % were started
on HD, and among the infants and toddlers less than two years of age, 96 % were started on
PD and the remainder was treated with HD, PD is especially well suited for the younger age
groups because it avoids the many difficulities associated with the maintenance of vascular
access in children and minimizes the need for severe fluid and dietary restrictions (Grade II
recommendation A). In this patient, we didnt do the dialysis because we treat the main cause
first which is spina bifida, and we treat another complications such as anemia, hypertension,
metabolic acidosis, and UTI. 7,8
Anemia is one of the clinical and laboratory manifestations of CKD. Relatively little is
known about the developement and progression of anemia in patients with CKD. As kidney
function declines and in patients with more advanced CKD stages, the incidence and
prevalence of anemia increased, but in children, the relationship between GFR and anemia
is less clear. Usually anemia is normocytic and the absolute reticulocyte count is normal or

13

low (chronic disease anemia).The presence of anemia in patients with CKD has a wide
range of clinical manifestation, these include reduced physical performance, fatigue,
shortness of breath, los of appetite, insomnia, cognitive function disorders, and reduce
immunological function, short stature and failure to thrive, In this patient we found anemia
normocytic normochrom, with high ferritine level so we considered chronic disease anemia,
and from the presentation of this patient were fatigue, shortness of breath, and malnutrition
with short stature.9
There are several causes of anemia in patients with CKD. EPO deficiency and iron
deficiency are the leading causes regardless of dialysis status, other causes contributint to
anemia in CKD patients are inflammation, chronic blood los, hyperparathyroidisme,
hemoglobinopathies and hemolysis. The major cause of anemia in patients with CKD is lack
of EPO synthesis in the diseased kidneys, The liver is the primary source of EPO production
in the fetus, but after birth, a group of peritubular interstitial cells in the kidney take over this
function, becoming the major sites of EPO production, in chronic kidney disease, A reduced
GFR may cause decreased sodium reabsorption in the tubules and because sodium reabsorption is the main determinant of energy consumption in the nephron, this may lead to a
relative excess of oxygen, signaling a decrease in EPO production. The second major cause
of anemia in kidney disease is iron deficiency, Iron deficiency is common in HD patients due
to chronic blood loss from repeated blood sampling, surgical interventions, blood loss
through the use of dialyzers and tubing and shortened red blood cell lifespan. 9

The first reports of EPO use in children described five patients on continuous cycling
peritoneal dialysis (CCPD) who received 150 U/kg three times per week; this resulted in the
successful treatment of anemia, although hypertension was exacerbated in three of the
patients. A larger patient group of 14 children on CCPD were described in a subsequent
study in Germany. These patients received an initial EPO dose of 300 U/kg once weekly,
which was adjusted downwards to a maintenance dose of approximately 100 U/kg once per
week, with side effect is hypertension. Following publication of these studies, EPO became
the standard treatment for renal anemia in childhood and was prescribed at a dose of
approximately 150 U/kg per week in clinical practice, divided into three doses per week. Iron
repletion and maintenance is the second pillar of anemia management in kidney disease.
Iron-deficient patients are also known to require higher doses of EPO to maintain target
hemoglobin levels, non-dialysis CKD patients or PD patients can be managed with oral iron.
The current NKF-KDOQI guidelines recommend oral iron therapy to be given in doses
ranging from 23 mg/kg up to 6 mg/kg of elemental iron per day in two to three divided
doses per day. In this patient we didnt treat with dialysis, and we give Recombinant Human
14

EPO 100 IU/kgBW divided into three doses a week with addition of sulfas ferrosus orally.
NKF-KDOQI guideline recommend that the target hemoglobin level should be 11 g/dl or
greater, but in our hospital, we use the target hemoglobin is above or equal with 9 g/dl 9
The progression of kidney disease leads to obsolete or sclerotic glomeruli, tubular
atrophy and interstitial fibrosis, and anemia with subsequent tissue hypoxia may contribute
to this progression to end stage kidney disease , therefore the correction of anemia is very
important to improve the prognosis cause they may lead to increased oxygen delivery to
tubular cells, decrease tubular damage and protect against nephron loss induced by tubular
injury. 9
Growth retardation also a major problem in patients with chronic kidney disease. The
United States Renal Data System (USRDS) Pediatric Growth and Development Study
showed that children with ESRD with moderate or severe growth retardation have a higher
rates of morbidity and mortality than children with normal growth rate.Short stature is defined
as height below 3rd percentile or 2 SD at growth chart that use in population or standart
NCHS curve. Children at the highest risk of short stature are affected infants (under one
year) and patients with GFR less than 15 % of normal. (Grade II Reccomendation A) Growth
retardation in CKD is multifactorial and influenced by the degree of renal dysfunction, but
also by comorbidities such as malnutrition, factors associated with the treatment modality,
and genetic growth potential determined by midparental height. Several factors contribute to
malnutrition : proggresive anorexia, decreased protein synthesis and increased catabolism.
Other factors such as metabolic acidosis, acute and chronic may lead to growth retardation.
Metabolic acidosis is influenced by protein intake and acid load, protein catabolism, and
electrolyte abnormalities. There is a significant relationship between protein catabolism and
decrease linear growth. In this patient we found malnutrition and metabolic acidosis
comorbidity with CKD, as a factors that may contribute to short stature for this patient.9,10
Treatment of short stature in patient with CKD is to optimize all aspects of treatment,
including correction of metabolic disorders, set-up the nutrition requirement, and use of
hormone therapy. In infants and young children with CKD, the most important action to
prevent growth retardation is to achieve an adequate caloric intake. It is recommended that
the caloric intake should reach 80 100 % of the RDA, wih protein intake also according to
RDA for age. Higher protein intakes are harmful because they promote metabolic acidosis
and phospor overload. To treat the metabolic acidosis NKF-KDOGI guidelines suggest
treating with alkali, to reach level HCO3 about 22 24 meq, in this case we use Natrium
Bicarbonat tablet, and for the malnutrition we treat with 3 phase of treatment for
malnutrition.10

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. Vesicouretral reflux (VUR) refers to the retrograde flow of urine from the bladder to
the ureter and kidney. It can occurs primarily and secondary. The ureteral attachment to the
bladder normally is oblique, between the bladder mucosa and detrusor muscle, creating a
flap valve mechanism that prevents reflux, however, reflux occurs when the submucosal
tunnel between the mucosa and detrusor muscle is short or absent. This reflux predisposes
to infection of the kidney, by facilitating the transport of bacteria from the bladder to the
upper urinary tract and result renal scarring. Renal scar will cause arterial disruption and
segmental sichemia, which in turn activates the renin angiotensin system. The activation of
this system, along with the abnormality of sodium transport due to reduced area containing
the Na/K Atpase pumps and renal arteri stenosis found in neuromuscular dysplasia, can
result in hypertension. For renal insufficiency, reflux accounted for about 15 20 % risk to
become end stage renal disease. 5,
Reflux may be primary or secondary, primary often cause by congenital
incompetence of the valvular mechanism, and secondary can cause by increased
intravesical pressure (ex : neuropathic bladder) and inflamatory process (ex recurrent
cysitis). This patient, classified as vesicoureteral reflux grade IV V from the VCUG result,
we consider the cause is secondary reflux due to both intravesical along with an inflamatory
process. 5
Diagnosis VUR are based on history taking, physical examination and additional
exam which is laboratory and radiological exam. Laboratory exam such as urinanalysis,
urine culture, blood routine, C-reactive protein, and renal function test may be needed. To
diagnose the UTI, we should found proteinuria, leukosit cast (WBC > 5), and hematuria
(RBC > 5), and for exact diagnosis we should find pyuria in urine culture, based on urine
sample method.11
Radiological examination are main parameter to diagnose and also treatment for the
VUR. From the literatur, gold standard for diagnose VUR is Voiding Cystourethrogram/
Mictiocystouretrogram (VCUG/MCUG). Based on the answer to the main question about the
relevance of VUR in the causal pathway between UTI and renal scarring, two imaging
approaches have evolved: top-down and bottom-up. The bottom-up approach focuses on
diagnosing VUR during UTI; therefore a VCUG is obtained first. The top-down approach
focuses on kidney involvement during UTI, with a goal of diagnosing APN and/or renal
dysplasia; therefore, a DMSA scan is obtained first. A VCUG is performed only if renal
involvement is observed3,41 because children with normal DMSA scans rarely have highgrade VUR. Benefits of the top-down approach include decreased urethral catheterizations,
decreased ionizing radiation to the gonads, and decreased detection of clinically insignificant
VURs not involving the kidneys.Studies have demonstrated that use of the top-down
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approach could reduce about 50% of the number of VCUGs performed while missing a VUR
diagnosis in 5% to 27% of cases, with the cases of missed VUR being presumably less
significant.4, 11

Figure 8 Bottom up and Top down approach for diagnosing VUR 10

Reflux severity is graded using from 1 to 5 based on the appearance of the urinary
tract on a contrast voiding cystourethrogram (VCUG),it classified by International Reflux
Study Commitee (IRSC).

The higher the reflux grade, the greater the likelihood of renal

injury, and indirect indication of the degree of abnormality of the ureterovesical junction.

Figure 9 Classification of VUR from

IRSC 10
Grade 1 : reflux into a nondilated ureter, Grade II : reflux into the upper collecting
system without dilatation. Grade 3 reflux into dilated ureter and/or blunting of calyceal

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fornices. Grade IV : reflux into a grossly dilated ureter. Grade V : Massive reflux, with
significant ureteral dilatation and tortuosity and loss of the pappilary impression.
There are two main treatment approaches for patient with VUR. Conservative and
surgical. Aim of conservatif therapy based on the understanding that VUR can resolve
spontaneously, mostly in low grade reflux (grade I III). Resolution os nearly 80 % in VUR
grade I II and 30 50 % in VUR grade III - V within 4 5 years of follow up. However,
spontanoeus resolution is low for bilateral high grade reflux. This conservative therapy
includes watchful waiting, intermittent or continous antibiotic prophylaxis (CAP), bladder
rehabilitation in patients with Lower urinary tract dysfunction (LUTS), and regular follow up
with imaging studies (USG, MCU, DMSA scanning) to monitor spontaneous resolution and
kidney status, although the frequency of the follow up may differ depends on the physician
preference, however some center use 2 times a year for USG, and annualy for cystography
and DMSA scan.11
For antibiotics,

agent with single low dose (on third of dose) of amoxicillin and

trimetoprim (age < 2 mo) or trimetophrim sulfametoxazole or nitrofurantoin (older age)

preferably taken at bedtime.

While some trials show no benefit for giving antibiotics,

especially in low grades of reflux, other trials show that can prevents further renal damage,
especially in patients with grades III and IV reflux. Decision making for giving or not the
antibiotics may be influenced by the presence of risk factors for UTI, such as young age,
high grade VUR, status of toilet training/LUTD, female sex, and circumcision status. In this
patient, we give prophylaxis antibiotics cotrimoxazole and then change to cefixime. 11
Surgical treatment can be carried out by endoscopic injection of bulking agents or
ureteral reimplantation. Indication for surgical in VUR are : 1) recurrent UTI accompanied
with fever, eventhough patient has got the prophylaxis antibiotics, 2) Severe VUR (Grade
IV/V bilateral), especially with renal scarring, 3) Mild or moderate VUR in female patient
which persistent until pubertal age), 4) Poor drug response, 5) Anomaly of ureteral orifice, 6)
poor renal function. 11
Bulking material injection, most common use are polytetrafluoroethylene (PTFE,
Teflon), but in children Teflon has not beenm approved for use in children because of
concerncs about particle migration. Newer agent, solution of dextranomer/hyaluronic acid
(Deflux) has been use in many clinical trial, demonstrated that this agent is effective in
treating reflux other than any agents. This injected bulking agent elevates the ureteral orifice
and the distal ureter and the distak ureter so coaptation is increased, the lumen narrowed,
and prevents reflux while still allowing the urine antegrad flow. In a meta-analysis including
5527 patients and 8101 renal units, the reflux resolution rate by ureter following one
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treatment of grades I and II reflux was 78,5 %, 72 % for grade III, 63 % for grade IV, and 51
% for grade V (Grade I, Recommendation A). The aggregate succes rate with one or more
injection was 85 % 11
In open surgical technique, various intra and extravesical techniques have been
described for the surgical correction of VUR. The most popular and reliable open procedure
is the Cohen cross trigonal reimplantation. The main concern is the difficulty of accesing the
ureters endoscopically if needed when the child is older. In patients with bilateral reflux, an
intravesical antireflux procedure may be considered, because simultaneous bilateral
extravesical reflux repair carries a postoperative urine retention. Furthermore, all surgical
procedures offer very high and similar success rates for correcting VUR. 11
Malnutrition or Nutritional Marasmus (from ICD 10) from World Health Organization
is celluler imbalance between nutrient intake and the requirement of growth, development
and specific function. From Basic Health Research 2010 (RISKEDAS 2010) shown that
prevalence of malnutrition was 4,9 % . Malnutrition classified into mild, moderate, and
severe, based on the antrophometric state and clinical condition. Furthemore, severe type
classified into 3 type based on clinical feature. First marasmic type, we can found irritability,
failure to thrive, old man face, piano chest, wrinkled skin, muscle atrophy, and hypotoni,
hepatomegaly. Second type is kwarsiorkor type, it had edema, alteration of mental state,
flag sign, lack of muscle tissue, crazy pavement dermatosis, anoreksia, and anemia. And
the last type is combination between 2 type, marasmus and kwarsiorkor. Spesific clinical
pattern are essential for diagnosing malnutrition, like severe growth retardation, edema, and
crazy pavement dermatosis. In kwarsiorkor, we should differentiate the edema from the renal
cause such as syndrome nefrotic. Which is in kwarsiorkor, we didnt found any sign of
proteinuria. This patient, we diagnose as having nutritional marasmus, marasmic type from
the clinical and antrophometric, and may result from the poor intake and chronic disease of
this patient (chronic kidney disease and recurrent urinary tract infection).12
Treatment of the malnutriton including 3 main phase, which is stabilization, transition,
and rehabilitation, and additional follow up phase. Stabilization phase start from the patient
admitted to the hospital until stable, usually between 3 7 days. Aim of this phase are to
treat hipoglycemia, hypotermia, dehydration, electrolyte imbalance, cure the infection with
intravena or oral antibiotics, and treat the micronutrient deficiency (without Fe). For dietary
intake we give Formula 75 milk (F75), depend on patient tolerance. From intravenous fluid
we give High potassium fluid such as Kaen 3B. Micronutrient deficiency is treated with
supplementation of vitamin and mineral such as Vitamin A, Vitamin C (Ascorbic Acid), and

19

Folic Acid. Iron supplementation was postpone until the rehabilitation phase, according to
iron function that can be used for microorganism nutrition. 12

SUMMARY
A case of Chronic Kidney Disease and Vesicouretral Reflux in Spina Bifida patient
has been reported. The diagnosis were established based on history taking, physical
examination, laboratory and radiology finding. Oxygen, Antibiotics, Antihypertensive, Natrium
Bicarbonat, and Erythropoietin were given. The prognosis was doubtful

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