Learning Issue #11

Based on your
possible final
diagnosis, what are
z the treatment plans
for our patient?
PIANO, Alona
PILIEN, Lea Nadine
PLETE, Apollo
PILONES, Matthew
POSADAS, Adrian
z Possible final diagnosis:

Chronic Kidney Disease

 How? Why?
z
 History ROS
z
• Easy fatigability • Nausea
• Difficulty of breathing • Fever
• Oliguria with occasional dysuria • Blurred vision
• Shortness of breath + orthopnea • Dry cough
• Bipedal edema • Weight change
• Sometimes with puffy face and
abdominal enlargement

Physical Examination Description

Vital Signs • Stage 2 HTN (170/100)
• Tachycardia (112/min)
• Tachypnea (26/min)
• BMI: 26 (Obese 1)

** based on IOTF-proposed classification of BMI

categories for Asia
Skin Dry and sallow
Pertinent
z Laboratory Result of the Patient

Laboratory Measures Description

Kidney ultrasound • Kidneys are SMALL in size.
• Renal parenchyma is hyperechoic when
compared with the adjacent spleen and right
hepatic lobe.
• The CMD is indistinct, bilaterally.
SCr • Increased by 3.05-3.85 mg/d (Px: 4.75 mg/dl)
 z

Risk Factors of CKD Description

Age 59 years old
Hypertension For 20 years (Losartan 100 mg/d; amlodipine 5 mg/d)
- ~30% attributed to ESRD
cases
Diabetes Mellitus For 20 years
(leading cause of ESRD)
- 45% (newly diagnosed)
Family history • Hypertension (both parents)
• Diabetes (both parents)
• Kidney disease (Considering that the father is
undergoing hemodialysis 3x/ week)

Harrison’s Principle of Internal Medicine pp1811,1822

z

KDIGO Clinical Practice Guideline for Acute Kidney Injury, pp35

z
z TREATMENT
Chronic Kidney Disease
CONSERVATIVE MANAGEMENT
z
CONSERVATIVE
z MANAGEMENT

 Management should be conservative until it becomes

impossible for the patient to continue their customary lifestyle.
 Reducing
z
Intraglomerular Hypertension and
Proteinuria
 2 categories of response considered:

 If the progression is strongly associated with systemic and

intraglomerular hypertension and proteinuria. (eg diabetic
nephropathy/ glomerular disease)
 First choice of drug: ACE inhibitors and ARBs

 Proteinuria is mild or absent initially, where the contribution of

intraglomerular hypertension is less prominent, (eg adult polycstic
kidne disease/other tubulointerstitial disease)
 Second line antihypertensive agent (ca channel blockers,
diltiazem, verapamil)
 TREATMENTS
z AIMED
AT
SPECIFIC CAUSE
 FLUID, ELECTROLYTE, AND ACID-BASE DISORDER

 Dietary restriction of dietary protein (0.5/kg/day)

 Dietary salt restriction (close sodium balance)
 Use of loop diuretics occasionally in combination with metolazone
 Water restriction is indicated only if there is a problem with hyponatremia
 Dietary restriction of potassium, use of kaliuretic diuretics, avoidance of both
potassium supplements and potassium retaining medication if there is
hyperkalemia
 Sodium bicarbonate replacement if concentration fall below 20-30 mmol/L
 TREATMENTS
z AIMED
AT
 DISORDERSPECIFIC
OF CALCIUM ANDCAUSE
PHOSPHATE METABOLISM

 Careful attention to plasma phosphate concentration in CKD patients should be

paid.
 Low-phosphate diet
 Appropriate use of phosphate binding agents
 calcium acetate, calcium carbonate
 Sevelamer, lanthanum
 Cinacalcet
 Calcimimetic agent that enhances sensitivit of the parathroid cell to the
suppressive effect of calcium
 It produces a dose dependent reduction in PTH and plasma concentration
of calcium in some patients.
*target PTH level 150 and 300pg/mL
 TREATMENTS
z AIMED
AT
SPECIFIC CAUSE
 ANEMIA
 Recombinant human ESA
 Given subcutaneously to treat anemia
 Adequate bone marrow iron stores should be available before treatment
 iron supplementation
 or thru IV infusion if there is GI intolerance
 Adequate supply of other major substrate and co factors for red cell
production
 Vitamin B12 and folate
*target hemoglobin concentration 100-115g/L
 TREATMENTS
z AIMED
AT
SPECIFIC CAUSE
 ABNORMAL HOMEOSTASIS

 Desmopressin (DDAVP) , croprecipitate, IV conjugated estrogen, blood

transfusion, ESA therapy
 Reverse abnormal bleeding time and coagulopathy in patient with CKD
temporarily

 Anticoagulants ma not be applicable for patients with advanced CKD

 Warfarin (greater risk for bleeding complication)
 Low molecular weight heparin (avoided or dose adjusted)
 z Other Treatment
Options
for the Patient
Treatment Options:
1. Hemodialysis
2. Peritoneal Dialysis (CCPD or CAPD)
2. Transplantation
 z Hemodialysis

- Blood is put through a filter outside the body, cleaned, and

then returned to the patient.
- Relies on the principles of solute diffusion across a semi-
permeable membrane

TREATMENT
• Intermittent treatment—usually 3–5 hours, three times weekly.
• Treatments may be given in a kidney center, a satellite unit, or the
home.
z
z
 z Hemodialysis
Three essential components to hemodialysis:
- dialyzer ，
- the composition and delivery of the dialysate
- blood delivery system

A. Dialyzer
- plastic chamber with the ability to perfuse blood and dialysate
compartments simultaneously at very high flow rates.
- composed of bundles of capillary tubes through which blood
circulates while dialysate travels on the outside of the fiber bundle.
 z Hemodialysis
B. Dialysate

- potassium concentration of dialysate may be varied from

0 to 4 mmol/L depending on the predialysis serum potassium
concentration.

- usual dialysate calcium concentration is 1 .25 mmol/L

(2.5 meq/L) ， although modification may be required in selected
settings

- Higher dialysate sodium concentrations and sodium modeling

may predispose patients to positive sodium balance and increased
thirst; thus ， these strategies to ameliorate intradialytic hypotension
may be undesirable in hypertensive patients or in patients with large
interdialytic weight gains.
 z Hemodialysis
C. Blood Delivery System
- composed of the extracorporeal circuit and the dialysis access.
- The dialysis machine consists of a blood pump ， dialysis
solution delivery system ， and various safety monitors
- The blood pump moves blood from the access site ， through
the dialyzer ， and back to the patient. The blood flow rate may range
from 250-500 mL/min ， depending on the type and integrity of the
vascular access
- The dialysis solution delivery system dilutes the concentrated
dialysate with water and monitors the temperature ， conductivity ，
and flow of dialysate.
 z Hemodialysis
Goals of Dialysis

1. urea reduction ratio (the fractional reduction in blood urea nitrogen

per hemodialysis session) of >65-70% and a body water indexed
clearance x time product (KT!V) above 1.2 or 1 .05 ， depending on
whether urea concentrations are "equilibrated.“
2. Improved control of hypertension and hyperphosphatemia ， reduced
left ventricular mass and improved self-reported physical health with
six times per week hemodialysis compared to the usual three times
per week therapy.
3. Significant increase in mortality and hospitalization for heart failure
after the longer interdialytic interval that occurs over the dialysis
"weekend."
 z Dialysis Access

3 Types:
1. Fistula
2. Graft
3. Catheter
 DIALYSIS ACCESS

1. FISTULA -anastomosis of an artery to a vein

-Use in the placement of large needles (typically 15 gauge) to access the
circulation.
-Many patients undergo placement of an arteriovenous graft (i.e., the
interposition of prosthetic material, usually polytetrafluoroethylene,
between an artery and a vein) or a tunneled dialysis catheter.

2. GRAFT -“arteriovenous graft”

-used among persons with smaller caliber veins or persons whose veins have
been damaged by repeated venipuncture, or after prolonged hospitalization.

-Most important complication of arteriovenous grafts is thrombosis of the graft and

graft failure, due principally to intimal hyperplasia at the anastomosis between the
graft and recipient vein.

-When grafts (or fistulas) fail, catheter-guided angioplasty can be used to dilate
stenoses; monitoring of venous pressures on dialysis and of access flow, although
not routinely performed, may assist in the early recognition of impending vascular
access failure.
 DIALYSIS ACCESS

3. CATHETERS Intravenous large-bore catheters, used in patients with acute and

chronic kidney disease.

-For persons on maintenance hemodialysis, tunneled catheters (either

two separate catheters or a single catheter with two lumens) are often
used when arteriovenous fistulas and grafts have failed or are not
feasible due to anatomic considerations.

-These catheters are tunneled under the skin; the tunnel reduces
bacterial translocation from the skin, resulting in a lower infection rate
than with nontunneled temporary catheters. Most tunneled catheters
are placed in the internal jugular veins; the external jugular, femoral,
and subclavian veins may also be used.
z Complications during
Hemodialysis
 Hypotension

 High-Output Cardiac Failure

 Muscle cramps

 Anaphylactoid reactions
 z Peritoneal Dialysis

 1.5–3 L of a dextrose-containing solution is infused into the

peritoneal cavity
 The solution is allowed to dwell for a set period of time, usually
2–4 h.
 z

 The clearance of solutes and water during a peritoneal dialysis

exchange depends on the balance between the movement of
solute and water into the peritoneal cavity versus absorption from
the peritoneal cavity.
 The rate of diffusion diminishes with time and eventually stops
when equilibration between plasma and dialysate is reached.
 z Flow of absorption of solutes &
water
-peritoneal cavity
-across the peritoneal membrane
-peritoneal capillary circulation

-via peritoneal lymphatics

-lymphatic circulation
z FORMS OF PERITONEAL
DIALYSIS

 Chronic Ambulatory Peritoneal Dialysis (CAPD)

 Continuous Cycler-assisted Peritoneal Dialysis (CCPD)

 combination of both
 z
Types of peritoneal dialysis

 There are three types of peritoneal dialysis

 Continuous ambulatory peritoneal dialysis (CAPD), the most
common type, needs no machine and can be done at home.
Exchanges of fluid are done throughout the day, usually four
exchanges a day.
 Continuous cyclic peritoneal dialysis(CCPD) uses a machine
and is usually performed at night when the person Is sleeping.
 Intermittent peritoneal dialysis(IPD) uses the same type of
machine as CCPD – if done overnight is called nocturnal intermittent
peritoneal dialysis(NIPD)
z Chronic Ambulatory Peritoneal
Dialysis (CAPD)
 z Chronic Ambulatory Peritoneal
Dialysis (CAPD)

 In CAPD, dialysate is manually infused into the peritoneal

cavity and exchanged three to five times during the day.
 A nighttime dwell is frequently instilled at bedtime and remains
in the peritoneal cavity through the night.
 z Continuous Cycler-assisted
Peritoneal Dialysis (CCPD)

 In CCPD, exchanges are performed in an automated fashion, usually

at night; the patient is connected to an automated cycler that
performs a series of exchange cycles while the patient sleeps.

 The number of exchange cycles required to optimize peritoneal

solute clearance varies by the peritoneal membrane characteristics

 For some patients in whom CCPD does not provide sufficient solute
clearance, a hybrid approach can be adopted where one or more
daytime exchanges are added to the CCPD regimen.
 z Peritoneal dialysis
solutions
 volumes typically ranging from 1.5 to 3 L.

 Typically, dextrose at varying concentrations contributes to the

hypertonicity of peritoneal dialysate.

 The most common additives to peritoneal dialysis solutions are

heparin

 Insulin may also be added in patients with diabetes mellitus.

 z Icodextrin

 a nonabsorbable carbohydrate that can be used in place of

dextrose.

 more efficient ultrafiltration than with dextrose-containing

solutions.

 typically used as the “last fill” for patients on

CCPD or for the longest dwell in patients on CAPD.
 z Peritoneal Equilibrium Test

 a formal evaluation of peritoneal membrane characteristics

 measures the transfer rates of creatinine and glucose across

the peritoneal membrane.
 z
MAJOR COMPLICATIONS DURING
PERITONEAL DIALYSIS

 Peritonitis
 Catheter Associated Non-Peritonitis
 Infections
 Weight gain
 Metabolic disturbances
 z Chronic Peritoneal Dialysis

• Used electively or when circumstances (ex: no available vascular

access) prohibit chronic hemodialysis.
• small molecules (such as creatinine and urea) are cleared less
effectively than larger molecules
• Intermittent thrice-weekly treatment (IPPD), continuous cycler-
assisted peritoneal dialysis (CCPD), or chronic ambulatory
peritoneal dialysis (CAPD) is possible.
• the patient performs 3–5 daily exchanges using 1–2 L of dialysate
at each exchange.
• The dialysate contains a high glucose concentration and the
peritoneal surface serves as the semipermeable membrane.
peritoneal dialysis
 z Renal
Transplant
The treatment of choice for advanced chronic renal failure.
o Selection for Renal Transplant

 Patients older than 65 – 70 years

 Clear indications for CKD patients include uremic pericarditis, encephalopathy, intractable
muscle cramping, anorexia, and nausea not attributable to reversible causes such as peptic
ulcer disease, evidence of malnutrition and fluid and electrolyte abnormalities, principally
hyperkalemia or ECFV overload, that are refractory to other measures.
 Most patients with end-stage renal disease (ESRD)

 Contraindications: Infections, cancer, severe vasculopathy and metabolic diseases likely

to recur.
 Other factors such as psychosocial status, environment, and ability to follow a complex
medical regimen.
o Preparation for Renal Transplant

 Temporary relief of symptoms and signs of impending uremia, such as anorexia, nausea,
vomiting, lassitude and pruritus, may sometimes be achieved with protein restriction.
 After immunosuppression techniques and genetic matching were developed, renal
homotransplantations became an acceptable alternative to maintenance hemodialysis.
o Renal Transplantation
 Results are best with living-related transplantation, in part because of optimized
tissue matching and in part because waiting time and ischemic time can be
minimized; ideally, these pts are transplanted prior to the onset of symptomatic
uremia or indications for dialysis.
 Transplant centers now also perform living-unrelated donor (e.g., spousal)
transplants, often in “chains” involving multiple donors to optimize tissue
matching.
 Graft survival in these cases is far superior to that observed with deceased donor
transplants, although less favorable than with living-related transplants.
 In an attempt to increase utilization of deceased-donor kidneys and reduce
discard rates of organs, criteria for the use of so-called expanded criteria donor
(ECD) kidneys and kidneys from donors after cardiac death (DCD) have been
developed. ECD kidneys are usually used for older pts who are expected to fare
less well on dialysis.
 Pretransplant blood transfusion should be avoided, so as to reduce the
likelihood of sensitization to incompatible HLA antigens; if transfusion is
necessary, leukocyte-reduced irradiated blood is preferred.
 Overall, the current standard of care is that the pt should have >5 years of life
expectancy to be eligible for a renal transplant, since the benefits of transplantation
are only realized after a perioperative period in which the mortality rate is higher than
in comparable pts on dialysis.

 Rejection
 Immunologic rejection is the major hazard to the short-term success of renal
transplantation. Rejection may be (1) hyperacute (immediate graft dysfunction due
to presensitization) or (2) acute (sudden change in renal function occurring within
weeks to months).
 Usually detected by a rise in serum creatinine but may also lead to hypertension,
fever, reduced urine output, and occasionally graft tenderness. A percutaneous
renal transplant biopsy confirms the diagnosis.
 Treatment usually consists of a “pulse” of methylprednisolone (500–1000 mg/d for
3 days). In refractory or particularly severe cases, 7–10 days of a monoclonal
antibody directed at human T lymphocytes may be given.
z
IMMUNOSUPPRESIVE
TREATMENT
 z I. INDUCTION THERAPY

A. DEPLETING AGENTS
 Peripheral human lymphocytes, thymocytes or lymphocytes from
spleens or thoracic duct fistulas are injected into horses, rabbits, or
goats to produce antilymphocyte serum, from which the globulin
fraction is then separated, resulting in antithymocyte globulin.
 Polyclonal antibodies induce lymphocyte depletion and the immune
system may take several months to recover.
 Monoclonal antibodies against defined lymphocyte subsets offer a
more precise and standardized form of therapy.
 Alemtuzumab - directed to the CD52 protein, widely distributed on
immune cells such as B and T cells, natural killer cells,
macrophages, and some granulocytes.
 z

B. NONDEPLETING AGENTS
 Target the 55-kDa alpha chain of the IL-2 receptor, which is
expressed only on T cells that have been recently activated.
 Used as prophylaxis for acute rejection in the immediate
posttransplant period and is effective at decreasing the early acute
rejection rate with few adverse effects
 z II. MAINTENANCE THERAPY

A. ANITIMETABOLITES

1. Azathioprine
- an analogue of mercaptopurine
- inhibit synthesis of DNA, RNA, or both
- is administered in doses of 1.5-2 mg/kg/day
- reduction in dose is required because of leukopenia and
occasionally thrombocytopenia.
- excessive amounts may cause jaundice, anemia,
and alopecia
 z

2. Mycophenolate mofetil/ Mycophenolate sodium

- metabolized to mycophenolic acid
- has similar mode of action to azathioprine and a mild degree of
gastrointestinal toxicity but produces less bone marrow
suppression.

Advantage: increased potency in preventing or reversing

rejection
 z

B. STEROIDS
Major effect: preventing the release of IL-6 and IL-1 by monocytes-macrophages

1. Glucocorticoids
- important adjuncts to immunosuppressive therapy.
a. Predinisone
-has effects that are easiest to assess
- effective for the reversal of rejection (large doses)
- 200-300 mg predinisone is given immediately before or at the time of
transplantation, and the dose is reduced to 30 mg within a week.
- maintenance of 5-10 mg/d dose is used for patients whose renal function
is stable after 6mos or a year.
 z

B. STEROIDS
1. Glucocorticoids

b. Methylprednisolone
- for treatment of acute rejection
- 0.5-1 g IV, is administered immediately upon
diagnosis of beginning rejection and continued once daily for 3
days.
- “pulse” doses are not effective in chronic rejection
 z

C. Calcineurin inhibitors
1. Cyclosporine
- a fungal peptide with potent immunosuppresive activity
- acts on the calcineurin pathway to block transcription of mRNA for
IL-2 and other proinflammatory cytokines, thereby inhibiting T
cell proliferation.
- more effective in conjunction with glucocorticoids and
mycophenolate.

Toxic effects: Nephrotoxicity, hepatotoxicity, hirsutism, tremor, gingival

hyperplasia, and diabetes
 z

C. Calcineurin inhibitors

2. Tacrolimus
-previously called FK506
- fungal macrolide that has the same mode of action as
cyclosporine as well as similar side effect profile
- does not produce hirsutism or gingival hyperplasia
- De novo diabetes mellitus is more common with tacrolimus
- first used in liver transplantation
- may substitute for cyclosporine entirely or as an alternative in
renal patients whose rejections are poorly controlled by
cyclosporine
 z

D. Belatacept

- is a fusion protein that binds costimulatory ligands (CD80 and

CD86) present on antigen-presenting cells, interrupting their binding
to CD28 on T cells.
- this inhibition leads to T cell anergy and apoptosis
- FDA approved for kidney transplant recipients and is given
monthly as an IV infusion.
z
 z CLINICAL COURSE AND
MANAGEMENT OF THE RECIPIENT

 Adequate hemodialysis should be performed within 48h of surgery, and

care should be taken that the serum potassium levels is not markedly
elevated so that intraoperative cardiac arrhythmias can be averted.
 Diuresis that commonly occurs postoperatively must be carefully
monitored. In some instances, it may be massive, reflecting the inability of
ischemic tubules to regulate sodium and water excretion; with large
diureses, massive potassium losses may occur.
 z CLINICAL COURSE AND
MANAGEMENT OF THE RECIPIENT

 Acute tubular necrosis (ATN) due to ischemia may cause immediate oliguria or
may follow an initial short period of graft function.
 Recovery usually occurs within 3 weeks, although periods as long as 6 weeks
have been reported.
 Superimposition of rejection on ATN is common, and the differential diagnosis may
be difficult without a graft biopsy.
 Cyclosporine therapy prolongs ATN, and some patients diurese until the dose is
reduced drastically.
 Many centers avoid starting cyclosporine for the first several days, using
antilympocyte globulin (ALG) or a monoclonal antibody along with mycophenolic
acid and predinisone until renal function is established.
z
z
z
References

 Harrison's Principles of Internal Med(19th ed); Dialysis in the

treatment of Renal Failure pg. 1822-1824
 Smiths General Urology 17th ed; Chronic Renal Failure &
Dialysis pg. 535-537
 KDIGO Clinical Practice Guideline for Acute Kidney Injury/
Chronic Kidney Disease