Chronic_Renal_Failure.

doc
Андрій Миколайович Лобода

2014
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Chronic Renal Failure

Chronic renal failure (CRF) implies permanent, irreversible, severe decrease of renal function. This
eventually results in end-stage renal disease.
As it is recommended by the 4th European congress of pediatricians-nephrologists it is necessary to
diagnose CRF in the children with renal diseases when glomerular filtration is less than 20 ml/min/1,73m 2,
creatinine level is more than 0,177mmol/l and urea level is more than 8,5 mmol/l.
Cause of CRF
1. Glomerular diseases
a) Glomerulonephritis:

of unknown etiology
associated with systemic lupus erythematosus (SLE), polyarteriitis nodosa;

- Henoch-Schönlein vasculitis.
b) Familial nephropathy:

nephronophthisis;
Alport’s syndrome.

3. Hemolytic uremic syndrome;

4. Amyloidosis.

2. Congenital anomalies:

bilateral renal dysplasia;

polycystic kidney disease.

3. Reflux nephropathy.
4. Obstructive nephropathy:

pelviureteric junction obstruction;

posterior urethral valve;
calculi.

5. Miscellaneous: bilateral Wilms’ tumor.

Clinical features and altered physiology. Increased thirst and frequent passage of urine including
nocturia are common because of loss of urinary concentrating power. Moderate and at times severe
normocytic and normochromic anemia is present. There is bone marrow depression and decrease in iron
utilization for hemoglobin synthesis. Erythropoietin production is low mainly because of reduction of
functional renal mass. Mild hemolysis and increased loss of blood from gastrointestinal tract also occur.
Growth retardation is a main feature, contributed to by chronic azotemia, anorexia and resultant
inadequate nutrition, and bony changes. Skeletal deformities, including rickets and genu valgum may be
striking and occasionally present. Osteodystrophy results from a lack of renal formation of 1,25(OH)2 D3,
malabsorption of calcium and chronic acidosis. The blood pressure is increased and the optic fundus
shows hypertensive retinopathy.
Systemic acidosis results from severe loss of nephrons with decreased ammonia formation and
consequent failure to buffer H+ ions and conserve bicarbonate. Initially it is asymptomatic, but in late
stages there may be acidotic breathing, nausea and vomiting. Muscular weakness (severe, proximal
myopathy may occasionally occur), peripheral neuropathy, itching, purpura, pericarditis and infections
are late features. Infections are common and may precipitate terminal renal failure.
It is important to remember that failure to thrive, growth retardation, anemia, hypertension and rickets
may occasionally be present in CRF, without there being a clear history of a previous renal disease.
Investigations. The patient should be investigated to find the cause of renal failure and detect
reversible factors (e.g., urinary tract obstruction, urinary tract or other infections). Appropriate imaging
studies should be done. Hemogram, serum calcium, phosphate and alkaline phosphatase levels and acid
base studies should be obtained. Blood urea and serum creatinine clearance should be done. X-ray films
of the hands, knees, pelvis and spine should be obtained to document bony abnormalities, and
periodically repeated to evaluate the effect of therapy.
Diagnostic criteria
/. Clinical:

Tiredness, fatigue, headache, loss of appetite, vomiting;

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Polyuria, nicturia, polydypsia, bone and joint pains, retardation of growth, dryness and itching of
skin;
Muscular convulsions, paresthesias, signs of sensor or motor neuropathy;

- Heart failure and hemodynamic disorders.

//. Laboratory:

Decrease of glomerular filtration rate;

Metabolic acidosis;
Anemia;
Decrease of thrombocytes’ adhesion;
Hyperkalemia, hyperphosphatemia, hypocalcemia, hypoproteinemia, hyperuricemia;
Isostenuria;
Renal osteodystrophy;
X-ray examination of the chest may reveal cardiomegaly, hypertrophy of the left ventricle,
aortectasia, lung’s edema, pleural exudate.

Treatment of Chronic Renal Failure (CRF)

Management. Although a cure is not possible, adequate conservative management, prevention and
treatment of complications can preserve renal function and prolong active life.
Diet. Careful attention to details is essential. Inadequate caloric intake once renal function falls below
50% is a major cause of growth failure in children. Protein restriction is important (1,5 g/kg) in severe
uremia. The minimal protein intake should be 1 g/kg/day, preferably of high biologic value.
Calories and vitamins. Recommended daily amounts should be given. Water-soluble vitamins are
recommended to avoid deficiency states. There is no restriction of carbohydrates and fats.
Water. Liberal water intake should be provided. Dehydration should be quickly corrected since it may
rapidly cause reduction of renal perfusion and aggravate azotemia.
Sodium. The dietary intake of salt should be individualized. Renal regulation of sodium reabsorption is
impaired. Some patients lose large amounts of sodium which can be determined by measuring 24 hours
excretion on a fixed sodium intake. Excess sodium will lead to water retention and aggravation of
hypertension, where as a low intake will cause reduction in fluid volume, decreased renal perfusion and
increase in azotemia.
Potassium. Renal regulation of potassium balance is maintained until very late stages, but the
capacity to excrete a rapid potassium load is impaired. Dietary articles with large potassium content
should be avoided.
Calcium and phosphorus. Calcium supplements are given in the form of calcium gluconate or calcium
carbonate. Dairy products contain large amounts of phosphates are restricted.
Acidosis. Development of acidosis is a late phenomenon and is easily treated with sodium bicarbonate
at approximately 2 mEq/kg/24 hr.
Anemia. Iron and folic acid supplements may be given if the blood picture shows hypochromic anemia.
Usually the anemia is normocytic and normochromic and results from a deficiency of erythropoietin. The
availability of recombinant human erythropoietin has revolutionized the management of anemia in
chronic renal failure. With its administration, satisfactory levels of hemoglobin and hematocrit can be
maintained. Recombinant human erythropoietin is given subcutaneously or i.v. if the child is on dialysis.
The drug, however, is very expensive. Blood transfusion, if Hb<50 g/l (but effect is not stable). Blood
should be transfused very slowly, under careful supervision, since it may occasionally aggravate
hypertension and precipitate heart failure.
Hypertension. It should be adequately treated to keep the diastolic values below 75-80 mmHg.
Nifedipin or diazoxide is given for acute hypertension, and beta-blockers, diuretics, salt restriction, and
hydralazine may be administered.
Renal osteodystrophy. Initially the symptoms are vague and nonspecific. Bone pains and muscular
weakness may be present. Growth retardation and later skeletal deformities such as genu valgum are
marked. Other features of rickets are present.
Azotemic osteodystrophy is a more serious problem in children as it occurs during the period of
growth. Its prevention and adequate treatment are crucial, the lack of which may result in crippling
deformities and incapacitation. The proximal nephron is the chief site of synthesis of calcitriol, the most
potent metabolite of vitamin D. Its deceased production is an important factor in the pathogenesis of
secondary hyperparathyroidism in CRF. During reduction of renal function, phosphate balance is initially
maintained by its increased excretion from the remaining normal nephrons. However, when the GFR falls
below 25% blood phosphate levels rise.
Blood examination shows hypocalcemia, hyperphosphatemia and raised levels of alkaline
phosphatase and parathormone. Radiological abnormalities include metaphyseal changes suggestive of
rickets. Features of secondary hyperpara-thyroidism such as bone resorption, typically seen in the
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phalanges, clavicles, ischium, pubis and sacroiliac joints may be visible. The skull may show ground glass
appearance, mottling and focal sclerosis.
The treatment is based on dietary restriction of phosphate and administration of phosphate binders
and vitamin D. When GRF is reduced below 50%, phosphate containing dietary articles (mostly dairy
products) should be curtailed. Calcium carbonate or calcium acetate should be used to reduce intestinal
absorption of phosphate. These are given in a dose of 0,5-1 g/day with meals. Aluminum salts are not
used as aluminum may cause bone disease. Blood phosphate levels should be maintained in the normal
range and hypophosphatemia avoided. Vitamin D analogs with short half life are preferable. Calcitriol 20-
60 mg/kg/day or standard vitamin D in standard dose 4000-10000 IU/day or in large doses (10000-50000
IU/day) may be used under the control of Sulkowich’s reaction, also calcium orally. Hypercalcemia and
hypercalciuria should be avoided otherwise renal damage may be aggravated. Orthopedic treatment
may be required to correct deformities of lower extremities.
Growth. Administration of recombinant human growth hormone has been shown to increase the rate
of growth in children with chronic renal failure.
Infections. Urinary tract infections and other infections should be promptly treated with effective and
least toxic drugs. The dosage of drugs should be modified (reduction of dosage or increase in dosing
interval or both of these measures), depending upon the serum creatinine levels or the creatinine
clearance.
Long term care. The rate of progression of chronic renal injury is very variable. In some disorders (e.g.,
hemolytic uremic syndrome, crescentic glomerulonephritis) the final stage of a renal disease may
develop within a few weeks or months. In several other conditions, particularly reflux nephropathy and
some forms of glomerulonephritis, the rate of deterioration of renal function may be very slow lasting
over a period of several years.
A rapid deterioration in renal function indicates a search for a reversible complication (infection, fluid
loss, hypertension, use of nephrotoxic drug). Eventually, however, the final stage of a renal disease
necessitates some form of renal replacement therapy.
Optimal management of chronic renal failure involves a team approach including pediatric
nephrologist, trained nurse, dietitian, social worker and orthopedic surgeon. Every attempt should be
made to keep the child ambulatory and let him carry out his usual activity. Constant encouragement and
emotional support are necessary.
Chronic dialysis. Appropriate dialysis catheters and dialysis bags are now available. Chronic dialysis,
peritoneal or hemodialysis, should be undertaken when renal transplantation is an option. The
socioeconomic factors should always be taken into account.
Renal transplantation. The feasibility and efficacy of renal transplantation in children has been well
established. In economically advanced countries the procedure is employed as standard therapeutic
modality for children with the final stage of a renal disease. Successful renal transplants have been
carried out even in infants. With advances in surgical skills, technical problems have become rare. The
immunosuppressive management is now safer and more effective with the use of antilymphocyte
globulin and cyclosporin A, and that of acute rejection of OKT3. Renal transplantation requires teamwork
and long-term supervision. The procedure should be employed in carefully selected cases at centers
where adult transplant services are well established.
Regular dialysis is necessary when creatinine in blood serum is more than 0,528 mmol/l and clearance
of endogenous creatinine is less than 10 ml/min/1,73m 2.

Dysmetabolic Nephropathies
Dysmetabolic nephropathies are renal lesions because of the severe disorders of metabolism. All the
children with dysmetabolic nephropathies have pathology of the bile ducts. Hyperoxaluria may be
primary (rare hereditary enzymopathy with elevated synthesis of oxalates) and secondary (hereditable
on polygenic type family instability of membranes).
Diagnostic criteria
/. Clinical:

recurrent pains in joints and their swelling;

abdominal pains (renal colic);
lesions of the lungs.

//. Laboratory:

hematuria;
elevated urine level of glycolate, glyoxalates and oxalates in the primary type and D-glyceric acid
with oxalates in the secondary type;
elevated daily excretion of oxalates.
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Uraturia may be primary (gout, Lesch-Nyhan syndrome) and secondary (because of the lysis of the
great quantity of nuclear cells).
/. Clinical signs and symptoms:
Gout manifests usually in childhood as neuroarthritic diathesis. Lesch-Nyhan syndrome is diagnosed in
boys only. There is hyperreflexia, foot clonus, spasms of extremities, choreoathetoid movements,
selftraumatic behavior (children bite and chew theirs fingers, lips, tear their hair). Mental retardation of
different degree is typical.
//. Laboratory findings:

elevated blood and urine level (more than 3,9 mmol/l and 3,6 mmol/day correspondingly) of uric
acid.