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Saudi Journal of Kidney Diseases and Transplantation
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Year : 1997  |  Volume : 8  |  Issue : 3  |  Page : 269-273
Chronic Renal Failure in Children: Medical Management

Department of Pediatrics, State University of New York, Stony Brook, New York, USA

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How to cite this article:
Rahman AJ, Fine RN. Chronic Renal Failure in Children: Medical Management. Saudi J Kidney Dis Transpl 1997;8:269-73

How to cite this URL:
Rahman AJ, Fine RN. Chronic Renal Failure in Children: Medical Management. Saudi J Kidney Dis Transpl [serial online] 1997 [cited 2021 Apr 22];8:269-73. Available from: https://www.sjkdt.org/text.asp?1997/8/3/269/39353

   Introduction Top

Chronic renal failure (CRF) is defined as an irreversible loss of renal function, characterized by a decrease of glomerular filtration rate (GFR). The management of a child with CRF depends upon the degree of renal insufficiency. The prevention of long­term complications and amelioration of current clinical problems are the focus of an optimal management strategy. According to data from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) 1996 annual report, 1725 patients less than 18 years of age have been enrolled with CRF; 26% had obstructive uropathy, 20%', renal hypoplasia/dysplasia, 9% reflux nephropathy and 6% focal segmental glomerulosclerosis (FSGS).

A major goal of treatment in the infant, child or adolescent with CRF is to maximize growth potential and prevent the clinical consequences associated with renal functional impairment and promote normal development. The medical management of CRF focuses on the following aspects:

a. Promoting linear growth
b. Preventing renal osteodystrophy
c. Correcting anemia
d. Preventing metabolic acidosis
e. Maintaining fluid and electrolyte balance
f. Controlling hypertension

   Growth Top

Factors affecting growth in infants, children and adolescents with CRF are illustrated in [Figure - 1]. The current hypothesis proposes that growth retardation associated with CRF is related to end-organ hypo-responsiveness to the growth hormone (GH)/insulin-like growth factor (IGF) axis [1],[2] . Introduction of recombinant human growth hormone (rhGH), to improve growth in children with CRF has proven effective [3] . Short-term trials by Koch, et al and Rees, et al have found that children given rhGH in a dose of 0.125 mg/kg thrice weekly or a similar weekly dose given daily, almost doubled the growth velocity compared to the prior years growth velocity [4],[5] . Ideally, the goal of rhGH treatment is attaining one's genetic potential for height (i.e. 50th percentile for mid-parental height). This frequently requires treatment until the patient is transplanted or attains adult height. Fine, et al studied 17 pediatric patients with CRF who discontinued rhGH on reaching target height and found a marked reduction in growth velocity (< 4 cm/yr) following discontinuation of rhGH in 70% of the patients [6] . The potential complications of rhGH therapy are hyperglyceraia, hypercalciuria, hyperinsuline­mia, hyperfiltration which may further compromise renal function, pseudo tumor cerebri, aseptic necrosis of femoral head, and progressive renal osteodystrophy. However, the incidence of complications is quite low. Other factors such as inadequate calorie intake, renal osteodystrophy, persistent acidosis and fluid and electrolyte abnormalities adversely affect growth in children with CRF and should be corrected before initiating rhGH.

   Nutrition Top

Nutritional assessment and evaluation is an important aspect of management of children with CRF. On each visit, a detailed review of dietary intake and assessment of caloric intake is mandatory. Nutritional support to provide at least 75% RDA for calories in order to ensure anabolic potential in these patients is imperative. Caloric recommendations are estimated by using 100 kilocalories/ kg for first 10 kg of body weight, 50 kilocalories/kg for the next 10 kg of body weight and 20 kilocalories/kg for additional kilograms of body weight, or by following the RDA recommendations for age. In children with CRF, altered taste, dietary restrictions and anorexia may make adequate caloric intake difficult. The caloric content of infant formula can be increased up to 27 kilocalories/oz by adding polycose, MCT oil or corn oil to achieve caloric requirements. In older children, supplementing the diet with high calorie carbohydrates or fats such as margarine may result in a somewhat more palatable diet. It is recommended that 60-70% of protein allowance should be given to maintain a positive nitrogen balance. Sodium restriction between 1 to 4 gms per day is indicated only when there is hypertension or fluid retention. Potassium restriction is necessary only if the serum potassium is greater than 5 mmol/L. In young infants, formulas such as Similac PM 60/40 or Wyeth S-29 (low in sodium, potassium, phosphorus and a preferable calcium to phosphorus ratio) can be helpful in providing adequate calories while avoiding electrolyte abnormalities.

   Renal Osteodystrophy Top

The kidney plays an important role in bone mineralization and calcium and phosphorus homeostasis. Renal osteodystrophy (ROD) can be divided into four entities which are not categorically separable and often occur concurrently. Osteitis fibrosa is characterized by elevated PTH levels and excessive woven bone which is poorly mineralized and aligned. This entity arises because of hypo-calcernia and hyperphosphatemia, and altered vitamin D metabolism giving rise to elevated levels of PTH. Osteomalacia is due to an increase in lamellar bone with abnormal bone mineralization. A third type of ROD is the mixed variety with elements of the two previously described entities. Lastly, adynamic bone disease is characterized by low PTH levels and a low rate of bone formation. Adynamic bone disease, osteomalacia or osteitis fibrosa are often potentially avoidable complications of CRF. In order to prevent ROD it is important to maintain serum phosphorus levels between 1.4 - 1.8 mmol/L. This can be achieved by limiting foods with high phosphorus content (dairy products) and by adding oral medications which bind phosphorus in the gastrointestinal tract thus preventing its absorption. These medications include calcium carbonate, calcium citrate and calcium acetate which are effective phosphate binders. Aluminum and magnesium are not used as binders because of their cumulative potentially toxic effects. Care should be taken to give iron supplements between meals as calcium may interfere with its absorption.

Patients with CRF are in negative calcium balance due to limited intake of dairy products and altered vitamin D metabolism. It is estimated that dietary restriction alone can decrease calcium intake by up to 12 mmol/day (normal 400-500 mmol/day). Calcium supplementation as compared with calcium administration as a phosphate binder can vary according to the extent of CRF. It can range from 500 mg for mild CRF to 1500 mg/day in advanced cases. Calcium supplements should be taken on an empty stomach separate from that taken as phosphate binders. Salusky has shown that calcium supplementation can increase intake up to 1.5 gm/day in adults with CRF [7] . Calcium supplements should be administered with caution after controlling hyperphosphatemia because the calcium x phosphorus product (mg/dl Ca x mg/dl phos) greater than 70 predisposes to ectopic tissue calcification. Ideally, the serum calcium level should be maintained between 2.5 and 2.75 mmol/L. Higher serum levels are needed to suppress PTH levels secreted by hyperplastic parathyroid glands. In bone, the trophic action of growth hormone (GH) is counterbalanced by the inhibitory action of 1,25 dihydroxy vitamin D3 . Growth hormone influences bone and cartilage growth by stimulating local production of IGF 1 [8] .

The overall goal of mineral therapy is to prevent secondary hyperparathyroidism by giving oral vitamin D analogues, to keep serum calcium and phosphorus levels within an acceptable range. Periodic monitoring of PTH levels is required to prevent or suppress excessive elevations and to improve bone mineralization. The most appropriate vitamin D analogue is either 1,25 dihydroxy vit D3 (calcitriol) in a dose of 10-15 mg/kg/day or dihydrotachysterol (DHT) in a dose of 100­200 micrograms/day. The adequacy of vitamin D therapy is monitored by evaluating-serum PTH N-terminal peptide or intact PTH at 6-month intervals and the serum alkaline phosphatase, calcium and phosphorus levels every 4-6 weeks.

   Anemia Top

Anemia in CRF is primarily related to a decrease in the circulating erythropoietin (EPO) level. Erythropoietin is a glycoprotein with 165 amino acids. It acts by increasing hemoglobin synthesis and by increasing the terminal differentiation of erythroid progenitors. Recombinant human erythropoietin (r-HuEPO) can be administered intravenous (i.v.), subcutaneously (s.c.) or intraperitone-ally. The s.c. route is usually preferred because of its slow absorption and a longer half-life [9],[10],[11] . The increase in hematocrit following r-HuEPO is usually dose related [12] . Once the target hematocrit is achieved, the dose of r-HuEPO can be decreased to a lower maintenance level. The expected response is usually seen within eight weeks of initiating treatment i.e. an increase in the hematocrit of 5 to 6%. The recommended dose is 50-100 units/kg one to three times a week depending on the severity of anemia. Currently two preparations are available in the United States; epoten alpha and epoten beta with the major difference in these preparations being the vehicle. The former has citrate, which is painful when given s.c. and the latter has hyper-osmolar phosphate with polysorbate 20 which is relatively less painful. Administration of r-HuEPO has potential adverse affects including hypertension, hyperkalemia, headaches, seizures and iron deficiency resulting from incorporation into the expanding hemoglobin level. Oral iron supplementation is usually needed during r-HuEPO therapy to prevent and/or treat iron deficiency following rapid formation of new red blood cells. Such supplementation is required to maintain the transferrin saturation of >20%.

   Acidosis Top

Chronic metabolic acidosis is a major cause of catabolism in CRF. Correction of acidosis to a bicarbonate level between 23-­25 mEq/L by giving alkali 1-5 meq/kg/day optimizes growth potential in children. Betts and Magrath have indicated that growth velocity may proceed at a relatively normal rate once infants with CRF are identified and the metabolic abnormalities corrected [13] .

   Fluid and Electrolytes Top

The spectrum of fluid balance in CRF can vary between oliguria and polyuria. Therefore, the fluid required has to be adjusted according to each individual patient's need. CRF which is not complicated by hypertension usually does not require strict sodium restriction. When the GFR has fallen to less than 10% of normal, sodium restriction may be required before dialysis is instituted in order to minimize hypertension. Hyperkalemia can be a complication of decreased GFR with CRF or can be a side effect of medication used for treating hypertension (e.g beta adrenergic antagonists and ACE inhibitors). Potassium restricted diets usually maintain normokalemia until renal function is severely compromised.

   Hypertension Top

Hypertension in CRF may be mediated by high renin output from the diseased kidney or volume overload from fluid and sodium retention. Over a period of time hypertension increases cardiac output. Once the peripheral circulatory adaptation fails, the blood pressure begins to rise. In addition, arginine vasopressin is elevated in advanced CRF [14] and may contribute to volume overload.

Drugs often used to control blood pressure in children include diuretics (many of which are less effective as GFR is reduced), beta adrenergic antagonists, angiotensin converting enzyme (ACE) inhibitors such as enalapril, and calcium channel blockers. Serum potassium levels will need to be evaluated in children with CRF when beta adrenergic antagonists and ACE inhibitors are utilized. Other antihypertensive medications can be used according to each physician's preference and the patient's response.

   Dialysis Top

The preferred mode of dialysis has changed over the past few years, with peritoneal dialysis (PD) becoming the therapy of choice for many children with CRF [15] . Patients and parents often prefer this modality because it avoids frequent visits to the dialysis unit with repetitive fistula or graft punctures.

   Transplantation Top

Renal transplantation should be thought of as the preferred treatment for children with end-stage renal disease (ESRD). Recent advances in immunology and immune suppressing medications has improved the outlook of transplant survival. According to the NAPRTCS 1996 annual report, there has been a steady improvement in cadaveric graft survival rate over the past five years. For index (first) transplants performed in 1987-1993, improvement may be accounted for in part by the increased use of anti-T­cell induction therapy, the use of higher maintenance cyclosporine doses and less frequent random transfusions due to r­HuEPO therapy prior to transplant. In children, post-transplant growth improves only in those children less than six years of age. Trials have shown that administration of rhGH in growth retarded recipients in a dose at 0.35 mg/week improves growth; however, the potential for rhGH producing graft dysfunction requires further study.

   Summary Top

Management of ESRD in the pediatric age-group focuses on physical, emotional, and intellectual growth. The optimal treatment modalities in such a patient population should be those that optimize growth potential and allow children a normal life style. The role of the pediatric nephrologist is not only to treat the child, but to co-ordinate a team of health care professionals including dialysis nurses, transplant surgeons, nutritionists and social workers to meet the many complex needs of these patients. Renal transplantation is a potentially rewarding treatment. "When successful, it can offer children full rehabilitation from the clinical and psycho­social consequences of CRF.

   References Top

1.Mehls O, Tonshoff B. Growth hormone in renal transplantation - the mode of action, animal studies, and clinical use. J Am Soc Nephrol 1992;2(12Suppl):S284-9.  Back to cited text no. 1    
2.Schaefar F, Hamill G, Stanhope R, Preece MA, Scharer K. Pulsatile growth hormone secretion in peripubertal patients with chronic renal failure. J Pediatr 1991;119:568-77.  Back to cited text no. 2    
3.Fine RN. Stimulatory growth in uremic children. Kidney Int 1992;42:188-97.  Back to cited text no. 3  [PUBMED]  
4.Koch VL, Nelson PA, Boechat MI, Sherman BM, Fine RN. Accelerated growth after recombinant human growth hormone treatment of children with chronic renal failure. J Pediatr I989;l 15:365-71.  Back to cited text no. 4    
5.Rees L, Ridgeti SP, Ward G, Preece MA. Treatment of short stature in renal disease with recombinant human growth hormone. Arch Dis Child 1990;65:856-60.  Back to cited text no. 5    
6.Fine RN, Yadin O, Moulton L, Nelson PA, Boechat MI, Lippe BM. Five year experience with recombinant human growth hormone treatment of children with chronic renal failure. J Pediatr Endocrin 1994;7:1-12.  Back to cited text no. 6    
7.Salusky IB. Bone and mineral metabolism in childhood with ESRD. (Review). Pediatr Clin North Am 1995;42:(6)531-50.  Back to cited text no. 7    
8.Fine RN. Recombinant human growth hormone therapy of children with chronic renal insufficiency: an update 1996. Growth Genetics Hormones 1996;12:4.  Back to cited text no. 8    
9.Evans JH, Brocklebank JT, Bowmer CJ, Ng PC. Pharmacokinetics of recombinant human erythropoietin in children with renal failure. Nephrol Dial Transplant 1991;6(10):709-14.  Back to cited text no. 9    
10.Bargman JM, Jones JE, Petro JM. The pharmacokinetics of intraperitoneal erythropoietin administered undiluted or diluted in dialysate. Peril Dial Int 1992;12(4):369-72.  Back to cited text no. 10    
11.Escbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial. N Engl J Med 1987;316:73-8.  Back to cited text no. 11    
12.Davis JM, Arakawa T, Strickland TW, Yphantis DA. Characterization of recombinant human erythropoietin produce in Chinese hamster ovary cells. Biochemistry 1987;26:2633.  Back to cited text no. 12  [PUBMED]  
13.Betts PR, Magrath G. Growth pattern and dietary intake of children with chronic renal insufficiency. Br Med J 1974;2:189-93.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Hundle RN, Sohl G, et al. Vasoactive hormone in children with CRF. Kidney Int Suppl 1982;15:527.  Back to cited text no. 14    
15.Fine RN, Salusky IB, Ettenger RB. The therapeutic approach to the infant, child, and adolescents with end-stage renal disease. Pediatr Clin North Am 1987;34:(3)789-801.  Back to cited text no. 15    

Correspondence Address:
Arshalooz J Rahman
Department of Pediatrics, State University of New York, Stony Brook, New York, 11794-8111
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