Susan B. Conley, M.D.
National Kidney Foundation of Northern California
September 20, 1996

Impact of Renal Failure on Bones and Nutrition in Children

The promotion a growth is the special challenge to the caregivers of children and adolescents with chronic renal failure (CRF) defined here as having a glomerular filtration rate (GFR) ~less than 40-50 cc/min/1.73m2 body surface area (BSA). The kidney has many functions; kidney failure impacts on the functions of all of the other major organs. To perform their duties, the kidneys receive 20% of cardiac output. The most important functions performed by the kidneys are

  1. filter waste products, toxins1 unwanted chemical compounds out of the blood stream and into urine1
  2. maintain fluid, electrolyte1 acid-base, and mineral balance in the body - done by the combination of glomerular filtration, tubular reabsorption (i.e. from tubular urine back into blood), and tubular secretion (Le. from blood into tubular urine through tubular cell action)
  3. 'activate" (i.e. add an hydroxy group at the 1-position) 25-hydroxyl vitamin D
  4. make erythropoietin - erythropoietin is a hormone that directs the bone marrow to make and release red blood cells.
  5. make renin and angiotensin which regulate blood pressure and blood vessel constriction and also stimulate release of aldosterone.

In kidney failure the breakdown products of protein metabolism buildup from lack of filtration (function number one) resulting In the symptoms of uremia.  One of the earliest symptoms of uremia is often anorexia, so that patients with kidney failure tend to eat poorly. The growing child and adolescent needs a very high number of calories to promote growth, making the lack of appetite a major challenge in the care of these patients. In addition, there is considerable evidence that these children may use energy (i.e. calories) less efficiently than do healthy children, making their caloric needs higher than normal. High density caloric supplements (Pediasure, Nepro, Suplena, Magnacal) or high calorie food additives Polycose, vegetable oil, MCT oil) are often helpful. (See Tables I and ii.) Young children especially may not be able to take sufficient calories orally and so may need nasogastric tube feeding, gastrostomy feeding, or jejunostomy feeding. The children whose CRF is caused by obstructive uropathy or dysplasia may lose large amounts of salt (NaCl) in the urine and need salt supplements. Infants and children on peritoneal dialysis who lose large amounts of ultrafiltrate also require sodium supplements. Potassium chloride supplements may also be needed in a few patients. Acidosis occurs frequently, necessitating sodium bicarbonate supplements. Acidosis may be secondary to retained acids or to renal tubular acidosis or both. Bath sodium deficiency arid acidosis, untreated, are known to slow growth.

Although protein restriction Is useful in adults to slow the deterioration of renal function and to lessen uremia symptoms, it has been shown in the few studies available to inhibit the growth of at least the younger children. I usually only advise avoiding excess protein intake. Children on peritoneal dialysis, who lose protein Into dialysate, may actually need a high protein Intake to maintain a reasonable serum albumin levels.

In any case. the overall approach to the underweight child or child who is growing poorly with CRF should be to encourage a higher caloric intake. The fewer restrictions in what foods the child can eats the more the child is likely to eat.

Bone disease is a difficult problem in CRF. It is multifactorial and includes a combination of the following factors: 1) hyperparathyroidism, 2) abnormal vitamin D hydroxylation and regulation, 3) lack of calcium intake and 4) acidosis with buffering resulting in leaching of calcium compounds from bone.

The etiology of the hyperparathyroldism (HPTH) is very complex arid not completely understood, but the traditional explanation works well for clinically managing the patient As GFR decreases, phosphate Is retained and because of the natural binding of calcium and phosphate, calcium phosphate precipitates in tissue1 and the serum calcium level drops. Parathyroid hormone Is released in response to the low serum calcium level and causes calcium to be extracted from bones to raise the serum calcium level. The typical lesion of HPTH occurs in bone if this process continues over a long period of time.

In children rickets usually occurs simultaneously with HFTH, related to the decreased one-hydroxylation at vitamin D by the kidney (done in the proximal tubule). Rickets starts early and is most severe in children who have one of the diseases that causes fibrosis of the tubulointerstition of the kidney such as dysplasia, obstructive uropathy, juvenile nephronophthisis (autosomal recessive medullary cystic disease)1 or reflux nephropathy. Children who have these diseases may develop early rickets and/or HPTH at a GFR as high as 70 cc/min/1.73 m2 BSA.

"Activated vitamin D", I.e. 1,25 dihydroxyvitamin D (calcitriol): 1) promotes calcium absorption in the gut, 2) causes the proper laying down of calcium in bone, and 3) directly acts on the parathyroid gland to decrease PTH secretion. Its action of promoting calcium absorption in the gut raises serum calcium levels. also helping to prevent HPTH. Cactiriol (1,25 dihydroxyvitamin vitamin D) obviously depends on adequate calcium Intake to increase calcium absorption in the gut.

Acidosis secondary to tubular dysfunction usually occurs in children who have dysplasia or obstructive uropathy and results In the leaching of calcium containing buffers from bone, further depleting bone of calcium.

The first step in treatment of bone disease is detection and delineation of the specific factors causing the disease. PTH levels (of intact hormone) should be measured in any child with CRF, especially when a slow or decreasing growth rate is noted. Children with tubulointerstitial disease should be monitored for the biochemical perturbations causing bone disease by determining levels of serum electrolytes, intact Pm, and 1,25 dihydroxyvitamin D when the patient's GFR drops below 70 cc/min/1.73m2 BSA. Children with primarily glomerular disease usually don't develop bone disease until GFR is less than ~50 cc/min/1.73m2 BSA.

PTH levels up to two times the upper limit of normal are fine, with this mild level of elevation even being desirable, since It seems to protect against decreased bone mineralization recently described and termed "adynamic bone disease". Adynamic bone disease appears to be the result of aluminum deposition in bone in about half the patients who have it and as a result of oversuppression of PTH In the other half. Although adynamic bone disease is not weIl described in children, several prominent pediatric renal bone specialists believe that it exists in children. The current recommendation is that PTH levels should Ideally be 1.5-2 times normal.

Treatment of hyperphosphatemla or significant hyperparathyriodism consists of dietary phosphorus restriction and/or the administration of oral phosphate binders (see Table Ill). Infants should be given a low phosphate formula It is best to restrict dietary phosphorus Intake as little as possible in older children1 since restriction often also results in decreased caloric Intake. Education followed by compromise and negotiation between medical team and patient are often necessary to decide on a diet and phosphate binder prescription that the patient is likely to accomplish. Calcium carbonate (Table IV) is generally the best phosphate binder for pediatric patients4. Aluminum antacids bind phosphorus but aluminum is excreted from the body in the urine and so is retained in patients who have renal failure. High tissue aluminum levels are associated with a progressive encephalopathy in infants and small children and with a severe specific bone lesion. No aluminum should be given to infants and young children with renal failure. and it is best to avoid it in older children and adolescents.

Rickets can be prevented or treated with calcitriol (1,25 dihydroxyvitamin D, trade name Rocaltrol) or with dihydrotachysterol (DHT). DHT Is an one alpha- analog of 1.25 dihydroxyvitamin D and as such needs only to be hydrolated at the 25 position by the liver, which is generally no problem. Adequate calcium intake is necessary for vitamin D to work.

As explained, acidosis can lead to the leeching of calcium from bone, so must be treated with alkali. Sodium bicarbonate is used most frequently as it is cheap and universally available. The daily dose must be divided into at least three and preferably four doses in 24 hours given as closely to every six hours as possible, since its effect is transient. Sodium bicarbonate comes In 850 mg tablets (7.7 mq each). when needed for an infant or small child we have the pharmacist make a solution of 1 mEq/ml so that the dose cannot be given wrong, since the number of mEq and cc's per dose are the Same. A sodium citrate/citric acid solution containing I mEq/mI alkali (Bicitra) is also used to neutralize acidosis and is used in the same way as is sodium bicarbonate. Citrate enhances aluminum absorption in the gut so should never be given to a child taking aluminum containing phosphate binders. I am hesitant to give it at all, especially to infants and young children who generally suffer the worst encephalopathy and bone disease related to aluminum deposition. Since there is environmental aluminum present frequently in households (sic aluminum cookware and occasionally water pipes), I think that it is best to avoid giving citrate and to use bicarbonate instead.

Conclusion

The care of the child with CRF is exacting and time consuming but the reward of good care is watching the child continue to grow and develop in spite of declining renal function. Children with CRF need regular and usually frequent followup, with frequency determined by their progress. Nutrition and bone status must be assessed at each regular visit including plotting of growth, looking at both weight and height, and in toddlers assessing head circumference too. Growth and development remain the ultimate measure of success of therapy. Cessation of growth In a child with CRF who is being managed aggressively may signal that it is time to proceed with transplantation.