By Valerie L. Johnson, MD, PhD

Most children with chronic kidney disease (CKD) were born with a urologic disease or inherited the disorders. The most common causes of pediatric CKD are: blockage of the urinary tract, unusual growth of the kidneys, reflux nephropathy and focal segmental glomerulosclerosis. Unlike adults who have completed their physiological and intellectual maturation, infants and children are at the early stages of their developmental processes and are particularly vulnerable to the down side effects of chronic disease. The metabolic changes associated with kidney failure are known to be associated with abnormal growth.

The cause of delayed growth in children with kidney disease has been attributed to protein-calorie malnutrition, kidney losses of essential salts, increased tissue breakdown, metabolic acidosis, anemia, kidney related bone disease, and disturbances in the growth hormone-insulin-like growth factor-1 (IGF-1) axis.

However, not all children with CKD experience growth failure. Why some children grow and others do not is not clear. The age at onset of CKD is important in terms of height deficit. Adolescents (>13 years old) have less severe height deficits relative to infants (<24 months) and toddlers (2-5 years old). Infants are the worst off overall. There does not seem to be a difference between males and females. Anemic children (Hematocrit less than 33%) have a worse height deficit than non-anemic children. The height deficit is also worse in those children with the worst kidney function.

Standardized growth charts are used to monitor growth in all children. There are separate charts for boys and girls. There are also separate charts from birth to 36 months of age and from ages 2 to 20 years. Ideally, growth should be evaluated over time. Each chart is composed of 7 or 8 percentile curves from 5th to 95th percentiles representing the distribution of weight, length, stature or head circumference. When the height or weight measurement falls below the 5th percentile a child is usually considered to have growth failure. Of concern, are those children whose growth percentiles also decline over time.

The growth failure seen in children with CKD often results in short stature in adulthood. Early study results reveal among patients with CKD who were 18-20 years of age, 18.6 percent were less than the 3rd percentile for height, suggesting many patients had significant short stature as they approached their final adult height. International data shows 30-50 percent of patients with childhood CKD show reduced final adult height. 

Studies of short stature in adulthood have demonstrated a significant negative impact on quality of life. Increases in final adult height are associated with increased likelihood of being married or living outside the parent’s home. There is also a relationship with being employed full-time. Short stature is, in addition, associated with an increased risk of morbidity and mortality. 

There are a number of causes for growth failure in children with CKD. Every attempt should be made to correct any of the possible reasons for the growth failure. Nutritional deficiencies or metabolic disorders should be corrected prior to the start of recombinant growth hormone therapy. This may include dietary supplementation, including tube feedings in those patients with insufficient intake of protein, energy or other nutrients. Treatment of any anemia should be undertaken. This usually requires giving the child an erythropoietin agent. Adequate alkali therapy, salt and water to correct deficits should be provided through use of sodium chloride, bicitra, sodium bicarbonate or like products. Abnormalities of bone and mineral metabolism should be treated. Parathyroid hormone control should be optimized as should levels of vitamin D (both 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D). Abnormalities of thyroid hormone should also be treated. 

Treatment with recombinant human growth hormone (rhGH) - an engineered form of growth hormone - in children with CKD is safe and effective, including those children on dialysis and kidney transplant recipients. Its use is now considered the standard of care. It is not thought to accelerate the deterioration of kidney function in those with CKD or affect transplant kidney function in transplant recipients. Treatment with rhGH results in significant improvements in height. Under utilization of rhGH treatment of children with CKD has been repeatedly documented. 

Impaired growth in children with CKD results from many complex and interacting factors. The recognition that a child has growth failure in its most early stages and treating its causes will have a significant long term effect on the medical and psychosocial outcome of the child with CKD. Recombinant human growth hormone therapy should be introduced as early as possible when appropriate. Research is focusing on other potential causes of growth hormone resistance in these children that may allow children with CKD to grow better. 

Valerie L. Johnson, MD, PhD, is Chief of the Division of Pediatric Nephrology and Associate Professor of Clinical Pediatrics at Weill Medical College of Cornell University in New York. Dr. Johnson also serves as the Director of the Rogosin Pediatric Kidney Center for the Rogosin Institute. 

This article originally appeared in the March 2010 issue of aakpRENALIFE.

Posted 3/18/10.

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