Children on chronic dialysis face numerous medical and psychosocial challenges that can alter their physical appearance and isolate them from their peers. The restrictive dietary regimen prescribed for patients on dialysis can cause further alienation, preventing these children from enjoying many of the foods that are popular in our society. Pediatric nephrologists and renal dietitians often have to balance the provision of high-quality nutrition with patient acceptance to promote growth and development in this vulnerable population.
Assessing Nutritional Status
Until recently, the definition and assessment of malnutrition was not standardized, so determining the exact prevalence of malnutrition in children with end-stage renal disease (ESRD) was difficult.
In 2009, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) published a revised and expanded Clinical Practice Guideline for Nutrition in Children with Chronic Kidney Disease (CKD); the original guideline was published in 2000.1 As the revised guideline recommends, the following parameters of nutritional status and growth should be considered in combination in children with CKD Stages 2 to 5 and 5D:
* Dietary intake (three-day diet record or three 24-hour dietary recalls).
* Length or height-for-age percentile or standard deviation score (SDS).
* Length or height velocity-for-age percentile or SDS.
* Estimated dry weight and weight-for-age percentile or SDS.
* Body mass index-for-height-age percentile or SDS.
* Head circumference-for-age percentile or SDS (only in children 3 years of age or younger).
* Normalized protein catabolic rate (nPCR) in adolescents with CKD stage 5D on hemodialysis.
The KDOQI guideline also says, “Identification and treatment of existing nutritional deficiencies and metabolic abnormalities should be aggressively pursued in children with CKD Stages 2 to 5 and 5D, short stature [height standard deviation score below −1.88 or height-for-age below the third percentile], and potential for linear growth.”1
Use of a −1.88 SDS threshold to diagnose growth failure yields worrisome epidemiologic data. In 2008 data from the North American Pediatric Renal Trials and Collaborative Studies, for example, the mean height standard deviation score in children with chronic kidney disease was −1.44, with 35% of children having a height SDS below −1.88.
It is concerning that height scores have not improved over the past decade, as substantial resources have been devoted to promoting growth in this vulnerable population, including aggressive nutrition administration practices2 and the availability of recombinant human growth hormone.3
Malnutrition and Outcomes
While the profound psychosocial and quality-of-life impacts of short stature on children with ESRD are well-documented and have face validity, few large-scale studies have assessed the impact of malnutrition on long-term outcomes in children on maintenance dialysis.
In a study by Wong et al, each decrease in height of one standard deviation score increased adjusted mortality risk by 14% in a study population of 1,949 children with ESRD.4 In addition, each decrease in growth velocity of one SDS increased mortality risk by 12%. The association between height SDS, growth velocity SDS, and mortality held true across all ages and was independent of ESRD treatment modality. Subsequently, Furth et al demonstrated an increased risk of death in children with severe growth failure compared with children with normal growth, with a relative risk of 2.9.5
In a separate study of 1,723 children with ESRD, multivariate analysis revealed that patients with a serum albumin less than 3.5 g/dL exhibited a 90% greater risk of death than did patients with a serum albumin of 3.5 g/dL or greater, Wong et al reported.6 Age, ESRD treatment modality, and height SDS also were independently associated with mortality.
Markers of Nutritional Status
Although the aforementioned studies demonstrate that low height SDS and serum albumin levels are independent risk factors for mortality, both variables may be influenced by factors other than nutritional status, such as inflammation, growth hormone axis derangements, and medications. Furthermore, these markers are extremely late indicators of malnutrition.
While weight loss may be an earlier marker of malnutrition in patients with suboptimal body mass, accurate assessment of target weight is often difficult in children with ESRD, as clinicians must interpret weight changes in the context of fluid accumulation or loss and of the normal expected visceral weight gain of growth and development.
One measure, the normalized protein catabolic rate, has recently been evaluated as a marker of protein intake and, by extension, a surrogate marker of nutritional status in children receiving maintenance hemodialysis.
The nPCR is calculated from the difference in blood urea nitrogen concentrations between two dialysis treatments. Assuming the patient is in a steady state, the catabolized protein can reflect protein intake.7
In two studies of children with severe malnutrition, nPCR, but not serum albumin, improved significantly in patients who gained weight in response to intensive nutritional supplementation with intradialytic parenteral nutrition over a three-to-five-month period.8,9
Similarly, nPCR values but not serum albumin were lower for adolescent patients in another study who had persistent weight loss for at least three consecutive months,10 suggesting that nPCR may serve well as a temporal marker of nutrition status.
Similar calculations exist for patients receiving peritoneal dialysis, where it is important to take the protein losses in the peritoneal dialysate into account.11,12
The KDQOI pediatric nutrition Work Group evaluated studies of numerous other nutrition status markers, including mid-arm anthropometry, dual-energy X-ray absorptiometry, and bioelectrical impedance analysis (BIA); their use was not recommended.1
Of note, a composite measure of BIA and anthropometrics has been evaluated in children receiving maintenance peritoneal dialysis, as no single score is likely to be predictive. Further research is required to validate this approach and other potential composite scores to assure their generalizability across the ESRD spectrum.
The determination of energy requirements for children on maintenance hemodialysis has not been the subject of randomized assessment. When dialysis was in its infancy, protein restriction to limit uremic symptoms was common. However, with the introduction of technologies that can achieve substantial urea and small-molecule clearance in children of all sizes, nutritional goals should be aimed toward promoting growth and development.
The current KDOQI pediatric nutrition Work Group suggests that energy expenditure requirements for children on dialysis should be the same as for age-matched healthy children and individualized for BMI and activity level. To limit volume, energy-dense foods or supplements can be prescribed.
Once a child is identified as being at risk for malnourishment, an intensive effort must be made to ensure adequate nutrition provision.
Patient and family education from the entire ESRD team is paramount to optimizing chances for success. Two key members of the team include the pediatric renal dietitian and social worker.
Adolescents are extremely vulnerable to malnutrition, as their chronic disease sets them apart from their healthy peers and they have little control over many aspects of their lives. One area they can control is their diet.
On one hand, they may completely ignore their restrictions, but all too often they become depressed and anorexic. Such malnutrition is often refractory to even intensive nutritional intervention.8
The pediatric renal social worker should screen for signs of familial stress and patient depression as well as for insufficient access to food. The pediatric renal dietitian's focus should be trained on patient education, emphasizing how to live within the medically necessary restrictions without overemphasizing their negative psychological implications. Contests for best phosphorus or fluid control, monthly feedback, and rewards for improved labs can be very motivating for children and adolescents.
A number of studies have demonstrated improved weight gain after administration of the appetite stimulant megestrol acetate to malnourished adults on dialysis.13,14 While no pediatric dialysis studies have assessed the effectiveness of this agent, one recent study showed an impressive benefit in 25 pediatric patients with CKD and low body weight.15 These patients all exhibited increases in BMI and weight within six months of starting megestrol acetate, and only one patient had an adverse effect.
At this time, the KDOQI pediatric nutrition Work Group has not endorsed the use of megestrol or other appetite stimulants in children with kidney disease, but this should be an area of future research.
Early, standardized identification of children with protein-energy malnutrition is critical to mobilizing efforts to reverse catabolism. A few studies have defined at-risk patients as being below their ideal body weight and having lost 6% to10% of their weight over a three-month period.8,10
Once these patients have been identified, aggressive intervention, including high-energy supplementation by naso-gastrostomy tube feeding2 or, in the case of children receiving maintenance hemodialysis, a trial of intradialytic parenteral nutrition (IDPN), should be initiated.
IDPN, which is able to provide approximately 1.3 g protein/kg body weight/dialysis treatment, has been shown to be effective in reversing weight loss in patients with an organic cause of malnutrition who could not meet their nutritional needs via the enteral route.8,9,16
These and other studies17 suggest that prescription of 150% of the recommended nutrient intake of protein for healthy children, combined with adequate urea clearance, can promote growth and reversal of catabolism in children receiving maintenance hemodialysis.
Assurance of normal growth and development is the core mission of any pediatric practitioner. The dietary constraints for children with ESRD are formidable, and promotion of visceral growth is often quite challenging in this vulnerable population.
Dialysis programs caring for pediatric patients should appropriate substantial team resources to meet the individual needs of the child, combining pediatric-trained personnel and aggressive nutritional intervention to prevent or address malnutrition and allow these patients the best opportunity to thrive into adulthood. •
1. National Kidney Foundation. KDOQI Clinical Practice Guideline for Nutrition in Children with CKD: 2008 update. Am J Kidney Dis 2009;53(suppl 2):S11-S104.
2. Brewer ED. Pediatric experience with intradialytic parenteral nutrition and supplemental tube feeding. Am J Kidney Dis
3. Fine RN. Growth hormone treatment of children with chronic renal insufficiency, end-stage renal disease, and following renal transplantation—update 1997. J Pediatr Endocrinol Metab
4. Wong CS, Gipson DS, Gillen DL, et al. Anthropometric measures and risk of death in children with end-stage renal disease. Am J Kidney Dis
5. Furth SL, Hwang W, Yang C, Neu AM, Fivush BA, Powe NR. Growth failure, risk of hospitalization, and death for children with end-stage renal disease. Pediatr Nephrol
6. Wong CS, Hingorani S, Gillen DL, et al. Hypoalbuminemia and risk of death in pediatric patients with end-stage renal disease. Kidney Int
7. Goldstein SL. Hemodialysis in the pediatric patient: state of the art. Adv Ren Replace Ther 2001;8:173-179.
8. Orellana P, Juarez-Congelosi M, Goldstein SL. Intradialytic parenteral nutrition treatment and biochemical marker assessment for malnutrition in adolescent maintenance hemodialysis patients. J Ren Nutr
9. Goldstein SL, Baronette S, Gambrell TV, Currier H, Brewer ED. nPCR assessment and IDPN treatment of malnutrition in pediatric hemodialysis patients. Pediatr Nephrol
10. Juarez-Congelosi M, Orellana P, Goldstein SL. Normalized protein catabolic rate versus serum albumin as a nutrition status marker in pediatric patients receiving hemodialysis. J Ren Nutr
11. Edefonti A, Paglialonga F, Picca M, et al. A prospective multicenter study of the nutritional status in children on chronic peritoneal dialysis. Nephrol Dial Transplantation 2006;21:1946-1951.
12. Mendley SR, Majkowski NL, Schoeller DA. Validation of estimates of total body water in pediatric dialysis patients by deuterium dilution. Kidney Int
13. Yeh SS, Marandi M, Thode HC Jr., et al. Report of a pilot, double-blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr
14. Rammohan M, Kalantar-Zadeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr
15. Hobbs DJ, Bunchman TE, Weismantel DP, et al. Megestrol acetate improves weight gain in pediatric patients with chronic kidney disease. J Ren Nutr
16. Krause I, Shamir R, Davidovits M, et al. Intradialytic parenteral nutrition in malnourished children treated with hemodialysis. J Ren Nutr
17. Tom A, McCauley L, Bell L, et al. Growth during maintenance hemodialysis: impact of enhanced nutrition and clearance. J Pediatr