Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Nutrition and growth in children with chronic kidney disease

Nature Reviews Nephrology volume 7, pages 615–623 (2011)Cite this article

Subjects

Abstract

Poor growth in chronic kidney disease (CKD) is a marker of disease severity and of quality of care. Causes are multifactorial, and include malnutrition, cachexia, hematological factors, endocrine problems and metabolic abnormalities. In this Review, we focus on the impact of inadequate nutrition on growth disturbances in children with CKD, and discuss all aspects of the epidemiology, causes and potential treatments. Regional variations in resources may be a factor that contributes to the observed differences. Successful nutritional management requires a multidisciplinary team that includes not only doctors but also skilled nurses and dieticians. Extremes of body mass index, representing undernutrition and overnutrition, are associated with poor outcomes and should be avoided when designing therapeutic strategies for optimizing nutrition and growth in children with CKD. Improved understanding of the pathophysiology of cachexia and wasting in patients with CKD could lead to the development of novel therapeutic strategies.

Key Points

  • The rate of growth of children with chronic kidney disease (CKD) declines progressively as CKD advances; by stage 5 CKD, approximately 25% of patients are below the normal range for their height

  • Poor nutrition is a well-described cause of growth failure in CKD; however, other factors are involved because even with the institution of an appropriate diet it is rare for a child to reach their full height potential

  • Disturbances of the insulin-like growth factor I and growth hormone (GH) axis can also interfere with growth in children with CKD; recombinant human GH therapy may improve the growth rate in CKD

  • The issue of poor growth in children with CKD is important because as well as influencing psychosocial development, it is also associated with increased mortality

  • Extremes of body mass index, representing undernutrition and overnutrition, are associated with poor outcomes in children with CKD; such extremes should be avoided when designing therapeutic strategies for optimizing nutrition and growth in this setting

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The effect of age at transplantation on height SDS over the first 6 years after transplantation.
Figure 2: The deranged GH and IGF-I axis in CKD.
Figure 3: Schematic representation of the causes and manifestations of PEW in children with CKD.
Figure 4: The relative risk of death and confidence intervals for BMI SDS among children with stage 5 CKD.

Similar content being viewed by others

References

  1. Wong, C. S. et al. Anthropometric measures and risk of death in children with end-stage renal disease. Am. J. Kidney Dis. 36, 811–819 (2000).

    Article  CAS  Google Scholar 

  2. Norman, L. J., Coleman, J. E., Macdonald, I. A., Tomsett, A. M. & Watson, A. R. Nutrition and growth in relation to severity of renal disease in children. Pediatr. Nephrol. 15, 259–265 (2000).

    Article  CAS  Google Scholar 

  3. Mekhali, D., Shaw, V., Ledermann, S. E. & Rees, L. Long-term outcome of infants with severe chronic kidney disease. Clin. J. Am. Soc. Nephrol. 5, 10–17 (2010).

    Article  Google Scholar 

  4. Schaefer, F., Wingen, A. M., Hennicke, M., Rigden, S. & Mehls, O. Growth charts for prepubertal children with chronic renal failure due to congenital renal disorders. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. Pediatr. Nephrol. 10, 288–293 (1996).

    Article  CAS  Google Scholar 

  5. Zivicnjak, M. et al. Growth impairment shows an age-dependent pattern in boys with chronic kidney disease. Pediatr. Nephrol. 22, 420–429 (2007).

    Article  Google Scholar 

  6. Jander, A. et al. Does a late referral to a nephrologist constitute a problem in children starting renal replacement therapy in Poland?—a nationwide study. Nephrol. Dial. Transplant. 21, 957–961 (2006).

    Article  Google Scholar 

  7. Shroff, R., Rees, L., Trompeter, R., Hutchinson, C. & Ledermann, S. Long-term outcome of chronic dialysis in children. Pediatr. Nephrol. 21, 257–264 (2005).

    Article  Google Scholar 

  8. Seikaly, M. G., Salhab, N., Warady, B. A. & Stablein, D. Use of rhGH in children with chronic kidney disease: lessons from NAPRTCS. Pediatr. Nephrol. 22, 1195–1205 (2007).

    Article  Google Scholar 

  9. North American Pediatric Renal Trials and Collaborative Studies Online. NAPRTCS 2005 Annual Report: Renal Transplantation, Dialysis, Chronic Renal Insufficiency [online], (2005).

  10. United States Renal Data System. 2008 USRDS Report. Eight: Pediatric ESRD [online], (2008).

  11. International Pediatric Peritoneal Dialysis Network. About IPPN [online], (2011).

  12. North American Pediatric Renal Trials and Collaborative Studies Online. NAPRTCS 2006 Annual Report: Renal Transplantation, Dialysis, Chronic Renal Insufficiency [online], (2006).

  13. Ledermann, S. E. et al. Long-term outcome of peritoneal dialysis in infants. J. Pediatr. 136, 24–29 (2000).

    Article  CAS  Google Scholar 

  14. Kari, J. A., Gonzalez, C., Ledermann, S. E., Shaw, V. & Rees, L. Outcome and growth of infants with severe chronic renal failure. Kidney Int. 57, 1681–1687 (2000).

    Article  CAS  Google Scholar 

  15. Hölttä, T., Rönnholm, K., Jalanko, H. & Holmberg, C. Clinical outcome of pediatric patients on peritoneal dialysis under adequacy control. Pediatr. Nephrol. 14, 889–897 (2000).

    Article  Google Scholar 

  16. Cansick, J., Waller, S., Ridout, D. & Rees, L. Growth and PTH in prepubertal children on long-term dialysis. Pediatr. Nephrol. 22, 1349–1354 (2007).

    Article  Google Scholar 

  17. Fine, R. N., Martz, K. & Stablein, D. What have 20 years of data from the North American Pediatric Renal Transplant Cooperative Study taught us about growth following renal transplantation in infants, children, and adolescents with end-stage renal disease? Pediatr. Nephrol. 25, 739–746 (2010).

    Article  Google Scholar 

  18. Hijazi, R. et al. Twenty-five years of infant dialysis: a single center experience. J. Pediatr. 155, 111–117 (2009).

    Article  Google Scholar 

  19. Hussain, F. et al. UK Renal Registry 12th Annual Report (December 2009): chapter 15: clinical, haematological and biochemical parameters in patients receiving renal replacement therapy in paediatric centres in the UK in 2008: national and centre-specific analyses. Nephron Clin. Pract. 115 (Suppl. 1), c289–c308 (2010).

    Article  Google Scholar 

  20. Bérard, E. et al. Long-term results of rhGH treatment in children with renal failure: experience of the French Society of Pediatric Nephrology. Pediatr. Nephrol. 23, 2031–2038 (2008).

    Article  Google Scholar 

  21. André, J. L., Bourquard, R., Guillemin, F., Krier, M. J. & Briançon, S. Final height in children with chronic renal failure who have not received growth hormone. Pediatr. Nephrol. 18, 685–691 (2003).

    PubMed  Google Scholar 

  22. Rosenkranz, J. et al. Psychosocial rehabilitation and satisfaction with life in adults with childhood-onset of end-stage renal disease. Pediatr. Nephrol. 20, 1288–1294 (2005).

    Article  Google Scholar 

  23. Furth, S. L., Stablein, D., Fine, R. N., Powe, N. R. & Fivush, B. A. Adverse clinical outcomes associated with short stature at dialysis initiation: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatrics 109, 909–913 (2002).

    Article  Google Scholar 

  24. Haffner, D. & Nissel, R. in Comprehensive Pediatric Nephrology (eds Geary, D. F. & Schaefer, F.) 709–732 (Mosby Elsevier, Philadelphia, 2008).

    Book  Google Scholar 

  25. Jones, R. W., Rigden, S. P., Barratt, T. M. & Chantler, C. The effects of chronic renal failure in infancy on growth, nutritional status and body composition. Pediatr. Res. 16, 784–791 (1982).

    Article  CAS  Google Scholar 

  26. Arnold, W. C., Danford, D. & Holliday, M. A. Effect of calorie supplementation on growth in children with uremia. Kidney Int. 24, 205–209 (1983).

    Article  CAS  Google Scholar 

  27. Betts, P. R., Magrath, C. & White, R. H. Role of dietary energy supplementation in growth of children with chronic renal insufficiency. Br. Med. J. 1, 416–418 (1977).

    Article  CAS  Google Scholar 

  28. Norman, L. J., Macdonald, I. A. & Watson, A. R. Optimising nutrition in chronic renal insufficiency–growth. Pediatr. Nephrol. 19, 1245–1252 (2004).

    Article  Google Scholar 

  29. Seikaly, M. G., Salhab, N., Gipson, D., Yiu, V. & Stablein, D. Stature in children with chronic kidney disease: analysis of NAPTRCS database. Pediatr. Nephrol. 21, 793–799 (2006).

    Article  Google Scholar 

  30. Schaefer, F., Klaus, G. & Mehls, O. Peritoneal transport properties and dialysis dose affect growth and nutritional status in children on chronic peritoneal dialysis. Mid-European Pediatric Peritoneal Dialysis Study Group. J. Am. Soc. Nephrol. 10, 1786–1792 (1999).

    CAS  PubMed  Google Scholar 

  31. Fischbach, M. et al. Daily on line haemodiafiltration promotes catch-up growth in children on chronic dialysis. Nephrol. Dial. Transplant. 25, 867–873 (2010).

    Article  CAS  Google Scholar 

  32. Hoppe, A. et al. A hospital-based intermittent nocturnal hemodialysis program for children and adolescents. J. Pediatr. 158, 95–99 (2011).

    Article  Google Scholar 

  33. Mak, R. H., Cheung, W. W. & Roberts, C. T. Jr. The growth hormone-insulin-like growth factor-I axis in chronic kidney disease. Growth Horm. IGF Res. 18, 17–25 (2008).

    Article  CAS  Google Scholar 

  34. Schaefer, F., Velhuis, J. D., Stanhope, R., Jones, J. & Schärer, K. Alterations in growth hormone secretion and clearance in peripubertal boys with chronic renal failure and after renal transplantation. Cooperative Study Group of Pubertal Development in Chronic Renal Failure. J. Clin. Endocrinol. Metab. 78, 1298–1306 (1994).

    CAS  PubMed  Google Scholar 

  35. Tönshoff, B., Veldhuis, J. D., Heinrich, U. & Mehls, O. Deconvolution analysis of spontaneous nocturnal growth hormone secretion in prepubertal children with preterminal chronic renal failure and with end-stage renal disease. Pediatr. Res. 37, 86–93 (1995).

    Article  Google Scholar 

  36. Veldhuis, J. D., Iranmanesh, A., Wilkowski, M. J. & Samojlik, E. Neuroendocrine alterations in the somatotropic and lactrotropic axes in uremic men. Eur. J. Endocrinol. 131, 489–498 (1994).

    Article  CAS  Google Scholar 

  37. García, E. et al. Impaired secretion of growth hormone in experimental uremia: relevance of caloric deficiency. Kidney Int. 52, 648–653 (1997).

    Article  Google Scholar 

  38. Metzger, D. L., Kerrigan, J. R., Krieg, R. J. Jr, Chan, J. C. & Rogol, A. D. Alterations in the neuroendocrine control of growth hormone secretion in the uremic rat. Kidney Int. 43, 1042–1048 (1993).

    Article  CAS  Google Scholar 

  39. Challa, A., Krieg, R. J. Jr, Thabet, M. A., Veldhuis, J. D. & Chan, J. C. Metabolic acidosis inhibits growth hormone secretion in rats: mechanism of growth retardation. Am. J. Physiol. 265, E547–E553 (1993).

    CAS  PubMed  Google Scholar 

  40. Rees, L. et al. Growth and endocrine function after renal transplantation. Arch. Dis. Child. 63, 1326–1332 (1988).

    Article  CAS  Google Scholar 

  41. Haffner, D., Schaefer, F., Girard, J., Ritz, E. & Mehls, O. Metabolic clearance of recombinant human growth hormone in health and chronic renal failure. J. Clin. Invest. 93, 1163–1171 (1994).

    Article  CAS  Google Scholar 

  42. Sun, D. F. et al. Chronic uremia attenuates growth hormone-induced signal transduction in skeletal muscle. J. Am. Soc. Nephrol. 15, 2630–2636 (2004).

    Article  CAS  Google Scholar 

  43. Schaefer, F., Chen, Y., Tsao, T., Nouri, P. & Rabkin, R. Impaired JAK-STAT signal transduction contributes to growth hormone resistance in chronic uremia. J. Clin. Invest. 108, 467–475 (2001).

    Article  CAS  Google Scholar 

  44. Tönshoff, B., Blum, W. F., Wingen, A. M. & Mehls, O. Serum insulin-like growth factors (IGFs) and IGF binding proteins 1, 2, and 3 in children with chronic renal failure: relationship to height and glomerular filtration rate. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. J. Clin. Endocrinol. Metab. 80, 2684–2691 (1995).

    PubMed  Google Scholar 

  45. Ulinski, T. et al. Serum insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 in children with chronic renal failure: relationship to growth and glomerular filtration rate. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. German Study Group for Growth Hormone Treatment in Chronic Renal Failure. Pediatr. Nephrol. 14, 589–597 (2000).

    Article  CAS  Google Scholar 

  46. Powell, D. R. et al. Insulin-like growth factor-binding protein-6 levels are elevated in serum of children with chronic renal failure: a report of the Southwest Pediatric Nephrology Study Group. J. Clin. Endocrinol. Metab. 82, 2978–2984 (1997).

    CAS  PubMed  Google Scholar 

  47. Powell, D. R. et al. Effect of chronic renal failure and growth hormone therapy on the insulin-like growth factors and their binding proteins. Pediatr. Nephrol. 14, 579–583 (2000).

    Article  CAS  Google Scholar 

  48. Ding, H., Gao, X. L., Hirschberg, R., Vadgama, J. V. & Kopple, J. D. Impaired actions of insulin-like growth factor 1 on protein synthesis and degradation in skeletal muscle of rats with chronic renal failure. Evidence for a postreceptor defect. J. Clin. Invest. 97, 1064–1075 (1996).

    Article  CAS  Google Scholar 

  49. Tsao, T., Fervenza, F., Friedlaender, M., Chen, Y. & Rabkin, R. Effect of prolonged uremia on insulin-like growth factor-I receptor autophosphorylation and tyrosine kinase activity in kidney and muscle. Exp. Nephrol. 10, 285–292 (2002).

    Article  CAS  Google Scholar 

  50. Tönshoff, B. & Mehls, O. Interaction between glucocorticoids and the somatrophic axis. Acta Paediatr. Suppl. 417, 72–75 (1996).

    Article  Google Scholar 

  51. Mehls, O. et al. Growth hormone treatment in short children with chronic kidney disease. Acta Paediatr. 97, 1159–1164 (2008).

    Article  CAS  Google Scholar 

  52. Vimalachandra, D. et al. Growth hormone for children with chronic kidney disease. Cochrane Database Syst. Rev. Issue 3. Art. No.: CD003264. http://dx.doi.org/10.1002/14651858.CD003264.pub2 (2006).

  53. Haffner, D. et al. Effect of growth hormone treatment on the adult height of children with chronic renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal Failure. N. Engl. J. Med. 343, 923–930 (2000).

    Article  CAS  Google Scholar 

  54. Foster, B. J. et al. Association of chronic kidney disease with muscle deficits in children. J. Am. Soc. Nephrol. 22, 377–386 (2011).

    Article  Google Scholar 

  55. Armstrong, J. E., Laing, D. G., Wilkes, F. J. & Kainer, G. Smell and taste function in children with chronic kidney disease. Pediatr. Nephrol. 25, 1497–1504 (2010).

    Article  Google Scholar 

  56. Mak, R. H., Cheung, W., Cone, R. D. & Marks, D. L. Leptin and inflammation-associated cachexia in chronic kidney disease. Kidney Int. 69, 794–797 (2006).

    Article  CAS  Google Scholar 

  57. Ravelli, A. M. et al. Foregut motor function in chronic renal failure. Arch. Dis. Child. 67, 1343–1347 (1992).

    Article  CAS  Google Scholar 

  58. Rees, L. & Shaw, V. Nutrition in children with CRF and on dialysis. Pediatr. Nephrol. 22, 1689–1702 (2007).

    Article  Google Scholar 

  59. KDOQI Work Group. KDOQI Clinical Practice Guideline for Nutrition in Children with CKD: 2008 Update. Executive summary. Am. J. Kidney Dis. 53 (Suppl. 2), S11–S104 (2009).

  60. Chaturvedi, S. & Jones, C. Protein restriction for children with chronic renal failure. Cochrane Database Syst. Rev. Issue 4. Art. No.: CD006863. http://dx.doi.org/10.1002/14651858.CD006863 (2007).

  61. Rees, L. & Brandt, M. L. Tube feeding in children with chronic kidney disease: technical and practical issues. Pediatr. Nephrol. 25, 699–704 (2010).

    Article  Google Scholar 

  62. Sienna, J. L. et al. Body size in children with chronic kidney disease after gastrostomy tube feeding. Pediatr. Nephrol. 25, 2115–2121 (2010).

    Article  Google Scholar 

  63. Karlberg, J. et al. Early age-dependent growth impairment in chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. Pediatr. Nephrol. 10, 283–287 (1996).

    Article  CAS  Google Scholar 

  64. Rees, L. et al. Growth in very young children undergoing chronic peritoneal dialysis. J. Am. Soc. Nephrol. (in press).

  65. Mak, R. H. et al. Wasting in chronic kidney disease. J. Cachex. Sarcopenia Muscle 2, 9–25 (2011).

    Article  Google Scholar 

  66. Mak, R. H., Cheung, W. W., Zhan, J. Y., Shen, Q. & Foster, B. J. Cachexia and protein-energy wasting in children with chronic kidney disease. Pediatr. Nephrol. http://dx.doi.org/10.1007/s00467-011-1765-5.

  67. Fouque, D. et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int. 73, 391–398 (2008).

    Article  CAS  Google Scholar 

  68. Tisdale, M. J. Biomedicine. Protein loss in cancer cachexia. Science 289, 2293–2294 (2000).

    Article  CAS  Google Scholar 

  69. Adams, V. et al. Induction of iNOS-expression in skeletal muscle by IL-1β and NFκβ activation: an in vitro and in vivo study. Cardiovasc. Res. 54, 95–104 (2002).

    Article  CAS  Google Scholar 

  70. Ungureanu-Longrois, D., Balligand, J. L., Kelly, R. A. & Smith, T. W. Myocardial contractility dysfunction in the systemic inflammatory response syndrome: role of a cytokine-inducible nitric oxide synthase in cardiac myocytes. J. Mol. Cell. Cardiol. 27, 155–167 (1995).

    Article  CAS  Google Scholar 

  71. Rashid, R. et al. Body composition and nutritional intake in children with chronic kidney disease. Pediatr. Nephrol. 21, 1730–1738 (2006).

    Article  Google Scholar 

  72. Cheung, W. W. & Mak, R. H. Ghrelin and its analogues as therapeutic agents for anorexia and cachexia in end-stage renal disease. Kidney Int. 76, 135–137 (2009).

    Article  CAS  Google Scholar 

  73. Cheung, W. W. et al. Role of leptin and melanocortin signaling in uremia-associated cachexia. J. Clin. Invest. 115, 1659–1665 (2005).

    Article  CAS  Google Scholar 

  74. Cheung, W. W. et al. Peripheral administration of the melanocortin receptor-4 antagonist NBI-12i ameliorates uremia-associated cachexia in mice. J. Am. Soc. Nephrol. 18, 2517–2524 (2007).

    Article  CAS  Google Scholar 

  75. Wong, C. S. et al. Hypoalbuminemia and risk of death in pediatric patients with end-stage renal disease. Kidney Int. 61, 630–637 (2002).

    Article  Google Scholar 

  76. Amaral, S. et al. Serum albumin level and risk for mortality and hospitalization in adolescents on hemodialysis. Clin. J. Am. Soc. Nephrol. 3, 759–767 (2008).

    Article  CAS  Google Scholar 

  77. Hanevold, C. D., Ho, P. L., Talley, L. & Mitsnefes, M. M. Obesity and renal transplant outcome: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatrics 115, 352–356 (2005).

    Article  Google Scholar 

  78. Filler, G. et al. Changing trends in the referral patterns of pediatric nephrology patients. Pediatr. Nephrol. 20, 603–608 (2005).

    Article  Google Scholar 

  79. Srivaths, P. R., Wong, C. & Goldstein, S. L. Nutrition aspects in children receiving maintenance hemodialysis: impact on outcome. Pediatr. Nephrol. 25, 951–957 (2009).

    Article  Google Scholar 

  80. Kopple, J. D., Zhu, X., Lew, N. L. & Lowrie, E. G. Body weight-for-height relationships predict mortality in maintenance hemodialysis patients. Kidney Int. 56, 1136–1148 (1999).

    Article  CAS  Google Scholar 

  81. Kalantar-Zadeh, K., Abbott, K. C., Salahudeen, A. K., Kilpatrick, R. D. & Horwich, T. B. Survival advantages of obesity in dialysis patients. Am. J. Clin. Nutr. 81, 543–554 (2005).

    Article  CAS  Google Scholar 

  82. Lindsted, K. D. & Singh, P. N. Body mass and 26-year risk of mortality among women who never smoked: findings from the Adventist Mortality Study. Am. J. Epidemiol. 46, 1–11 (1997).

    Article  Google Scholar 

  83. de Mutsert, R. et al. Association between body mass index and mortality is similar in the hemodialysis population and the general population at high age and equal duration of follow up. J. Am. Soc. Nephrol. 18, 967–974 (2007).

    Article  Google Scholar 

  84. Srivaths, P. R., Wong, C. & Goldstein, S. L. Nutritional aspects in children receiving hemodialysis: impact on outcome. Pediatr. Nephrol. 24, 951–957 (2009).

    Article  Google Scholar 

Download references

Acknowledgements

R. H. Mak is supported by grants from the National Institute of Health (NIH) U01 DK-03-012, Cystinosis Research Foundation and Abbott.

Author information

Authors and Affiliations

  1. Department of Nephrology, Great Ormond Street Hospital for Children National Health Service (NHS) Trust, Great Ormond Street, London, WC1N 3JH, UK

    Lesley Rees

  2. Division of Pediatric Nephrology, University of California San Diego, 9500 Gilman Drive, MC0634, La Jolla, 92093, CA, USA

    Robert H. Mak

Authors
  1. Lesley Rees
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert H. Mak
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

L. Rees and R. H. Mak contributed equally to researching data for the article, discussion of the content, writing and reviewing/editing of the manuscript before submission.

Corresponding author

Correspondence to Lesley Rees.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rees, L., Mak, R. Nutrition and growth in children with chronic kidney disease. Nat Rev Nephrol 7, 615–623 (2011). https://doi.org/10.1038/nrneph.2011.137

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneph.2011.137

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing