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Growth hormone treatment in children with chronic kidney disease and postrenal transplantation

Author
Burkhard Tönshoff, MD, PhD
Section Editor
Patrick Niaudet, MD
Deputy Editor
Melanie S Kim, MD

INTRODUCTION

Growth impairment is a common problem in children with chronic kidney disease (CKD) and is associated with significant morbidity and mortality [1,2]. Several factors may contribute, including inadequate nutrition, metabolic acidosis, renal osteodystrophy, and insensitivity to the action of growth hormone (GH) [3-7].

Management to prevent and correct growth impairment due to CKD includes supportive measures that correct amenable complications of CKD (eg, poor nutrition and metabolic acidosis) and renal replacement therapy (RRT), particularly renal transplantation. However, despite these interventions, poor growth persists in a significant proportion of children with CKD, including renal allograft recipients. In children who have persistent growth impairment, recombinant human growth hormone therapy (rhGH) is an effective and well-tolerated intervention that improves growth.

The use of rhGH in children with CKD, including efficacy, indications, and dosing will be reviewed here. The pathogenesis, risk factors, evaluation, and overall management of growth impairment in children with CKD are discussed separately. (See "Pathogenesis, evaluation and diagnosis of growth impairment in children with chronic kidney disease" and "Prevention and management of growth failure in children with chronic kidney disease".)

DEFINITION

Z-height score — The growth measurement Z-score for height is a conversion of height/length that represents the number of standard deviations (SD) from the mean height for age. A child with a height Z-score <-1.88 has short stature. (See "Measurement of growth in children", section on 'Z-scores'.)

Growth or height velocity — Growth or height velocity, the change in growth over time, is a more sensitive index of growth than is a single measurement. Current height/length measures are compared with previous growth points to determine the interval growth/height velocity (figure 1 and figure 2).

                         

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Literature review current through: Nov 2016. | This topic last updated: Tue Mar 01 00:00:00 GMT+00:00 2016.
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References
Top
  1. André JL, Bourquard R, Guillemin F, et al. Final height in children with chronic renal failure who have not received growth hormone. Pediatr Nephrol 2003; 18:685.
  2. Mahan JD, Warady BA, Consensus Committee. Assessment and treatment of short stature in pediatric patients with chronic kidney disease: a consensus statement. Pediatr Nephrol 2006; 21:917.
  3. Tönshoff B, Mehls O. Growth retardation in children with chronic renal insufficiency: Current aspects of pathophysiology and treatment. J Nephrol 1995; 8:133.
  4. Tom A, McCauley L, Bell L, et al. Growth during maintenance hemodialysis: impact of enhanced nutrition and clearance. J Pediatr 1999; 134:464.
  5. Kari JA, Gonzalez C, Ledermann SE, et al. Outcome and growth of infants with severe chronic renal failure. Kidney Int 2000; 57:1681.
  6. Boirie Y, Broyer M, Gagnadoux MF, et al. Alterations of protein metabolism by metabolic acidosis in children with chronic renal failure. Kidney Int 2000; 58:236.
  7. Tönshoff B, Kiepe D, Ciarmatori S. Growth hormone/insulin-like growth factor system in children with chronic renal failure. Pediatr Nephrol 2005; 20:279.
  8. Mehls O, Ritz E, Hunziker EB, et al. Improvement of growth and food utilization by human recombinant growth hormone in uremia. Kidney Int 1988; 33:45.
  9. Powell DR, Durham SK, Liu F, et al. The insulin-like growth factor axis and growth in children with chronic renal failure: a report of the Southwest Pediatric Nephrology Study Group. J Clin Endocrinol Metab 1998; 83:1654.
  10. Bereket A, Lang CH, Blethen SL, et al. Growth hormone treatment in growth retarded children with end stage renal failure: effect on free/dissociable IGF-I levels. J Pediatr Endocrinol Metab 1997; 10:197.
  11. Santos F, Moreno ML, Neto A, et al. Improvement in growth after 1 year of growth hormone therapy in well-nourished infants with growth retardation secondary to chronic renal failure: results of a multicenter, controlled, randomized, open clinical trial. Clin J Am Soc Nephrol 2010; 5:1190.
  12. Van Dyck M, Gyssels A, Proesmans W, et al. Growth hormone treatment enhances bone mineralisation in children with chronic renal failure. Eur J Pediatr 2001; 160:359.
  13. Guest G, Bérard E, Crosnier H, et al. Effects of growth hormone in short children after renal transplantation. French Society of Pediatric Nephrology. Pediatr Nephrol 1998; 12:437.
  14. Fine RN, Stablein D, Cohen AH, et al. Recombinant human growth hormone post-renal transplantation in children: a randomized controlled study of the NAPRTCS. Kidney Int 2002; 62:688.
  15. Powell DR, Liu F, Baker BK, et al. Modulation of growth factors by growth hormone in children with chronic renal failure. The Southwest Pediatric Nephrology Study Group. Kidney Int 1997; 51:1970.
  16. Fine RN, Kohaut EC, Brown D, Perlman AJ. Growth after recombinant human growth hormone treatment in children with chronic renal failure: report of a multicenter randomized double-blind placebo-controlled study. Genentech Cooperative Study Group. J Pediatr 1994; 124:374.
  17. Hodson EM, Willis NS, Craig JC. Growth hormone for children with chronic kidney disease. Cochrane Database Syst Rev 2012; :CD003264.
  18. Seikaly MG, Salhab N, Warady BA, Stablein D. Use of rhGH in children with chronic kidney disease: lessons from NAPRTCS. Pediatr Nephrol 2007; 22:1195.
  19. Fine RN, Kohaut E, Brown D, et al. Long-term treatment of growth retarded children with chronic renal insufficiency, with recombinant human growth hormone. Kidney Int 1996; 49:781.
  20. Seikaly MG, Waber P, Warady BA, Stablein D. The effect of rhGH on height velocity and BMI in children with CKD: a report of the NAPRTCS registry. Pediatr Nephrol 2009; 24:1711.
  21. Tönshoff B, Dietz M, Haffner D, et al. Effects of two years of growth hormone treatment in short children with renal disease. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure. Acta Paediatr Scand Suppl 1991; 379:33.
  22. Tönshoff B, Mehis O, Heinrich U, et al. Growth-stimulating effects of recombinant human growth hormone in children with end-stage renal disease. J Pediatr 1990; 116:561.
  23. Nissel R, Lindberg A, Mehls O, et al. Factors predicting the near-final height in growth hormone-treated children and adolescents with chronic kidney disease. J Clin Endocrinol Metab 2008; 93:1359.
  24. Fischbach M, Terzic J, Menouer S, et al. Daily on line haemodiafiltration promotes catch-up growth in children on chronic dialysis. Nephrol Dial Transplant 2010; 25:867.
  25. Bacchetta J, Wesseling-Perry K, Kuizon B, et al. The skeletal consequences of growth hormone therapy in dialyzed children: a randomized trial. Clin J Am Soc Nephrol 2013; 8:824.
  26. Schaefer F, Wühl E, Haffner D, Mehls O. Stimulation of growth by recombinant human growth hormone in children undergoing peritoneal or hemodialysis treatment. German Study Group for Growth Hormone Treatment in Chronic Renal Failure. Adv Perit Dial 1994; 10:321.
  27. Bérard E, Crosnier H, Six-Beneton A, et al. Recombinant human growth hormone treatment of children on hemodialysis. French Society of Pediatric Nephrology. Pediatr Nephrol 1998; 12:304.
  28. North American Pediatric Renal Trials and Collaborative Studies. 2011 Annual dialysis report. https://web.emmes.com/study/ped/annlrept/annualrept2011.pdf.
  29. Nissel R, Brázda I, Feneberg R, et al. Effect of renal transplantation in childhood on longitudinal growth and adult height. Kidney Int 2004; 66:792.
  30. Tönshoff B, Haffner D, Mehls O, et al. Efficacy and safety of growth hormone treatment in short children with renal allografts: three year experience. Members of the German Study Group for Growth Hormone Treatment in Children with Renal Allografts. Kidney Int 1993; 44:199.
  31. Acott PD, Pernica JM. Growth hormone therapy before and after pediatric renal transplant. Pediatr Transplant 2003; 7:426.
  32. Tönshoff B, Mehls O. Use of rhGH post transplant in children. In: Pediatric Renal Transplantation, Wiley & Sons, New York 1994. p.441.
  33. Hokken-Koelega AC, Stijnen T, de Jong RC, et al. A placebo-controlled, double-blind trial of growth hormone treatment in prepubertal children after renal transplant. Kidney Int Suppl 1996; 53:S128.
  34. Fine RN, Stablein D. Long-term use of recombinant human growth hormone in pediatric allograft recipients: a report of the NAPRTCS Transplant Registry. Pediatr Nephrol 2005; 20:404.
  35. Fine RN, Attie KM, Kuntze J, et al. Recombinant human growth hormone in infants and young children with chronic renal insufficiency. Genentech Collaborative Study Group. Pediatr Nephrol 1995; 9:451.
  36. Mencarelli F, Kiepe D, Leozappa G, et al. Growth hormone treatment started in the first year of life in infants with chronic renal failure. Pediatr Nephrol 2009; 24:1039.
  37. KDOQI Work Group. KDOQI Clinical Practice Guideline for Nutrition in Children with CKD: 2008 update. Executive summary. Am J Kidney Dis 2009; 53:S11.
  38. Haffner D, Schaefer F, Nissel R, 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 2000; 343:923.
  39. Hokken-Koelega AC, Stijnen T, de Ridder MA, et al. Growth hormone treatment in growth-retarded adolescents after renal transplant. Lancet 1994; 343:1313.
  40. Bérard E, André JL, Guest G, et al. Long-term results of rhGH treatment in children with renal failure: experience of the French Society of Pediatric Nephrology. Pediatr Nephrol 2008; 23:2031.
  41. Hokken-Koelega A, Mulder P, De Jong R, et al. Long-term effects of growth hormone treatment on growth and puberty in patients with chronic renal insufficiency. Pediatr Nephrol 2000; 14:701.
  42. Fine RN, Sullivan EK, Tejani A. The impact of recombinant human growth hormone treatment on final adult height. Pediatr Nephrol 2000; 14:679.
  43. Rees L, Ward G, Rigden SP. Growth over 10 years following a 1-year trial of growth hormone therapy. Pediatr Nephrol 2000; 14:309.
  44. Haffner D, Wühl E, Schaefer F, et al. Factors predictive of the short- and long-term efficacy of growth hormone treatment in prepubertal children with chronic renal failure. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure. J Am Soc Nephrol 1998; 9:1899.
  45. National Kidney Foundation Kidney Disease Outcomes Quality Initiative (2000) Clinical practice guidelines for nutrition in chronic renal failure. National Kidney Foundation. Accessed 15 Jan 2004.
  46. Fine RN, Fine SE, Sherman BM. Absorption of recombinant human growth hormone (rhGH) following intraperitoneal instillation. Perit Dial Int 1989; 9:91.
  47. Tönshoff B, Fine R. Growth and growth hormone treatment in children with chronic renal insufficiency. In: Clinical Dialysis, Medical Publishing Division /The McGraw-Hill Companies Inc, 2005. p.611.
  48. Fine RN, Ho M, Tejani A, Blethen S. Adverse events with rhGH treatment of patients with chronic renal insufficiency and end-stage renal disease. J Pediatr 2003; 142:539.
  49. Filler G, Franke D, Amendt P, Ehrich JH. Reversible diabetes mellitus during growth hormone therapy in chronic renal failure. Pediatr Nephrol 1998; 12:405.
  50. Stefanidis CJ, Papathanassiou A, Michelis K, et al. Diabetes mellitus after therapy with recombinant human growth hormone (rhGH). Br J Clin Pract Suppl 1996; 85:66.
  51. Haffner D, Nissel R, Wühl E, et al. Metabolic effects of long-term growth hormone treatment in prepubertal children with chronic renal failure and after kidney transplantation. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure. Pediatr Res 1998; 43:209.
  52. Yadin O, Fine RN. Long-term use of recombinant human growth hormone in children with chronic renal insufficiency. Kidney Int Suppl 1997; 58:S114.
  53. Koller EA, Stadel BV, Malozowski SN. Papilledema in 15 renally compromised patients treated with growth hormone. Pediatr Nephrol 1997; 11:451.
  54. Akchurin OM, Schneider MF, Mulqueen L, et al. Medication adherence and growth in children with CKD. Clin J Am Soc Nephrol 2014; 9:1519.