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Open Access 01-07-2009 | Educational Review

Growth after renal transplantation

Authors: Jérôme Harambat, Pierre Cochat

Published in: Pediatric Nephrology | Issue 7/2009

Abstract

Growth may be severely impaired in children with chronic renal insufficiency. Since short stature can have major consequences on quality of life and self-esteem, achieving a ‘normal’ height is a crucial issue for renal transplant recipients. However, despite successful renal transplantation, the final height attained by most recipients is not the calculated target height. Catch-up growth spurts post-transplantation are usually insufficient to compensate for the retardation in growth that has occurred during the pre-transplant period. Longitudinal growth post-transplantation is therefore influenced by the age at transplantation but also by subsequent allograft function and steroid exposure, both of which interfere with the growth hormone/insulin-like growth factor axis. The management of growth retardation in renal transplant recipients includes adequate nutritional intake, correction of metabolic acidosis, prevention of bone disease, steroid-sparing strategies and a supraphysiological dose of recombinant human growth hormone in selected cases.

Abbud-Filho M, Adams PL, Alberu J, Cardella C, Chapman J, Cochat P, Cosio F, Danovitch G, Davis C, Gaston RS, Humar A, Hunsicker LG, Josephson MA, Kasiske B, Kirste G, Leichtman A, Munn S, Obrador GT, Tibell A, Wadström J, Zeier M, Delmonico FL (2007) A report of the Lisbon Conference on the care of the kidney transplant recipient. Transplantation 83:S1–22PubMed

Tanner JM, Goldstein H, Whitehouse RH (1970) Standards for children’s height at ages 2–9 years allowing for heights of parents. Arch Dis Child 45:755–762PubMedPubMedCentral

Hermanussen M, Cole J (2003) The calculation of target height reconsidered. Horm Res 59:180–183PubMed

North American Pediatric Renal Trials and Collaborative Studies (2006) Annual Report. Available at https://doi.org/web.emmes.com/study/ped/annlrept/annlrept2006.pdf. Accessed 1 June 2007

André JL, Bourquard R, Guillemin F, Krier MJ, Briançon S (2003) Final height in children with chronic renal failure who have not received growth hormone. Pediatr Nephrol 18:685–691PubMed

Englund MS, Tydén G, Wikstad I, Berg UB (2003) Growth impairment at renal transplantation: a determinant of growth and final height. Pediatr Transplant 7:192–199PubMed

Ninik A, McTaggart SJ, Gulati S, Powell HR, Jones CL, Walker RG (2002) Factors influencing growth and final height after renal transplantation. Pediatr Transplant 6:219–223PubMed

Nissel R, Brazda I, Feneberg R, Wigger M, Greiner C, Querfeld U, Haffner D (2004) Effect of renal transplantation in childhood on longitudinal growth and adult height. Kidney Int 66:792–800PubMed

Offner G, Latta K, Hoyer PF, Baum HJ, Ehrich JH, Pichlmayr R, Brodehl J (1999) Kidney transplanted children come of age. Kidney Int 55:1509–1517PubMed

10.

Rodriguez-Soriano J, Vallo A, Quintela MJ, Malaga S, Loris C (2000) Predictors of final adult height after renal transplantation during childhood: a single-center study. Nephron 86:266–273PubMed

11.

Potter D, Feduska N, Melzer J, Garovoy M, Hopper S, Duca R, Salvatierra O Jr (1986) Twenty years of renal transplantation in children. Pediatrics 77:465–470PubMed

12.

Hokken-Koelega AC, van Zaal MA, van Bergen W, de Ridder MA, Stijnen T, Wolff ED, de Jong RC, Donckerwolcke RA, de Muinck Keizer-Schrama SM, Drop SL (1994) Final height and its predictive factors after renal transplantation in childhood. Pediatr Res 36:323–328PubMed

13.

Furth SL, Hwang W, Yang C, Neu AM, Fivush BA, Powe NR (2002) Growth failure, risk of hospitalization and death for children with end-stage renal disease. Pediatr Nephrol 17:450–455PubMed

14.

Stabler B, Clopper RR, Siegel PT, Stoppani C, Compton PG, Underwood LE (1994) Academic achievement and psychological adjustment in short children. The National Cooperative Growth Study. J Dev Behav Pediatr 15:1–6PubMed

15.

Qvist E, Jalanko H, Holmberg C (2003) Psychosocial adaptation after solid organ transplantation in children. Pediatr Clin North Am 50:1505–1519PubMed

16.

Stabler B, Siegel PT, Clopper RR, Stoppani CE, Compton PG, Underwood LE (1998) Behavior change after growth hormone treatment of children with short stature. J Pediatr 133:366–373PubMed

17.

Broyer M, Le Bihan C, Charbit M, Guest G, Tête MJ, Gagnadoux MF, Niaudet P (2004) Long-term social outcome of children after kidney transplantation. Transplantation 77:1033–1037PubMed

18.

Rosenkranz J, Reichwald-Klugger E, Oh J, Turzer M, Mehls O, Schaefer F (2005) Psychosocial rehabilitation and satisfaction with life in adults with childhood-onset of end-stage renal disease. Pediatr Nephrol 20:1288–1294PubMed

19.

Rees L, Rigden SP, Ward GM (1989) Chronic renal failure and growth. Arch Dis Child 64:573–577PubMedPubMedCentral

20.

Schaefer F, Seidel C, Binding A, Gasser T, Largo RH, Prader A, Schärer K (1990) Pubertal growth in chronic renal failure. Pediatr Res 28:5–10PubMed

21.

Kari JA, Gonzalez C, Ledermann SE, Shaw V, Rees L (2000) Outcome and growth of infants with severe chronic renal failure. Kidney Int 57:1681–1687PubMed

22.

Schaefer F, Wingen AM, Hennicke M, Rigden S, Mehls O (1996) 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 10:288–293PubMed

23.

Haffner D, Schaefer F, Nissel R, Wühl E, Tönshoff B, Mehls O (2000) 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 343:923–930PubMed

24.

Tejani A, Fine R, Alexander S, Harmon W, Stablein D (1993) Factors predictive of sustained growth in children after renal transplantation. The North American pediatric renal transplant cooperative study. J Pediatr 122:397–402PubMed

25.

Maxwell H, Haffner D, Rees L (1998) Catch-up growth occurs after renal transplantation in children of pubertal age. J Pediatr 133:435–440PubMed

26.

Pennisi AJ, Costin G, Phillips LS, Uittenbogaart C, Ettenger RB, Malekzadeh MH, Fine RN (1977) Linear growth in long-term renal allograft recipients. Clin Nephrol 8:415–421PubMed

27.

Fine RN, Ho M, Tejani A, North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) (2001) The contribution of renal transplantation to final adult height: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatr Nephrol 16:951–956PubMed

28.

Guest G, Broyer M (1991) Growth after renal transplantation: correlation with immunosuppressive therapy. Pediatr Nephrol 5:143–146PubMed

29.

Blodgett FM, Burgin L, Iezzoni D, Gribetz D, Talbot NB (1956) Effects of prolonged cortisone therapy on the statural growth, skeletal maturation and metabolic status of children. N Engl J Med 254:636–641PubMed

30.

Sarna S, Hoppu K, Neuvonen PJ, Laine J, Holmberg C (1997) Methylprednisolone exposure, rather than dose, predicts adrenal suppression and growth inhibition in children with liver and renal transplants. J Clin Endocrinol Metab 82:75–77PubMed

31.

Seikku P, Raivio T, Janne OA, Neuvonen PJ, Holmberg C (2006) Methylprednisolone exposure in pediatric renal transplant patients. Am J Transplant 6:1451–1458PubMed

32.

Chavatte C, Guest G, Proust V, Le Bihan C, Gimenez F, Maisin A, Loirat C, Mogenet A, Bresson JL, Hankard R, Broyer M, Niaudet P, Singlas E (2004) Glucocorticoid pharmacokinetics and growth retardation in children with renal transplants. Pediatr Nephrol 19:898–904PubMed

33.

Pape L, Ehrich JH, Zivicnjak M, Offner G (2005) Growth in children after kidney transplantation with living related donor graft or cadaveric graft. Lancet 366:151–153PubMed

34.

Tejani A, Cortes L, Sullivan EK (1996) A longitudinal study of the natural history of growth post-transplantation. Kidney Int 53:S103–108

35.

Daughaday WH (2000) Growth hormone axis overview—somatomedin hypothesis. Pediatr Nephrol 14:537–540PubMed

36.

Jux C, Leiber K, Hugel U, Blum W, Ohlsson C, Klaus G, Mehls O (1998) Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of local insulin-like growth factor (IGF)-I production and expression of GH- and IGF-I-receptor in cultured rat chondrocytes. Endocrinology 139:3296–3305PubMed

37.

Koedam JA, Hoogerbrugge CM, Van Buul-Offers SC (2000) Differential regulation of IGF-binding proteins in rabbit costal chondrocytes by IGF-I and dexamethasone. J Endocrinol 165:557–567PubMed

38.

Jonsson KB, Ljunghall S, Karlström O, Johansson AG, Mallmin H, Ljunggren O (1993) Insulin-like growth factor I enhances the formation of type I collagen in hydrocortisone-treated human osteoblasts. Biosci Rep 13:297–302PubMed

39.

Clark RG (2005) Recombinant insulin-like growth factor-1 as a therapy for IGF-1 deficiency in renal failure. Pediatr Nephrol 20:290–294PubMed

40.

Smink JJ, Buchholz IM, Hamers N, van Tilburg CM, Christis C, Sakkers RJ, de Meer K, van Buul-Offers SC, Koedam JA (2003) Short-term glucocorticoid treatment of piglets causes changes in growth plate morphology and angiogenesis. Osteoarthritis Cartilage 11:864–871PubMed

41.

Chrysis D, Ritzen EM, Savendahl L (2003) Growth retardation induced by dexamethasone is associated with increased apoptosis of the growth plate chondrocytes. J Endocrinol 176:331–337PubMed

42.

Harmon WE, Jabs K (1992) Factors affecting growth after renal transplantation. J Am Soc Nephrol 2:S295–303PubMed

43.

Schaefer F, Hamill G, Stanhope R, Preece MA, Schärer K (1991) Pulsatile growth hormone secretion in peripubertal patients with chronic renal failure. Cooperative study group on pubertal development in chronic renal failure. J Pediatr 119:568–577PubMed

44.

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

45.

Rabkin R, Sun DF, Chen Y, Tan J, Schaefer F (2005) Growth hormone resistance in uremia, a role for impaired JAK/STAT signaling. Pediatr Nephrol 20:313–318PubMed

46.

Ulinski T, Mohan S, Kiepe D, Blum WF, Wingen AM, Mehls O, Tönshoff B (2000) 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 14:589–597PubMed

47.

Tönshoff B, Kiepe D, Ciarmatori S (2005) Growth hormone/insulin-like growth factor system in children with chronic renal failure. Pediatr Nephrol 20:279–289PubMed

48.

Kuizon BD, Salusky IB (1999) Growth retardation in children with chronic renal failure. J Bone Miner Res 14:1680–1690PubMed

49.

Maniar S, Kleinknecht C, Zhou X, Motel V, Yvert JP, Dechaux M (1996) Growth hormone action is blunted by acidosis in experimental uremia or acid load. Clin Nephrol 46:72–76PubMed

50.

Green J, Maor G (2000) Effect of metabolic acidosis on the growth hormone/IGF-I endocrine axis in skeletal growth centers. Kidney Int 57:2258–2267PubMed

51.

Carbajo E, Lopez JM, Santos F, Ordonez FA, Nino P, Rodriguez J (2001) Histologic and dynamic changes induced by chronic metabolic acidosis in the rat growth plate. J Am Soc Nephrol 12:1228–1234PubMed

52.

Koch Nogueira PC, David L, Cochat P (2000) Evolution of secondary hyperparathyroidism after renal transplantation. Pediatr Nephrol 14:342–346PubMed

53.

Thissen JP, Ketelslegers JM, Underwood LE (1994) Nutritional regulation of the insulin-like growth factors. Endocr Rev 15:80–101PubMed

54.

VandeHaar MJ, Moats-Staats BM, Davenport ML, Walker JL, Ketelslegers JM, Sharma BK, Tönshoff B (1991) Reduced serum concentrations of insulin-like growth factor-I (IGF-I) in protein-restricted growing rats are accompanied by reduced IGF-I mRNA levels in liver and skeletal muscle. J Endocrinol 130:305–312PubMed

55.

Thissen JP, Davenport ML, Pucilowska JB, Miles MV, Underwood LE (1992) Increased serum clearance and degradation of 125I-labeled IGF-I in protein-restricted rats. Am J Physiol 262:E406–411PubMed

56.

Schaefer F, Veldhuis JD, Robertson WR, Dunger D, Schërer K (1994) Immunoreactive and bioactive luteinizing hormone in pubertal patients with chronic renal failure. Cooperative Study Group on Pubertal Development in Chronic Renal Failure. Kidney Int 45:1465–1476PubMed

57.

McEnery PT, Gonzalez LL, Martin LW, West CD (1973) Growth and development of children with renal transplants. Use of alternate-day steroid therapy. J Pediatr 83:806–814PubMed

58.

Broyer M, Guest G, Gagnadoux MF (1992) Growth rate in children receiving alternate-day corticosteroid treatment after kidney transplantation. J Pediatr 120:721–725PubMed

59.

Jabs K, Sullivan EK, Avner ED, Harmon WE (1996) Alternate-day steroid dosing improves growth without adversely affecting graft survival or long-term graft function. A report of the North American pediatric renal transplant cooperative study. Transplantation 61:31–36PubMed

60.

Ferraris JR, Pasqualini T, Legal S, Sorroche P, Galich AM, Pennisi P, Domene H, Jasper H (2000) Effect of deflazacort versus methylprednisone on growth, body composition, lipid profile, and bone mass after renal transplantation. The deflazacort study group. Pediatr Nephrol 14:682–688PubMed

61.

Klare B, Strom TM, Hahn H, Engelsberger I, Meusel E, Illner WD, Abendroth D, Land W (1991) Remarkable long-term prognosis and excellent growth in kidney-transplant children under cyclosporine monotherapy. Transplant Proc 23:1013–1017PubMed

62.

Ellis D (2000) Growth and renal function after steroid-free tacrolimus-based immunosuppression in children with renal transplants. Pediatr Nephrol 14:689–694PubMed

63.

Hocker B, John U, Plank C, Wuhl E, Weber LT, Misselwitz J, Rascher W, Mehls O, Tönshoff B (2004) Successful withdrawal of steroids in pediatric renal transplant recipients receiving cyclosporine A and mycophenolate mofetil treatment: results after four years. Transplantation 78:228–234PubMed

64.

Sarwal MM, Vidhun JR, Alexander SR, Satterwhite T, Millan M, Salvatierra O Jr (2003) Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extended daclizumab induction in pediatric renal transplantation. Transplantation 76:1331–1339PubMed

65.

Kovàcs G, Fine RN, Worgall S, Schaefer F, Hunziker EB, Mehls O (1991) Recombinant human growth hormone overcomes the growth-suppressive effect ofmethylprednisolone in uraemic rats. Pediatr Nephrol 5:552–555PubMed

66.

Tönshoff B, Mehls O (1997) Factors affecting growth and strategies for treatment in children after renal transplantation. Pediatr Transplant 1:176–182PubMed

67.

Hokken-Koelega AC, Stijnen T, de Jong RC, Donckerwolcke RA, Groothoff JW, Wolff ED, Blum WF, de Muinck Keizer-Schrama SM, Drop SL (1996) A placebo-controlled, double-blind trial of growth hormone treatment in prepubertal children after renal transplant. Kidney Int 53:S128–134

68.

Maxwell H, Rees L (1998) Randomised controlled trial of recombinant human growth hormone in prepubertal and pubertal renal transplant recipients. British association for pediatric nephrology. Arch Dis Child 79:481–487PubMedPubMedCentral

69.

Guest G, Bérard E, Crosnier H, Chevallier T, Rappaport R, Broyer M (1998) Effects of growth hormone in short children after renal transplantation. French society of pediatric nephrology. Pediatr Nephrol 12:437–446PubMed

70.

Fine RN, Stablein D, Cohen AH, Tejani A, Kohaut E (2002) Recombinant human growth hormone post-renal transplantation in children: a randomized controlled study of the NAPRTCS. Kidney Int 62:688–696PubMed

71.

Tydén G, Berg U, Reinholt F (1990) Acute renal graft rejection after treatment with human growth hormone. Lancet 336:1455–1456PubMed

72.

Maxwell H, Nair DR, Dalton RN, Rigden SP, Rees L (1995) Differential effects of recombinant human growth hormone on glomerular filtration rate and renal plasma flow in chronic renal failure. Pediatr Nephrol 9:458–463PubMed

73.

Chavers BM, Doherty L, Nevins TE, Cook M, Sane K (1995) Effects of growth hormone on kidney function in pediatric transplant recipients. Pediatr Nephrol 9:176–181PubMed

74.

Fine RN, Stablein D (2005) Long-term use of recombinant human growth hormone in pediatric allograft recipients: a report of the NAPRTCS Transplant Registry. Pediatr Nephrol 20:404–408PubMed

75.

Snow EC, Felldbush TL, Oaks JA (1981) The effect of growth hormone and insulin upon MLC responses and the generation of cytotoxic lymphocytes. J Immunol 126:161–164PubMed

76.

Benfield MR, Kohaut EC (1997) Growth hormone is safe in children after renal transplantation. J Pediatr 131:S28–31PubMed

77.

Maxwell H, Amlot P, Rees L (2000) Growth hormone and markers of immune function in children with renal transplants. Pediatr Nephrol 14:473–475PubMed

78.

Dharnidharka V, Talley L, Stablein D, Fine RN (2007) Recombinant human growth hormone (rhGH) use pretransplant and risk of lymphoproliferative disease (LPD) post transplant (abstract no. 35). Pediatr Transplant 11[Suppl1]:43

79.

Tydén G, Wernersson A, Sandberg J, Berg U (2000) Development of renal cell carcinoma in living donor kidney grafts. Transplantation 70:1650–1656PubMed

80.

Mehls O, Wilton P, Lilien M, Berg U, Broyer M, Rizzoni G, Waldherr R, Opelz G (2002) Does growth hormone treatment affect the risk of post-transplant renal cancer? Pediatr Nephrol 17:984–989PubMed

81.

Filler G, Amendt P, Kohnert KD, Devaux S, Ehrich JH (1998) Glucose tolerance and insulin secretion in children before and during recombinant growth hormone treatment. Horm Res 50:32–37PubMed

82.

Ghio L, Damiani B, Garavaglia R, Oppizzi G, Taioli E, Edefonti A (2002) Lipid profile during rhGH therapy in pediatric renal transplant patients. Pediatr Transplant 6:127–131PubMed

83.

Querfeld U, Dopper S, Gradehand A, Kiencke P, Wahn F, Zeisel HJ (1999) Long-term treatment with growth hormone has no persisting effect on lipoprotein (a) in patients with Turner’s syndrome. J Clin Endocrinol Metab 84:967–970PubMed

84.

Sanchez CP, He YZ (2005) Daily or intermittent calcitriol administration during growth hormone therapy in rats with renal failure and advanced secondary hyperparathyroidism. J Am Soc Nephrol 16:929–938PubMed

85.

Koller EA, Stadel BV, Malozowski SN (1997) Papilledema in 15 renally compromised patients treated with growth hormone. Pediatr Nephrol 11:451–454PubMed

86.

Gharib H, Cook DM, Saenger PH, Bengtsson BA, Feld S, Nippoldt TB, Rodbard HW, Seibel JA, Vance ML, Zimmerman D, Palumbo PJ, Bergman DA, Garber JR, Hamilton CR Jr, Petak SM, Rettinger HI, Service FJ, Shankar TP, Stoffer SS, Tourletot JB, American Association of Clinical Endocrinologists Growth Hormone Task Force (2003) American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children-2003 update. Endocr Pract 9:64–76PubMed

87.

National Kidney Foundation (NKF) (2005) K/DOQI Clinical Practice Guidelines for bone metabolism and disease in children with chronic kidney disease. Available at: https://doi.org/www.kidney.org/professionals/KDOQI/guidelines_pedbone/guide11.htm. Accessed 1 June 1 2007

Title: Growth after renal transplantation
Authors: Jérôme Harambat
Pierre Cochat
Publication date: 01-07-2009
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 7/2009
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-008-0787-0

At a glance: The STEP trials

Springer Medicine

Growth after renal transplantation

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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