Skip to main content
SpringerLink
Log in

Growth hormone in pediatric chronic kidney disease: more than just height

  • Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Recombinant human growth hormone therapy, which was introduced in the 1980s, is now routine for children with advanced chronic kidney disease (CKD) who are exhibiting growth impairment. Growth hormone usage remains variable across different centers, with some showing low uptake. Much of the focus on growth hormone supplementation has been on increasing height because of social and psychological effects of short stature. There are, however, numerous other changes that occur in CKD that have not received as much attention but are biologically important for pediatric growth and development. This article reviews the current knowledge about the multisystem effects of growth hormone therapy in pediatric patients with CKD and highlights areas where additional clinical research is needed. We also included clinical data on children and adults who had received growth hormone for other indications apart from CKD. Ultimately, having robust clinical studies which examine these effects will allow children and their families to make more informed decisions about this therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Haffner D, Grund A, Leifheit-Nestler M (2021) Renal effects of growth hormone in health and in kidney disease. Pediatr Nephrol 36:2511–2530

    Article  PubMed  PubMed Central  Google Scholar 

  2. Hokken-Koelega AC, Stijnen T, de Muinck Keizer-Schrama SM, Wit JM, Wolff ED, de Jong MC, Donckerwolcke RA, Abbad NC, Bot A, Blum WF et al (1991) Placebo-controlled, double-blind, cross-over trial of growth hormone treatment in prepubertal children with chronic renal failure. Lancet 338:585–590

    Article  CAS  PubMed  Google Scholar 

  3. Fine RN, Kohaut EC, Brown D, Perlman AJ (1994) 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 124:374–382

    CAS  Google Scholar 

  4. Hokken-Koelega AC, Stijnen T, De Jong MC, Donckerwolcke RA, De Muinck Keizer-Schrama SM, Blum WF, Drop SL (1994) Double blind trial comparing the effects of two doses of growth hormone in prepubertal patients with chronic renal insufficiency. J Clin Endocrinol Metab 79:1185–1190

    CAS  PubMed  Google Scholar 

  5. Haffner D, Schaefer F, Nissel R, Wuhl E, Tonshoff 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 343:923–930

    Article  CAS  PubMed  Google Scholar 

  6. Drube J, Wan M, Bonthuis M, Wühl E, Bacchetta J, Santos F, Grenda R, Edefonti A, Harambat J, Shroff R, Tönshoff B, Haffner D (2019) European Society for Paediatric Nephrology Chronic Kidney Disease Mineral and Bone Disorders, Dialysis, and Transplantation Working Groups. Clinical practice recommendations for growth hormone treatment in children with chronic kidney disease. Nat Rev Nephrol 15:577–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Akchurin OM, Kogon AJ, Kumar J, Sethna CB, Hammad HT, Christos PJ, Mahan JD, Greenbaum LA, Woroniecki R (2017) Approach to growth hormone therapy in children with chronic kidney disease varies across North America: the Midwest Pediatric Nephrology Consortium report. BMC Nephrol 18:181

    Article  PubMed  PubMed Central  Google Scholar 

  8. Nissel R, Lindberg A, Mehls O, Haffner D, Pfizer International Growth Database (KIGS) International Board (2008) Factors predicting the near-final height in growth hormone-treated children and adolescents with chronic kidney disease. J Clin Endocrinol Metab 93:1359–1365

    Article  CAS  PubMed  Google Scholar 

  9. Adema AY, de Roij van Zuijdewijn CLM, Hoenderop JG, de Borst MH, Ter Wee PM, Heijboer AC, Vervloet MG; NIGRAM Consortium (2018) Influence of exogenous growth hormone administration on circulating concentrations of α-klotho in healthy and chronic kidney disease subjects: a prospective, single-center open case-control pilot study. BMC Nephrol 19:327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Akchurin OM, Schneider MF, Mulqueen L, Brooks ER, Langman CB, Greenbaum LA, Furth SL, Moxey-Mims M, Warady BA, Kaskel FJ, Skversky AL (2014) Medication adherence and growth in children with CKD. Clin J Am Soc Nephrol 9:1519–1525

    Article  PubMed  PubMed Central  Google Scholar 

  11. van Huis M, Bonthuis M, Sahpazova E, Mencarelli F, Spasojevic B, Reusz G, Caldas-Afonso A, Bjerre A, Baiko S, Vondrak K, Molchanova EA, Kolvek G, Zaikova N, Bohm M, Ariceta G, Jager KJ, Schaefer F, van Stralen KJ, Groothoff JW (2016) Considerable variations in growth hormone policy and prescription in paediatric end-stage renal disease across European countries-a report from the ESPN/ERA-EDTA registry. Nephrol Dial Transplant 31:609–619

    Article  PubMed  Google Scholar 

  12. Mahesh S, Kaskel F (2008) Growth hormone axis in chronic kidney disease. Pediatr Nephrol 23:41–48

    Article  PubMed  PubMed Central  Google Scholar 

  13. Tannenbaum GS, Ling N (1984) The interrelationship of growth hormone (GH)-releasing factor and somatostatin in generation of the ultradian rhythm of GH secretion. Endocrinology 115:1952–1957

    Article  CAS  PubMed  Google Scholar 

  14. Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, Olsson I, Edlund K, Lundberg E, Navani S, Szigyarto CA, Odeberg J, Djureinovic D, Takanen JO, Hober S, Alm T, Edqvist PH, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk JM, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Pontén F (2015) Proteomics. Tissue-based map of the human proteome. Sci 347:1260419

  15. GHRHR tissue cell type data from https://www.v23.proteinatlas.org. Accessed 3/7/2024

  16. Blum WF, Albertsson-Wikland K, Rosberg S, Ranke MB (1993) Serum levels of insulin-like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion. J Clin Endocrinol Metab 76:1610–1616

    CAS  PubMed  Google Scholar 

  17. Allard JB, Duan C (2018) IGF-binding proteins: why do they exist and why are there so many? Front Endocrinol (Lausanne) 9:117

    Article  PubMed  Google Scholar 

  18. Niemczyk S, Sikorska H, Wiecek A, Zukowska-Szczechowska E, Zalecka K, Gorczynska J, Kubik M, Czerwienska B, Gosek K, Veldhuis JD, Wagner DA, Gaudreau P, Hakonen T, Kay SW, Jouhikainen T, Schaefer F (2010) A super-agonist of growth hormone-releasing hormone causes rapid improvement of nutritional status in patients with chronic kidney disease. Kidney Int 77:450–458

    Article  CAS  PubMed  Google Scholar 

  19. Hellstrom A, Ley D, Hansen-Pupp I, Hallberg B, Lofqvist C, van Marter L, van Weissenbruch M, Ramenghi LA, Beardsall K, Dunger D, Hard AL, Smith LE (2016) Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development. Acta Paediatr 105:576–586

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wang S, Chi K, Wu D, Hong Q (2021) Insulin-like growth factor binding proteins in kidney disease. Front Pharmacol 12:807119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Russell-Jones DL, Bates AT, Umpleby AM, Hennessy TR, Bowes SB, Hopkins KD, Jackson N, Kelly J, Shojaee-Moradie F, Jones RH et al (1995) A comparison of the effects of IGF-I and insulin on glucose metabolism, fat metabolism and the cardiovascular system in normal human volunteers. Eur J Clin Invest 25:403–411

    Article  CAS  PubMed  Google Scholar 

  22. Jia T, Gama Axelsson T, Heimburger O, Barany P, Lindholm B, Stenvinkel P, Qureshi AR (2014) IGF-1 and survival in ESRD. Clin J Am Soc Nephrol 9:120–127

    Article  CAS  PubMed  Google Scholar 

  23. Prelevic V, Radunovic D, Antunovic T, Ratkovic M, Gligorovic-Bahranovic N, Gledovic B, Vujosevic S, Nedovic-Vukovic M, Basic-Jukic N (2018) Increased serum level of IGF-1 correlates with better cognitive status in end-stage renal disease patients undergoing hemodialysis. Ther Apher Dial 22:118–123

    Article  CAS  PubMed  Google Scholar 

  24. Karava V, Dotis J, Christoforidis A, Liakopoulos V, Kondou A, Tsigaras G, Tsioni K, Kollios K, Printza N (2021) Association between insulin growth factor-1, bone mineral density, and frailty phenotype in children with chronic kidney disease. Pediatr Nephrol 36:1861–1870

    Article  PubMed  Google Scholar 

  25. Mitsnefes MM (2012) Cardiovascular disease in children with chronic kidney disease. J Am Soc Nephrol 23:578–585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mitsnefes MM, Xu Y, Ng DK, Hill G, Kimball T, Furth SL, Warady BA (2021) Diastolic function and ambulatory hypertension in children with chronic kidney disease. Hypertension 78:1347–1354

    Article  CAS  PubMed  Google Scholar 

  27. Wilson AC, Schneider MF, Cox C, Greenbaum LA, Saland J, White CT, Furth S, Warady BA, Mitsnefes MM (2011) Prevalence and correlates of multiple cardiovascular risk factors in children with chronic kidney disease. Clin J Am Soc Nephrol 6:2759–2765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Rieger AC, Bagno LL, Salerno A, Florea V, Rodriguez J, Rosado M, Turner D, Dulce RA, Takeuchi LM, Kanashiro-Takeuchi RM, Buchwald P, Wanschel A, Balkan W, Schulman IH, Schally AV, Hare JM (2021) Growth hormone-releasing hormone agonists ameliorate chronic kidney disease-induced heart failure with preserved ejection fraction. Proc Natl Acad Sci USA 118:e2019835118

  29. Maison P, Griffin S, Nicoue-Beglah M, Haddad N, Balkau B, Chanson P, Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials (2004) Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a metaanalysis of blinded, randomized, placebo-controlled trials. J Clin Endocrinol Metab 89:2192–2199

    Article  CAS  PubMed  Google Scholar 

  30. Hirschberg RR, Kopple JD (1988) Increase in renal plasma flow and glomerular filtration rate during growth hormone treatment may be mediated by insulin-like growth factor I. Am J Nephrol 8:249–254

    Article  CAS  PubMed  Google Scholar 

  31. Nissel R, Fischer DC, Puhlmann A, Holdt-Lehmann B, Mitzner A, Petzsch M, Korber T, Tiess M, Schmidt R, Haffner D (2009) Short-term growth hormone treatment and microcirculation: effects in patients with chronic kidney disease. Microvasc Res 78:246–252

    Article  CAS  PubMed  Google Scholar 

  32. Rubinek T, Shahmoon S, Shabtay-Orbach A, Ben Ami M, Levy-Shraga Y, Mazor-Aronovitch K, Yeshayahu Y, Doolman R, Hemi R, Kanety H, Wolf I, Modan-Moses D (2016) Klotho response to treatment with growth hormone and the role of IGF-I as a mediator. Metabolism 65:1597–1604

    Article  CAS  PubMed  Google Scholar 

  33. Ewert A, Leifheit-Nestler M, Hohenfellner K, Büscher A, Kemper MJ, Oh J, Billing H, Thumfart J, Stangl G, Baur AC, Föller M, Feger M, Weber LT, Acham-Roschitz B, Arbeiter K, Tönshoff B, Zivicnjak M, Haffner D (2020) Bone and Mineral Metabolism in Children with Nephropathic Cystinosis Compared with other CKD Entities. J Clin Endocrinol Metab 105:dgaa267

  34. Hu MC, Shiizaki K, Kuro-o M, Moe OW (2013) Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol 75:503–533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kim HR, Nam BY, Kim DW, Kang MW, Han JH, Lee MJ, Shin DH, Doh FM, Koo HM, Ko KI, Kim CH, Oh HJ, Yoo TH, Kang SW, Han DS, Han SH (2013) Circulating alpha-klotho levels in CKD and relationship to progression. Am J Kidney Dis 61:899–909

    Article  CAS  PubMed  Google Scholar 

  36. Semba RD, Cappola AR, Sun K, Bandinelli S, Dalal M, Crasto C, Guralnik JM, Ferrucci L (2011) Plasma klotho and cardiovascular disease in adults. J Am Geriatr Soc 59:1596–1601

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kitagawa M, Sugiyama H, Morinaga H, Inoue T, Takiue K, Ogawa A, Yamanari T, Kikumoto Y, Uchida HA, Kitamura S, Maeshima Y, Nakamura K, Ito H, Makino H (2013) A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease. PLoS One 8:e56695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lim K, Lu TS, Molostvov G, Lee C, Lam FT, Zehnder D, Hsiao LL (2012) Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation 125:2243–2255

    Article  CAS  PubMed  Google Scholar 

  39. Six I, Okazaki H, Gross P, Cagnard J, Boudot C, Maizel J, Drueke TB, Massy ZA (2014) Direct, acute effects of Klotho and FGF23 on vascular smooth muscle and endothelium. PLoS One 9:e93423

    Article  PubMed  PubMed Central  Google Scholar 

  40. Carlstrom M (2021) Nitric oxide signalling in kidney regulation and cardiometabolic health. Nat Rev Nephrol 17:575–590

    Article  PubMed  PubMed Central  Google Scholar 

  41. Capaldo B, Guardasole V, Pardo F, Matarazzo M, Di Rella F, Numis F, Merola B, Longobardi S, Sacca L (2001) Abnormal vascular reactivity in growth hormone deficiency. Circulation 103:520–524

    Article  CAS  PubMed  Google Scholar 

  42. Lilien MR, Schroder CH, Levtchenko EN, Koomans HA (2004) Growth hormone therapy influences endothelial function in children with renal failure. Pediatr Nephrol 19:785–789

    Article  PubMed  Google Scholar 

  43. Böger RH, Skamira C, Bode-Böger SM, Brabant G, von zur Muhlen A, Frolich JC (1996) Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study. J Clin Invest 98:2706–2713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Canete MD, Valle-Martos R, Martos R, Canete R, Valle M, Jimenez-Reina L (2019) Effects of growth hormone therapy on metabolic parameters, adipokine and endothelial dysfunction in prepuberal children. Acta Paediatr 108:2027–2033

    Article  CAS  PubMed  Google Scholar 

  45. Tidblad A, Bottai M, Kieler H, Albertsson-Wikland K, Savendahl L (2021) Association of childhood growth hormone treatment with long-term cardiovascular morbidity. JAMA Pediatr 175:e205199

    Article  PubMed  Google Scholar 

  46. van der Steen M, Kerkhof GF, Smeets CCJ, Hokken-Koelega ACS (2017) Cardiovascular risk factors and carotid intima media thickness in young adults born small for gestational age after cessation of growth hormone treatment: a 5-year longitudinal study. Lancet Diabetes Endocrinol 5:975–985

    Article  PubMed  Google Scholar 

  47. Howard BV, Rossouw JE (2013) Estrogens and cardiovascular disease risk revisited: the women’s health initiative. Curr Opin Lipidol 24:493–499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ferruzzi A, Vrech M, Pietrobelli A, Cavarzere P, Zerman N, Guzzo A, Flodmark CE, Piacentini G, Antoniazzi F (2023) The influence of growth hormone on pediatric body composition: a systematic review. Front Endocrinol (Lausanne) 14:1093691

    Article  PubMed  Google Scholar 

  49. Kubo H, Sawada S, Satoh M, Asai Y, Kodama S, Sato T, Tomiyama S, Seike J, Takahashi K, Kaneko K, Imai J, Katagiri H (2022) Insulin-like growth factor-1 levels are associated with high comorbidity of metabolic disorders in obese subjects; a Japanese single-center, retrospective-study. Sci Rep 12:20130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Vikman K, Carlsson B, Billig H, Eden S (1991) Expression and regulation of growth hormone (GH) receptor messenger ribonucleic acid (mRNA) in rat adipose tissue, adipocytes, and adipocyte precursor cells: GH regulation of GH receptor mRNA. Endocrinology 129:1155–1161

    Article  CAS  PubMed  Google Scholar 

  51. Hansen LH, Madsen B, Teisner B, Nielsen JH, Billestrup N (1998) Characterization of the inhibitory effect of growth hormone on primary preadipocyte differentiation. Mol Endocrinol 12:1140–1149

    Article  CAS  PubMed  Google Scholar 

  52. Rashid R, Neill E, Smith W, King D, Beattie TJ, Murphy A, Ramage IJ, Maxwell H, Ahmed SF (2006) Body composition and nutritional intake in children with chronic kidney disease. Pediatr Nephrol 21:1730–1738

    Article  PubMed  Google Scholar 

  53. Johnson VL, Wang J, Kaskel FJ, Pierson RN (2000) Changes in body composition of children with chronic renal failure on growth hormone. Pediatr Nephrol 14:695–700

    Article  CAS  PubMed  Google Scholar 

  54. van der Sluis IM, Boot AM, Nauta J, Hop WC, de Jong MC, Lilien MR, Groothoff JW, van Wijk AE, Pols HA, Hokken-Koelega AC, de Muinck Keizer-Schrama SM (2000) Bone density and body composition in chronic renal failure: effects of growth hormone treatment. Pediatr Nephrol 15:221–228

    Article  PubMed  Google Scholar 

  55. Boot AM, Nauta J, de Jong MC, Groothoff JW, Lilien MR, van Wijk JA, Kist-van Holthe JE, Hokken-Koelega AC, Pols HA, de Muinck Keizer-Schrama SM (1998) Bone mineral density, bone metabolism and body composition of children with chronic renal failure, with and without growth hormone treatment. Clin Endocrinol (Oxf) 49:665–672

    Article  CAS  PubMed  Google Scholar 

  56. Vaisman N, Zadik Z, Duchan R, Voet H, Lotan D, Drukker A (1994) Changes in body composition of children with chronic renal failure during growth hormone treatment. Pediatr Nephrol 8:201–204

    Article  CAS  PubMed  Google Scholar 

  57. Foster BJ, Kalkwarf HJ, Shults J, Zemel BS, Wetzsteon RJ, Thayu M, Foerster DL, Leonard MB (2011) Association of chronic kidney disease with muscle deficits in children. J Am Soc Nephrol 22:377–386

    Article  PubMed  PubMed Central  Google Scholar 

  58. Kalantar-Zadeh K, Block G, McAllister CJ, Humphreys MH, Kopple JD (2004) Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients. Am J Clin Nutr 80:299–307

    Article  CAS  PubMed  Google Scholar 

  59. Kalantar-Zadeh K, Kopple JD, Block G, Humphreys MH (2001) A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients. Am J Kidney Dis 38:1251–1263

    Article  CAS  PubMed  Google Scholar 

  60. Johannsson G, Bengtsson BA, Ahlmen J (1999) Double-blind, placebo-controlled study of growth hormone treatment in elderly patients undergoing chronic hemodialysis: anabolic effect and functional improvement. Am J Kidney Dis 33:709–717

    Article  CAS  PubMed  Google Scholar 

  61. Hansen TB, Gram J, Jensen PB, Kristiansen JH, Ekelund B, Christiansen JS, Pedersen FB (2000) Influence of growth hormone on whole body and regional soft tissue composition in adult patients on hemodialysis. A double-blind, randomized, placebo-controlled study. Clin Nephrol 53:99–107

    CAS  PubMed  Google Scholar 

  62. Davies PS, Evans S, Broomhead S, Clough H, Day JM, Laidlaw A, Barnes ND (1998) Effect of growth hormone on height, weight, and body composition in Prader-Willi syndrome. Arch Dis Child 78:474–476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Gotsman I, Keren A, Amir O, Zwas DR (2022) Increased estimated fat-free mass and fat mass associated with improved clinical outcome in heart failure. Eur J Clin Invest 52:e13655

    Article  CAS  PubMed  Google Scholar 

  64. Karava V, Printza N, Dotis J, Demertzi D, Antza C, Kotsis V, Papachristou F, Stabouli S (2019) Body composition and arterial stiffness in pediatric patients with chronic kidney disease. Pediatr Nephrol 34:1253–1260

    Article  PubMed  Google Scholar 

  65. Sanchez CP, Goodman WG, Brandli D, Goldenhersh M, Murray C, Carlton E, Hahn T, Salusky IB (1995) Skeletal response to recombinant human growth hormone (rhGH) in children treated with long-term corticosteroids. J Bone Miner Res 10:2–6

    Article  CAS  PubMed  Google Scholar 

  66. Doyon A, Fischer DC, Bayazit AK, Canpolat N, Duzova A, Sozeri B, Bacchetta J, Balat A, Buscher A, Candan C, Cakar N, Donmez O, Dusek J, Heckel M, Klaus G, Mir S, Ozcelik G, Sever L, Shroff R, Vidal E, Wuhl E, Gondan M, Melk A, Querfeld U, Haffner D, Schaefer F, 4C Study Consortium (2015) Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease. PLoS One 10:e0113482

    Article  PubMed  PubMed Central  Google Scholar 

  67. Bacchetta J, Wesseling-Perry K, Kuizon B, Pereira RC, Gales B, Wang HJ, Elashoff R, Salusky IB (2013) The skeletal consequences of growth hormone therapy in dialyzed children: a randomized trial. Clin J Am Soc Nephrol 8:824–832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Van Dyck M, Gyssels A, Proesmans W, Nijs J, Eeckels R (2001) Growth hormone treatment enhances bone mineralisation in children with chronic renal failure. Eur J Pediatr 160:359–363

    Article  PubMed  Google Scholar 

  69. Nawrot-Wawrzyniak K, Misof BM, Roschger P, Panczyk-Tomaszewska M, Ziolkowska H, Klaushofer K, Fratzl-Zelman N (2013) Changes in bone matrix mineralization after growth hormone treatment in children and adolescents with chronic kidney failure treated by dialysis: a paired biopsy study. Am J Kidney Dis 61:767–777

    Article  CAS  PubMed  Google Scholar 

  70. Troib A, Guterman M, Rabkin R, Landau D, Segev Y (2016) Endurance exercise and growth hormone improve bone formation in young and growth-retarded chronic kidney disease rats. Nephrol Dial Transplant 31:1270–1279

    Article  CAS  PubMed  Google Scholar 

  71. Lalan S, Jiang S, Ng DK, Kupferman F, Warady BA, Furth S, Mitsnefes MM (2018) Cardiometabolic risk factors, metabolic syndrome, and chronic kidney disease progression in children. J Pediatr 202:163–170

    Article  PubMed  PubMed Central  Google Scholar 

  72. Mitsnefes MM, Laskin BL, Dahhou M, Zhang X, Foster BJ (2013) Mortality risk among children initially treated with dialysis for end-stage kidney disease, 1990–2010. JAMA 309:1921–1929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Stabouli S, Polderman N, Nelms CL, Paglialonga F, Oosterveld MJS, Greenbaum LA, Warady BA, Anderson C, Haffner D, Desloovere A, Qizalbash L, Renken-Terhaerdt J, Tuokkola J, Walle JV, Shaw V, Mitsnefes M, Shroff R (2022) Assessment and management of obesity and metabolic syndrome in children with CKD stages 2–5 on dialysis and after kidney transplantation-clinical practice recommendations from the Pediatric Renal Nutrition Taskforce. Pediatr Nephrol 37:1–20

    Article  PubMed  Google Scholar 

  74. Shroff R, Weaver DJ Jr, Mitsnefes MM (2011) Cardiovascular complications in children with chronic kidney disease. Nat Rev Nephrol 7:642–649

    Article  CAS  PubMed  Google Scholar 

  75. Sgambat K, Roem J, Mitsnefes M, Portale AA, Furth S, Warady B, Moudgil A (2018) Waist-to-height ratio, body mass index, and cardiovascular risk profile in children with chronic kidney disease. Pediatr Nephrol 33:1577–1583

    Article  PubMed  PubMed Central  Google Scholar 

  76. Brady TM, Roem J, Cox C, Schneider MF, Wilson AC, Furth SL, Warady BA, Mitsnefes M (2020) Adiposity, sex, and cardiovascular disease risk in children with CKD: a longitudinal study of youth enrolled in the Chronic Kidney Disease in Children (CKiD) study. Am J Kidney Dis 76:166–173

    Article  PubMed  PubMed Central  Google Scholar 

  77. Ahn CW, Kim CS, Nam JH, Kim HJ, Nam JS, Park JS, Kang ES, Cha BS, Lim SK, Kim KR, Lee HC, Huh KB (2006) Effects of growth hormone on insulin resistance and atherosclerotic risk factors in obese type 2 diabetic patients with poor glycaemic control. Clin Endocrinol (Oxf) 64:444–449

    Article  CAS  PubMed  Google Scholar 

  78. Pan CS, Weiss JJ, Fourman LT, Buckless C, Branch KL, Lee H, Torriani M, Misra M, Stanley TL (2021) Effect of recombinant human growth hormone on liver fat content in young adults with nonalcoholic fatty liver disease. Clin Endocrinol (Oxf) 94:183–192

    Article  CAS  PubMed  Google Scholar 

  79. Bredella MA, Gerweck AV, Lin E, Landa MG, Torriani M, Schoenfeld DA, Hemphill LC, Miller KK (2013) Effects of GH on body composition and cardiovascular risk markers in young men with abdominal obesity. J Clin Endocrinol Metab 98:3864–3872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Ejtahed HS, Kelishadi R, Hasani-Ranjbar S, Angoorani P, Motlagh ME, Shafiee G, Ziaodini H, Taheri M, Qorbani M, Heshmat R (2019) Discriminatory ability of visceral adiposity index as an indicator for modeling cardio-metabolic risk factors in pediatric population: the CASPIAN-V study. J Cardiovasc Thorac Res 11:280–286

    Article  PubMed  PubMed Central  Google Scholar 

  81. Sharma R, Kopchick JJ, Puri V, Sharma VM (2020) Effect of growth hormone on insulin signaling. Mol Cell Endocrinol 518:111038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Haffner D, Nissel R, Wuhl E, Schaefer F, Bettendorf M, Tonshoff B, Mehls O (1998) 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 43:209–215

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  84. 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 79:481–487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Hokken-Koelega AC, Stijnen T, de Ridder MA, de Muinck Keizer-Schrama SM, Wolff ED, de Jong MC, Donckerwolcke RA, Groothoff JW, Blum WF, Drop SL et al (1994) Growth hormone treatment in growth-retarded adolescents after renal transplant. Lancet 343:1313–1317

    Article  CAS  PubMed  Google Scholar 

  86. Guest G, Berard 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 12:437–446

    Article  CAS  PubMed  Google Scholar 

  87. Jagodzinski C, Mueller S, Kluck R, Froede K, Pavicic L, Gellermann J, Mueller D, Querfeld U, Haffner D, Zivicnjak M (2022) Growth hormone treatment in the pre-transplant period is associated with superior outcome after pediatric kidney transplantation. Pediatr Nephrol 37:859–869

    Article  PubMed  Google Scholar 

  88. Soler Palacios B, Nieto C, Fajardo P, Gonzalez de la Aleja A, Andres N, Dominguez-Soto A, Lucas P, Cuenda A, Rodriguez-Frade JM, Martinez AC, Villares R, Corbi AL, Mellado M (2020) Growth hormone reprograms macrophages toward an anti-inflammatory and reparative profile in an MAFB-dependent manner. J Immunol 205:776–788

    Article  PubMed  Google Scholar 

  89. Soler Palacios B, Villares R, Lucas P, Rodriguez-Frade JM, Cayuela A, Piccirillo JG, Lombardia M, Delgado Gestoso D, Fernandez-Garcia M, Risco C, Barbas C, Corrales F, Sorzano COS, Martinez-Martin N, Conesa JJ, Iborra FJ, Mellado M (2023) Growth hormone remodels the 3D-structure of the mitochondria of inflammatory macrophages and promotes metabolic reprogramming. Front Immunol 14:1200259

    Article  PubMed  PubMed Central  Google Scholar 

  90. Kimata H, Fujimoto M (1994) Growth hormone and insulin-like growth factor I induce immunoglobulin (Ig)E and IgG4 production by human B cells. J Exp Med 180:727–732

    Article  CAS  PubMed  Google Scholar 

  91. Hooper SR, Gerson AC, Butler RW, Gipson DS, Mendley SR, Lande MB, Shinnar S, Wentz A, Matheson M, Cox C, Furth SL, Warady BA (2011) Neurocognitive functioning of children and adolescents with mild-to-moderate chronic kidney disease. Clin J Am Soc Nephrol 6:1824–1830

    Article  PubMed  PubMed Central  Google Scholar 

  92. Chen K, Didsbury M, van Zwieten A, Howell M, Kim S, Tong A, Howard K, Nassar N, Barton B, Lah S, Lorenzo J, Strippoli G, Palmer S, Teixeira-Pinto A, Mackie F, McTaggart S, Walker A, Kara T, Craig JC, Wong G (2018) Neurocognitive and educational outcomes in children and adolescents with CKD: a systematic review and meta-analysis. Clin J Am Soc Nephrol 13:387–397

    Article  PubMed  PubMed Central  Google Scholar 

  93. Lande MB, Gerson AC, Hooper SR, Cox C, Matheson M, Mendley SR, Gipson DS, Wong C, Warady BA, Furth SL, Flynn JT (2011) Casual blood pressure and neurocognitive function in children with chronic kidney disease: a report of the children with chronic kidney disease cohort study. Clin J Am Soc Nephrol 6:1831–1837

    Article  PubMed  PubMed Central  Google Scholar 

  94. Kogon AJ, Vander Stoep A, Weiss NS, Smith J, Flynn JT, McCauley E (2013) Depression and its associated factors in pediatric chronic kidney disease. Pediatr Nephrol 28:1855–1861

    Article  PubMed  PubMed Central  Google Scholar 

  95. Amin R, Sharma N, Al-Mokali K, Sayal P, Al-Saleh S, Narang I, Harvey E (2015) Sleep-disordered breathing in children with chronic kidney disease. Pediatr Nephrol 30:2135–2143

    Article  PubMed  Google Scholar 

  96. Morselli LL, Nedeltcheva A, Leproult R, Spiegel K, Martino E, Legros JJ, Weiss RE, Mockel J, Van Cauter E, Copinschi G (2013) Impact of GH replacement therapy on sleep in adult patients with GH deficiency of pituitary origin. Eur J Endocrinol 168:763–770

    Article  CAS  PubMed  Google Scholar 

  97. Zhou Z, Luo Y, Gao X, Zhu Y, Bai X, Yang H, Bi Q, Chen S, Duan L, Wang L, Gong F, Feng F, Gong G, Zhu H, Pan H (2022) Alterations in brain structure and function associated with pediatric growth hormone deficiency: a multi-modal magnetic resonance imaging study. Front Neurosci 16:1043857

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    Katie Marie Sullivan & Alison J. Kriegel

  2. Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA

    Katie Marie Sullivan & Alison J. Kriegel

  3. Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA

    Katie Marie Sullivan & Alison J. Kriegel

Authors
  1. Katie Marie Sullivan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alison J. Kriegel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alison J. Kriegel.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sullivan, K.M., Kriegel, A.J. Growth hormone in pediatric chronic kidney disease: more than just height. Pediatr Nephrol (2024). https://doi.org/10.1007/s00467-024-06330-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00467-024-06330-8

Keywords

Search

Navigation