Growth disturbance in chronic renal failure: Etiology and treatment

  • O. Mehls
  • F. S. Schaefer
  • B. Tönshoff

Abstract

One of the major somatic consequences and psychological burdens of chronic renal failure (CRF) is the disturbance of body growth. Since the start of dialysis improves renal clearance, it was the hope of patients and clinicians that the improved renal clearance may also result in a better growth rate. Unfortunately, those expectations have not been fulfilled. Furthermore, the time of dialysis is usually too short to correct for a previous height deficit. As a consequence, treatment of growth failure in renal patients should be diagnosed and treated early. Since the majority of children with CRF have congenital renal disorders, the problem of prevention and treatment of growth failure starts immediately after birth.

Keywords

Chronic Renal Failure Growth Hormone Treatment Growth Hormone Therapy Pubertal Growth Spurt Pediatric Dialysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Karlberg J, Schaefer F, Hennicke M, Wingen AM, Rigden S, Mehls O. Early age-dependent growth impairment in chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. Pediatr Nephrol. 1996;10:283–7.PubMedGoogle Scholar
  2. 2.
    Kleinknecht C, Broyer M, Huot D, Marti-Henneberg C, Dartois A. Growth and development of nondialyzed children with chronic renal failure. Kidney Int. 1983;24:40–7.Google Scholar
  3. 3.
    Warady BA, Kriley MA, Lovell H, Farrell SE, Hellerstein S. Growth and development of infants with end-stage renal disease receiving long-term peritoneal dialysis. J Pediatr. 1988;112:714–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Schaefer F, Wingen AM, 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. 1996;10:288–93.PubMedGoogle Scholar
  5. 5.
    Schärer K, Chantier C, Brunner FP, Gurland HJ, Jacobs C, Seiwood NH et al. Combined report on regular dialysis and transplantation of children in Europe 1975. Proc Eur Dial Transplant Assoc. 1976;13:3–103.Google Scholar
  6. 6.
    Schärer K. Study on pubertal development in chronic renal failure. Growth and development of children with chronic renal failure. Acta Paediatr Scand Suppl. 1990;366:90–2.PubMedCrossRefGoogle Scholar
  7. 7.
    Rizzoni G, Broyer M, Brunner FP, Brynger H, Challah S, Kramer P et al. Combined report on regular dialysis and transplantation of children in Europe, XIII, 1983. Proc Eur Dial Transplant Assoc Eur Ren Assoc. 1985;21:66–95.Google Scholar
  8. 8.
    Schaefer F, Seidel C, Binding A, Gasser T, Largo RH, Prader A et al. Pubertal growth in chronic renal failure. Pediatr Res. 1990;28:5–10.PubMedCrossRefGoogle Scholar
  9. 9.
    Schaefer F, Gilli G, Schärer K. Pubertal growth and final height in chronic renal failure. In: Schärer K, editor. Growth and Endocrine Changes in Children and Adolescents with Chronic Renal Failure. Pediatric and Adolescent Endocrinology. Vol. 22. Basel: Karger, 1989: pp. 59–69.Google Scholar
  10. 10.
    Hokken-Koelega AC, Van Zaal MA, van Bergen W, de Ridder MA, Stijnen T, Wolff ED et al Final height and its predictive factors after renal transplantation in childhood. Pediatr Res. 1994;36:323–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Orejas G, Santos F, Malaga S, Rey C, Cobo A, Simarro M. Nutritional status of children with moderate chronic renal failure. Pediatr Nephrol. 1995;9:52–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Foreman JW, Abitbol CL, Trachtman H, Garin EH, Feld LG, Strife CF et al Nutritional intake in children with renal insufficiency: a report of the Growth Failure in Children with Renal Diseases Study. J Am Coll Nutr. 1996;15:579–85.PubMedGoogle Scholar
  13. 13.
    Mehls O, Ritz E, Gilli G, Bartholomé K, Beiβbarth H, Hohenegger M et al. Nitrogen metabolism and growth in experimental uremia. Int J Pediatr Nephrol. 1980;1:34–41.PubMedGoogle Scholar
  14. 14.
    Arnold WC, Danford D, Holliday MA. Effects of calorie supplementation on growth in uremia. Kidney Int. 1983;24:205–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Wassner SJ. The effect of sodium repletion on growth and protein turnover in sodium-depleted rats. Pediatr Nephrol. 1981;5:501–4.CrossRefGoogle Scholar
  16. 16.
    Grossman H, Duggan E, McCamman S, Welchert E, Hellerstein S. The dietary chloride deficiency syndrome. Pediatrics. 1980;66:366–74.PubMedGoogle Scholar
  17. 17.
    Bailey JL, Wang X, England BK, Price SR, Ding X, Mitch BE. The acidosis of chronic renal failure activates muscle proteolysis in rats by augmenting transcription of genes encoding proteins of the ATP-dependent ubiquitin-proteasome pathway. J Clin Invest. 1996;97:1447–53.PubMedCrossRefGoogle Scholar
  18. 18.
    Challa A, Krieg RJ, Jr., Thabet MA, Veldhuis JD, Chan JC. Metabolic acidosis inhibits growth hormone secretion in rats: mechanism of growth retardation. Am J Physiol. 1993;265:547–53.Google Scholar
  19. 19.
    Challa A, Chan W, Krieg RJ, Jr., Thabet MA, Liu F, Hintz RL et al Effect of metabolic acidosis on the expression of insulin-like growth factor and growth hormone receptor. Kidney Int. 1993;44:1224–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Kattamis CA, Kattamis AC. Management of thalassemias: growth and development, hormone substitution, vitamin supplementation, and vaccination. Semin Hematol. 1995;32:269–79.PubMedGoogle Scholar
  21. 21.
    Mehls O, Ritz E. Skeletal growth in experimental uremia. Kidney Int Suppl. 1983;15:S53–62.PubMedGoogle Scholar
  22. 22.
    Mehls O, Ritz E, Gilli G, Wangdak T, Krempien B. Effect of vitamin D on growth in experimental uremia. Am J Clin Nutr. 1978;31:1927–31.PubMedGoogle Scholar
  23. 23.
    Mehls O, Ritz E, Gilli G, Heinrich U. Role of hormonal disturbances in uremic growth failure. Contrib Nephrol. 1986;50:119–29.PubMedGoogle Scholar
  24. 24.
    Chesney RW, Moorthy AV, Eisman JA, Jax DK. Influence of oral 1,25-vitamin D in childhood renal osteodystrophy. Contrib Nephrol. 1980;18:55–71.PubMedGoogle Scholar
  25. 25.
    Schmitt CP, Hessing S, Oh J, Weber L, Ochlich P, Mehls O. Intermittent administration of parathyroid hormone (1-37) improves growth and bone mineral density in uremic rats. Kidney Int. 2000;57:1484–92.PubMedCrossRefGoogle Scholar
  26. 26.
    Kreusser W, Weinkauf R, Mehls O, Ritz E. Effect of parathyroid hormone, calcitonin and growth hormone on CAMP content of growth cartilage in experimental uremia. Eur J Clin Invest. 1982;12:337–27.PubMedCrossRefGoogle Scholar
  27. 27.
    Kuizon BD, Goodman WG, Jiippner H, Boechat I, Nelson P, Gales B et al. Diminished linear growth during intermittent calcitriol therapy in children undergoing CCPD. Kidney Int. 1998;53:205–11.PubMedCrossRefGoogle Scholar
  28. 28.
    Schaefer F, Daschner M, Veldhuis JD, Oh J, Qadri F, Schärer K. In vivo alterations in the gonadotropin-releasing hormone pulse generator and the secretion and clearance of luteinizing hormone in the castrate uremic rat. Neuroendocrinology. 1994;59:285–96.PubMedCrossRefGoogle Scholar
  29. 29.
    Van Kämmen E, Thijssen JHH, Schwarz F. Sex hormones in male patients with chronic renal failure. I. The production of testosterone and androstendione. Clin Endocrinol. 1978;8:7–12.CrossRefGoogle Scholar
  30. 30.
    Lim VS, Sievertsen G, Kathpalie S, Frohman LA. Ovarian function in women with chronic renal failure: evidence suggesting central and end organ disturbances. Kidney Int. 1978; 14:679.Google Scholar
  31. 31.
    Schaefer F, Veldhuis JD, Robertson WR, Dunger D, Schärer K. Immunoreactive and bioactive luteinizing hormone in pubertal patients with chronic renal failure. Cooperative Study Group on Pubertal Development in Chronic Renal Failure. Kidney Int. 1994;45:1465–76.PubMedCrossRefGoogle Scholar
  32. 32.
    Green H, Morikawa M, Nixon T. A dual effector theory of growth-hormone action. Differentiation. 1985;29:195–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Strauss DS, Takemoto CD. Effect of fasting on insulin-like growth factor-I (IGF-I) and growth hormone receptor mRNA levels and IGF-I gene transcription in rat liver. Mol Endocrinol. 1990;4:91–100.CrossRefGoogle Scholar
  34. 34.
    Sjogren K, Liu JL, Blad K, Skrtic S, Vidal O, Wallenius V et al. Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci USA. 1999;96:7088–92.PubMedGoogle Scholar
  35. 35.
    Ueki I, Ooi GT, Tremblay ML, Hurst KR, Bach LA, Boisclair YR. Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system. Proc Natl Acad Sci USA. 2000;97:6868–73.PubMedCrossRefGoogle Scholar
  36. 36.
    Tönshoff B, Veldhuis JD, Heinrich U, Mehls O. Deconvolution analysis of spontaneous nocturnal growth hormone secretion in prepubertal children with chronic renal failure. Pediatr Res. 1995;37:86–93.PubMedCrossRefGoogle Scholar
  37. 37.
    Schaefer F, Veldhuis JD, Jones J, Schärer K. Alterations in growth hormone secretion and clearance in peripubertal boys with chronic renal failure and after renal transplantation. J Clin Endocrinol Metab. 1994;78:1298–306.PubMedCrossRefGoogle Scholar
  38. 38.
    Haffner D, Schaefer F, Girard J, Ritz E, Mehls O. Metabolie clearance of recombinant human growth hormone in health and chronic renal failure. J Clin Invest. 1994;93:1163–71.PubMedCrossRefGoogle Scholar
  39. 39.
    Tönshoff B, Blum WF, Wingen AM, 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. J Clin Endocrinol Metab. 1995;80:2684–91.PubMedCrossRefGoogle Scholar
  40. 40.
    Burch WM, Correa J, Shively JE, Powell DR. The 25-kilodalton insulin-like growth factor (IGF)-binding protein inhibits both basal and IGF-I mediated growth of chick embryo pelvic cartilage in children with end-stage renal disease. J Pediatr. 1990;4:561–66.Google Scholar
  41. 41.
    Tönshoff B, Powell DR, Zhao D, Durham SK, Coleman ME, Domene HM et al. Decreased hepatic insulin-like growth factor (IGF)-I and increased IGF binding protein-1 and-2 gene expression in experimental uremia. Endocrinology. 1997; 138:938–46.PubMedCrossRefGoogle Scholar
  42. 42.
    Tönshoff B, Cronin MJ, Reichert M, Haffner D, Wingen AM, Blum WF et al. Reduced concentration of serum growth hormone (GH)-binding protein in children with chronic renal failure: correlation with GH insensitivity. J Clin Endocrinol Metab. 1997;82:1007–13.PubMedCrossRefGoogle Scholar
  43. 43.
    Tönshoff B, Eden S, Weiser E, Carlsson B, Robinson IC, Blum WF, Mehls O et al. Reduced hepatic growth hormone (GH) receptor gene expression and increased plasma GH binding protein in experimental uremia. Kidney Int. 1994;45:1085–92.PubMedCrossRefGoogle Scholar
  44. 44.
    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. 2001;108:467–75.PubMedGoogle Scholar
  45. 45.
    Blum WF, Ranke MB, Kietzmann K, Tönshoff B, Mehls O. Growth hormone resistance and inhibition of somatomedin activity by excess of insulin-like growth factor binding protein in uraemia. Pediatr Nephrol. 1991;5:539–44.PubMedCrossRefGoogle Scholar
  46. 46.
    Ulinski T, Mohan S, Kiepe D, Blum WF, Wingen AM, Mehls O 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. Pediatr Nephrol. 2000;14:589–97.PubMedCrossRefGoogle Scholar
  47. 47.
    Powell DR, Liu F, Baker BK, Lee PD, Belsha CW, Brewer ED, Hintz RL. Characterization of insulin-like growth factor binding protein-3 in chronic renal failure serum. Pediatr Res. 1993;33:136–43.PubMedCrossRefGoogle Scholar
  48. 48.
    Strife CF, Quinlan M, Mears K, Davey ML, Clardy C. Improved growth of three uremic children by nocturnal nasogastric feedings. Am J Dis Child. 1986; 140:438–43.PubMedGoogle Scholar
  49. 49.
    Kleinknecht C, Broyer M, Gagnadoux M, Marti-Henneberg C, Dartois A, Kermanach C et al. Growth in children treated with long-term dialysis. A study of 76 patients. Adv Nephrol. 1980;9:133–66.Google Scholar
  50. 50.
    Trachtman H, Hackney P, Tejani A. Pediatric hemodialysis: a decade’s (1974-1984) perspective. Kidney Int. 1986;30:15–22.Google Scholar
  51. 51.
    Chantier C, Donckerwolcke RA, Brunner FP, Gurland HJ, Jacobs C, Seiwood NH et al. Combined report on regular dialysis and transplantation of children in Europe 1976. In: Robinson BHB, Hawkins JB, Vereerstraete P, editors. Dialysis Transplantation Nephrology. Vol. 14. Tunbridge Wells: Pitman Medical Publications, 1977: pp. 70–126.Google Scholar
  52. 52.
    Anonymous. Continuous ambulatory and continuous cycling peritoneal dialysis in children. A report of the Southwest Pediatric Nephrology Study Group. Kidney Int. 1985;27:558–64.CrossRefGoogle Scholar
  53. 53.
    von Lilien T, Gilli G, Salusky IB. Growth in children undergoing continuous ambulatory or cycling peritoneal dialysis. In: Schärer K, editor. Pediatric and Adolescent Endocrinology. Vol. 20. Basel: Karger; 1989,27–35.Google Scholar
  54. 54.
    Mehls O, Ritz E, Hunziker EB, Eggli P, Heinrich U, Zapf J. Improvement of growth and food utilization by human recombinant growth hormone in uremia. Kidney Int. 1988;33:45–52.PubMedCrossRefGoogle Scholar
  55. 55.
    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;124:374–82.PubMedCrossRefGoogle Scholar
  56. 56.
    Wingen AM, Fabian-Bach C, Schaefer F, Mehls O. Randomised multicentre study of a low protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood. Lancet. 1997;349:1117–23.PubMedCrossRefGoogle Scholar
  57. 57.
    Haffner D, Wühl E, Schaefer F, Nissel R, Tönshoff B, Mehls O. Factors predictive of the short-and long-term efficacy of growth hormone treatment in prepubertal children with chronic renal failure. German Study Group for Growth Hormone Treatment in Children with Chronic Renal Failure. J Am Soc Nephrol. 1998;9:1899–907.PubMedGoogle Scholar
  58. 58.
    Fine RN, Kohaut E, Brown D, Kuntze J, Attie KM. Long-term treatment of growth retarded children with chronic renal insufficiency, with recombinant human growth hormone. Kidney Int. 1996;49:781–5.PubMedCrossRefGoogle Scholar
  59. 59.
    Hokken-Koelega A, Mulder P, De Jong R, Lilien M, Donckerwolcke R, Groothof J. Long-term effects of growth hormone treatment on growth and puberty in patients with chronic renal insufficiency. Pediatr Nephrol. 2000;14:701–6.PubMedCrossRefGoogle Scholar
  60. 60.
    Wühl E, Haffner D, Tönshoff B, Mehls O. Predictors of growth response to rhGH in short children before and after renal transplantation. German Study Group for Growth Hormone Treatment in Chronic Renal Failure. Kidney Int. 1993;43:76–82.Google Scholar
  61. 61.
    Berard E, Crosnier H, Six-Beneton A, Chevallier T, Cochat P, Broyer M. Recombinant human growth hormone treatment of children on hemodialysis. French Society of Pediatric Nephrology. Pediatr Nephrol. 1998;12:304–10.PubMedCrossRefGoogle Scholar
  62. 62.
    Schaefer F, Wühl E, Haffner D, Mehls O, German Study Group for Growth Hormone Treatment in Chronic Renal Failure. Stimulation of growth hormone in children undergoing peritoneal or hemodialysis treatment. Adv Perit Dial. 1994;10:321–6.PubMedGoogle Scholar
  63. 63.
    Wühl E, Haffner D, Offner G, Broyer M, van’t Hoff WG, Mehls O, European Study Group on Growth Hormone Treatment in children with nephropatic cystinosis. Long-term treatment with growth hormone in short children with nephropatic cystinosis. J Pediatr. 2001;138:880–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Guest G, Berard E, Crosnier H, Chevallier T, Rappaport R, Broyer M. Effects of growth hormone in short children after renal transplantation. Pediatr Nephrol. 1998; 12:437–46.PubMedCrossRefGoogle Scholar
  65. 65.
    Haffner D, Wühl E, Tönshoff B, Mehls O. Growth hormone treatment in short children: 5-year experience German Study Group for Growth Hormone Treatment in Chronic Renal Failure. Nephrol Dial Transplant, 1994;9:960–1.Google Scholar
  66. 66.
    Hokken-Koelega AC, Stijnen T, de Muinck Keizer-Schrama SM, Wit JM, Wolff ED, de Jong MC et al. Placebo-controlled, double-blind, cross-over trial of growth hormone treatment in prepubertal children with chronic renal failure. Lancet. 1991;338:585–90.PubMedCrossRefGoogle Scholar
  67. 67.
    Haffner D, Schaefer F, Nissel R, Wühl E, Tönshoff B, Mehls O, German Study Group for Growth Hormone Treatment in Chronic Renal Failure. Effect of growth hormone treatment on adult height of children with chronic renal failure. N Engl J Med. 2000;343:923–30.PubMedCrossRefGoogle Scholar
  68. 68.
    Haffner D, Schaefer F. Does recombinant growth hormone improve adult height in children with chronic renal failure? Semin Nephrol. 2001;21:490–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2004

Authors and Affiliations

  • O. Mehls
  • F. S. Schaefer
  • B. Tönshoff

There are no affiliations available

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