UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Growth hormone metabolism in chronic kidney disease

Authors
Biff F Palmer, MD
William L Henrich, MD, MACP
Section Editor
Steve J Schwab, MD
Deputy Editor
Alice M Sheridan, MD

INTRODUCTION

Progression to end-stage renal disease is associated with a variety of abnormalities in growth hormone regulation, including changes in its plasma concentration, in the regulation of its release, and in end-organ responsiveness. As an example, the plasma growth hormone concentration is commonly elevated in chronic kidney disease due to the interplay of several factors [1,2].

Decreased renal clearance appears to play a major role in the genesis of this problem since filtered growth hormone is normally reabsorbed in and metabolized by the proximal tubule [3].

Enhanced growth hormone secretion also may contribute to the rise in plasma levels, although it is likely to be of lesser importance. Children with end-stage renal disease have an increase in the number of secretory bursts of growth hormone when compared with children with normal renal function [4]. Why this occurs is not clear, but protein-calorie malnutrition and stress may play a role.

Plasma growth hormone levels fall to low-normal values after the institution of maintenance dialysis, an effect that may be mediated in part by acetate (which has now been largely replaced by bicarbonate) in the dialysis bath [5]. For reasons that are not well understood, the administration of recombinant human erythropoietin also leads to a reduction in the basal concentration of growth hormone [6].

REGULATION OF GROWTH HORMONE RELEASE

A number of observations suggest that the hypothalamic-pituitary regulation of growth hormone is perturbed in chronic kidney disease [7]. As an example, normal individuals suppress growth hormone release in response to induced hyperglycemia; in contrast, glucose induces a paradoxical rise in growth hormone levels in advanced renal failure [8]. In addition, insulin-induced hypoglycemia, which is a potent stimulus to growth hormone release in normal subjects, elicits a blunted response in chronic kidney disease patients [9].

   

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Fri Feb 19 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Veldhuis JD, Johnson ML, Wilkowski MJ, et al. Neuroendocrine alterations in the somatotrophic axis in chronic renal failure. Acta Paediatr Scand Suppl 1991; 379:12.
  2. Kaskel F. Chronic renal disease: a growing problem. Kidney Int 2003; 64:1141.
  3. Johnson V, Maack T. Renal extraction, filtration, absorption, and catabolism of growth hormone. Am J Physiol 1977; 233:F185.
  4. Tönshoff B, Veldhuis JD, 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 1995; 37:86.
  5. Orskov H, Hansen AP, Hansen HE, et al. Acetate: inhibitor of growth hormone hypersecretion in diabetic and non-diabetic uraemic subjects. Acta Endocrinol (Copenh) 1982; 99:551.
  6. Kokot F, Wiecek A, Grzeszczak W, Klin M. Influence of erythropoietin treatment on function of the pituitary-adrenal axis and somatotropin secretion in hemodialyzed patients. Clin Nephrol 1990; 33:241.
  7. Ramirez G. Abnormalities in the hypothalamic-hypophyseal axes in patients with chronic renal failure. Semin Dial 1994; 7:138.
  8. Rodger RS, Dewar JH, Turner SJ, et al. Anterior pituitary dysfunction in patients with chronic renal failure treated by hemodialysis or continuous ambulatory peritoneal dialysis. Nephron 1986; 43:169.
  9. Ramirez G, O'Neill WM, Bloomer HA, Jubiz W. Abnormalities in the regulation of growth hormone in chronic renal failure. Arch Intern Med 1978; 138:267.
  10. Díez JJ, Iglesias PL, Sastre J, et al. Influence of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in uremic patients. Kidney Int 1994; 46:1387.
  11. Santos F, Chan JC, Krieg RJ, et al. Growth hormone secretion from pituitary cells in chronic renal insufficiency. Kidney Int 1992; 41:356.
  12. Metzger DL, Kerrigan JR, Krieg RJ Jr, et al. Alterations in the neuroendocrine control of growth hormone secretion in the uremic rat. Kidney Int 1993; 43:1042.
  13. Blum WF. Insulin-like growth factors (IGFs) and IGF binding proteins in chronic renal failure: evidence for reduced secretion of IGFs. Acta Paediatr Scand Suppl 1991; 379:24.
  14. Chan W, Valerie KC, Chan JC. Expression of insulin-like growth factor-1 in uremic rats: growth hormone resistance and nutritional intake. Kidney Int 1993; 43:790.
  15. Mak RH, Pak YK. End-organ resistance to growth hormone and IGF-I in epiphyseal chondrocytes of rats with chronic renal failure. Kidney Int 1996; 50:400.
  16. Tönshoff B, Edén S, Weiser E, et al. Reduced hepatic growth hormone (GH) receptor gene expression and increased plasma GH binding protein in experimental uremia. Kidney Int 1994; 45:1085.
  17. Rees L, Maxwell H. The hypothalamo-pituitary-growth hormone insulin-like growth factor 1 axis in children with chronic renal failure. Kidney Int Suppl 1996; 53:S109.
  18. Mehls O, Irzynjec T, Ritz E, et al. Effects of rhGH and rhIGF-1 on renal growth and morphology. Kidney Int 1993; 44:1251.
  19. Hanna JD, Santos F, Foreman JW, et al. Insulin-like growth factor-I gene expression in the tibial epiphyseal growth plate of growth hormone-treated uremic rats. Kidney Int 1995; 47:1374.
  20. Benfield MR, Parker KL, Waldo FB, et al. Growth hormone in the treatment of growth failure in children after renal transplantation. Kidney Int Suppl 1993; 43:S62.
  21. Kovács GT, Oh J, Kovács J, et al. Growth promoting effects of growth hormone and IGF-I are additive in experimental uremia. Kidney Int 1996; 49:1413.
  22. Fine RN. Recombinant human growth hormone in children with chronic renal insufficiency--clinical update: 1995. Kidney Int Suppl 1996; 53:S115.
  23. Challa A, Chan W, Krieg RJ Jr, et al. Effect of metabolic acidosis on the expression of insulin-like growth factor and growth hormone receptor. Kidney Int 1993; 44:1224.
  24. 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.
  25. Takano K, Hall K, Kastrup KW, et al. Serum somatomedin A in chronic renal failure. J Clin Endocrinol Metab 1979; 48:371.
  26. Goldberg AC, Trivedi B, Delmez JA, et al. Uremia reduces serum insulin-like growth factor I, increases insulin-like growth factor II, and modifies their serum protein binding. J Clin Endocrinol Metab 1982; 55:1040.
  27. Phillips LS, Kopple JD. Circulating somatomedin activity and sulfate levels in adults with normal and impaired kidney function. Metabolism 1981; 30:1091.
  28. Phillips LS, Fusco AC, Unterman TG, del Greco F. Somatomedin inhibitor in uremia. J Clin Endocrinol Metab 1984; 59:764.
  29. Fouque D. Insulin-like growth factor 1 resistance in chronic renal failure. Miner Electrolyte Metab 1996; 22:133.
  30. Fouque D, Le Bouc Y, Laville M, et al. Insulin-like growth factor-1 and its binding proteins during a low-protein diet in chronic renal failure. J Am Soc Nephrol 1995; 6:1427.
  31. Buyan N, Cinaz P, Hasanoğlu E, et al. Changes in serum levels of IGF-I and IGFBP-3 in children with chronic renal failure. Endocr J 1995; 42:429.
  32. Krieg RJ Jr, Santos F, Chan JC. Growth hormone, insulin-like growth factor and the kidney. Kidney Int 1995; 48:321.