Skip to main content
Log in

Acidosis prevents growth hormone-induced growth in experimental uremia

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

The effects of 2 weeks of a daily injection (2 IU/day) of recombinant human growth hormone (GH) were studied in young (60-g) growing rats in two experiments. Experiment 1 was performed in uremic animals (mean plasma creatinine 65–71 μmol/l) who were either acidotic (mean bicarbonate 11.5 mmol/l) or had acidosis corrected (mean bicarbonate 26 mmol/l) by addition of sodium bicarbonate to the diet. Experiment 2 used rats with normal renal function (plasma creatinine 25 μmol/l) who were either non-acidotic but restricted to the dietary intake of uremic rats or rendered acidotic by ammonium chloride. GH induced an increase in body weight and length in nonacidotic uremic (+33% and +41%) and in non-acidotic food-restricted (+13% and +42%) rats, associated with an increased rate of protein synthesis and little change in plasma insulin-like growth factor 1 (IGF 1). In both acidotic rat groups, GH altered none of the parameters studied. Thus: (1) the presence of severe metabolic acidosis blunts the response to GH in uremic and non-uremic rats and (2) the increment of growth rate does not depend on a rise in plasma IGF 1.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Samaan N, Freeman RM (1970) Growth hormone levels in severe renal failure. Metabolism 19: 102–113

    PubMed  Google Scholar 

  2. Rees L, Rigden SPA, Ward G, Preece MA (1990) Treatment of short stature in renal disease with recombinant human growth hormone. Arch Dis Child 65: 856–860

    PubMed  Google Scholar 

  3. Tonshoff B, Mehls O, Heinrich U, Blum WF, Ranke MB, Shaner A (1990) Growth stimulating effects of recombinant human growth hormone in children with end-stage renal disease. J Pediatr 116: 561–566

    PubMed  Google Scholar 

  4. Fine RN, Koch VH, Nelson PA, et al (1990) Recombinant human growth hormone (rhGH) treatment of children with renal insufficiency. Adv Nephrol 19: 187–208

    Google Scholar 

  5. Hokken-Koelaga ACS, Stijnen T, De Muinck Kreizer-Schrama SMPF, Wet JM, Wolff ED, DeJong MCJW, Donckerwolke RA, Abbad NCB, Bot A, Blum WF, Prop SLS (1991) Placebo-controlled, double-blind, cross-over trial of growth hormone treatment in prepubertal children with chronic renal failure. Lancet 338: 585–590

    PubMed  Google Scholar 

  6. Mehls O, Ritz E, Hunziker EB, Eggli P, Heinrich U, Zapf J (1988) Improvement of growth and food utilization by human recombinant growth hormone in uremia. Kidney Int 33: 45–52

    PubMed  Google Scholar 

  7. Powell DR, Rosenfeld RG, Hintz RL (1988) Effects of growth hormone therapy and malnutrition on the growth of rats with renal failure. Pediatr Nephrol 2: 425–430

    PubMed  Google Scholar 

  8. Nakano M, Kainer G, Foreman JW, Daijin K, Chan JC (1989) The effects of exogenous rat growth hormone therapy on growth of uremic rats fed an 8% protein diet. Pediatr Res 26: 204–207

    PubMed  Google Scholar 

  9. Allen DB, Fogo A, El-Hayek R, Langhough R, Friedman AL (1992) Effects of prolonged grwoth hormone administration in rats with chronic renal insufficiency. Pediatr Res 31: 406–410

    PubMed  Google Scholar 

  10. Mehls O, Irzynjec T, Ritz E, Eden S, Kovacs G, Klaus G, Floege J, Mall G (1993) Effect of rhGH and rhIGF-I on renal growth and morphology. Kidney Int 44: 1251–1258

    PubMed  Google Scholar 

  11. Tizianello A, De Ferri G, Garibotto G, Gurreri G (1978) Effects of chronic renal insufficiency and metabolic acidosis on glutamine metabolism in man. Clin Sci Mol Med 55: 391–397

    PubMed  Google Scholar 

  12. May RC, Kelly RA, Mitch WE (1986) Metabolic acidosis stimulates protein degradation in rat muscle by a glucocorticoid-dependent mechanism. J Clin Invest 77: 614–621

    PubMed  Google Scholar 

  13. May RC, Kelly RA, Mitch WE (1987) Mechanisms for defects in muscle protein metabolism in rats with chronic uremia. J Clin Invest 79: 1099–1103

    PubMed  Google Scholar 

  14. Maniar S, Laouari D, Déchaux M, Motel V, Yvert JP, Mathian B, Kleinknecht C (1994) In vivo unaltered muscle protein synthesis in experimental chronic metabolic acidosis. Kidney Int 46: 1705–1712

    PubMed  Google Scholar 

  15. May RC, Masud T, Logue B, Bailey S, England B (1992) Chronic metabolic acidosis accelerates whole body proteolysis and oxidation in awake rats. Kidney Int 41: 1535–1542

    PubMed  Google Scholar 

  16. Reaich D, Channon SM, Scrimgeour CM, Goodship THJ (1992) Ammonium chloride-induced acidosis increases protein breakdown and amino acid oxidation in humans. Am J Physiol 263: E735-E739

    PubMed  Google Scholar 

  17. Reaich D, Channon SM, Scrimgeour CM, Goodship THJ (1993) Correction of acidosis in humans with CRF decreases protein degradation and amino acid oxidation. Am J Physiol 265: E230-E235

    PubMed  Google Scholar 

  18. Flaim KE, Li JB, Jefferson LS (1978) Protein turnover in rat skeletal muscle: effects of hypophysectomy and growth hormone. Am J Physiol 3: E38-E43

    Google Scholar 

  19. Fryburg DA, Gelfand RA, Barrett EJ (1991) Growth hormone acutely stimulates forearm muscle protein synthesis in normal humans. Am J Physiol 260: E499-E504

    PubMed  Google Scholar 

  20. Horber FF, Haymond MH (1990) Human growth hormone prevents the protein catabolic side effects of prednisone in humans. J Clin Invest 86: 265–272

    PubMed  Google Scholar 

  21. Kovàcs G, Fine RN, Worgall S, Schaeffer F, Huntiker EB, Skottner-Lindun A, Mehls O (1991) Growth hormone prevents steroid-induced grwoth depression in health and uremia. Kidney Int 40: 1032–1040

    PubMed  Google Scholar 

  22. Breier BH, Gallaher BW, Gluckman PD (1991) Radioimmunoassay for insulin-like growth factor-1: solutions to some potential problems and pitfalls. J Endocrinol 128: 347–357

    PubMed  Google Scholar 

  23. Garlick PJ, McNurlan MA, Preedy VR (1980) A rapid and convenient technique for measuring the rate of protein synthesis in tissue by injection of [3H]phenylalanine. Biochem J 192: 719–723

    PubMed  Google Scholar 

  24. Challa A, Krieg RJ Jr, Thabet MA, Veldhuis JD, Chan JCM (1993) Metabolic acidosis inhibits growth hormone secretion in rats: mechanism of growth retardation. Am J Physiol 265: E547-E553

    PubMed  Google Scholar 

  25. Caldas A, Fontoura M (1993) Effects of chronic metabolic acidosis in 24-hour growth hormone secretion (abstract). J Am Soc Nephrol 4: 828

    Google Scholar 

  26. Martin AA, Thomas FM, Owens PC, Knowles SE, Ballard FJ, Read LC (1991) IGF-1 and its variant, des-(1–3)IGF-1, enhance growth in rats with reduced renal mass. Am J Physiol 261: F626-F633

    PubMed  Google Scholar 

  27. Villares SMF, Goujon L, Maniar S, Delehaye-Zervas MC, Martini JF, Kleinknecht C, Postel-Vinay MC (1994) Reduced food intake is the main cause of low growth hormone receptor expression in uremic rats. Mol Cell Endocrinol 106: 51–56

    PubMed  Google Scholar 

  28. Finidori J, Postel-Vinay MC, Kleinknecht C (1980) Lactogenic and somatotropic binding sites in liver membranes of rats with chronic renal insufficiency. Endocrinology 106: 1960–1965

    PubMed  Google Scholar 

  29. Challa A, Chan W, Krieg RJ, Thabet AM, Liu F, Hintz RL, Chan JCM (1993) Effect of metabolic acidosis on the expression of insulin-like growth factor and growth hormone receptor. Kidney Int 44: 1224–1227

    PubMed  Google Scholar 

  30. Chan W, Valerie KC, Chan JCM (1993) Expression of insulin-like growth factor-1 in uremic rats: growth hormone resistance and nutritional intake. Kidney Int 43: 790–795

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kleinknecht, C., Maniar, S., Zhou, X. et al. Acidosis prevents growth hormone-induced growth in experimental uremia. Pediatr Nephrol 10, 256–260 (1996). https://doi.org/10.1007/BF00866751

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00866751

Key words

Navigation