Skip to main content
Log in

Effects of grwoth hormone therapy and malnutrition on the growth of rats with renal failure

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

Abstract

We examined the effects of methionylhuman growth hormone (met-hGH) and malnutrition on the growth of 5/6 nephrectomized rats and sham-operated controls. One group of shamoperated rats (PFS) was pair-fed with a group of nephrectomized rats in renal failure (RF); another group of sham-operated rats was fed ad libitum (ALS), and a final group of rats with renal failure (RF-GH) was treated with 4 IU/day met-hGH. After 4 weeks, RF-GH rats gained 12.3±1.7 cm in length; this was more than the 10.2±1.2 cm gain of RF rats (P<0.05). Ingested food was converted into weight gain more efficiently by RF-GH rats than RF rats (267±26 vs 235±38 mg weight gain/g food intake,P<0.05). RF-GH rats also gained more weight (122±25 g) than RF rats (98±27 g), but this difference was not significant (0.05<P<0.1). Insulin-like growth factor (IGF)-I, glucose and insulin levels were not different between RF and RF-GH rats. Food intake of RF and PFS rats was 64% of ALS intake and was associated with poor gains in weight and length by the PFS and RF groups (relative weight and length gains were ALS>PFS>RF,P<0.05 for all comparisons); this suggests that the poor growth of RF rats when compared with PFS rats was due to factors other, than food intake. Serum IGF-I levels of 771±249 ng/ml in PFS rats were lower than levels of 1109±253 ng/ml found in the ALS group (P<0.05); this is consistent with the malnourished state of PFS rats. Serum IGF-I levels in RF rats (950±236 ng/ml) were not different from ALS or PFS levels despite the fact that RF rats gained less weight and length than either the ALS or PFS rats. We conclude that RF rats increase in length, use ingested calories more efficiently, and fail to develop marked insulin resistance when treated with met-hGH. We find that, in addition to poor food intake, other factors contribute to growth failure in this model of renal failure. Finally, we find that RF rats have normal levels of IGF-I, suggesting that low IGF-I levels are not a major cause of growth failure in rats with renal failure.

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. Potter D, Greifer I (1978) Statural growth in children with renal disease. Kidney Int 14: 334–339

    Google Scholar 

  2. Betts PR, Magrath G (1974) Growth pattern and dietary intake in children with chronic renal renal insufficiency. Br Med J 2: 189–193

    Google Scholar 

  3. Broyer M (1982) Growth in children with renal insufficiency. Pediatr Clin North Am 29: 991–1003

    Google Scholar 

  4. Simmons JM, Wilson CJ, Potter DE, Holliday MA (1971) Relation of calorie deficiency to growth failure in children on hemodialysis and the growth response to calorie supplementation. N Engl J Med 285: 653–656

    Google Scholar 

  5. Arnold WC, Danford D, Holliday MA (1983) Effect of caloric supplementation on growth in children with uremia. Kidney Int 24: 205–209

    Google Scholar 

  6. Guillot M, Broyer M, Cathelineau L (1980) Nutrition enterale a debit constant en nephrologie pediatrique. Arch Fr Pediatr 37: 479–485

    Google Scholar 

  7. Mehls O, Ritz E, Gilli G, Bartholome K, Beissbarth H, Hohenegger M, Schafnitzel W (1980) Nitrogen metabolism and growth in experimental uremia. Int J Pediatr Nephrol 1: 34–42

    Google Scholar 

  8. Wang M, Vyhmeister I, Kopple JD, Swendseid ME (1976) Effect of protein intake on weight gain and plasma amino acid levels in uremic rats. Am J Physiol. 230: 1455–1459

    Google Scholar 

  9. Schalch DS, Burstein PJ, Tewel SJ, Draznin B, Emler CA (1981) The effect of renal impairment on growth in the rat: relationship to malnutrition and serum somatomedin levels. Endocrinology 108: 1683–1689

    Google Scholar 

  10. Schoenle E, Zapf J, Humbel RE, Froesch ER (1982) Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature 296: 252–253

    Google Scholar 

  11. Scheiwiller E, Guler H-P, Merryweather J, Scandella C, Maerkl W, Zapf J, Froesch ER (1986) Growth restoration of insulin-deficient diabetic rats by, recombinant human insulin-like, growth factor I. Nature 323: 169–171

    Google Scholar 

  12. Maes M, Underwood L, Gerard G, Ketelslegers J-M (1984) Relationship between plasma somatomedin-C and liver somatogenic binding sites in neonatal rats during malnutrition and after short and long term refeeding. Endocrinology 115: 786–792

    Google Scholar 

  13. Goldberg A, Trivedi B, Delmez J, Harter H, Daughaday WH (1982) Uremia reduces insulin-like growth factor-I, increases insulin-like growth factor-II and modifies their serum protein binding. J Clin Endocrinol Metab 55: 1040–1045

    Google Scholar 

  14. Lynch R, Furlanetto RW, Travis L, Cinningham R, Mauer S (1983) Serum RIA-somatomedin-C (Sm-C) is depressed in children and adolescents with end stage renal disease. Kidney Int 23: 217

    Google Scholar 

  15. Mehls O, Ritz E (1983) Skeletal growth in experimental uremia. Kidney Int [Suppl] 15: S53-S60

    Google Scholar 

  16. Powell DR, Rosenfeld RG, Baker B, Hintz RL (1986) Serum somatomedin levels in adults with chronic renal failure: the importance of measuring insulin-like growth factor (IGF)-I and IGF-II in acid chormatographed uremic serum. J Clin Endocrinol Metab 63: 1186–1192

    Google Scholar 

  17. Powell DR, Rosenfeld RG, Sperry JB, Baker BK, Hintz RL (1987) Serum concentrations of insulin-like growth factor (IGF)-I, IGF-2 and unsaturated somatomedin carrier proteins in children with chronic renal failure. Am J Kidney Dis 10: 287–292

    Google Scholar 

  18. Phillips LS, Fusco AC, Unterman, TG, DelGreco F (1984) Somatomedin inhibitor in uremia. J Clin Endocrinol Metab 59: 764–772

    Google Scholar 

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

    Google Scholar 

  20. El-Bishti MM, Counahan R, Bloom SR, Chantler C (1978) Hormonal and metabolic responses to intravenous glucose in children on regular dialysis. Am J Clin Nutr 31: 1865–1869

    Google Scholar 

  21. Westervelt FB (1968) Abnormal carbohydrate metabolism in uremia. Am J Clin Nutr 21: 423–427

    Google Scholar 

  22. DeFronzo RA, Alvestrand A, Smith D, Hendler R, Hendler E, Wahren J (1980) Glucose intolerance in uremia: site and mechanism. Am J Clin Nutr 33: 1438–1445

    Google Scholar 

  23. Laouari D, Kleinknecht C, Gubler MC, Ravet V, Broyer M (1982) Effect of protein intake on the growth of uremic rats. Int J Pediatr Nephrol 3: 263–269

    Google Scholar 

  24. Flodh H, Johansson H-E, Jonsson M, Ekvarn S (1982) General toxicity in rats of biosynthetic and pituitary human growth hormones. In: Gueriguian J (ed) Hormone drugs. US Pharmacopeial Convention, pp 327–334

  25. Furlanetto RW, Underwood LE, Van Wyk JJ, D'Ercole AJ (1977) Estimation of Sm-C levels in normals and patients with pituitary disease by RIA. J Clin Invest 60: 648–657

    Google Scholar 

  26. Rosenfeld RG, Dollar LA (1982) Characterization, of the somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) receptor on cultured human fibroblast monolayers: regulation of receptor concentrations by Sm-C/IGF-I and insulin. J Clin Endocrinol Metab 55: 434–440

    Google Scholar 

  27. Hunter WM, Greenwood FC (1962) Preparation of iodine-131 labeled human growth hormone of high specific activity. Nature 194: 495–496

    Google Scholar 

  28. Thorell JI, Larson SM (1978) Radioimmunoassay and related techniques. Mosby, St. Louis, p 271

    Google Scholar 

  29. Hales CN, Randle PJ (1963) Immunoassay of insulin with insulin-antibody precipitate. Biochem J 88: 137–145

    Google Scholar 

  30. Wright A, Lowy G, Fraser T, Spitz I, Rubenstein A, Bersohn I (1968) Serum growth hormone and glucose intolerance in renal failure. Lancet II: 798–800

    Google Scholar 

  31. Rosenfeld RG, Wilson DM, Dollar LA, Bennett A, Hintz RL (1982) Both human pituitary growth hormone and recombinant DNA-derived human growth hormone cause insulin resistance at a postreceptor site. J Clin Endocrinol Metab 54: 1033–1038

    Google Scholar 

  32. Isakson OG, Lindahl A, Nilsson A, Isgaard J (1987) Mechanism of the stimulatory effect of growth hormone on longitudinal bone growth. Endocr Rev 8: 426–438

    Google Scholar 

  33. Kemp SF, Rosenfeld RG, Liu F, Gaspich S, Hintz RL (1981) Acute somatomedin response to growth hormone: radioreceptor assay versus radioimmunoassay. J Clin Endocrinol Metab 52: 616–621

    Google Scholar 

  34. Reddan JR, Dziedzic DC (1982) Insulin-like growth factors, IGF-1, IGF-2 and somatomedin-C trigger cell proliferation in mammalian epithelial cells cultured in serum free medium. Exp Cell Res 142: 293–300

    Google Scholar 

  35. Soliman AT, Hassan AI, Aref MK, Hintz RL, Rosenfeld RG, Rogol AD (1986) Serum insulin-like growth factors I and II concentrations and growth hormone and insulin responses to arginine infusion in children with protein-energy malnutrition before and after nutritional rehabilitation. Pediatr Res 20: 1122–1128

    Google Scholar 

  36. Schimpff RM, Donnadieu M, Gourmelen M, Girard F (1974) The effects of hGH treatment on somatomedin levels in serum. Horm Metab Res 6: 494–498

    Google Scholar 

  37. Powell DR, Lee PDK, Chang D, Liu F, Hintz RL (1987) Antiserum developed for the E peptide of insulin-like growth factor IA prohormone recognizes a serum protein by both immunoblot and radioimmunoassay. J Clin Endocrinol Metab 65: 868–875

    Google Scholar 

  38. Baxter RC, Martin JL (1986) Radioimmunoassay of growth hormone-dependent insulinike growth factor binding protein in human plasma. J Clin Invest 78: 1504–1512

    Google Scholar 

  39. Gertner JM, Horst RL, Broadus AE, Rasmussen H, Genel M (1979) Parathyroid function and vitamin D metabolism during human growth hormone replacement. J Clin Endocrinol Metab 49: 185–188

    Google Scholar 

  40. Christiansen JS, Gammelgaard J, Frandsen M, Orskov H, Parving H-H (1982) Kidney function and size in type I (insulin-dependent) diabetic patients before and during growth hormone administration for one week. Diabetologia 22: 333–337

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Powell, D.R., Rosenfeld, R.G. & Hintz, R.L. Effects of grwoth hormone therapy and malnutrition on the growth of rats with renal failure. Pediatr Nephrol 2, 425–430 (1988). https://doi.org/10.1007/BF00853436

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00853436

Key words

Navigation