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Short-term Protein Loading in Diabetics With a Ten-Year Duration of Disease

Short-term Protein Loading in Diabetics With a Ten-Year Duration of Disease Abstract • The concept of renal functional reserve has recently been introduced. To test this ability of the kidneys to increase the glomerular filtration rate (GFR) above the baseline level, the GFR response to short-term protein load was measured. Recent studies have provided conflicting data concerning the GFR response to a protein load in insulin-dependent diabetics who are known to have increased baseline GFRs. Thus, we studied nine insulin-dependent diabetics with a disease of at least a ten-year duration (none were hypertensive or proteinuric) and compared their data with those of five nondiabetic controls with normal renal function. All the diabetics, except one, showed a significant increase in GFR (mean ± SEM, 60±9 to 74±14 mL/min/sq m); the controls also had increased GFRs (mean± SEM, 53±6 to 69±6 mL/min/sq m). The one patient who demonstrated no rise in the GFR had the lowest GFR measured, 33 mL/min/sq m. To explore the mechanism of this response, we measured the plasma levels of putative mediators glucagon and human growth hormone. Although glucagon showed the expected rise after the protein meal, the variability was so large that no statistically significant relationship could be identified. Human growth hormone remained constant and low in the controls and showed more variability and was higher in the diabetics; again, no relationship to the GFR could be demonstrated. Thus, our data demonstrated a normal response to a short-term protein load by a group of well-defined diabetic subjects who would be at risk to show subtle renal abnormalities. (AJDC 1986;140:473-476) References 1. Brenner BM, Meyer TW, Hostetler TH: Dietary protein intake and the progressive nature of renal disease: The rate of hemodynamically mediated injury in the pathogenesis of progressive glomerulosclerosis in aging, renal ablation and intrinsic renal disease . N Engl J Med 1982;307:652-659.Crossref 2. Machio G, Oldrizzi L, Tessitore N, et al: Effects of dietary protein and phosphorus restriction on the progression of early renal failure . Kidney Int 1982;22:371-376.Crossref 3. Oldrizzi L, Rugiu C, Valvo E, et al: Progression of renal failure in patients with renal disease of diverse etiology on protein-restricted diet . Kidney Int 1985;27:553-557.Crossref 4. Hostetler TH, Olson JL, Rennke HG, et al: Hyperfiltration in remnant nephrons: A potentially adverse response to renal ablation . Am J Physiol 1981;241:F85-F93. 5. Friend PS, Fernandez G, Good RA, et al: Dietary restrictions early and late: Effects on the nephropathy of the NZB × NZW mouse . Lab Invest 1978;38:629-632. 6. Berg BN, Simms HS: Nutrition and longevity in the rats: II. Longevity and onset of disease with different levels of food intake . J Nutr 1960;71:255-263. 7. Kleinknecht C, Salusky I, Broyer M, et al: Effect of various protein diets on growth, renal function and survival of uremic rats . Kidney Int 1979;15:534-541.Crossref 8. Bosch JP, Saccaggi A, Lauer A, et al: Renal functional reserve in humans: Effect of protein intake on glomerular filtration rate . Am J Med 1983;75:943-950.Crossref 9. Davison JM, Hytten FE: Glomerular filtration during and after pregnancy . J Obstet Gynaecol Br Commonw 1974;81:588-595.Crossref 10. Vincente F, Amend WJC, Kaysen G, et al: Long-term renal function in kidney donors: Sustained compensatory hyperfiltration with no adverse effects . Transplantation 1983;36:626-629.Crossref 11. Mogensen CE: Renal function changes in diabetes . Diabetes 1976;25:872-879. 12. Wiseman MJ, Saunder AJ, Keen N, et al: Effect of blood glucose control on increased glomerular filtration rate and kidney size in insulin-dependent diabetes . N Engl J Med 1985;312:617-621.Crossref 13. Zatz R, Meyer TW, Noddin JL, et al: Dietary protein restriction limits glomerular hyperfiltration in experimental diabetes . Kidney Int 1985;25:255. 14. Hostetler TH, Rennke HG, Brenner BM: The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies . Am J Med 1982;72:375-380.Crossref 15. Bosch JP, Lauer A, Glabman S: Short-term protein loading in assessment of patients with renal disease . Am J Med 1984;77:873-879.Crossref 16. Lauer A, Lew S, Glabman S, et al: Protein loading in diabetic patients: Paradoxical effect on glomerular filtration rate (GFR) . Kidney Int 1984;25:248. 17. Brouhard BH, Travis LB, Cunningham RJ, et al: Simultaneous iothalamate, creatinine, and urea clearances in children with renal disease . Pediatrics 1977;59:219-223. 18. Blythe WB: The endogenous creatinine clearance . Am J Kidney Dis 1982;2:321-323.Crossref 19. Schreiner GE: Determination of inulin by means of resorcinal . Proc Soc Exp Biol Med 1950;74:117-119.Crossref 20. Brouhard BH, Allen K, Sapire D, et al: Effect of exercise on urinary N-acetyl-beta-D-glucosaminidase and albumin excretion in children with type I diabetes mellitus . Diabetes Care 1985;8:466-472.Crossref 21. Faloona GR, Unger RH: Glucagon , in Jaffe BM, Behrman HP (eds): Methods of Radioimmunoassay . Orlando, Fla, Academic Press Inc, 1974, chap 18, p 317. 22. Mogensen CE, Christensen CK, Vittinghus E: The stages of diabetic renal disease . Diabetes 1983;32( (suppl 2) ):64-78.Crossref 23. Rodriguez-Iturbe B, Herrera J, Garcia R: Response to acute protein load in kidney donors and in apparently normal post-acute glomerulonephritis patients: Evidence of glomerular hyperfiltration . Lancet 1985;2:461-464.Crossref 24. Viberti GC, Bognetti E, Wiseman MJ: Renal response to protein loading and modulating effect of plasma glucose in insulin-dependent diabetics with high and normal glomerular filtration rate . Kidney Int 1985;27:258A. 25. Levy M: Further observations on the response of the glomerular filtration rate to glucagon: Comparison with secretin . Can J Physiol Pharmacol 1975;53:81-85.Crossref 26. Muller WA, Faloona GR, Aguilar-Parada E, et al: Abnormal alpha-cell function in diabetes: Response to carbohydrate and protein ingestion . N Engl J Med 1970;283:109-116.Crossref 27. Kleinman KS, Glassock RJ: GFR fails to increase following protein ingestion in growth hormone deficient adults . Kidney Int 1985;27: 201A. 28. Alvestrand A, Bergstrom J: Glomerular hyperfiltration after protein ingestion, during glucagon infusion, and insulin-dependent diabetes is induced by a liver hormone: Deficient production of this hormone in hepatic failure causes hepatorenal syndrome . Lancet 1984;1: 195-197.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Diseases of Children American Medical Association

Short-term Protein Loading in Diabetics With a Ten-Year Duration of Disease

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Publisher
American Medical Association
Copyright
Copyright © 1986 American Medical Association. All Rights Reserved.
ISSN
0002-922X
DOI
10.1001/archpedi.1986.02140190083032
Publisher site
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Abstract

Abstract • The concept of renal functional reserve has recently been introduced. To test this ability of the kidneys to increase the glomerular filtration rate (GFR) above the baseline level, the GFR response to short-term protein load was measured. Recent studies have provided conflicting data concerning the GFR response to a protein load in insulin-dependent diabetics who are known to have increased baseline GFRs. Thus, we studied nine insulin-dependent diabetics with a disease of at least a ten-year duration (none were hypertensive or proteinuric) and compared their data with those of five nondiabetic controls with normal renal function. All the diabetics, except one, showed a significant increase in GFR (mean ± SEM, 60±9 to 74±14 mL/min/sq m); the controls also had increased GFRs (mean± SEM, 53±6 to 69±6 mL/min/sq m). The one patient who demonstrated no rise in the GFR had the lowest GFR measured, 33 mL/min/sq m. To explore the mechanism of this response, we measured the plasma levels of putative mediators glucagon and human growth hormone. Although glucagon showed the expected rise after the protein meal, the variability was so large that no statistically significant relationship could be identified. Human growth hormone remained constant and low in the controls and showed more variability and was higher in the diabetics; again, no relationship to the GFR could be demonstrated. Thus, our data demonstrated a normal response to a short-term protein load by a group of well-defined diabetic subjects who would be at risk to show subtle renal abnormalities. (AJDC 1986;140:473-476) References 1. Brenner BM, Meyer TW, Hostetler TH: Dietary protein intake and the progressive nature of renal disease: The rate of hemodynamically mediated injury in the pathogenesis of progressive glomerulosclerosis in aging, renal ablation and intrinsic renal disease . N Engl J Med 1982;307:652-659.Crossref 2. Machio G, Oldrizzi L, Tessitore N, et al: Effects of dietary protein and phosphorus restriction on the progression of early renal failure . Kidney Int 1982;22:371-376.Crossref 3. Oldrizzi L, Rugiu C, Valvo E, et al: Progression of renal failure in patients with renal disease of diverse etiology on protein-restricted diet . Kidney Int 1985;27:553-557.Crossref 4. Hostetler TH, Olson JL, Rennke HG, et al: Hyperfiltration in remnant nephrons: A potentially adverse response to renal ablation . Am J Physiol 1981;241:F85-F93. 5. Friend PS, Fernandez G, Good RA, et al: Dietary restrictions early and late: Effects on the nephropathy of the NZB × NZW mouse . Lab Invest 1978;38:629-632. 6. Berg BN, Simms HS: Nutrition and longevity in the rats: II. Longevity and onset of disease with different levels of food intake . J Nutr 1960;71:255-263. 7. Kleinknecht C, Salusky I, Broyer M, et al: Effect of various protein diets on growth, renal function and survival of uremic rats . Kidney Int 1979;15:534-541.Crossref 8. Bosch JP, Saccaggi A, Lauer A, et al: Renal functional reserve in humans: Effect of protein intake on glomerular filtration rate . Am J Med 1983;75:943-950.Crossref 9. Davison JM, Hytten FE: Glomerular filtration during and after pregnancy . J Obstet Gynaecol Br Commonw 1974;81:588-595.Crossref 10. Vincente F, Amend WJC, Kaysen G, et al: Long-term renal function in kidney donors: Sustained compensatory hyperfiltration with no adverse effects . Transplantation 1983;36:626-629.Crossref 11. Mogensen CE: Renal function changes in diabetes . Diabetes 1976;25:872-879. 12. Wiseman MJ, Saunder AJ, Keen N, et al: Effect of blood glucose control on increased glomerular filtration rate and kidney size in insulin-dependent diabetes . N Engl J Med 1985;312:617-621.Crossref 13. Zatz R, Meyer TW, Noddin JL, et al: Dietary protein restriction limits glomerular hyperfiltration in experimental diabetes . Kidney Int 1985;25:255. 14. Hostetler TH, Rennke HG, Brenner BM: The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies . Am J Med 1982;72:375-380.Crossref 15. Bosch JP, Lauer A, Glabman S: Short-term protein loading in assessment of patients with renal disease . Am J Med 1984;77:873-879.Crossref 16. Lauer A, Lew S, Glabman S, et al: Protein loading in diabetic patients: Paradoxical effect on glomerular filtration rate (GFR) . Kidney Int 1984;25:248. 17. Brouhard BH, Travis LB, Cunningham RJ, et al: Simultaneous iothalamate, creatinine, and urea clearances in children with renal disease . Pediatrics 1977;59:219-223. 18. Blythe WB: The endogenous creatinine clearance . Am J Kidney Dis 1982;2:321-323.Crossref 19. Schreiner GE: Determination of inulin by means of resorcinal . Proc Soc Exp Biol Med 1950;74:117-119.Crossref 20. Brouhard BH, Allen K, Sapire D, et al: Effect of exercise on urinary N-acetyl-beta-D-glucosaminidase and albumin excretion in children with type I diabetes mellitus . Diabetes Care 1985;8:466-472.Crossref 21. Faloona GR, Unger RH: Glucagon , in Jaffe BM, Behrman HP (eds): Methods of Radioimmunoassay . Orlando, Fla, Academic Press Inc, 1974, chap 18, p 317. 22. Mogensen CE, Christensen CK, Vittinghus E: The stages of diabetic renal disease . Diabetes 1983;32( (suppl 2) ):64-78.Crossref 23. Rodriguez-Iturbe B, Herrera J, Garcia R: Response to acute protein load in kidney donors and in apparently normal post-acute glomerulonephritis patients: Evidence of glomerular hyperfiltration . Lancet 1985;2:461-464.Crossref 24. Viberti GC, Bognetti E, Wiseman MJ: Renal response to protein loading and modulating effect of plasma glucose in insulin-dependent diabetics with high and normal glomerular filtration rate . Kidney Int 1985;27:258A. 25. Levy M: Further observations on the response of the glomerular filtration rate to glucagon: Comparison with secretin . Can J Physiol Pharmacol 1975;53:81-85.Crossref 26. Muller WA, Faloona GR, Aguilar-Parada E, et al: Abnormal alpha-cell function in diabetes: Response to carbohydrate and protein ingestion . N Engl J Med 1970;283:109-116.Crossref 27. Kleinman KS, Glassock RJ: GFR fails to increase following protein ingestion in growth hormone deficient adults . Kidney Int 1985;27: 201A. 28. Alvestrand A, Bergstrom J: Glomerular hyperfiltration after protein ingestion, during glucagon infusion, and insulin-dependent diabetes is induced by a liver hormone: Deficient production of this hormone in hepatic failure causes hepatorenal syndrome . Lancet 1984;1: 195-197.Crossref

Journal

American Journal of Diseases of ChildrenAmerican Medical Association

Published: May 1, 1986

References