Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 Aug;88(2):524–530. doi: 10.1172/JCI115335

Glomerular function in Pima Indians with noninsulin-dependent diabetes mellitus of recent onset.

B D Myers 1, R G Nelson 1, G W Williams 1, P H Bennett 1, S A Hardy 1, R L Berg 1, N Loon 1, W C Knowler 1, W E Mitch 1
PMCID: PMC295379  PMID: 1864963

Abstract

Differential solute clearances were used to characterize glomerular function in 20 Pima Indians with noninsulin-dependent diabetes mellitus (NIDDM) of less than 3 yr duration. 28 Pima Indians with normal glucose tolerance served as controls. In the diabetic group, the glomerular filtration rate (GFR, iothalamate clearance) exceeded the control value by 15% (140 +/- 6 vs. 122 +/- 5 ml/min, P less than 0.01). A corresponding 12% increase in renal plasma flow (RPF) was not statistically significant and did not account fully for the observed hyperfiltration, suggesting a concomitant elevation of the ultrafiltration pressure or coefficient. The median albumin excretion ratio in NIDDM exceeded control by almost twofold (10.1 vs. 5.8 mg/g creatinine), a trend which just failed to achieve statistical significance (P = 0.06). Fractional clearances of dextrans of broad size distribution were also elevated in diabetic subjects, significantly so for larger dextrans of between 48 and 60 A radius. A theoretical analysis of dextran transport through a heteroporous membrane revealed glomerular pores in NIDDM to be uniformly shifted towards pores of larger size than in controls. We conclude that an impairment of barrier size selectivity combined with high GFR elevates the filtered protein load in NIDDM of recent onset. We propose that enhanced transglomerular trafficking of protein may predispose to sclerosis of glomeruli in those Pima Indians with NIDDM who ultimately develop diabetic nephropathy.

Full text

PDF
524

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chang R. L., Ueki I. F., Troy J. L., Deen W. M., Robertson C. R., Brenner B. M. Permselectivity of the glomerular capillary wall to macromolecules. II. Experimental studies in rats using neutral dextran. Biophys J. 1975 Sep;15(9):887–906. doi: 10.1016/S0006-3495(75)85863-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Christensen E. I., Rennke H. G., Carone F. A. Renal tubular uptake of protein: effect of molecular charge. Am J Physiol. 1983 Apr;244(4):F436–F441. doi: 10.1152/ajprenal.1983.244.4.F436. [DOI] [PubMed] [Google Scholar]
  3. Christiansen J. S., Gammelgaard J., Frandsen M., Parving H. H. Increased kidney size, glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics. Diabetologia. 1981 Apr;20(4):451–456. doi: 10.1007/BF00253406. [DOI] [PubMed] [Google Scholar]
  4. Christiansen J. S., Gammelgaard J., Tronier B., Svendsen P. A., Parving H. H. Kidney function and size in diabetics before and during initial insulin treatment. Kidney Int. 1982 May;21(5):683–688. doi: 10.1038/ki.1982.81. [DOI] [PubMed] [Google Scholar]
  5. DAVIES D. F., SHOCK N. W. Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest. 1950 May;29(5):496–507. doi: 10.1172/JCI102286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dalton R. N., Wiseman M. J., Turner C., Viberti G. Measurement of urinary para-aminohippuric acid in glycosuric diabetics. Kidney Int. 1988 Jul;34(1):117–120. doi: 10.1038/ki.1988.153. [DOI] [PubMed] [Google Scholar]
  7. Deen W. M., Bridges C. R., Brenner B. M., Myers B. D. Heteroporous model of glomerular size selectivity: application to normal and nephrotic humans. Am J Physiol. 1985 Sep;249(3 Pt 2):F374–F389. doi: 10.1152/ajprenal.1985.249.3.F374. [DOI] [PubMed] [Google Scholar]
  8. Deen W. M., Robertson C. R., Brenner B. M. A model of glomerular ultrafiltration in the rat. Am J Physiol. 1972 Nov;223(5):1178–1183. doi: 10.1152/ajplegacy.1972.223.5.1178. [DOI] [PubMed] [Google Scholar]
  9. Ditzel J., Schwartz M. Abnormally increased glomerular filtration rate in short-term insulin-treated diabetic subjects. Diabetes. 1967 Apr;16(4):264–267. doi: 10.2337/diab.16.4.264. [DOI] [PubMed] [Google Scholar]
  10. Galaske R. G., Van Liew J. B., Feld L. G. Filtration and reabsorption of endogenous low-molecular-weight protein in the rat kidney. Kidney Int. 1979 Sep;16(3):394–403. doi: 10.1038/ki.1979.142. [DOI] [PubMed] [Google Scholar]
  11. Ginsberg J. M., Chang B. S., Matarese R. A., Garella S. Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med. 1983 Dec 22;309(25):1543–1546. doi: 10.1056/NEJM198312223092503. [DOI] [PubMed] [Google Scholar]
  12. Hannedouche T. P., Delgado A. G., Gnionsahe D. A., Boitard C., Lacour B., Grünfeld J. P. Renal hemodynamics and segmental tubular reabsorption in early type 1 diabetes. Kidney Int. 1990 Apr;37(4):1126–1133. doi: 10.1038/ki.1990.95. [DOI] [PubMed] [Google Scholar]
  13. Hostetter T. H., Rennke H. G., Brenner B. M. The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med. 1982 Mar;72(3):375–380. doi: 10.1016/0002-9343(82)90490-9. [DOI] [PubMed] [Google Scholar]
  14. Hostetter T. H., Troy J. L., Brenner B. M. Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int. 1981 Mar;19(3):410–415. doi: 10.1038/ki.1981.33. [DOI] [PubMed] [Google Scholar]
  15. Kamenetzky S. A., Bennett P. H., Dippe S. E., Miller M., LeCompte P. M. A clinical and histologic study of diabetic nephropathy in the Pima Indians. Diabetes. 1974 Jan;23(1):61–68. doi: 10.2337/diab.23.1.61. [DOI] [PubMed] [Google Scholar]
  16. Knowler W. C., Bennett P. H., Bottazzo G. F., Doniach D. Islet cell antibodies and diabetes mellitus in Pima Indians. Diabetologia. 1979 Sep;17(3):161–164. doi: 10.1007/BF01219743. [DOI] [PubMed] [Google Scholar]
  17. Knowler W. C., Bennett P. H., Hamman R. F., Miller M. Diabetes incidence and prevalence in Pima Indians: a 19-fold greater incidence than in Rochester, Minnesota. Am J Epidemiol. 1978 Dec;108(6):497–505. doi: 10.1093/oxfordjournals.aje.a112648. [DOI] [PubMed] [Google Scholar]
  18. Kunzelman C. L., Knowler W. C., Pettitt D. J., Bennett P. H. Incidence of proteinuria in type 2 diabetes mellitus in the Pima Indians. Kidney Int. 1989 Feb;35(2):681–687. doi: 10.1038/ki.1989.39. [DOI] [PubMed] [Google Scholar]
  19. Mauer S. M., Steffes M. W., Ellis E. N., Sutherland D. E., Brown D. M., Goetz F. C. Structural-functional relationships in diabetic nephropathy. J Clin Invest. 1984 Oct;74(4):1143–1155. doi: 10.1172/JCI111523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Menard L., Dempsey M. E., Blankstein L. A., Aleyassine H., Wacks M., Soeldner J. S. Quantitiative determination of glycosylated hemoglobin A1 by agar gel electrophoresis. Clin Chem. 1980 Oct;26(11):1598–1602. [PubMed] [Google Scholar]
  21. Mogensen C. E. Glomerular filtration rate and renal plasma flow in short-term and long-term juvenile diabetes mellitus. Scand J Clin Lab Invest. 1971 Sep;28(1):91–100. doi: 10.3109/00365517109090667. [DOI] [PubMed] [Google Scholar]
  22. Myers B. D., Peterson C., Molina C., Tomlanovich S. J., Newton L. D., Nitkin R., Sandler H., Murad F. Role of cardiac atria in the human renal response to changing plasma volume. Am J Physiol. 1988 Apr;254(4 Pt 2):F562–F573. doi: 10.1152/ajprenal.1988.254.4.F562. [DOI] [PubMed] [Google Scholar]
  23. Nakamura Y., Myers B. D. Charge selectivity of proteinuria in diabetic glomerulopathy. Diabetes. 1988 Sep;37(9):1202–1211. doi: 10.2337/diab.37.9.1202. [DOI] [PubMed] [Google Scholar]
  24. Nathan D. M., Rosenbaum C., Protasowicki V. D. Single-void urine samples can be used to estimate quantitative microalbuminuria. Diabetes Care. 1987 Jul-Aug;10(4):414–418. doi: 10.2337/diacare.10.4.414. [DOI] [PubMed] [Google Scholar]
  25. Nelson R. G., Kunzelman C. L., Pettitt D. J., Saad M. F., Bennett P. H., Knowler W. C. Albuminuria in type 2 (non-insulin-dependent) diabetes mellitus and impaired glucose tolerance in Pima Indians. Diabetologia. 1989 Dec;32(12):870–876. doi: 10.1007/BF00297452. [DOI] [PubMed] [Google Scholar]
  26. Nyberg G., Granerus G., Aurell M. Renal extraction ratios for 51Cr-EDTA, PAH, and glucose in early insulin-dependent diabetic patients. Kidney Int. 1982 May;21(5):706–708. doi: 10.1038/ki.1982.85. [DOI] [PubMed] [Google Scholar]
  27. Oken D. E., Kirschbaum B. B., Landwehr D. M. Micropuncture studies of the mechanisms of normal and pathologic albuminuria. Contrib Nephrol. 1981;24:1–7. doi: 10.1159/000395223. [DOI] [PubMed] [Google Scholar]
  28. Palmisano J. J., Lebovitz H. E. Renal function in black Americans with type II diabetes. J Diabet Complications. 1989 Jan-Mar;3(1):40–44. doi: 10.1016/0891-6632(89)90009-3. [DOI] [PubMed] [Google Scholar]
  29. Rennke H. G., Venkatachalam M. A. Glomerular permeability of macromolecules. Effect of molecular configuration on the fractional clearance of uncharged dextran and neutral horseradish peroxidase in the rat. J Clin Invest. 1979 Apr;63(4):713–717. doi: 10.1172/JCI109354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schmitz A., Christensen T., Taagehoej Jensen F. Glomerular filtration rate and kidney volume in normoalbuminuric non-insulin-dependent diabetics--lack of glomerular hyperfiltration and renal hypertrophy in uncomplicated NIDDM. Scand J Clin Lab Invest. 1989 Apr;49(2):103–108. doi: 10.3109/00365518909105406. [DOI] [PubMed] [Google Scholar]
  31. Schmitz A., Hansen H. H., Christensen T. Kidney function in newly diagnosed type 2 (non-insulin-dependent) diabetic patients, before and during treatment. Diabetologia. 1989 Jul;32(7):434–439. doi: 10.1007/BF00271263. [DOI] [PubMed] [Google Scholar]
  32. Scholey J. W., Meyer T. W. Control of glomerular hypertension by insulin administration in diabetic rats. J Clin Invest. 1989 Apr;83(4):1384–1389. doi: 10.1172/JCI114026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schwab S. J., Christensen R. L., Dougherty K., Klahr S. Quantitation of proteinuria by the use of protein-to-creatinine ratios in single urine samples. Arch Intern Med. 1987 May;147(5):943–944. [PubMed] [Google Scholar]
  34. Selby J. V., FitzSimmons S. C., Newman J. M., Katz P. P., Sepe S., Showstack J. The natural history and epidemiology of diabetic nephropathy. Implications for prevention and control. JAMA. 1990 Apr 11;263(14):1954–1960. [PubMed] [Google Scholar]
  35. Shemesh O., Golbetz H., Kriss J. P., Myers B. D. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int. 1985 Nov;28(5):830–838. doi: 10.1038/ki.1985.205. [DOI] [PubMed] [Google Scholar]
  36. Sumpio B. E., Maack T. Kinetics, competition, and selectivity of tubular absorption of proteins. Am J Physiol. 1982 Oct;243(4):F379–F392. doi: 10.1152/ajprenal.1982.243.4.F379. [DOI] [PubMed] [Google Scholar]
  37. Zatz R., Meyer T. W., Rennke H. G., Brenner B. M. Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5963–5967. doi: 10.1073/pnas.82.17.5963. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES