Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1984 Oct;74(4):1143–1155. doi: 10.1172/JCI111523

Structural-functional relationships in diabetic nephropathy.

S M Mauer, M W Steffes, E N Ellis, D E Sutherland, D M Brown, F C Goetz
PMCID: PMC425280  PMID: 6480821

Abstract

Renal biopsies in 45 patients with insulin-dependent diabetes mellitus (IDDM) were examined by semiquantitative light microscopy and quantitative electron microscopic stereologic morphometry. In these 14 males and 31 females, aged 13-52 yr, who had had IDDM for 2.5-29 yr there was no strong relationship between either glomerular basement membrane (GBM) thickness or mesangial expansion and duration of IDDM. There was only a weak relationship between the thickness of the GBM and expansion of the mesangium. Thus, GBM thickening and mesangial expansion in IDDM occur at rates that often differ from one another and that vary greatly among patients. The clinical manifestations of diabetic nephropathy, albuminuria, hypertension, and decreased glomerular filtration rate related poorly or not at all to GBM thickening. In contrast, all light and electron microscopic measures of mesangial expansion were strongly related to the clinical manifestations of diabetic nephropathy, although in the absence of these clinical findings, it was not possible to predict the severity of any of the diabetic glomerular lesions. Mesangial expansion had strong inverse correlations with capillary filtering surface area density. It is hypothesized that mesangial expansion could lead to glomerular functional deterioration in IDDM by restricting the glomerular capillary vasculature and its filtering surface. However, capillary closure, glomerular sclerosis, and interstitial fibrosis could also contribute to the clinical manifestations of this disorder.

Full text

PDF
1147

Images in this article

1145Image
on p.1145
1146Image
on p.1146

Selected References

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

  1. Bader R., Bader H., Grund K. E., Mackensen-Haen S., Christ H., Bohle A. Structure and function of the kidney in diabetic glomerulosclerosis. Correlations between morphological and functional parameters. Pathol Res Pract. 1980;167(2-4):204–216. doi: 10.1016/S0344-0338(80)80051-3. [DOI] [PubMed] [Google Scholar]
  2. Carrie B. J., Myers B. D. Proteinuria and functional characteristics of the glomerular barrier in diabetic nephropathy. Kidney Int. 1980 May;17(5):669–676. doi: 10.1038/ki.1980.78. [DOI] [PubMed] [Google Scholar]
  3. Caulfield J. P., Farquhar M. G. The permeability of glomerular capillaries to graded dextrans. Identification of the basement membrane as the primary filtration barrier. J Cell Biol. 1974 Dec;63(3):883–903. doi: 10.1083/jcb.63.3.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Falk R. J., Scheinman J. I., Mauer S. M., Michael A. F. Polyantigenic expansion of basement membrane constituents in diabetic nephropathy. Diabetes. 1983 May;32 (Suppl 2):34–39. doi: 10.2337/diab.32.2.s34. [DOI] [PubMed] [Google Scholar]
  5. GELLMAN D. D., PIRANI C. L., SOOTHILL J. F., MUEHRCKE R. C., MADUROS W., KARK R. M. Structure and function in diabetic nephropathy; the importance of diffuse glomerulosclerosis. Diabetes. 1959 Jul-Aug;8(4):251–256. doi: 10.2337/diab.8.4.251. [DOI] [PubMed] [Google Scholar]
  6. Gundersen H. J., Osterby R. Glomerular size and structure in diabetes mellitus. II. Late abnormalities. Diabetologia. 1977 Jan;13(1):43–48. doi: 10.1007/BF00996326. [DOI] [PubMed] [Google Scholar]
  7. Gundersen H. J., Osterby R. Glomerular size and structure in diabetes mellitus. II. Late abnormalities. Diabetologia. 1977 Jan;13(1):43–48. doi: 10.1007/BF00996326. [DOI] [PubMed] [Google Scholar]
  8. Hirose K., Osterby R., Nozawa M., Gundersen H. J. Development of glomerular lesions in experimental long-term diabetes in the rat. Kidney Int. 1982 May;21(5):689–695. doi: 10.1038/ki.1982.82. [DOI] [PubMed] [Google Scholar]
  9. Hirose K., Tsuchida H., Osterby R., Gundersen H. J. A strong correlation between glomerular filtration rate and filtration surface in diabetic kidney hyperfunction. Lab Invest. 1980 Nov;43(5):434–437. [PubMed] [Google Scholar]
  10. Hostetter T. H., Olson J. L., Rennke H. G., Venkatachalam M. A., Brenner B. M. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol. 1981 Jul;241(1):F85–F93. doi: 10.1152/ajprenal.1981.241.1.F85. [DOI] [PubMed] [Google Scholar]
  11. Jones R. H., Hayakawa H., Mackay J. D., Parsons V., Watkins P. J. Progression of diabetic nephropathy. Lancet. 1979 May 26;1(8126):1105–1106. doi: 10.1016/s0140-6736(79)91788-4. [DOI] [PubMed] [Google Scholar]
  12. KNOWLES H. C., Jr, GUEST G. M., LAMPE J., KESSLER M., SKILLMAN T. G. THE COURSE OF JUVENILE DIABETES TREATED WITH UNMEASURED DIET. Diabetes. 1965 May;14:239–273. doi: 10.2337/diab.14.5.239. [DOI] [PubMed] [Google Scholar]
  13. Kanwar Y. S., Rosenzweig L. J., Jakubowski M. L. Distribution of de novo synthesized sulfated glycosaminoglycans in the glomerular basement membrane and mesangial matrix. Lab Invest. 1983 Aug;49(2):216–225. [PubMed] [Google Scholar]
  14. Kaplan C., Pasternack B., Shah H., Gallo G. Age-related incidence of sclerotic glomeruli in human kidneys. Am J Pathol. 1975 Aug;80(2):227–234. [PMC free article] [PubMed] [Google Scholar]
  15. Killingsworth L. M., Savory J. Nephelometric methods for the determination of urinary albumin, transferrin and alpha-2 macroglobulin. Ann Clin Lab Sci. 1974 Jan-Feb;4(1):46–52. [PubMed] [Google Scholar]
  16. Kussman M. J., Goldstein H., Gleason R. E. The clinical course of diabetic nephropathy. JAMA. 1976 Oct 18;236(16):1861–1863. [PubMed] [Google Scholar]
  17. MARKS H. H. LONGEVITY AND MORTALITY OF DIABETICS. Am J Public Health Nations Health. 1965 Mar;55:416–423. doi: 10.2105/ajph.55.3.416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mauer S. M., Steffes M. W., Brown D. M. The kidney in diabetes. Am J Med. 1981 Mar;70(3):603–612. doi: 10.1016/0002-9343(81)90582-9. [DOI] [PubMed] [Google Scholar]
  19. Mauer S. M., Steffes M. W., Chern M., Brown D. M. Mesangial uptake and processing of macromolecules in rats with diabetes mellitus. Lab Invest. 1979 Nov;41(5):401–406. [PubMed] [Google Scholar]
  20. Mauer S. M., Steffes M. W., Sutherland D. E., Najarian-S, Michael A. F., Brown D. M. Studies of the rate of regression of the glomerular lesions in diabetic rats treated with pancreatic islet transplantation. Diabetes. 1975 Mar;24(3):280–285. doi: 10.2337/diab.24.3.280. [DOI] [PubMed] [Google Scholar]
  21. Michael A. F., Yang J. Y., Falk R. J., Bennington M. J., Scheinman J. I., Vernier R. L., Fish A. J. Monoclonal antibodies to human renal basement membranes: heterogenic and ontogenic changes. Kidney Int. 1983 Jul;24(1):74–86. doi: 10.1038/ki.1983.128. [DOI] [PubMed] [Google Scholar]
  22. Mogensen C. E. Progression of nephropathy in long-term diabetics with proteinuria and effect of initial anti-hypertensive treatment. Scand J Clin Lab Invest. 1976 Jul;36(4):383–388. doi: 10.1080/00365517609055274. [DOI] [PubMed] [Google Scholar]
  23. Mogensen C. E. Renal function changes in diabetes. Diabetes. 1976;25(2 Suppl):872–879. [PubMed] [Google Scholar]
  24. Olivetti G., Anversa P., Rigamonti W., Vitali-Mazza L., Loud A. V. Morphometry of the renal corpuscle during normal postnatal growth and compensatory hypertrophy. A light microscope study. J Cell Biol. 1977 Nov;75(2 Pt 1):573–585. doi: 10.1083/jcb.75.2.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Olson J. L., Hostetter T. H., Rennke H. G., Brenner B. M., Venkatachalam M. A. Altered glomerular permselectivity and progressive sclerosis following extreme ablation of renal mass. Kidney Int. 1982 Aug;22(2):112–126. doi: 10.1038/ki.1982.143. [DOI] [PubMed] [Google Scholar]
  26. Osterby R., Gundersen H. J. Glomerular size and structure in diabetes mellitus. I. Early abnormalities. Diabetologia. 1975 Jun;11(3):225–229. doi: 10.1007/BF00422326. [DOI] [PubMed] [Google Scholar]
  27. Parving H. H., Smidt U. M., Friisberg B., Bonnevie-Nielsen V., Andersen A. R. A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy. Diabetologia. 1981 Apr;20(4):457–461. doi: 10.1007/BF00253407. [DOI] [PubMed] [Google Scholar]
  28. Parving H. H., Smidt U. M., Friisberg B., Bonnevie-Nielsen V., Andersen A. R. A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy. Diabetologia. 1981 Apr;20(4):457–461. doi: 10.1007/BF00253407. [DOI] [PubMed] [Google Scholar]
  29. Steffes M. W., Barbosa J., Basgen J. M., Sutherland D. E., Najarian J. S., Mauer S. M. Quantitative glomerular morphology of the normal human kidney. Lab Invest. 1983 Jul;49(1):82–86. [PubMed] [Google Scholar]
  30. Steffes M. W., Brown D. M., Basgen J. M., Matas A. J., Mauer S. M. Glomerular basement membrane thickness following islet transplantation in the diabetic rat. Lab Invest. 1979 Aug;41(2):116–118. [PubMed] [Google Scholar]
  31. Steffes M. W., Brown D. M., Basgen J. M., Mauer S. M. Amelioration of mesangial volume and surface alterations following islet transplantation in diabetic rats. Diabetes. 1980 Jul;29(7):509–515. doi: 10.2337/diab.29.7.509. [DOI] [PubMed] [Google Scholar]
  32. Steffes M. W., Vernier R. L., Brown D. M., Basgen J. M., Mauer S. M. Diabetic glomerulopathy in the uninephrectomized rat resists amelioration following islet transplantation. Diabetologia. 1982 Oct;23(4):347–353. doi: 10.1007/BF00253743. [DOI] [PubMed] [Google Scholar]
  33. Vernier R. L., Resnick J. S., Mauer S. M. Recurrent hematuria and focal glomerulonephritis. Kidney Int. 1975 Apr;7(4):224–231. doi: 10.1038/ki.1975.34. [DOI] [PubMed] [Google Scholar]
  34. Viberti G. C., Hill R. D., Jarrett R. J., Argyropoulos A., Mahmud U., Keen H. Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet. 1982 Jun 26;1(8287):1430–1432. doi: 10.1016/s0140-6736(82)92450-3. [DOI] [PubMed] [Google Scholar]
  35. Viberti G. C., Mackintosh D., Bilous R. W., Pickup J. C., Keen H. Proteinuria in diabetes mellitus: role of spontaneous and experimental variation of glycemia. Kidney Int. 1982 May;21(5):714–720. doi: 10.1038/ki.1982.87. [DOI] [PubMed] [Google Scholar]
  36. Viberti G. C., Pickup J. C., Jarrett R. J., Keen H. Effect of control of blood glucose on urinary excretion of albumin and beta2 microglobulin in insulin-dependent diabetes. N Engl J Med. 1979 Mar 22;300(12):638–641. doi: 10.1056/NEJM197903223001202. [DOI] [PubMed] [Google Scholar]
  37. Winetz J. A., Golbetz H. V., Spencer R. J., Lee J. A., Myers B. D. Glomerular function in advanced human diabetic nephropathy. Kidney Int. 1982 May;21(5):750–756. doi: 10.1038/ki.1982.93. [DOI] [PubMed] [Google Scholar]

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

RESOURCES