Structural-functional relationships in diabetic nephropathy.
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
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- MARKS HH. LONGEVITY AND MORTALITY OF DIABETICS. Am J Public Health Nations Health. 1965 Mar;55:416–423.[PMC free article] [PubMed] [Google Scholar]
- KNOWLES HC, Jr, GUEST GM, LAMPE J, KESSLER M, SKILLMAN TG. THE COURSE OF JUVENILE DIABETES TREATED WITH UNMEASURED DIET. Diabetes. 1965 May;14:239–273. [PubMed] [Google Scholar]
- Mogensen CE. Renal function changes in diabetes. Diabetes. 1976;25(2 Suppl):872–879. [PubMed] [Google Scholar]
- Viberti GC, Pickup JC, Jarrett RJ, 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. [PubMed] [Google Scholar]
- Jones RH, Hayakawa H, Mackay JD, Parsons V, Watkins PJ. Progression of diabetic nephropathy. Lancet. 1979 May 26;1(8126):1105–1106. [PubMed] [Google Scholar]
- Parving HH, Smidt UM, Friisberg B, Bonnevie-Nielsen V, Andersen AR. 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. [PubMed] [Google Scholar]
- Mauer SM, Steffes MW, Brown DM. The kidney in diabetes. Am J Med. 1981 Mar;70(3):603–612. [PubMed] [Google Scholar]
- GELLMAN DD, PIRANI CL, SOOTHILL JF, MUEHRCKE RC, MADUROS W, KARK RM. Structure and function in diabetic nephropathy; the importance of diffuse glomerulosclerosis. Diabetes. 1959 Jul-Aug;8(4):251–256. [PubMed] [Google Scholar]
- Gundersen HJ, Osterby R. Glomerular size and structure in diabetes mellitus. II. Late abnormalities. Diabetologia. 1977 Jan;13(1):43–48. [PubMed] [Google Scholar]
- Bader R, Bader H, Grund KE, 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. [PubMed] [Google Scholar]
- Killingsworth LM, 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]
- Steffes MW, Brown DM, Basgen JM, Mauer SM. Amelioration of mesangial volume and surface alterations following islet transplantation in diabetic rats. Diabetes. 1980 Jul;29(7):509–515. [PubMed] [Google Scholar]
- Mauer SM, Steffes MW, Sutherland DE, Najarian-S, Michael AF, Brown DM. 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. [PubMed] [Google Scholar]
- Hirose K, Osterby R, Nozawa M, Gundersen HJ. Development of glomerular lesions in experimental long-term diabetes in the rat. Kidney Int. 1982 May;21(5):689–695. [PubMed] [Google Scholar]
- Steffes MW, Brown DM, Basgen JM, Matas AJ, Mauer SM. Glomerular basement membrane thickness following islet transplantation in the diabetic rat. Lab Invest. 1979 Aug;41(2):116–118. [PubMed] [Google Scholar]
- Steffes MW, Barbosa J, Basgen JM, Sutherland DE, Najarian JS, Mauer SM. Quantitative glomerular morphology of the normal human kidney. Lab Invest. 1983 Jul;49(1):82–86. [PubMed] [Google Scholar]
- 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]
- Kussman MJ, Goldstein H, Gleason RE. The clinical course of diabetic nephropathy. JAMA. 1976 Oct 18;236(16):1861–1863. [PubMed] [Google Scholar]
- Kanwar YS, Rosenzweig LJ, Jakubowski ML. 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]
- Steffes MW, Vernier RL, Brown DM, Basgen JM, Mauer SM. Diabetic glomerulopathy in the uninephrectomized rat resists amelioration following islet transplantation. Diabetologia. 1982 Oct;23(4):347–353. [PubMed] [Google Scholar]
- Michael AF, Yang JY, Falk RJ, Bennington MJ, Scheinman JI, Vernier RL, Fish AJ. Monoclonal antibodies to human renal basement membranes: heterogenic and ontogenic changes. Kidney Int. 1983 Jul;24(1):74–86. [PubMed] [Google Scholar]
- Falk RJ, Scheinman JI, Mauer SM, Michael AF. Polyantigenic expansion of basement membrane constituents in diabetic nephropathy. Diabetes. 1983 May;32 (Suppl 2):34–39. [PubMed] [Google Scholar]
- Mauer SM, Steffes MW, Chern M, Brown DM. Mesangial uptake and processing of macromolecules in rats with diabetes mellitus. Lab Invest. 1979 Nov;41(5):401–406. [PubMed] [Google Scholar]
- Parving HH, Smidt UM, Friisberg B, Bonnevie-Nielsen V, Andersen AR. 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. [PubMed] [Google Scholar]
- Caulfield JP, Farquhar MG. 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.[PMC free article] [PubMed] [Google Scholar]
- Hirose K, Tsuchida H, Osterby R, Gundersen HJ. 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]
- Osterby R, Gundersen HJ. Glomerular size and structure in diabetes mellitus. I. Early abnormalities. Diabetologia. 1975 Jun;11(3):225–229. [PubMed] [Google Scholar]
- Olivetti G, Anversa P, Rigamonti W, Vitali-Mazza L, Loud AV. 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.[PMC free article] [PubMed] [Google Scholar]
- Winetz JA, Golbetz HV, Spencer RJ, Lee JA, Myers BD. Glomerular function in advanced human diabetic nephropathy. Kidney Int. 1982 May;21(5):750–756. [PubMed] [Google Scholar]
- Gundersen HJ, Osterby R. Glomerular size and structure in diabetes mellitus. II. Late abnormalities. Diabetologia. 1977 Jan;13(1):43–48. [PubMed] [Google Scholar]
- Viberti GC, Mackintosh D, Bilous RW, Pickup JC, Keen H. Proteinuria in diabetes mellitus: role of spontaneous and experimental variation of glycemia. Kidney Int. 1982 May;21(5):714–720. [PubMed] [Google Scholar]
- Carrie BJ, Myers BD. Proteinuria and functional characteristics of the glomerular barrier in diabetic nephropathy. Kidney Int. 1980 May;17(5):669–676. [PubMed] [Google Scholar]
- Olson JL, Hostetter TH, Rennke HG, Brenner BM, Venkatachalam MA. Altered glomerular permselectivity and progressive sclerosis following extreme ablation of renal mass. Kidney Int. 1982 Aug;22(2):112–126. [PubMed] [Google Scholar]
- Mogensen CE. 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. [PubMed] [Google Scholar]
- Viberti GC, Hill RD, Jarrett RJ, 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. [PubMed] [Google Scholar]
- Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol. 1981 Jul;241(1):F85–F93. [PubMed] [Google Scholar]
- Vernier RL, Resnick JS, Mauer SM. Recurrent hematuria and focal glomerulonephritis. Kidney Int. 1975 Apr;7(4):224–231. [PubMed] [Google Scholar]


