Renal Structure in Non Insulin-Dependent Diabetic Patients with Microalbuminuria

  • Paola Fioretto
  • Michael Mauer
  • Romano Nosadini


Although more than 50% of diabetic patients receiving renal replacement therapy have type 2 diabetes [1–4], the renal pathology and natural history of diabetic nephropathy (DN) in type 2 diabetes has been studied much less intensely than in type 1 diabetes and thus many important questions remain unclear. The clinical manifestations of DN, proteinuria, declining glomerular filtration rate (GFR) and increasing blood pressure, are similar in type 1 and type 2 diabetes [5–6], as in many other renal diseases; nevertheless whether these clinical features are consequences of similar underlying renal lesions is unknown. In type 1 diabetes it is generally accepted that glomerulopathy is the most important structural change, leading to progressive renal function loss [7–12]; concomitantly and roughly proportionally to the degree of glomerulopathy, the arterioles, tubules and interstitium also undergo structural changes, including hyalinosis of the arteriolar wall, thickening and reduplication of tubular basement membranes, tubular atrophy and interstitial expansion and fibrosis. [7–12]. These lesions become progressive and severe only when glomerulopathy is far advanced. Quantitative morphometric studies have demonstrated that the lesion most closely related to the decline in renal function in type 1 diabetes is mesangial expansion, caused especially by mesangial matrix accumulation [11,13]. Also we have recently observed, in sequential renal biopsies of type 1 diabetic patients performed 5 years apart, that the only structural change associated with increasing albuminuria was mesangial expansion [12]; GBM width, interstitial expansion and the number of globally sclerosed glomeruli did not change over 5 years in this group of patients, several of whom were studied while in transition from normal to microalbuminuria or from microalbuminuria to overt nephropathy. Thus in type 1 diabetes severe arteriolar, tubular and interstitial lesions are rare unless advanced diabetic glomerulopathy is present.


Diabetic Nephropathy Overt Nephropathy Tubular Basement Membrane Mesangial Expansion Renal Structure 
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  1. 1.
    Cordonnier DJ, Zmirou D, Benhamou PY, Halimi S, Ledoux F, Guiserix J. Epidemiology, development and treatment of end-stage renal failure in type 2 diabetes. The case of mainland France and of overseas French territories. Diabetologia 1993; 36: 1109–1112.PubMedCrossRefGoogle Scholar
  2. 2.
    Stephen SGW, Gillaspry JA, Clyne D, Mejia A, Pollok VE. Racial differences in the incidence of end stage renal disease in type 1 and type 2 diabetes mellitus. Am J Kidney Dis 1990; 15: 562–567.Google Scholar
  3. 3.
    Ritz E, Nowack R, Fliser D, et al. Type II diabetes mellitus: is the renal risk adequately appreciated? Nephrol Dial Transplant 1991; 6: 679–682.PubMedCrossRefGoogle Scholar
  4. 4.
    Catalano C, Postorino M, Kelly PJ. Diabetes mellitus and renal replacement therapy in Italy: prevalence, main characteristic and complications. Nephrol Dial Transplant 1990; 5: 788–796.PubMedCrossRefGoogle Scholar
  5. 5.
    Mogensen CE, Schmitz A, Christensen CK. Comparative renal pathophysiology relevant to IDDM and NIDDM patients. Diabetes Metab Rev 1988; 4: 453–483.PubMedCrossRefGoogle Scholar
  6. 6.
    Schmitz A. Nephropathy in non-insulin dependent diabetes mellitus and perspectives for intervention. Diab Nutr Metab 1995; 7: 135–148.Google Scholar
  7. 7.
    Mauer SM, Steffes MW, Brown DM. The kidney in diabetes. Am J Med 1981; 70: 603–612.PubMedCrossRefGoogle Scholar
  8. 8.
    Fioretto P, Mogensen CE, Mauer SM. »Diabetic nephropathy.« In Pediatric Nephroplogy. Holliday MA, Barratt TM, Avner ED, eds. New York: Williams and Wilkins, 1994; pp 576–585.Google Scholar
  9. 9.
    Lane PH, Steffes MW, Fioretto P, Mauer SM. Renal interstitial expansion in insulin-dependent diabetes mellitus. Kidney Int 1993; 43: 661–667.PubMedCrossRefGoogle Scholar
  10. 10.
    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; 8: 251–256.PubMedGoogle Scholar
  11. 11.
    Mauer SM, Steffes MW, Ellis EN, Sutherland DER, Brown DM, Goetz FC. Structural functional relationships in diabetic nephropathy. J Clin Invest 1984; 74: 1143–55.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Fioretto P, Steffes MW, Sutherland DER, Mauer M. Sequential renal biopsies in IDDM patients: structural factors associated with clinical progression. Kidney Int 1995; 48: 1929–1935.PubMedCrossRefGoogle Scholar
  13. 13.
    Steffes MW, Bilous RW, Sutherland DER, Mauer SM. Cell and matrix components in the glomerular mesangium in type I diabetes. Diabetes 1992; 41: 679–684.PubMedCrossRefGoogle Scholar
  14. 14.
    Parving H-H, Gall M-A, Skøtt P, Jørgensen HE, Løkkegaard H, Jørgensen F, Nielsen B, Larsen S. Prevalence and causes of albuminuria in non-insulin-dependent diabetic patients. Kidney Int 1992; 41: 758–762.PubMedCrossRefGoogle Scholar
  15. 15.
    Gambara V, Mecca G, Remuzzi G, Bertani T. Heterogeneous nature of renal lesions in type II diabetes. JASN 1993; 3: 1458–1466.PubMedGoogle Scholar
  16. 16.
    Kahn S, Seghal V, Appel GB, D’Agati V. Correlates of diabetic and non-diabetic renal disease in NIDDM (Abstract). JASN 1995; 6: 451.Google Scholar
  17. 17.
    Olsen S, Mogensen CE. Non-diabetic renal disease in NIDDM proteinuric patients may be rare in biopsies from clinical practice (Abstract). JASN 1995; 6: 454.Google Scholar
  18. 18.
    Waldherr R, Ilkenhans C, Ritz E. How frequent is glomerulonephritis in diabetes mellitus type II? Clin Nephrol 1992; 37: 271–273.PubMedGoogle Scholar
  19. 19.
    Hayashi H, Karasawa R, Inn H, Saitou T, Ueno M, Nishi S, Suzuki Y, Ogino S, Maruyama Y, Kouda Y, Arakawa M. An electron microscopic study of glomeruli in Japanese patients with non-insulin dependent diabetes mellitus. Kidney Int 1992; 41: 749–757.PubMedCrossRefGoogle Scholar
  20. 20.
    Østerby R, Gall M-A, Schmitz A, Nielsen FS, Nyberg G, Parving H-H. Glomerular structure and function in proteinuric type 2 (non insulin dependent) diabetic patients. Diabetologia 1993; 36: 1064–1070.PubMedCrossRefGoogle Scholar
  21. 21.
    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; i: 1430–1432.CrossRefGoogle Scholar
  22. 22.
    Parving H-H, Oxenbøll B, Svensen PAA, Christiansen JS, Andersen AR. Early detection of patients at risk of developing diabetic nephropathy: a longitudinal study of urinary albumin excretion. Acta Endocrinol (Copenh) 1982; 100: 550–552.Google Scholar
  23. 23.
    Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent diabetic patients. N Engl J Med 1986; 331: 89–93.Google Scholar
  24. 24.
    Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984; 310: 356–360.PubMedCrossRefGoogle Scholar
  25. 25.
    Mogensen CE. Microalbuminuria as a predictor of clinical diabetic nephropathy. Kidney Int 1987; 31: 673–689.PubMedCrossRefGoogle Scholar
  26. 26.
    Schmitz A, Vaeth M. Microalbuminuria: a major risk factor in type 2 diabetes. A 10 year follow-up study of 503 patients. Diabetic Med 1988; 5: 126–134.PubMedCrossRefGoogle Scholar
  27. 27.
    Jarrett RJ, Viberti GC, Argyropoulos A, Hill RD, Mahmud U, Murrells TJ. Microalbuminuria predicts mortality in non-insulin-dependent diabetes. Diabetic Med 1984; 1: 17–19.PubMedCrossRefGoogle Scholar
  28. 28.
    Stehouwer CDA, Nauta JJP, Zeldenrust GC, Hackeng WHL, Donker AJM, den Ottolander GJH. Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin dependent diabetes mellitus. Lancet 1992; 340: 319–323.PubMedCrossRefGoogle Scholar
  29. 29.
    Fioretto P, Steffes MW, Mauer SM. Glomerular structure in non proteinuric IDDM patients with various levels of albuminuria. Diabetes 1994; 43: 1358–1364.PubMedCrossRefGoogle Scholar
  30. 30.
    Ruggenenti P, Mosconi L, Bianchi L, Cortesi L, Camparna M, Pagani G, Mecca G, Remuzzi G. Long-term treatment with either Enalapril or Nitrendipine stabilizes albuminuria and increases glomerular filtration rate in non-insulin-dependent diabetic patients. Am J Kidney Dis 1994; 24: 753–761.PubMedGoogle Scholar
  31. 31.
    Fioretto P, Mauer SM, Brocco E, Velussi M, Frigato F, Muollo B, Sambataro M, Abaterusso C, Baggio B, Crepaldi G, Nosadini R. Patterns of renal injury in type 2 (non insulin dependent) diabetic patients with microalbuminuria. Diabetologia 1996; in press.Google Scholar
  32. 32.
    Sambataro M, Thomaseth K, Pacini G, et al. Plasma clearance of 51 Cr-EDTA provides a precise and convenient technique for measurement of glomerular filtration rate in diabetic humans. JASN 1996; 7: 118–127.PubMedGoogle Scholar
  33. 33.
    The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Int Med 1993; 153: 154.CrossRefGoogle Scholar
  34. 34.
    Ellis EN, Basgen JM, Mauer SM, Steffes MW. »Kidney biopsy technique and evaluation.« In Methods in Diabetes Research, Volume II, Clinical Methods. Clarke WL, Larner J, Pohl SL, eds. New York: John Wiley & Sons, 1986; pp 633–647.Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Paola Fioretto
    • 1
    • 2
  • Michael Mauer
    • 1
    • 2
  • Romano Nosadini
    • 1
    • 2
  1. 1.The University of Minnesota Hospital and ClinicPediatric NephrologyMinneapolisUSA
  2. 2.Istituto di Medicina InternaUniversità di PadovaPadovaItaly

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