Glomerular Ultrastructural Changes in Microalbuminuric IDDM-Patients

  • Hans-Jacob Bangstad
  • Ruth Østerby


Since the term »microalbuminuria« (MA) was coined in 1982 [1] elevated albumin excretion rate has been regarded as the best indicator to signal early diabetic nephropathy [2–5]. Two main aspects of renal function at this stage of diabetic nephropathy, are the relation to glomerular structure and the impact of blood glucose control. Improved blood glucose control has been shown to reduce the risk of developing overt nephropathy in patients with MA [6,7] and retard the progression of AER [8], but the concomitant ultrastructural changes were not investigated.


Diabetic Nephropathy Glomerular Basement Membrane Blood Glucose Control Pancreas Transplantation Albumin Excretion Rate 
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  1. 1.
    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; 21: 714–720.CrossRefPubMedGoogle Scholar
  2. 2.
    Parving H-H, Oxenbøll B, Svendsen 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: 500–505.Google Scholar
  3. 3.
    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
  4. 4.
    Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 1984; 311: 89–93.CrossRefPubMedGoogle Scholar
  5. 5.
    Mathiesen ER, Oxenbøll B, Johansen K, Svendsen PA, Deckert T. Incipient nephropathy in type 1 (insulin-dependent) diabetes. Diabetologia 1984; 26: 406–410.CrossRefPubMedGoogle Scholar
  6. 6.
    Feldt-Rasmussen B, Mathiesen ER, Jensen T, Lauritzen T, Deckert T. Effect of improved metabolic control on loss of kidney function in type I (insulin-dependent) diabetic patients: an update of the Steno studies. Diabetologia 1991; 34: 164–170.CrossRefPubMedGoogle Scholar
  7. 7.
    Reichard P, Berglund B, Britz A, Cars I, Nilsson BY, Rosenquist U. Intensified conventional insulin treatment retards the microvascular complications of insulin dependent diabetes mellitus (IDDM): The Stockholm diabetes intervention study (SDIS) after five years. J Intern Med 1991; 230: 101–108.CrossRefPubMedGoogle Scholar
  8. 8.
    Dahl-Jørgensen K, Bjøro T, Kierulf P, Sandvik L, Bangstad H-J, Hanssen KF. Long-term glycemic control and kidney function in insulin-dependent diabetes mellitus. Kidney Int 1992; 41: 920–923.CrossRefPubMedGoogle Scholar
  9. 9.
    Hirose K, Østerby R, Nozawa M, Gundersen HJ. Development of glomerular lesions in experimental long-term diabetes in the rat. Kidney Int 1982; 21: 689–695.CrossRefPubMedGoogle Scholar
  10. 10.
    Østerby R. A quantitative electron microscopic study of mesangial regions in glomeruli from patients with short term juvenile diabetes mellitus. Lab Invest 1973; 29: 99–110.PubMedGoogle Scholar
  11. 11.
    Gundersen HJG, Bendtsen TF, Korbo L, et al. Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS 1988; 96: 379–394.CrossRefPubMedGoogle Scholar
  12. 12.
    Walker JD, Close CF, Jones SL, et al. Glomerular structure in type I (insulin-dependent) diabetic patients with normo-and microalbuminuria. Kidney Int 1992; 41: 741–748.CrossRefPubMedGoogle Scholar
  13. 13.
    Bangstad H-J, Østerby R, Dahl-Jørgensen K, et al. Early glomerulopathy is present in young Type 1 (insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 1993; 36: 523–529.CrossRefPubMedGoogle Scholar
  14. 14.
    Østerby R. »Research methodologies related to renal complications: structural changes.« In Research Methodologies in Human Diabetes, Part 2, Mogensen CE, Standi E, eds. Berlin, New York: Walter de Gruyter, 1995; pp 289–309.Google Scholar
  15. 15.
    Østerby R. Early phases in the development of diabetic nephropathy. Acta Med Scand 1975; 574: Suppl.: 1–80.Google Scholar
  16. 16.
    Steffes MW, Sutherland DER, Goetz FC, Rich SS, Mauer SM. Studies of kidney and muscle biopsies in identical twins discordant for type 1 diabetes mellitus. N Engl J Med 1985; 312: 1281–1287.Google Scholar
  17. 17.
    Chavers BM, Bilous RW, Ellis EN, Steffes MW, Mauer SM. Glomerular lesions and urinary albumin excretion in Type 1 diabetes without overt proteinuria. N Engl J Med 1989; 320: 966–970.CrossRefPubMedGoogle Scholar
  18. 18.
    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: 204–216.CrossRefPubMedGoogle Scholar
  19. 19.
    Lane PH, Steffes MW, Fioretto P, Mauer SM. Renal interstitial expansion in insulin-dependent diabetes mellitus. Kidney Int 1993; 43: 661–667.CrossRefPubMedGoogle Scholar
  20. 20.
    Østerby R, Bangstad H-J, Nyberg G, Walker JD, Viberti GC. A quantitative ultrastructural study of juxtaglomerular arterioles in IDDM patients with micro-and normoalbuminuria. Diabetologia 1995; 38: 1320–1327.CrossRefPubMedGoogle Scholar
  21. 21.
    Rasch R. Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. Glomerular basement membrane thickness. Diabetologia 1979; 16: 319–324.CrossRefPubMedGoogle Scholar
  22. 22.
    Rasch R. Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. The mesangial region. Diabetologia 1979; 17: 243–248.CrossRefPubMedGoogle Scholar
  23. 23.
    Kern TS, Engerman RL. Kidney morphology in experimental hyperglycemia. Diabetes 1987; 36: 244–249.CrossRefPubMedGoogle Scholar
  24. 24.
    Petersen J, Ross J, Rabkin R. Effect of insulin therapy on established diabetic nephropathy in rats. Diabetes 1988; 37: 1346–1350.CrossRefPubMedGoogle Scholar
  25. 25.
    Mauer SM, Brown DM, Matas AJ, Steffes MW. Effects of pancreatic islet transplantation on the increased urinary albumin excretion rates in intact and uninephrectomized rats with diabetes mellitus. Diabetes 1978; 27: 959–964.CrossRefPubMedGoogle Scholar
  26. 26.
    Steffes MW, Brown DM, Basgen JM, Mauer SM. Amelioration of mesangial volume and surface alterations following islet transplantation in diabetic rats. Diabetes 1980; 29: 509–515.CrossRefPubMedGoogle Scholar
  27. 27.
    Orloff MJ, Yamanaka N, Greenleaf GE, Huang Y, Huang D, Leng X. Reversal of mesangial enlargement in rats with long-standing diabetes by whole pancreas transplantation. Diabetes 1986; 35: 347–354.CrossRefPubMedGoogle Scholar
  28. 28.
    Bilous RW, Mauer SM, Sutherland DER, Najarian JS, Goetz FC, Steffes MW. The effect of pancreas transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes. N Engl J Med 1989; 321: 80–85.CrossRefPubMedGoogle Scholar
  29. 29.
    Bangstad H-J, Osterby R, Dahl-Jørgensen K, Berg KJ, Hartmann A, Hanssen KF. Improvement of blood glucose control retards the progression of morphological changes in early diabetic nephropathy. Diabetologia 1994; 37: 483–490.CrossRefPubMedGoogle Scholar
  30. 30.
    Barbosa J, Steffes MW, Connett J, Mauer M. Hyperglycemia is causally related to diabetic renal lesions. Diabetes 1992; 41: 9A.Google Scholar
  31. 31.
    Wilczek H, Jaremko G, Tyden G, Groth CG. Evolution of diabetic nephropathy in kidney grafts. Transplantation 1995; 59: 51–57.CrossRefPubMedGoogle Scholar
  32. 32.
    Lane PH, Steffes MW, Mauer SM. Glomerular structure in IDDM women with low glomerular filtration rate and normal urinary albumin excretion. Diabetes 1992; 41: 581–586.CrossRefPubMedGoogle Scholar
  33. 33.
    Fioretto P, Steffes MW, Mauer SM. Glomerular structure in nonproteinuric IDDM patients with various levels of albuminuria. Diabetes 1994; 43: 1358–1364.CrossRefPubMedGoogle Scholar
  34. 34.
    Mogensen CE, Hansen KW. Blood pressure elevation versus abnormal albuminuria in the genesis and prediction of renal disease in diabetes. Diabetes Care 1992; 15: 1192–1204.CrossRefPubMedGoogle Scholar
  35. 35.
    Bangstad H-J, Kofoed-Enevoldsen A, Dahl-Jørgensen K, Hanssen KF. Glomerular charge selectivity and the influence of improved blood glucose control in Type 1 diabetic patients with microalbuminuria. Diabetologia 1992; 35: 1165–1170.CrossRefPubMedGoogle Scholar
  36. 36.
    Silbiger S, Crowley S, Shan Z, Brownlee M, Satriano J, Schlondorff D. Nonenzymatic glycation of mesangial matrix and prolonged exposure of mesangial matrix to elevated glucose reduces collagen synthesis and proteoglycan charge. Kidney Int 1993; 43: 853–864.CrossRefPubMedGoogle Scholar
  37. 37.
    Brownlee M, Spiro RG. Glomerular basement membrane metabolism in the diabetic rat: in vivo studies. Diabetes 1979; 28: 121–125.CrossRefPubMedGoogle Scholar
  38. 38.
    Cagliero E, Roth T, Roy S, Lorenzi M. Characteristics and mechanisms of high-glucose-induced overexpression of basement membrane components in cultured human endothelial cells. Diabetes 1991; 40: 102–110.CrossRefPubMedGoogle Scholar
  39. 39.
    Roy S, Sala R, Cagliero E, Lorenzi M. Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory. Proc Natl Acad Sci USA 1990; 87: 404–408.CrossRefPubMedGoogle Scholar
  40. 40.
    Ledbetter S, Copeland EJ, Noonan D, Vogeli G, Hassel JR. Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthase inhibition. Diabetes 1990; 39: 196–203.CrossRefPubMedGoogle Scholar
  41. 41.
    Poulsom R, Kurkinen M, Prockop DJ, Boot-Handford RP. Increased steady-state levels of laminin B1 mRNA in kidneys of long term streptozotocin-diabetic rats. J Biol Chem 1988; 263: 10072–10076.PubMedGoogle Scholar
  42. 42.
    Ayo SH, Radnik RA, Garoni JA, Glass II WF, Kreisberg JI. High glucose causes an increase in extracellular matrix proteins in cultured mesangial cells. Am J Pathol 1990; 136: 1339–1348.PubMedGoogle Scholar
  43. 43.
    Shimomura H, Spiro RG. Studies on the macromolecular components of human glomerular basement membrane and alterations in diabetes: decreased levels of heparan sulfate proteoglycan and laminin. Diabetes 1987; 36: 374–381.CrossRefPubMedGoogle Scholar
  44. 44.
    Olgemøller B, Schwabbe S, Gerbitz KD, Schleicher ED. Elevated glucose decreases the content of a basement associated heparan sulphate proteoglycan in proliferating cultured porcine mesangial cells. Diabetologia 1992; 35: 183–186.CrossRefPubMedGoogle Scholar
  45. 45.
    Brownlee M, Vlassara H, Cerami A. Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Intern Med 1984; 101: 527–537.CrossRefPubMedGoogle Scholar
  46. 46.
    Berg TJ, Torjesen PA, bangstad H-J, Bucala R, Østerby R, Hanssen KF. Advanced glycosylation endproducts are related to changes in kidney morphology in type 1 diabetic patients (Abstract). Diabetologia 1995; 38: 179A.Google Scholar
  47. 47.
    Østerby R, Nyberg G. New vessel formation in the renal corpuscles in advanced diabetic glomerulopathy. J Diabetic Compl 1987; 1: 122–127.CrossRefGoogle Scholar
  48. 48.
    Østerby R. Renal pathology in diabetes mellitus. Curr Opin Nephrol Hypertens 1993; 2: 475–483.CrossRefPubMedGoogle Scholar
  49. 49.
    Kashgarian M, Sterzel RB. The pathobiology of the mesangium. Kidney Int 1992; 41: 524–529.CrossRefPubMedGoogle Scholar
  50. 50.
    Hawkins NJ, Wakefield D, Charlesworth JA. The role of mesangial cells in glomerular pathology. Pathology 1990; 22: 24–32.CrossRefPubMedGoogle Scholar
  51. 51.
    Rudberg S, Østerby R, Dahlquist G, Nyberg G, Persson B. Predictors of renal morphological changes in the transitional stage of microalbuminuria in IDDM adolescents. (Abstract). Diabetologia 1996; 39:Suppl. 1: A301.Google Scholar
  52. 52.
    Østerby R. Lessons from kidney biopsies. Diabetes/Metabolism Reviews 1996; 12: in press.Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Hans-Jacob Bangstad
    • 1
  • Ruth Østerby
    • 1
  1. 1.Department of PediatricsAker Sykehus, Oslo, Norway and Laboratory for Electron Microscopy, Aarhus KommunehospitalAarhusDenmark

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