Natural History of Diabetic Nephropathy

  • Eli A. Friedman
Part of the Developments in Nephrology book series (DINE, volume 9)


Pathophysiologic and clinical manifestations of kidney damage are duration related in the type I diabetic. They appear according to a well-described sequence beginning with glomerular hyperfiltration and reversible proteinuria, progressing through fixed massive proteinuria (nephrotic syndrome), and ending in renal insufficiency. Uremia, the end result of relentless nephropathy, is usually associated with severe visual loss or blindness (renal-retinal syndrome). A similar sequence may take place in the type II diabetic. Lack of precision in establishing the onset of type II diabetes, however, prevents construction of a timed natural history. Furthermore, the type II diabetic is older and may have systemic atherosclerosis, with consequent strokes and heart attacks, obscuring the course of kidney damage. Over the past decade, in the United States and Western Europe, uremia complicating diabetic nephropathy has emerged as the most prevalent (12.2% of Medicare funded uremic patients), accurately diagnosed cause of renal failure treated by maintenance hemodialysis or renal transplantation [1]. While “glomerulonephritis” (28.4%) and “hypertension” (17.4%) are reported more frequently, these diagnoses are usually employed as synonyms for unexplained kidney failure associated with small kidneys in the majority of patients so labeled. Diabetic nephropathy is the diagnosis applied to a minimum of 20% and as many as 45% of new dialysis patients, depending on the region of the country reporting.


Diabetic Nephropathy Plasma Renin Activity Glomerular Basement Membrane Serum Creatinine Concentration Congenital Nephrotic Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Sugimoto T, Rosansky SJ. The incidence of treated end stage renal disease in the Eastern United States: 1973–1979. Amer J Public Health 74: 14–17, 1984.Google Scholar
  2. 2.
    Mogensen CE. Editorial review: microalbuminuria and incipient diabetic nephropathy. Diabetic Nephropathy 3: 75–78, 1984.Google Scholar
  3. 3.
    Rasch R. Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. Kidney size and glomerular volume. Diabetologia 16: 125–128, 1979.PubMedCrossRefGoogle Scholar
  4. 4.
    Viberti GC. Early functional and morphological changes in diabetic nephropathy. Clin Nephrol 12: 47–53, 1979.PubMedGoogle Scholar
  5. 5.
    Parving HH, Osenboll B, Svendsen PA, Christiansen JS, Andersen AR. Early detection of patients at risk of developing diabetic nephropathy: a longitudinal study of urinary albumin excretion. Acta endocrinol 100: 550–555, 1982.PubMedGoogle Scholar
  6. 6.
    Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311: 89–93, 1984.PubMedCrossRefGoogle Scholar
  7. 7.
    Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity- onset diabetes. N Engl J Med 310: 356–360, 1984.PubMedCrossRefGoogle Scholar
  8. 8.
    Brenner BM, Hostetter TH, Humes HD. Molecular basis of proteinuria in glomerular origin. N Engl J Med 298: 826–833, 1978.PubMedCrossRefGoogle Scholar
  9. 9.
    Editorial. Charge and the kidney. Lancet 3: 732, 1984.Google Scholar
  10. 10.
    Vernier RL, Klein DJ, Sisson SP, Mahan JD, Oegema TR, Brown DM. Heparin sulfate rich anionic sites in the human glomerular basement membrane. Decreased concentration in congenital nephrotic syndrome. N Engl J Med 309: 1001–1009, 1983.PubMedCrossRefGoogle Scholar
  11. 11.
    Mauer SM, Fish AJ, Day NK, Michael AF. The glomerular mesangium. II. Quantitative studies of mesangial function in nephrotoxic nephritis in rats. J Clin Invest 53:431-–439, 1974.Google Scholar
  12. 12.
    Mauer SM, Shvil Y. The glomerular mesangium. In: Renal Disease, Black Sir D, Jones NF (eds). Oxford: Blackwell Sci Publ 93:106, 1979.Google Scholar
  13. 13.
    Mauer SM, Steffes MW, Brown DM. The kidney in diabetes. Am J Med 70: 603–612, 1981.PubMedCrossRefGoogle Scholar
  14. 14.
    Mauer SM, StefFes MW, Chern M, Brown DM. Mesangial uptake and processing of macromoleculles in rats with diabetes mellitus. Lab Invest 41: 401–406, 1979.PubMedGoogle Scholar
  15. 15.
    Osterby R. Early phases in the development of diabetic glomerulopathy. Acta Med Scand (Suppl) 574: 1–82, 1975.Google Scholar
  16. 16.
    Foglia VG, Manccini RE, CarCardeza AF. Glomerular lesions in the diabetic rat. Arch Pathol Lab Med 50: 75 - 83, 1950.Google Scholar
  17. 17.
    Ireland JT. Diagnostic criteria in the assessment of glomerular capillary basement membrane lesions in newly diagnosed juvenile diabetics. In: Early Diabetes, Camerini-Davalos RA, Cole HS (eds). New York: Academic Press, 1970, p. 273.Google Scholar
  18. 18.
    Castells S, Tejani A, Nicastri AD, Chen CK, Fusi M-A, Sen D. Diabetic nephropathy: early renal changes in adolescent insulin-dependent diabetics. Diabetic Nephropathy 3: 15–18, 1984.Google Scholar
  19. 19.
    Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J. Physiol 24: F85–93, 1981.Google Scholar
  20. 20.
    Olson JL, Hostetter TH, Rennke HG, Brenner BM, Venkatachalam MA. Altered glomerular permselectivity and progressive sclerosis. Kidney Internat 22: 112–116, 1982.CrossRefGoogle Scholar
  21. 21.
    Deckert T, Bo F-R, Mathiesen ER, Baker L. Pathogenesis of incipient nephropathy: a hypothesis. Diabetic Nephropathy 3: 83–88, 1984.Google Scholar
  22. 22.
    Kimmelstiel P, Wilson C. Intercapillary lesions in glomeruli of kidney. Am J Pathol 12: 83–98, 1936.PubMedGoogle Scholar
  23. 23.
    Gellman DD, Pirani CC, Soothill JF, Muehreke RC, Kark RM. Diabetic nephropathy; a clinical and pathologic study based on renal biopsies. Medicine 38: 321–368, 1959.PubMedGoogle Scholar
  24. 24.
    Burkholder PM. Renal disease associated with diabetes mellitus. In: Atlas of Human Glomerular Pathology, Burkholder PM (ed). Hagerstown, Md.: Harper and Row, 1974, p. 325.Google Scholar
  25. 25.
    Mogensen CE. Renal function changes in diabetes. Diabetes 25: 872–879, 1976.PubMedGoogle Scholar
  26. 26.
    Parving H-H, Oxenboll B, Svendsen PA, Christiansen JS, Andersen An AR. Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion. Acta Endo 100: 550–555, 1982.Google Scholar
  27. 27.
    Jerums G, Seeman E, Murray RML, Edgley S, Markwick K, Goodall I, Young VH. Remission and progression of trace proteinuria in type I diabetes. Diabetic Nephropathy 3: 104–111, 1984.Google Scholar
  28. 28.
    Viberti GC. Effect of control of blood glucose on urinary excretion of albumin and B2- microglobulin in insulin-dependent diabetes. New Eng J. Med 300: 638–641, 1979.PubMedCrossRefGoogle Scholar
  29. 29.
    Caird RI. Survival of diabetics with proteinuria. Diabetes 10: 178–181, 1961.PubMedGoogle Scholar
  30. 30.
    Mogensen CE. Renal function changes in diabetes. Diabetes 25: 872–879, 1976.PubMedGoogle Scholar
  31. 31.
    Rutherford WE, Blondin J, Miller JP, Greenwalt AS, Vavra JD. Chronic progressive renal disease: rate of change of serum creatinine concentration. Kid Int 11: 62–70, 1977.CrossRefGoogle Scholar
  32. 32.
    Jones RH, Mackay JD, Hayakawa H, Parsons V. Progression of diabetic nephropathy. Lancet 1: 1105–1106, 1979.PubMedCrossRefGoogle Scholar
  33. 33.
    Hatch FE, Watt MF, Kramer NC, Parrish AE, Howe JS. Diabetic glomerulosclerosis: a long- term follow-up study based on renal biopsies. Am J Med 31: 216–230, 1961.CrossRefGoogle Scholar
  34. 34.
    Lipson LG. Special problems in treatment of hypertension in the patient with diabetes mellitus. Arch Int Med 144: 1829–1831, 1984.CrossRefGoogle Scholar
  35. 35.
    Morgensen CE, Christensen CK, Christensen NJ, Gundersen HJG, Jacobssen FK, Pedersen EB, Vittinghus E. Renal protein handling in normal hypertensive and diabetic man. Contr Nephrol 24: 139–152, 1981.Google Scholar
  36. 36.
    Morgensen CE. Antihypertensive treatment inhibiting the progression of diabetic nephropathy. Acta endocr, Copenh 94: (suppl 238) 103–108, 1980.Google Scholar
  37. 37.
    Christlieb AP. Diabetes and hypertensive vascular disease. Am J Cardiol 32: 592–606, 1973.PubMedCrossRefGoogle Scholar
  38. 38.
    Christlieb AR, Kaldany A, D’Elia JA. Plasma renin activity and hypertension in diabetes mellitus. Diabetes 25: 969–974, 1976.PubMedCrossRefGoogle Scholar
  39. 39.
    Christensen NJ. Plasma catecholamines in long-term diabetics with and without neuropathy and in hypophysectomized subjects. J Clin Invest 51: 779–787, 1972.PubMedCrossRefGoogle Scholar
  40. 40.
    Day RP, Leutscher JA, Gonzales CM. Occurrence of big renin in human plasma, amniotic fluid, and kidney extracts. J Clin Endocrinol Metab 40: 1078–1084, 1975.PubMedCrossRefGoogle Scholar
  41. 41.
    Schindler AM, Sommers SC. Diabetic sclerosis of the renal juxtaglomerular apparatus. Lab Invest 15: 877–884, 1966.PubMedGoogle Scholar
  42. 42.
    Kass EH. Asymptomatic infections of the urinary tract. Trans Assoc Am Physicians 69: 56–64, 1956.PubMedGoogle Scholar
  43. 43.
    Kunin CM, Southall I, Paguin AJ. Epidemiology of urinary tract infection: pilot study of 3057 school children. N Engl J Med 263: 817–823, 1960.PubMedCrossRefGoogle Scholar
  44. 44.
    Harkonen S, Kjellstrand CM. Exacerbation of diabetic renal failure following intravenous pyelography. Am J. Med 63: 939–946, 1977.PubMedCrossRefGoogle Scholar
  45. 45.
    Bennett WM, Muther RS, Parker RA, Feig P, Morrison G, Golper TA, Singer I. Drug therapy in renal failure: dosing guidelines for adults. Part I: Antimicrobial agents, analgesics. Ann Int Med 93: 62–89, 1980.PubMedGoogle Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1986

Authors and Affiliations

  • Eli A. Friedman

There are no affiliations available

Personalised recommendations