Skip to main content
SpringerLink
Log in

Diabetic Nephropathy: Pathophysiology, Clinical Course and Susceptibility

  • Chapter
Renal Eicosanoids

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 259))

Abstract

The clinical diagnosis of diabetic nephropathy in an insulin-dependent patient relies on the detection of persistent proteinuria (i.e., urinary total protein excretion rate greater than 0.5 g/24h) after 10 years or more of the disease, with concomitant diabetic retinopathy and rising arterial pressure, but without signs of other renal disease, urinary tract infection or heart failure. Diabetic glomerulosclerosis is found at renal biopsy in over 90% of the cases, confirming the diagnosis (1,2). Epidemiological studies show that, cumulatively, nephropathy develops in approximately 35% of insulin-dependent patients, and it is mostly in this kind of patient that the natural history of this disorder has been outlined (1,3). Noninsulin-dependent diabetics of European origin seem to develop nephropathy less frequently than insulin-dependent patients, but because of their larger number, the actual number of patients developing end-stage renal failure is approximately the same (4).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. A.R. Andersen, J. S. Christiansen, J.K. Andersen, S. Kreiner, T. Deckert, Diabetic nephropathy in Type I (insulin-dependent) diabetes: an epidemiological study, Diabetologia 25:496–501 (1983).

    Article  PubMed  CAS  Google Scholar 

  2. A.C. Thomsen, The kidney in diabetes mellitus, Thesis, Copenhagen, Munksgaard (1965).

    Google Scholar 

  3. A.S. Krolewski, J.H. Warram, A.R. Christlieb, E.J. Busick, C.R. Kahn, The changing natural history of nephropathy in Type I diabetes, Am. J. Med. 78:785–794 (1985).

    Article  PubMed  CAS  Google Scholar 

  4. B. Rettig and S.M. Teusch, The incidence of end-stage renal failure in Type I and Type II diabetes mellitus, Diab. Nephropathy 3:26–27 (1984).

    Google Scholar 

  5. G.C. Viberti, R.W. Bilous, D. Mackintosh, H. Keen, Monitoring glomerular function in diabetic nephropathy. A prospective study, Am. J. Med. 74:256–264 (1983).

    Article  PubMed  CAS  Google Scholar 

  6. H.H. Parving, A.R. Andersen, U.M. Smidt, E. Hommel, E.R. Mathiesen, P.A. Svendsen, Effect of antihypertensive treatment on kidney function in diabetic nephropathy, Brit. Med. J. 294:1443–1447 (1987).

    Article  CAS  Google Scholar 

  7. E.R. Mathiesen, B. Oxenboll, K. Johansen, P. Aa Svendsen, T. Deckert, Incipient nephropathy in Type I (insulin-dependent) diabetes, Diabetologia 26:406–410 (1984).

    Article  PubMed  CAS  Google Scholar 

  8. M.J. Wiseman, G.C. Viberti, D. Mackintosh, R.J. Jarrett, H. Keen, Glycemia, arterial pressure and microalbuminuria in Type I (insulin-dependent) diabetes mellitus, Diabetologia 26:401–405 (1984).

    Article  PubMed  CAS  Google Scholar 

  9. G.C. Viberti and H. Keen, The patterns of proteinuria in diabetes mellitus, Diabetes 33:686–692 (1984).

    PubMed  CAS  Google Scholar 

  10. G.C. Viberti, R.W. Bilous, D. Mackintosh, J.J. Bending, H. Keen, Longterm correction of hyperglycemia and progression of renal failure in insulin-dependent diabetes, Br. Med. J. 286:598–602 (1983).

    Article  CAS  Google Scholar 

  11. J.J. Bending, G.C. Viberti, P.J. Watkins, H. Keen, Intermittent clinical proteinuria and renal function in diabetes: evolution and effect of glycemic control, Br. Med. J. 292:83–86 (1986).

    Article  CAS  Google Scholar 

  12. S. Bjorck, G. Nyberg, H. Mulec, G. Granerus, H. Herlitz, M. Aurell, Beneficial effects of angiotensin-converting enzyme inhibition on renal function in patients with diabetic nephropathy, Br. Med. J. 293:471–474 (1986).

    Article  CAS  Google Scholar 

  13. E. Hommel, H.H. Parving, E. Mathiensen, B. Edsberg, M.D. Nielsen, J. Giese, Effect of Captopril on kidney function in insulin-dependent diabetic patients with nephropathy, Br. Med. J. 293:467–470 (1986).

    Article  CAS  Google Scholar 

  14. A.C. Taguma, Y. Kitamoto, G. Futaki, H. Ueda, H. Monma, M. Ishizakli, H. Takalashli, H. Sekino, Y. Sasaki, Effects of Captopril on heavy proteinuria in azotemic diabetics, N. Engl. J. Med. 313:1617–1620 (1985).

    Article  PubMed  CAS  Google Scholar 

  15. R. Zatz, T. Dunn, S. Meyer, S. Anderson, H.G. Rennke, B.M. Brenner, Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension, J. Clin. Invest. 77: 1925–1930 (1986).

    Article  PubMed  CAS  Google Scholar 

  16. J. Bergstrom, Discovery and rediscovery of low-protein diet, Clin. Nephrol. 21(1):29–35 (1984).

    PubMed  CAS  Google Scholar 

  17. J.B. Rosman, S. Meijer, W.J. Sluilter, P.M.T. Wee, T. Piers-Becht, A.J.M. Dunker, Prospective randomized trial of early dietary protein restriction in chronic renal failure, Lancet II:1291–1295 (1984).

    Article  Google Scholar 

  18. P-O. Attman, H. Bucht, O. Larsson, G. Uddebom, Protein-reduced diet in diabetic renal failure, Clin. Nephrology 19:217–220 (1983).

    CAS  Google Scholar 

  19. J.J. Bending, R. Dodds, J.D. Walker, H. Keen, G.C. Viberti, Dietary protein restriction delays the progression of diabetic renal failure, Diabetologia 30:598A (1987).

    Google Scholar 

  20. K. Borch-Johnsen, P.K. Andersen, T. Deckert, The effect of proteinuria on the relative mortality in Type I (insulin-dependent) diabetes mellitus, Diabetologia 28:590–596 (1985).

    Article  PubMed  CAS  Google Scholar 

  21. K. Borch-Johnsen and S. Kreiner, Proteinuria: value as predictor of cardiovascular mortality in insulin-dependent diabetes mellitus, Br. Med. J. 294:1651–1654 (1987).

    Article  CAS  Google Scholar 

  22. C.E. Mogensen, Renal function changes in diabetes, Diabetes 25:872–879 (1976).

    PubMed  CAS  Google Scholar 

  23. H. Keen and C. Chlouverakis, An immunoassay for urinary albumin at low concentration, Lancet II:913–916 (1963).

    Article  Google Scholar 

  24. G.C. Viberti, J.C. Pickup, R.J. Jarrett, H. Keen, Effect of control of blood glucose on urinary excretion of albumin and B2 microglobulin in insulin-dependent diabetics, N. Engl. J. Med. 300:638–642 (1979).

    Article  PubMed  CAS  Google Scholar 

  25. C.E. Mogensen and C.K. Christensen, Predicting diabetic nephropathy insulin-dependent patients, N. Engl. J. Med. 311:89–93 (1984).

    Article  PubMed  CAS  Google Scholar 

  26. H.H. Parving, E. Hommel, E. Mathiesen, P. Skott, B. Edsberg, M. Bahnsen, M. Lauritzen, P. Hougaard, E. Lauritzen, Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin-dependent diabetes, Br. Med. J. 296:156–160 (1988).

    Article  CAS  Google Scholar 

  27. G.C. Viberti, M.J. Wiseman, S. Redmond, Microalbuminuria: Its history and potential for prevention of clinical nephropathy in diabetes mellitus, Diab. Nephropath. 3:70–82 (1984).

    Google Scholar 

  28. B. Feldt Rasmussen and E. Mathiesen, Variability of urinary albumin excretion in incipient diabetic nephropathy, Diab. Nephropath. 3:101–103 (1984).

    Google Scholar 

  29. D.J.F. Rowe, H. Bagga, P.B. Betts, Normal variations in the rate of albumin excretion and albumin to creatinine ratios in overnight and daytime urine collections in nondiabetic children, Br. Med. J. 291:693–694 (1985).

    Article  CAS  Google Scholar 

  30. D.L. Cohen, C.L. Close, G.C. Viberti, The variability of overnight urinary albumin excretion in insulin-dependent and normal subjects, Diab. Med. 4:437–440 (1987).

    Article  CAS  Google Scholar 

  31. G.C. Viberti, R.D. Hill, R.J. Jarrett, U. Mahamud, H. Keen, Microalbuminuria as predictor of clinical nephropathy in insulin-dependent diabetes mellitus, Lancet I:1430–1432 (1982).

    Article  Google Scholar 

  32. B. Feldt-Rasmussen, E.R. Mathiesen, T. Deckert, Effect of two years of strict metabolic control of progression of incipient nephropathy in insulin-dependent diabetes, Lancet II:1300–1304 (1986).

    Article  Google Scholar 

  33. C.F. Close, On behalf of the Microalbuminuria Collaborative Study. The prevalence of at-risk microalbuminurics in a population of nonproteinuric, insulin-dependent diabetic subjects, Diabetic Med.:328A (1986).

    Google Scholar 

  34. P. Cambier, Application de la theorie de Rehberg a l’etude clinique des affections renales et du diabete, Annales de Medicine 35:273–299 (1934).

    Google Scholar 

  35. E. Fiaschi, B. Grassi, G. Andres, La funzione renale nel diabete mellito, Rassegna di fisiopatologia clinica e terapeutica 4:373–410 (1952).

    Google Scholar 

  36. J. Ditzel and M. Schwartz, Abnormal glomerular filtration rate in shortterm insulin-treated diabetic subjects, Diabetes 16:264–267 (1967).

    PubMed  CAS  Google Scholar 

  37. C.E. Mogensen, Glomerular filtration rate and renal plasma flow in short-term and long-term juvenile diabetes mellitus, Scan. J. Clin. Lab. Invest. 28:91–100 (1971).

    Article  CAS  Google Scholar 

  38. J.S. Christiansen, J. Gammelgaard, M. Frandsen, H.H. Parving, Increased kidney size, glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics, Diabetologia 20:451–456 (1981).

    PubMed  CAS  Google Scholar 

  39. M.J. Wiseman, G.C. Viberti, H. Keen, Threshold effect of plasma glucose in the glomerular hyperfiltration of diabetes, Nephron 38:257–260 (1984).

    Article  PubMed  CAS  Google Scholar 

  40. G. Stalder and R. Schmid, Severe functional disorders of glomerular capillaries and renal hemodynamics in treated diabetes mellitus during childhood, Ann. Paediatri. 193:129–138 (1959).

    CAS  Google Scholar 

  41. T.H. Hostetter, J.C. Troy, B.M. Brenner, Glomerular hemodynamics in experimental diabetes mellitus, Kidney Int. 19:410–415 (1981).

    Article  PubMed  CAS  Google Scholar 

  42. P.K. Jensen, J.S. Christiansen, K. Steven, H.H. Paving, Renal function in streptozotocin-diabetic rats, Diabetologia 21:409–414 (1981).

    Article  PubMed  CAS  Google Scholar 

  43. E. Hommel, E. Mathiesen, S. Arnold-Larsen, B. Edsberg, U.B. Olsen, H.H. Parving, Effects of indomethacin on kidney function in Type I (insulin-dependent) diabetic patients with nephropathy, Diabetologia 30:78–81 (1987).

    PubMed  CAS  Google Scholar 

  44. M. Schambelan, S. Blake, J. Sraer, M. Bens, M.P. Nivez, F. Wahbe, Increased prostaglandin production by glomeruli isolated from rats with streptozotocin-induced diabetes mellitus, J. Clin. Invest. 75:404–412 (1985).

    Article  PubMed  CAS  Google Scholar 

  45. R. Barnett, L. Scharschmidt, K.O. Young-Hyeh, D. Schlondorff, Comparison of glomerular and mesangial prostaglandin synthesis and glomerular contraction in two rat models of diabetes mellitus, Diabetes 36:1468–1475 (1987).

    Article  PubMed  CAS  Google Scholar 

  46. D.M. Brown, M.W. Steffes, P. Thibert, S. Azar, S.H. Mauer, Glomerular manifestation of diabetes in the BB rat, Metabolism 32:5131–5135 (1983).

    Google Scholar 

  47. A.F. Nakhooda, A.A. Like, C.I. Chappel, F.T. Murray, B.B. Marliss, The spontaneously diabetic Wistar rat: metabolic and morphologic studies, Diabetes 26:100–112 (1977).

    Article  PubMed  CAS  Google Scholar 

  48. A.J. Cohen, D.M. McCarthy, R.R. Rossetti, Renin secretion by the spontaneously diabetic rat, Diabetes 35:341–346 (1986).

    Article  PubMed  CAS  Google Scholar 

  49. J.I. Kreisberg and P.Y. Patel, The effects of insulin, glucose and diabetes on prostaglandin production by rat kidney glomeruli and cultured glomerular mesangial cells, Prostaglandins Leukotrienes Med. 11:431–442 (1983).

    Article  CAS  Google Scholar 

  50. P.K. Jensen, K. Steven, H. Blaehr, J.S. Christiansen, H.H. Parving, Effects of indomethacin on glomerular hemodynamics in experimental diabetes, Kidney Int. 29:490–495 (1986).

    Article  PubMed  CAS  Google Scholar 

  51. P.A. Craven, M.A. Caines, F.R. DeRubertis, Sequential alterations in glomerular prostaglandin and thromboxane synthesis in diabetic rats: relationship to the hyperfiltration of early diabetes, Metabolism 36: 95–103 (1987).

    Article  PubMed  CAS  Google Scholar 

  52. O.I. Moel, R.L. Safirstein, R.C. McEvoy, W. Hsueh, Effect of aspirin onexperimental diabetic nephropathy, J. Lab. Clin. Med. 110:300–307 (1987).

    PubMed  CAS  Google Scholar 

  53. N. Bank, M.A.G. Lahorra, H.S. Aynedjian, D. Schlondorff, Vasoregulatory hormones and the hyperfiltration of diabetes, Am. J. Physiol. 254: F202-F209 (1988).

    PubMed  CAS  Google Scholar 

  54. E. Esmatjes, M.R. Fernandez, I. Halpern, J. Camps, J. Gaye et al., Renal hemodynamic abnormalities in patients with short-term insulin-dependent diabetes mellitus: role of renal prostaglandins, J. Clin. Endocrinol. Metab. 60:1231–1236 (1985).

    Article  PubMed  CAS  Google Scholar 

  55. S. Gambardella, G. Pugliese, A. Napoli, S. Morano, P. Pietravalle, F. Pugliese, G. Stirati, D. Andreani, Urinary excretion of prostaglandins and renal hemodynamics in Type I (insulin-dependent) diabetes at onset: effect of piroxicam, Diabetologia 29:53A (1986).

    Article  Google Scholar 

  56. G.C. Viberti, A. Benigni, E. Bognetti, G. Remuzzi, M.J. Wiseman, Glomerular hyperfiltration and urinary prostaglandins in insulin-dependent diabetes mellitus, In preparation.

    Google Scholar 

  57. J.S. Christiansen, B. Feldt-Rasmussen, H.H. Parving, Short-term inhibition of prostaglandin in synthesis has no effect on the elevated glomerular filtration rate of early insulin-dependent diabetes, Diabetic Med. 2:17–20 (1985).

    Article  PubMed  CAS  Google Scholar 

  58. M.J. Wiseman, R. Mangili, H. Alberetto, H. Keen, G.C. Viberti, Glomerular response mechanisms to glycemic changes in insulin-dependent diabetics, Kidney Int. 31:1012–1018 (1987).

    Article  PubMed  CAS  Google Scholar 

  59. B.L. Kasiske, M.P. O’Donneil, W.F. Keane, Glucose-induced increases in renal hemodynamic function: possible modulation by renal prostaglandins, Diabetes 34:360–364 (1985).

    Article  PubMed  CAS  Google Scholar 

  60. D.A. Collier, D.M. Matthews, G. Beel, M.L. Watson, B.F. Clarke, Increased urinary excretion of 6-keto PGF1α and PGE2 in male insulin-dependent diabetics, Diabetic Med. 3:358A (1986).

    Google Scholar 

  61. E. Esmatjes, I. Levy, J. Gaya, F. Rivera, Renal excretion of prostaglandin E2 and plasma renin activity in Type I diabetes mellitus: relationship to normoglycemia achieved with artificial pancreas, Diabetes Care 10:428–431 (1987).

    Article  PubMed  CAS  Google Scholar 

  62. G.C. Viberti and M.J. Wiseman, The kidney in diabetes: significance of early abnormalities, Clinics in Endocrin. Metab. 15:753–783 (1986).

    Article  CAS  Google Scholar 

  63. G.C. Viberti, R.J. Jarrett, M.J. Wiseman, Predicting diabetic nephropathy (letter), New Engl. J. Med. 311:1256–1257 (1984).

    Article  PubMed  CAS  Google Scholar 

  64. S.L. Jones, M.J. Wiseman, G.C. Viberti, H. Keen, Glomerular hyperfiltration and albuminuria — A 5-year prospective study in Type I (insulin-dependent) diabetes mellitus, Diabetologia 30:536A (1987).

    Article  Google Scholar 

  65. M.J. Wiseman, A.J. Saunders, H. Keen, G.C. Viberti, Effect of blood glucose control on increased glomerular filtration rate and kidney size in insulin-dependent diabetes, N. Engl. J. Med. 312:617–621 (1985).

    Article  PubMed  CAS  Google Scholar 

  66. J.J. Bending, G.C. Viberti, R.W. Bilous, H. Keen, For the Kroc Collaborative Study Group. Eight-month correction of hyperglycemia in insulin-dependent diabetes mellitus is associated with a significant and sustained reduction of urinary albumin excretion rates in patients with microalbuminuria, Diabetes 34 (Suppl.3):69–73 (1985).

    PubMed  Google Scholar 

  67. K. Dahl-Jorgensen, O. Brinchmann-Hansen, K. Hanssen et al., Effect of near normoglycemia for two years on progression of early diabetic retinopathy, nephropathy and neuropathy: The Oslo Study, Br. Med. J. 293:1195–1199 (1986).

    Article  CAS  Google Scholar 

  68. C.K. Christensen and C.K. Mogensen, Antihypertensive treatment: longterm reversal of progression of albuminuria in incipient diabetic nephropathy. A longitudinal study of renal function, J. Diab. Compilc. 1:45–53 (1987).

    CAS  Google Scholar 

  69. M. Marre, H. Leblanc, L. Suarez, T.T. Guyenne, J. Menard, P. Pasa, Converting enzyme inhibition and kidney function in normotensive diabetic patients with persistent microalbuminuria, Br. Med. J. 294:1448–1452 (1987).

    Article  CAS  Google Scholar 

  70. D.L. Cohen, R. Dodds, G.C. Viberti, Effects of protein restriction in insulin-dependent diabetics at risk of nephropathy, Br. Med. J. 294: 795–798 (1987).

    Article  CAS  Google Scholar 

  71. R. Zatz, T.W. Meyer, H. Rennke, B.M. Brenner, Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy, Proc. Natl. Acad. Sci. USA 82:5963–5967 (1985).

    Article  PubMed  CAS  Google Scholar 

  72. M.J. Wiseman, R. Hunt, A. Goodwin, J.L. Gross, H. Keen, G.C. Viberti, Dietary composition and renal function in healthy subjects, Nephron 46:37–42 (1987).

    Article  PubMed  CAS  Google Scholar 

  73. A. Beyer-Mears, The polyol pathway, sorbinil and renal dysfunction, Metabolism 35 (Suppl. 1):46–54 (1986).

    Article  PubMed  CAS  Google Scholar 

  74. W.G. Oakley, D.A. Pyke, R.B. Tattersail, P.J. Watkin, Long-term diabetes. A clinical study of 92 patients after forty years, Q. J. Med. 43:145–156 (1974).

    PubMed  CAS  Google Scholar 

  75. G.C. Viberti, H. Keen, M.J. Wiseman, Raised arterial pressure in parents of proteinuric insulin-dependent diabetics, Brit. Med. J. 295:575–577 (1987).

    Article  Google Scholar 

  76. R. Mangili, J.J. Bending, G.S. Scott, L.K. Li, A. Gupta, G.C. Viberti, Increased sodium-lithium countertransport activity in red cells of patients with insulin-dependent diabetes and nephropathy, N. Engl. J. Med. 318:146–149 (1988).

    Article  PubMed  CAS  Google Scholar 

  77. A.S. Krolewski, M. Canessa, J.H. Warram, L.M.B. Laffel, R. Christlieb, W.C. Knowles, L.I. Rand, Predisposition to hypertension and susceptibility to renal disease in insulin-dependent diabetes mellitus, N. Engl. J. Med. 318:140–145 (1988).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unit for Metabolic Medicine, UMDS (Guy’s Hospital Campus), London, SE1 9RT, UK

    GianCarlo Viberti M.D., MRCP & James D. Walker BSc, MRCP

Authors
  1. GianCarlo Viberti M.D., MRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James D. Walker BSc, MRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Case Western Reserve University, Cleveland, Ohio, USA

    Michael J. Dunn

  2. University Hospitals of Cleveland, Cleveland, Ohio, USA

    Michael J. Dunn

  3. Catholic University School of Medicine, Rome, Italy

    Carlo Patrono

  4. University of Rome “La Sapienza”, Rome, Italy

    Giulio A. Cinotti

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Plenum Press, New York

About this chapter

Cite this chapter

Viberti, G., Walker, J.D. (1989). Diabetic Nephropathy: Pathophysiology, Clinical Course and Susceptibility. In: Dunn, M.J., Patrono, C., Cinotti, G.A. (eds) Renal Eicosanoids. Advances in Experimental Medicine and Biology, vol 259. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5700-1_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-5700-1_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5702-5

  • Online ISBN: 978-1-4684-5700-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation