Clinical and Experimental Nephrology

, Volume 1, Issue 1, pp 3–11 | Cite as

Pathogenesis of diabetic nephropathy

  • Ryuichi Kikkawa
  • Masakazu Haneda
Review Article


Diabetic nephropathy is one of the most serious complications among patients with long-standing diabetes mellitus. In recent years, nearly one third of the patients newly admitted to dialysis therapy in Japan suffer from diabetic nephropathy. Hyperglycemia appears to play a major role in the pathogenesis of this disease, probably via glomerular hemodynamic changes, as well as via metabolic alterations in glomerular cells, although both pathways may interact with each other. Recently, an activation of protein kinase C has been advocated to be a critical mediator between hyperglycemia and diabetic nephropathy. Protein kinase C is known to induce the production of various extracellular matrix proteins, which may cause the expansion of glomerular mesangium. Administration of a specific inhibitor of the β isoform of protein kinase C corrected glomerular hyperfiltration in diabetic rats. In addition, genetic factors may be involved in the progression of diabetic nephropathy, since various clinical studies have indicated the familial clustering of this complication in diabetes mellitus. Although the association with gene polymorphism of angiotensin-converting enzyme has been extensively studied by several individual research groups, a decisive conclusion has not been obtained. Further research using multicenter studies enrolling large numbers of patients may be needed to detect nephropathic gene(s).

Key words

diabetic nephropathy protein kinase C glomerular hyperfiltration matrix proteins nephorpathic gene 


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Copyright information

© CEN/CLJ 1997

Authors and Affiliations

  • Ryuichi Kikkawa
    • 1
  • Masakazu Haneda
    • 1
  1. 1.Third Department of MedicineShiga UniversitySeta, OtsuJapan

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