Role of angiotensin II in diabetic nephropathy

Thomas M. Kennefick, Sharon Anderson

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations


Classically, the renin-angiotensin system (RAS) in diabetes was thought to be suppressed, and relatively unimportant in the regulation of hemodynamics and the development of complications. However, recent developments have caused reconsideration of this notion. Studies of pharmacological interruption of the RAS with angiotensin converting enzyme (ACE) inhibition have implicated this hormonal system in the progression of diabetic nephropathy, both experimentally and clinically. Preliminary evidence also suggests a beneficial effect of angiotensin II (ANG II) receptor antagonists. The relative roles of the systemic versus intrarenal RAS in the pathogenesis of diabetic nephropathy have recently been evaluated. Although plasma renin level is generally low, it is not yet clear whether RAS component processing is normal in diabetes; there may be subtle changes in ANG II metabolism that sustain relatively higher plasma ANG II levels. Furthermore, the intrarenal RAS may not be suppressed. Renal renin levels tend to be disproportionately elevated, as compared with plasma renin values. Renal ANG II levels are normal, and renal mRNAs for RAS components have been variable. In general, lack of RAS suppression (despite plasma volume volume and increased exchangeable sodium) may indicate inappropriate activity of the RAS in diabetes. RAS-mediated injury may occur via stimulation of a number of sclerosing mediators, and there is evidence that hyperglycemia acts synergistically with ANG II to promote cellular injury. Finally, various RAS candidate genes for development of diabetic nephropathy have been examined and, although controversy remains, ACE gene polymorphisms may be involved. Together, these recent investigations lend further support to the notion that the RAS plays an important role in diabetic nephropathy, and are beginning to shed light on the mechanisms of progressive renal injury.

Original languageEnglish (US)
Pages (from-to)441-447
Number of pages7
JournalSeminars in nephrology
Issue number5
StatePublished - 1997

ASJC Scopus subject areas

  • Nephrology


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