Angiotensin converting enzyme insertion/deletion polymorphism and renoprotection in diabetic and nondiabetic nephropathies

Piero Ruggenenti, Paola Bettinaglio, Franck Pinares, Giuseppe Remuzzi

Research output: Contribution to journalArticlepeer-review


Despite the huge amount of studies looking for candidate genes, the ACE gene remains the unique, well-characterized locus clearly associated with pathogenesis and progression of chronic kidney disease, and with response to treatment with drugs that directly interfere with the renin angiotensin system (RAS), such as angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA). The II genotype is protective against development and progression of type I and type II nephropathy and is associated with a slower progression of nondiabetic proteinuric kidney disease. ACE inhibitors are particularly effective at the stage of normoalbuminuria or microalbuminuria in both type I and type II diabetics with the Il genotype, whereas the DD genotype is associated with a better response to ARA therapy in overt nephropathy of type II diabetes and to ACE inhibitors in male patients with nondiabetic proteinuric nephropathies. The role of other RAS or non-RAS polymorphisms and their possible interactions with different ACE I/D genotypes are less clearly defined. Thus, evaluating the ACE I/D polymorphism is a reliable tool to identify patients at risk and those who may benefit the most of renoprotective therapy with ACE inhibitors or ARA. This may guide pharmacologic therapy in individual patients and help design clinical trials in progressive nephropathies. Moreover, it might help optimize prevention and intervention strategies at population levels, in particular, in countries where resources are extremely limited and 1 million patients continue to die every year of cardiovascular or renal disease.

Original languageEnglish
Pages (from-to)1511-1525
Number of pages15
JournalClinical Journal of the American Society of Nephrology
Issue number5
Publication statusPublished - Sep 2008

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Epidemiology
  • Critical Care and Intensive Care Medicine

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