The Dark Side of Blocking RAS in Diabetic Patients with Incipient or Manifested Nephropathy

Renin-angiotensin system (RAS) inhibitors are currently advocated as the first line approach for diabetic patients with high blood pressure, particularly if early signs of renal damage are manifest. This mostly relies on the supposed benefits of these drugs, either achieved indirectly by blood pressure lowering or directly by pleiotropic effects, on cardiovascular and renal outcomes. Yet, data from large randomized controlled trials and independent meta-analyses seem to raise some concerns on the compelling use of RAS-inhibitors in the whole diabetic population as improvements in cardiovascular and renal endpoints may not be as definite as generally believed. Furthermore, the risk of adverse events, such as hyperkalemia, deserves more attention in diabetic patients. In this brief review we aimed at summarizing the most relevant available evidence on "negative" or "null" effects of RAS-inhibitors on clinical outcomes in diabetic patients, providing reasons for a "personalized" rather than generalized use of these drugs according to individual characteristics.