Acute renal injury events in diabetic patients treated with SGLT2 inhibitors: A comprehensive review with a special reference to RAAS blockers.

Renin-angiotensin-aldosterone system (RAAS) blockers and sodium-glucose cotransporter type 2 inhibitors (SGLT2is) are two pharmacological classes that proved a remarkable nephroprotective effect, yet a risk of acute kidney injury (AKI) was also pointed out. In 2016, the US Food and Drug Administration recommended caution with the concomitant use of these medications. While the literature devoted to RAAS blockers remained surprisingly limited, numerous articles were published in recent years with SGLT2is. Safety analyses of large prospective cardiorenal trials showed a reduced rather than an increased number of AKI events in patients with type 2 diabetes treated with SGLT2is compared with those treated with placebo, despite the fact that a majority of patients received RAAS blockers at baseline. Interestingly, retrospective observational studies confirmed these reassuring findings in real-life conditions in more heterogeneous and possibly more frailty populations also commonly treated with RAAS blockers by showing a reduced risk of AKI with SGLT2is compared with other glucose-lowering drugs. Currently, there are no evidence of an increased risk of AKI with RAAS blocker-SGLT2i combinations in absence of haemodynamic instability. Several underlying mechanisms could explain a decreased rather than an increased risk of AKI with SGLT2is, including in patients treated with RAAS blockers.