Does SGLT2 inhibition with dapagliflozin overcome individual therapy resistance to RAAS inhibition?

Abstract

Individual patients show a large variation in their response to renin-angiotensin-aldosteron system (RAAS) inhibition (RAASi), both in surrogates such as albuminuria and in hard renal outcomes. Sodium-glucose co-transporter 2 inhibitors (SGLT2) have been shown to lower albuminuria and to confer cardiovascular and, possibly, renal protection. To establish whether individual therapy resistance to RAASi can be overcome by adding an SGLT2 inhibitor, we assessed individual albuminuria responses in patients exposed to both RAASi and the SGLT2 inhibitor dapagliflozin. We used data from a randomized controlled cross-over trial designed to assess the albuminuria-lowering effect of 6-week treatment with dapagliflozin 10 mg/d. We extracted from the electronic medical records data on the albuminuria response upon initiation of RAASi before the trial period, and analysed individual albuminuria responses to RAASi and to dapagliflozin. We retrieved data on RAASi for 26 patients (age, 62 years [SD, 8]; female gender, 6 [23%]; 24-hour urinary albumin excretion, 521 [187-921] mg/24 h). The mean albuminuria-lowering response to RAASi was 26.5% (range, −76.1% to 135.1%). The addition of dapagliflozin res in a further reduction of 34.9%, (range, −83.9 to 94.2). Interestingly, the albuminuria response to RAASi significantly correlated with the response to dapagliflozin (Pearson correlation coefficient, 0.635 [95% CI, 0.328-0.821]; P