In patients with chronic kidney disease, SGLT2 inhibitors and mineralocorticosteroid receptor agonists (MRAs) reduce urinary albumin-to-creatinine ratio (UACR) and impart renoprotective and cardioprotective effects. In the abstract presented below, the authors have examined the efficacy and safety of the SGLT2 inhibitor dapagliflozin and MRA eplerenone alone and in combination in patients with CKD with and without type 2 diabetes.

The trial was a randomized open-label cross-over in nature. The study population included individuals with urinary albumin excretion ≥100 mg/24-hour, eGFR 30-90 mL/min/1.73m2 who had been receiving maximum tolerated stable doses of ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB). The patients were randomized to 4-weeks treatment periods with dapagliflozin 10 mg/day, eplerenone 50 mg/day or their combination. These were separated by 4-week wash-out periods. The primary outcome was the correlation in UACR changes between treatments. Secondary outcome was the percent change in 24-hour UACR from baseline.

Overall, 57 patients were screened, of these 46 were randomly assigned (mean eGFR 58.1 mL/min/1.73m², median UACR 401 mg/g) of whom 32 had type 2 diabetes and 14 did not have diabetes. After 4 weeks of treatment, the mean percentage change from baseline in UACR with dapagliflozin, eplerenone, and dapagliflozin-eplerenone treatment was -19.6% (95%CI -34.3, -1.5), -33.7% (95%CI -46.1, -18.5), and -53.0% (95%CI -61.7, -42.4; p<0.001 vs dapagliflozin; p=0.0127 vs eplerenone). After 4 weeks treatment with dapagliflozin-eplerenone, the change in UACR was consistent in patients with type 2 diabetes (-54.5% [95%CI -64.6, -41.5]) and without diabetes (-49.1[95% -65.1, -28.2]). There was no correlation between the UACR change during dapagliflozin or eplerenone treatment and UACR change during dapagliflozin-eplerenone (r=-0.13; p=0.473; r=-0.08; p=0.658 respectively). Eplerenone group more frequently reported hyperkalemia (N = 8[17.4%]) as compared to dapagliflozin (N=0, [0%]), or dapagliflozin-eplerenone groups (N=2, [4.3%]; P between-groups=0.0033).

It can be concluded from this study that combination of dapagliflozin with eplerenone causes a considerable additive UACR lowering effect and this effect is similar between patients with and without type 2 diabetes.