Background: SGLT2 inhibitors and MRAs reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and mineralocorticoid receptor antagonists (MRA) eplerenone alone and in combination in patients with CKD. Methods: We conducted a randomized open-label cross-over trial in patients with urinary albumin excretion ≥100 mg/24-hour, eGFR 30-90 mL/min/1.73m2, who had been receiving maximum tolerated stable doses of an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients were assigned to 4-week treatment periods with dapagliflozin 10 mg/day, eplerenone 50 mg/day, or their combination in random order, separated by 4-week wash-out periods. Primary outcome was the correlation in UACR changes between treatments. Secondary outcome was the percent change in 24-hour UACR from baseline. Results: Of 57 patients screened, 46 were randomly assigned (mean eGFR 58.1 mL/min/1.73m2, median UACR 401 mg/g) to the three groups. Mean percentage change from baseline in UACR after 4 weeks treatment with dapagliflozin, eplerenone, and dapagliflozineplerenone 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). UACR change during dapagliflozin or eplerenone treatment did not correlate with UACR change during dapagliflozineplerenone (r=-0.13; p=0.473; r=-0.08; p=0.658 respectively). Hyperkalemia was more frequently reported with eplerenone (N=8, [17.4%]) compared to dapagliflozin (N=0, [0%]) or dapagliflozin-eplerenone (N=2, [4.3%]; Pbetween-groups=0.0033). Conclusion: Albuminuria changes in response to dapagliflozin and eplerenone did not correlate, supporting systematic rotation of these therapies to optimize treatment. Combining dapagliflozin with eplerenone resulted in a robust additive UACR lowering effect. A larger trial in this population is required to confirm long-term efficacy and safety of combined SGLT2 inhibitor and MRA treatment.
Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and their Combination in Patients with Chronic Kidney Disease: A Randomized Cross-over Clinical Trial
Garofalo C.Writing – Review & Editing
;De Nicola L.;
2022
Abstract
Background: SGLT2 inhibitors and MRAs reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and mineralocorticoid receptor antagonists (MRA) eplerenone alone and in combination in patients with CKD. Methods: We conducted a randomized open-label cross-over trial in patients with urinary albumin excretion ≥100 mg/24-hour, eGFR 30-90 mL/min/1.73m2, who had been receiving maximum tolerated stable doses of an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients were assigned to 4-week treatment periods with dapagliflozin 10 mg/day, eplerenone 50 mg/day, or their combination in random order, separated by 4-week wash-out periods. Primary outcome was the correlation in UACR changes between treatments. Secondary outcome was the percent change in 24-hour UACR from baseline. Results: Of 57 patients screened, 46 were randomly assigned (mean eGFR 58.1 mL/min/1.73m2, median UACR 401 mg/g) to the three groups. Mean percentage change from baseline in UACR after 4 weeks treatment with dapagliflozin, eplerenone, and dapagliflozineplerenone 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). UACR change during dapagliflozin or eplerenone treatment did not correlate with UACR change during dapagliflozineplerenone (r=-0.13; p=0.473; r=-0.08; p=0.658 respectively). Hyperkalemia was more frequently reported with eplerenone (N=8, [17.4%]) compared to dapagliflozin (N=0, [0%]) or dapagliflozin-eplerenone (N=2, [4.3%]; Pbetween-groups=0.0033). Conclusion: Albuminuria changes in response to dapagliflozin and eplerenone did not correlate, supporting systematic rotation of these therapies to optimize treatment. Combining dapagliflozin with eplerenone resulted in a robust additive UACR lowering effect. A larger trial in this population is required to confirm long-term efficacy and safety of combined SGLT2 inhibitor and MRA treatment.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
