Publications

J Am Soc Nephrol 2022; ahead of print doi:10.1681/ASN.2022020207

This trial demonstrates that the albuminuria-lowering effects of dapagliflozin and eplerenone alone are additive when used in combination. A larger trial in this population is required to confirm long-term efficacy and safety of combined sodium-glucose co-transporter-2 inhibitor (SGLT2i) and mineralocorticoid receptor antagonist (MRA) treatment, but this may support the idea that these classes have complementary nephroprotective effects.

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) have been used to prevent kidney failure in patients with chronic kidney disease (CKD) for decades – yet despite their proven efficacy, the risk of kidney failure remains high. New therapeutic options may be able to slow the progressive loss of kidney function in this population. SGLT2i and MRAs have been shown to reduce the urinary albumin-to-creatinine ratio (UACR) and confer both renal and cardiovascular protection. Recently it has been suggested that the nephroprotective effects of these two classes are possibly independent and complementary.

ROTATE-3 was a prospective, randomised, open-label, cross-over trial to assess efficacy and safety of dapagliflozin and eplerenone alone and in combination in 46 patients with CKD. The results showed a clinically relevant albuminuria reduction of 53% after 4 weeks of treatment. Combining dapagliflozin with eplerenone also resulted in a robust additive UACR-lowering effect. Overall the pattern of adverse events in these CKD patients was similar compared to previous reports in dapagliflozin or eplerenone, although the incidence of hyperkalaemia was significantly less with combination compared to eplerenone alone. These results have clinical significance, and support the idea of systematic rotation of these therapies to optimise treatment in CKD.