Efficacy and safety of non-steroidal mineralocorticoid receptor antagonist and SGLT2 inhibitor combination therapy versus SGLT2-inhibitor monotherapy in patients with chronic kidney disease with albuminuria: a systematic review and meta-analysis of randomized controlled trials.
Khubaib Mohammad Murtafa, Sadiya Sajad Khanday, Rohit Vondivillu Srinivasan et al.
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In 30 seconds
This systematic review and meta-analysis pooled four randomized controlled trials involving 1835 adults with albuminuric chronic kidney disease, comparing a non-steroidal mineralocorticoid receptor antagonist (nsMRA) plus an SGLT2 inhibitor with SGLT2-inhibitor monotherapy. Combination therapy was associated with a greater reduction in albumin-creatinine ratio (ratio of means 0.67, 95% CI 0.63-0.72), corresponding to an approximate 33% reduction. It also increased the likelihood of achieving specified albuminuria reductions, but raised serum potassium and hyperkalemia risk. Overall eGFR, adverse events, and serious adverse events did not differ.
Key findings
- Combination therapy reduced albumin-creatinine ratio versus monotherapy (ratio of means 0.67, 95% CI 0.63-0.72), an approximate 33% reduction.
- The likelihood of achieving ≥ 30% and ≥ 50% albumin-creatinine ratio reductions was higher with combination therapy (RR = 1.36 and RR = 1.76, respectively).
- Serum potassium increased modestly (MD = 0.11 mmol/L), and hyperkalemia risk was higher short term (RR = 1.55) and long term.
- There was no overall eGFR effect; adverse events and serious adverse events were comparable between groups.
Why it matters
The findings suggest that combining these drug classes can improve albuminuria, an important marker of kidney disease, while highlighting hyperkalemia as a safety concern. The absence of an overall eGFR effect and reliance on surrogate outcomes mean that the observed albuminuria benefit does not establish improved long-term clinical outcomes. The balance of benefit and risk therefore warrants cautious interpretation.
What to keep in mind
The review notes reliance on surrogate endpoints, heterogeneity, and limited long-term data; only four trials were included.