Lorundrostat added to SGLT2 inhibition lowered blood pressure and albuminuria in CKD

Design

Phase 2, randomised, double-blind, placebo-controlled crossover

Population

59 adults with uncontrolled hypertension, CKD and albuminuria on RASi and SGLT2i

Primary outcome

Change in automated office systolic blood pressure

Effect

−7.5 mmHg vs placebo (95% CI −12.3 to −2.7); UACR −25.6% (−37.7 to −11.2)

Explore-CKD was a double-blind, placebo-controlled crossover trial in 59 adults with uncontrolled hypertension, CKD and albuminuria, already taking a RAS blocker and an SGLT2 inhibitor. Mean cystatin C eGFR was 43 and three quarters had type 2 diabetes. Each participant took lorundrostat, an aldosterone synthase inhibitor, and placebo for four weeks each.

Lorundrostat lowered automated office systolic pressure by 7.5 mmHg and albuminuria by about 26% relative to placebo. eGFR fell by about 3 mL/min on lorundrostat, the expected haemodynamic dip. Three participants stopped for adverse events, including one for hyperkalaemia with worsening kidney function and one for acute kidney injury.

This is a four-week, phase 2 trial on surrogate endpoints, and it does not show kidney or cardiovascular protection. Its significance is that it tests aldosterone synthase inhibition in the population that would use it, on top of current standard care. Finerenone already offers mineralocorticoid blockade with outcome evidence in diabetic CKD; lorundrostat is investigational. Until outcome trials report, the lesson is to keep pursuing blood pressure and albuminuria targets in CKD, where residual risk on RAS blockade and SGLT2 inhibition remains high.

• Recheck blood pressure and albuminuria after optimising RAS blockade and an SGLT2 inhibitor; residual elevation is common.
• Consider finerenone where indicated for persistent albuminuria in diabetic CKD.
• Monitor potassium and eGFR closely when adding any aldosterone-pathway drug in CKD.
• Treat lorundrostat as investigational; its effect on kidney outcomes is unknown.

Why it matters

Aldosterone is the next target for residual risk in CKD after RAS blockade and SGLT2 inhibition.

Don't overread it

A short phase 2 surrogate-endpoint trial; no kidney or cardiovascular outcomes were measured.

The statistics, in plain English

A placebo-adjusted fall of 7.5 mmHg (95% CI 2.7 to 12.3) is clinically meaningful for blood pressure. Albuminuria reduction is a surrogate: it often predicts kidney benefit, but not always, and four weeks is far too short to show it.

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