Lorundrostat added to RAS blockade and an SGLT2 inhibitor lowered blood pressure 7.5 mmHg and albuminuria a quarter

Design

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

Population

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

Primary outcome

Change in automated office systolic blood pressure at 4 weeks

Effect

Placebo-adjusted −7.5 mmHg (−12.3 to −2.7); UACR −25.6%

Explore-CKD, a phase 2 randomised double-blind placebo-controlled crossover trial in Kidney International (23 September 2026), gave lorundrostat 25 mg daily — a selective aldosterone synthase inhibitor — or placebo for four weeks each, with a four-week washout, to 59 adults with uncontrolled hypertension, CKD (mean cystatin C eGFR 43) and albuminuria (geometric mean 517 mg/g) on a RAS blocker and an SGLT2 inhibitor. Three-quarters had type 2 diabetes.

Office systolic pressure fell by 9.3 mmHg with lorundrostat and 1.8 mmHg with placebo, a placebo-adjusted difference of −7.5 mmHg (95% CI −12.3 to −2.7). Albuminuria fell by 25.6% placebo-adjusted (−37.7% to −11.2%). eGFR fell from 42.9 to 40.1 on lorundrostat against 42.9 to 42.1 on placebo. Three participants stopped for adverse events: hyperkalaemia with CKD worsening, acute kidney injury and retinal detachment.

Four weeks in 59 people cannot establish kidney or cardiovascular outcomes, and the early eGFR dip — expected with aldosterone suppression — needs longer follow-up. This is research-stage, not a reason to change prescribing.

• Aldosterone synthase inhibitors are investigational in CKD; this is a phase 2 result
• Expect an early eGFR dip and hyperkalaemia risk with any drug that suppresses aldosterone
• Meanwhile, maximise RAS blockade, SGLT2 inhibitor and, where indicated, finerenone
• Check potassium and creatinine within two weeks of adding any aldosterone-pathway drug

Why it matters

It suggests a fourth pillar may be possible for albuminuric CKD with uncontrolled hypertension.

Don't overread it

Four-week phase 2 data in 59 patients; kidney outcomes and longer-term safety are unknown.

The statistics, in plain English

The placebo-adjusted fall of 7.5 mmHg has a confidence interval from 2.7 to 12.3 mmHg, so a real effect is likely but its size is uncertain. In a crossover trial each patient acts as their own control, which gives more power from few patients but cannot show long-term effects.

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