A novel aldosterone synthase inhibitor lowers BP and albuminuria in CKD

Design

Phase 2, randomised, double-blind, placebo-controlled crossover trial (Explore-CKD)

Population

59 adults with uncontrolled hypertension, CKD and albuminuria on RAAS blockade plus SGLT2 inhibitor

Primary outcome

Change in automated office systolic blood pressure

Effect

Placebo-adjusted systolic BP −7.5 mmHg (−12.3 to −2.7); albuminuria down ~26–30%

Aldosterone drives both hypertension and kidney damage, and blocking it is attractive but limited by hyperkalaemia. Explore-CKD, a phase 2 placebo-controlled crossover trial, added the selective aldosterone synthase inhibitor lorundrostat to existing RAAS blockade and an SGLT2 inhibitor in 59 adults with uncontrolled hypertension, CKD and albuminuria (76% had type 2 diabetes).

Against placebo, lorundrostat lowered automated office systolic blood pressure by 7.5 mmHg (95% CI −12.3 to −2.7) and reduced albuminuria by roughly a quarter to a third. There was the small, expected eGFR dip seen with effective RAAS-axis therapies. Three of 59 stopped for adverse events — hyperkalaemia with worsening CKD, acute kidney injury, and retinal detachment.

The appeal is a fourth lever for blood pressure and albuminuria on top of RAAS blockade and an SGLT2 inhibitor, in exactly the resistant-hypertension-with-CKD patients who are hard to control and common in India. But this is a small, short, phase-2 surrogate-endpoint study; it shows the drug moves the numbers, not yet that it protects kidneys or hearts, and the hyperkalaemia and AKI signals need watching.

• Lorundrostat added to RAAS blockade and an SGLT2 inhibitor cut systolic BP by about 7.5 mmHg versus placebo.
• It reduced albuminuria by roughly a quarter to a third.
• A small eGFR dip is expected; watch for hyperkalaemia and acute kidney injury.
• This is phase 2 with surrogate endpoints — not yet proof of kidney or cardiovascular protection.

Why it matters

It offers a potential new lever for the common, hard problem of uncontrolled hypertension in CKD already on standard therapy.

Don't overread it

59 patients, four-week crossover periods and surrogate endpoints (BP and albuminuria) — this cannot show kidney or cardiovascular protection, and the hyperkalaemia and AKI events warrant caution.

The statistics, in plain English

A placebo-adjusted 7.5 mmHg fall is a meaningful blood-pressure effect, but blood pressure and albuminuria are stand-ins; only a longer outcome trial can show whether they translate into slower kidney decline or fewer events.

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