Lorundrostat lowered blood pressure and albuminuria in a small kidney-disease trial

Lorundrostat has already posted positive numbers in ordinary uncontrolled and treatment-resistant hypertension. The harder question is what it does in the patients who most need blood-pressure control and have the most to lose: those with chronic kidney disease and protein leaking into their urine. Explore-CKD, published in Kidney International, is the first randomised look at the drug in that group [s1].

The pathway is the point. Lorundrostat is a selective aldosterone synthase inhibitor, and aldosterone drives both raised pressure and kidney damage. SGLT2 inhibitors — now standard for diabetic and much non-diabetic kidney disease — reduce that damage by a different route. Explore-CKD asks what happens when you add the aldosterone-blocking drug on top.

What Explore-CKD did

The trial was randomised, double-blind, placebo-controlled and used a crossover design: lorundrostat 25 mg a day was added to a background SGLT2 inhibitor in adults who had uncontrolled hypertension, chronic kidney disease and albuminuria, all while on a stable renin-angiotensin-aldosterone system blocker [s1]. Participants were randomised to a lorundrostat-then-placebo or placebo-then-lorundrostat sequence, each in four-week treatment periods separated by a four-week washout [s1]. The primary endpoint was change in automated office systolic pressure; secondary endpoints included the urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) [s1]. The trial is registered as NCT06150924 [s2].

This was a small, sick, high-risk group. The 59 participants had a mean age of 64.6 years, a mean body-mass index of 33 kg/m², and 76% had type 2 diabetes [s1]. At baseline, mean automated office systolic pressure was 149 mm Hg (SD 10.4), the geometric mean UACR was 516.8 mg/g (a heavy protein leak), and cystatin C-based eGFR was 43 mL/min per 1.73 m² (SD 15.0) — stage 3 kidney disease [s1].

The numbers

On blood pressure, the drug separated cleanly from placebo. The least-squares mean change in automated office systolic pressure was −1.8 mm Hg (95% CI −5.6 to 2.1) on placebo and −9.3 mm Hg (−13.1 to −5.4) on lorundrostat, a placebo-adjusted reduction of −7.5 mm Hg (95% CI −12.3 to −2.7) [s1].

The kidney signal is the more interesting one. Lorundrostat reduced the geometric mean UACR by 30.5%, for a placebo-adjusted reduction of 25.6% (95% CI −37.7 to −11.2) [s1]. A quarter off albuminuria is the kind of change that, in larger and longer trials of other drugs, has tracked with slower kidney decline — though a four-week crossover cannot demonstrate that here.

It is worth being clear about what albuminuria is and is not. It is a marker: the amount of protein leaking through the kidney's filters, which rises as those filters are damaged and falls when the pressure and inflammation driving the damage are eased. Lowering it is generally a good sign, and regulators have at times accepted a large, sustained albuminuria reduction as a surrogate for harder kidney outcomes. But surrogates can mislead — a drug can move the marker without changing the disease — and the confidence interval here is wide, as it will be in 59 people.

The caveats the authors flag

Two things temper the reading. The first is eGFR. Kidney function fell slightly on the drug — from 42.9 to 40.1 mL/min per 1.73 m² on lorundrostat, against 42.9 to 42.1 on placebo [s1]. A small early dip in eGFR is the expected haemodynamic response to drugs that relieve pressure inside the glomerulus, and it is usually reversible, but in a population already at stage 3 it is the number to watch, not to wave away.

The second is safety in the small print. Three participants discontinued because of adverse events — one for hyperkalaemia with worsening kidney disease, one for acute kidney injury, and one for retinal detachment [s1]. Hyperkalaemia is the predictable hazard of blocking aldosterone in people with reduced kidney function, and it is precisely why this combination needs careful monitoring rather than enthusiasm.

What it settles, and what it does not

Explore-CKD is a phase 2 trial of 59 people over a few weeks. It shows that lorundrostat, added to an SGLT2 inhibitor, lowers office blood pressure and albuminuria in a high-risk kidney population, and that it can be given with an acceptable short-term safety profile [s1]. It does not show that either change translates into what patients care about — slower progression to dialysis, fewer cardiovascular events, longer life. The authors are explicit that longer studies are needed to determine whether the albuminuria reduction signals durable kidney or cardiovascular benefit [s1].

The trial was funded by Mineralys Therapeutics, which is developing the drug [s2] — the usual reason to treat a small, sponsor-run phase 2 as a promising signal to be confirmed, not as settled practice. The cardiorenal question this trial raises is a real one, and the right answer to it is a properly powered outcome trial rather than a four-week crossover, however encouraging the surrogate numbers.

This article is informational and does not constitute medical advice.

Sources

• [s1] Results from the Phase 2 Explore-CKD Trial of lorundrostat, a novel aldosterone synthase inhibitor, in participants with uncontrolled hypertension, chronic kidney disease, and albuminuria. Kidney International, 23 September 2026. https://doi.org/10.1016/j.kint.2026.08.021
• [s2] Efficacy and Safety of Lorundrostat in Addition to Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in Subjects With Hypertension and Chronic Kidney Disease (CKD) With Albuminuria. ClinicalTrials.gov identifier NCT06150924, US National Library of Medicine. https://clinicaltrials.gov/study/NCT06150924