A new investigational drug called nurandociguat reduced albuminuria, a key marker of kidney damage, by up to 28% in patients with chronic kidney disease (CKD) who were already on standard treatments. The findings come from a phase 2 clinical trial presented at the European Renal Association Congress, suggesting a novel pathway for protecting kidneys in people whose disease continues to progress despite current medications.

What Is Albuminuria and Why Does It Matter?

Albuminuria refers to the presence of albumin, a protein, in the urine. In healthy kidneys, proteins stay in the bloodstream and don't leak into urine. When kidneys are damaged, they begin to lose this filtering ability, allowing albumin to escape. High levels of urinary albumin are a warning sign that kidney disease is worsening and that a person faces increased risk of kidney failure and heart disease. Reducing albuminuria is a major treatment goal because it signals that kidney damage is slowing or stabilizing.

How Does Nurandociguat Work Differently?

Nurandociguat is a soluble guanylate cyclase activator, which is a fancy way of saying it targets a specific biological pathway in the body. The drug works by restoring the production of a molecule called cyclic guanosine monophosphate, or cGMP, which helps blood vessels relax and improves oxygen delivery to tissues. Unlike some other kidney drugs, nurandociguat works independently of nitric oxide and heme, meaning it activates this protective pathway through a different mechanism than existing treatments.

This is important because many CKD patients are already taking standard medications like ACE inhibitors or angiotensin receptor blockers, which work through different pathways. Nurandociguat's novel approach means it could potentially offer additional benefits when added to existing therapy.

What Did the Clinical Trial Show?

The ALPINE-1 trial enrolled 751 participants across 149 sites in 15 countries between August 2024 and November 2025. Researchers tested five different doses of nurandociguat against placebo over 16 weeks. The study population was fairly representative of real-world CKD patients: average age was 62.5 years, 77% were male, and 61% had diabetes. Most participants (96.3%) were already taking ACE inhibitors or angiotensin receptor blockers, and nearly 70% were also on sodium-glucose cotransporter-2 inhibitors, a newer class of kidney-protective drugs.

"The study met its primary efficacy endpoint as a statistically significant dose-response signal was demonstrated," stated Christoph Wanner, MD, of the University Hospital of Würzburg in Germany, who presented the results.

Christoph Wanner, MD, University Hospital of Würzburg

The results showed consistent reductions in albuminuria across all tested doses. Compared to placebo, nurandociguat reduced urinary albumin levels by the following amounts:

• 2.5 mg dose: 21% reduction in albuminuria compared to placebo
• 5 mg dose: 16% reduction in albuminuria compared to placebo
• 10 mg dose: 28% reduction in albuminuria compared to placebo
• 15 mg dose: 19% reduction in albuminuria compared to placebo
• 20 mg dose: 20% reduction in albuminuria compared to placebo

The 10 mg dose showed the strongest effect, reducing albuminuria by 28% compared to placebo. These reductions were described as clinically meaningful, meaning they represent improvements that could translate into real health benefits for patients.

Did the Drug Harm Kidney Function?

One concern with blood pressure-lowering drugs is that they can sometimes reduce kidney filtration in the short term. However, nurandociguat did not significantly change estimated glomerular filtration rate, or eGFR, which measures how well kidneys are filtering waste. This is a reassuring finding because it suggests the drug can reduce albuminuria without causing acute kidney injury.

"Despite this blood pressure-lowering effect, this intervention did not significantly change eGFR in the acute period," noted Dr. Wanner.

Christoph Wanner, MD, University Hospital of Würzburg

What Side Effects Were Observed?

The most common side effect of concern was symptomatic hypotension, or abnormally low blood pressure that causes symptoms like dizziness or lightheadedness. This occurred in 10.7% of patients taking nurandociguat compared to 1.6% in the placebo group, and the risk increased at higher doses, reaching 20.6% at the highest 20 mg dose. Syncope, or fainting, occurred in 1.6% of nurandociguat patients versus 0.8% in placebo. Acute kidney injury, defined as a doubling of serum creatinine or a rise to 4.0 mg/dL, occurred in only 0.3% of nurandociguat patients and 0% of placebo patients.

What Happens Next?

These phase 2 results are promising but represent an early stage of drug development. The trial demonstrated that nurandociguat can reduce albuminuria in CKD patients already on standard therapy, and that it does so without acutely harming kidney function. However, researchers emphasize that longer-term studies are needed to determine whether these albuminuria reductions translate into durable protection against kidney failure and cardiovascular disease. Nurandociguat is still investigational and not yet approved by regulatory agencies.

For the estimated 37 million Americans with CKD, the potential for new treatment options is significant. Many patients continue to lose kidney function despite taking current standard medications, making them candidates for additional therapies that work through different biological pathways. Nurandociguat represents one such approach, targeting the impaired nitric oxide-sGC-cGMP pathway that appears to play a role in kidney disease progression.