Design and baseline characteristics of the ZENITH high proteinuria trial testing zibotentan/dapagliflozin…

Randomized trialNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association· Aug 2026

Design and baseline characteristics of the ZENITH high proteinuria trial testing zibotentan/dapagliflozin efficacy in CKD.

Hiddo J L Heerspink, Clare Arnott, Jonathan Barratt … Vlado Perkovic

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NephrologyRandomized trialQ1IF 6.2

Zibotentan plus dapagliflozin cut urinary albumin-to-creatinine ratio ~30% versus dapagliflozin alone

Design and baseline characteristics of the ZENITH high proteinuria trial testing zibotentan/dapagliflozin efficacy in CKD.

Hiddo J L Heerspink … Vlado Perkovic

Nephrology, dialysis, transplantation · Aug 2026 · Q1 in General Medicine

Background

A low dose of the selective endothelin A receptor antagonist zibotentan in combination with the sodium - glucose co-transporter 2 inhibitor (SGLT2i) dapagliflozin reduced urinary albumin-to-creatinine ratio (urinary albumin-to-creatinine ratio) by ~30% compared to dapagliflozin alone in a phase 2b study without increasing the risk of fluid retention.

Methods

Eligible participants were randomized 1:1 to zibotentan/dapagliflozin 0.25/10 mg (if eGFR<45 mL/min/1.73 m2)/0.75/10 mg (if eGFR ≥45 mL/min/1.73 m2) or placebo/dapagliflozin on top of standard of care, including maximum tolerated renin-angiotensin-system blockade.

n = 2910 patients

~30%

Results

~30%

less protein in urine, a sign of better kidney protection

n = 2910 patients

More results

Mean age at baseline was 61 years and 28% were female.

Mean (standard deviation) eGFR was 44.0 (18.2) mL/min/1.73 m2, median (interquartile range) urinary albumin-to-creatinine ratio was 1262 (801-2097) mg/g, and median (interquartile range) B-type natriuretic peptide was 44 (23-86) ng/L.

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Conclusion · 1 of 2

To evaluate the effect of zibotentan and dapagliflozin combination therapy, the ZENITH High Proteinuria study has successfully recruited a population at high risk of chronic kidney disease progression for whom novel therapies remain necessary.

Conclusion · 2 of 2

Results are expected in 2027.

Design and baseline characteristics of the ZENITH high proteinuria trial testing zibotentan/dapagliflozin efficacy in CKD.

Design and baseline characteristics of the ZENITH high proteinuria trial testing zibotentan/dapagliflozin efficacy in CKD.

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