Add on dapagliflozin may attenuate fluid retention caused by high doses of zibotentan in CKD: Study

Written By :  Dr. Shravani Dali
Medically Reviewed By :  Dr. Kamal Kant Kohli
Published On 2024-07-17 21:45 GMT   |   Update On 2024-07-18 06:28 GMT
Advertisement

Add-on dapagliflozin may attenuate fluid retention caused by high doses of zibotentan in CKD suggests a study published in the Journal of the American Society of Nephrology.

Endothelin receptor antagonists (ERAs) reduce albuminuria but are limited by fluid retention risk, particularly in patients with chronic kidney disease (CKD). Combining ERAs with sodium-glucose cotransporter 2 (SGLT2) inhibitors, which have diuretic effects, offers a promising strategy to mitigate fluid retention. In this post-hoc analysis of the ZENITH-CKD trial, we assessed fluid dynamics in patients with CKD treated with the ERA zibotentan alone, and in combination with the SGLT2 inhibitor dapagliflozin.In ZENITH-CKD, 508 patients with CKD (estimated glomerular filtration rate ≥ 20 mL/min/1.73m2 and a urinary albumin-to-creatinine ratio of 150–5000 mg/g) were randomized to treatment with placebo, dapagliflozin 10 mg plus placebo, zibotentan (0.25, 1.5 or 5 mg) plus dapagliflozin 10 mg and zibotentan 5 mg plus placebo. We evaluated correlations between changes in fluid retention markers and bioimpedance-measured extracellular fluid (ECF) in response to zibotentan treatment. We used Cox proportional hazards regression to assess the association between zibotentan/dapagliflozin treatment, baseline characteristics, and fluid retention, and the relationship between zibotentan plasma exposure and fluid retention.

Results: After 3 weeks of treatment with zibotentan 0.25, 1.5 or 5 mg plus dapagliflozin 10 mg, changes in body weight (β=0.36 [95%CI 0.26,0.45]) per kg, B-type natriuretic peptide (β=0.38 [95%CI 0.22, 0.54]) per doubling, and haemoglobin (β=-0.29 [95%CI -0.48, -0.10]) per g/dL were independently associated with changes in ECF. Higher doses of zibotentan were associated with a significantly higher risk of fluid retention compared to dapagliflozin alone (zibotentan 5 mg HR 8.50 (95%CI 3.40, 21.30). The hazard ratio attenuated when zibotentan was combined with dapagliflozin (HR zibotentan/dapagliflozin 5/10 mg 3.09 [95%CI 1.08, 8.80], zibotentan/dapagliflozin 1.5/10 mg 2.70 [95%CI 1.44, 5.07] and zibotentan/dapagliflozin 0.25/10 mg HR 1.21 [95%CI 0.50, 2.91]). The risk of fluid retention was higher with higher zibotentan exposure and lower eGFR. High doses of zibotentan were associated with a higher risk of fluid retention, which was attenuated with lower doses and the addition of dapagliflozin.

Reference:

Smeijer, J. David1; Wasehuus, Victor S2; Dhaun, Neeraj3; Gorriz, Jose Luis4; Soler, Maria José5; Åstrand, Magnus6; Mercier, Anne-Kristina6; Greasley, Peter J.6; Ambery, Phil6; Heerspink, Hiddo J.L.1,7,a. Effects of Zibotentan Alone and in Combination with Dapagliflozin on Fluid Retention in Patients with CKD. Journal of the American Society of Nephrology ():10.1681/ASN.0000000000000436, July 12, 2024. | DOI: 10.1681/ASN.0000000000000436

Tags:    
Article Source : Journal of the American Society of Nephrology

Disclaimer: This website is primarily for healthcare professionals. The content here does not replace medical advice and should not be used as medical, diagnostic, endorsement, treatment, or prescription advice. Medical science evolves rapidly, and we strive to keep our information current. If you find any discrepancies, please contact us at corrections@medicaldialogues.in. Read our Correction Policy here. Nothing here should be used as a substitute for medical advice, diagnosis, or treatment. We do not endorse any healthcare advice that contradicts a physician's guidance. Use of this site is subject to our Terms of Use, Privacy Policy, and Advertisement Policy. For more details, read our Full Disclaimer here.

NOTE: Join us in combating medical misinformation. If you encounter a questionable health, medical, or medical education claim, email us at factcheck@medicaldialogues.in for evaluation.

Our comments section is governed by our Comments Policy . By posting comments at Medical Dialogues you automatically agree with our Comments Policy , Terms And Conditions and Privacy Policy .

Similar News