Effect of Intensive Urate Lowering With Combined Verinurad and Febuxostat on Albuminuria in Patients With Type 2 Diabetes: A Randomized Trial
| Autor: | Robert Terkeltaub, Susanne Johansson, Fredrik Erlandsson, Austin G. Stack, Joanna Parkinson, Nalina Dronamraju, Eva Johnsson |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Pyridines medicine.drug_class 030232 urology & nephrology Urology Renal function Naphthalenes Placebo Gout Suppressants 03 medical and health sciences chemistry.chemical_compound Febuxostat 0302 clinical medicine Double-Blind Method medicine Albuminuria Humans Prospective Studies 030212 general & internal medicine Hyperuricemia Xanthine oxidase inhibitor Aged Creatinine business.industry Middle Aged medicine.disease Uric Acid Treatment Outcome Diabetes Mellitus Type 2 chemistry Nephrology Drug Therapy Combination Female Propionates medicine.symptom business Biomarkers Follow-Up Studies Glomerular Filtration Rate Kidney disease medicine.drug |
| Zdroj: | American Journal of Kidney Diseases. 77:481-489 |
| ISSN: | 0272-6386 |
| Popis: | Rationale & Objective Hyperuricemia has been implicated in the development and progression of chronic kidney disease. Verinurad is a novel, potent, specific urate reabsorption inhibitor. We evaluated the effects on albuminuria of intensive urate-lowering therapy with verinurad combined with the xanthine oxidase inhibitor febuxostat in patients with hyperuricemia and type 2 diabetes mellitus (T2DM). Study Design Phase 2, multicenter, prospective, randomized, double-blind, parallel-group, placebo-controlled trial. Setting & Participants Patients 18 years or older with hyperuricemia, albuminuria, and T2DM. Intervention Patients randomly assigned 1:1 to verinurad (9mg) plus febuxostat (80mg) or matched placebo once daily for 24 weeks. Outcomes The primary end point was change in urinary albumin-creatinine ratio (UACR) from baseline after 12 weeks' treatment. Secondary end points included safety and tolerability and effect on glomerular filtration. Results 60 patients were enrolled (n=32, verinurad and febuxostat; n=28, placebo). UACRs after treatment with verinurad plus febuxostat were lower than after placebo at 1, 12, and 24 weeks: −38.6% (90% CI, −60.9% to−3.6%), −39.4% (90% CI, −61.8% to−3.8%), and−49.3% (90% CI, −68.2% to−19.0%), respectively. Serum urate levels after treatment with verinurad plus febuxostat were 59.6% and 63.7% lower than after placebo at 12 and 24 weeks, respectively. No clinically meaningful changes were observed in estimated glomerular filtration rate or serum creatinine or serum cystatin C concentrations. Verinurad plus febuxostat was well tolerated. Limitations Sample size and study duration were insufficient to evaluate definitive effects of verinurad plus febuxostat on UACR and glomerular filtration. Generalizability was limited by exclusion of patients with stages 4 and 5 chronic kidney disease. Conclusions Verinurad plus febuxostat reduced albuminuria and lowered serum urate concentrations in patients with T2DM, albuminuria, and hyperuricemia. Definitive assessment of their combined impact on preservation of kidney function awaits larger clinical studies. Funding This study was supported by AstraZeneca. Trial Registration Registered at ClinicalTrials.gov with study number NCT03118739. |
| Databáze: | OpenAIRE |
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