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Bardoxolone Methyl and Kidney Function in CKD With Type 2 Diabetes
Study Questions:
What are the effects of three doses of bardoxolone methyl on the estimated glomerular filtration rate (eGFR) at 24 and 52 weeks in patients with chronic kidney disease (CKD) and type 2 diabetes?
Methods:
In this phase 2, double-blind, randomized, placebo-controlled trial, the investigators assigned 227 adults with CKD (defined as an eGFR of 20-45 ml/min/1.73 m2 of body-surface area) in a 1:1:1:1 ratio to receive placebo or bardoxolone methyl at a target dose of 25, 75, or 150 mg once daily. The primary outcome was the change from baseline in the eGFR with bardoxolone methyl, as compared with placebo, at 24 weeks; a secondary outcome was the change at 52 weeks.
Results:
Patients receiving bardoxolone methyl had significant increases in the mean (± standard deviation) eGFR, as compared with placebo, at 24 weeks (with between-group differences per minute per 1.73 m2 of 8.2 ± 1.5 ml in the 25 mg group, 11.4 ± 1.5 ml in the 75 mg group, and 10.4 ± 1.5 ml in the 150 mg group; p < 0.001). The increases were maintained through week 52, with significant differences per minute per 1.73 m2 of 5.8 ± 1.8 ml, 10.5 ± 1.8 ml, and 9.3 ± 1.9 ml, respectively. Muscle spasms, the most frequent adverse event in the bardoxolone methyl groups, were generally mild and dose-related. Hypomagnesemia, mild increases in alanine aminotransferase levels, and gastrointestinal effects were more common among patients receiving bardoxolone methyl.
Conclusions:
The authors concluded that bardoxolone methyl was associated with improvement in the eGFR in patients with advanced CKD and type 2 diabetes.
Perspective:
This study reports that treatment with bardoxolone methyl for 52 weeks led to sustained, significant improvements in the eGFR among patients receiving standard medical care for CKD and type 2 diabetes. The time course of changes in the eGFR among patients receiving bardoxolone methyl suggests that there was a short-term effect during the first 12 weeks, which was followed by a longer-term effect. Bardoxolone methyl beneficial effects on GFR could be due to a decrease in the inflammation and oxidative stress associated with CKD, and it appears to be an attractive therapeutic candidate, which requires further study in patients with CKD.
Keywords: Inflammation, Diabetes Mellitus, Type 2, Glomerular Filtration Rate, Renal Insufficiency, Chronic
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