A new study published in Clinical Journal of American Society of Nephrology suggests that after a 2-year trial period, bardoxolone methyl medication preserved eGFR in adolescent and adult patients with Alport syndrome receiving standard of care; off-treatment outcomes utilizing all available data did not vary substantially.
Type IV collagen anomalies describe the genetic kidney illness Alport syndrome. Management with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) is now recommended for individuals with Alport syndrome with proteinuria. The purpose of this study, which was carried out by Bradley Warady and colleagues were to assess the effectiveness and safety of bardoxolone methyl in individuals with Alport syndrome.

Patients with Alport syndrome, aged 12-70 and with an eGFR of 30-90 ml/min per 1.73 m2, were randomly allocated to receive bardoxolone methyl (n=77) or a placebo (n=80). At weeks 48 and 100, changes from baseline in eGFR served as the primary effectiveness endpoints. Change from baseline in eGFR at weeks 52 and 104, following an anticipated 4 weeks off therapy, were important secondary efficacy end objectives. In order to determine safety, vital signs, 12-lead electrocardiograms, laboratory measures (such as aminotransferases, magnesium, urine albumin-creatinine ratio, and B-type natriuretic peptide, among others), and body weight were tracked for adverse events and changes from baseline.
The key findings of this study were:
At 48 and 100 weeks, those who received bardoxolone methyl maintained their eGFR compared to those who received placebo.
Following a 4-week break from therapy, the corresponding mean eGFR differences at 52 and 104 weeks were 5.4 and 4.4 ml/min per 1.73 m2, respectively.
The difference at week 104 was not statistically significant when performed as a post hoc analysis without the use of imputation for missing eGFR data.
Patients who were randomly assigned to receive bardoxolone methyl experienced more treatment discontinuations; most of them were brought on by the occurrence of elevations in serum transaminases that matched the protocol's predefined criteria.
Patients who received a placebo were more likely to experience serious adverse effects. Each group had three individuals with renal failure.
Reference:
Warady, B. A., Pergola, P. E., Agarwal, R., Andreoli, S., Appel, G. B., Bangalore, S., Block, G. A., Chapman, A. B., Chin, M. P., Gibson, K. L., Goldsberry, A., Iijima, K., Inker, L. A., Kashtan, C. E., Knebelmann, B., Mariani, L. H., Meyer, C. J., Nozu, K., O’Grady, M., … Chertow, G. M. (2022). Effects of Bardoxolone Methyl in Alport Syndrome. In Clinical Journal of the American Society of Nephrology (Vol. 17, Issue 12, pp. 1763–1774). Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.2215/cjn.02400222