Bardoxolone methyl is an antioxidant inflammation modulator (AIM). It is a capsule taken by mouth,
and has been tested in over 2,600 patients with different diseases including Type II diabetes and chronic
kidney disease, cancer, and pulmonary arterial hypertension. Research completed to date suggests
that bardoxolone methyl:
*Decreases inflammation in the kidney, protects the kidney from injury, and prevents fibrosis
(changes in the structures) within the kidney, based on data from animal models
*Significantly increases glomerular filtration rate (GFR) in patients with diabetic kidney disease
*In patients with diabetic kidney disease, produces GFR increases that are sustained for at least one year,
with a portion of the increase retained even 4 weeks after stopping treatment
A previous large study in over 2000 diabetic patients with severe, stage 3 and 4 chronic kidney disease was
stopped early because bardoxolone methyl increased the risk for fluid retention in a subset of patients who
had previously been hospitalized for heart failure and who had fluid retention prior to the start of the study.
The increased risk for fluid retention was only observed in the first month after starting treatment. The
identified risk factors are now used to exclude patients who are more likely to retain fluid from participating
in studies with bardoxolone methyl. To date, bardoxolone methyl has not been shown to increase the risk
for fluid retention in subsequent studies, including those in diabetic chronic kidney disease and pulmonary
arterial hypertension patients. The CARDINAL trial will exclude patients with stage 4 chronic kidney disease
and these risk factors. Additionally, patients will be monitored closely during the first two months of the trial
to ensure that they do not develop fluid retention.
How Might Bardoxolone Methyl Treat Alport?
Your glomerular filtration rate (GFR) is an estimate of how well your kidneys are working. Inflammation
in Alport syndrome causes changes within your kidney that limit the kidney's ability to filter out wastes
and excess fluid in your body. Increased inflammation from Alport syndrome reduces
kidney function and causes decreases in GFR.
Decreasing GFR ultimately results in the need for dialysis or renal transplant. In previous studies in patients
with diabetes and chronic kidney disease, bardoxolone methyl produced an increase in estimated GFR (eGFR)
that was sustained for 1 year in some patients. It is not known whether an increase in GFR, if achieved, will
provide long-term benefit in patients with Alport syndrome. Consequently, the CARDINAL study is designed
to test the effects of bardoxolone methyl on eGFR in Alport patients through 2 years of treatment.