The cardinal trial of bardoxolone methyl in alport syndrome: when marketing interests prevail over patients clinical needs

Context. Alport syndrome (AS) is a hereditary chronic kidney disease (CKD) with X-linked, autosomal and digenic patterns of transmission. Sieving dysfunction of the glomerular basement membrane caused by congenitally defective type IV collagen results in persistent proteinuria, hematuria and progressive renal dysfunction. There are no disease-specific medications and treatment is based on conservative interventions in particular with renin-angiotensin-aldosterone system inhibitors. Subject of Review. Evidence that AS is accompanied by glomerular and tubular inflammatory changes and that bardoxolone methyl exerts anti-inflammatory effects through suppression of NF-kB and activation of transcription of antioxidant and anti-inflammatory genes, provided a justification for the CARDINAL study, a prospective, randomized controlled trial testing the potential renoprotective effect of bardoxolone methyl in 157 adolescent or adult patients with AS. The Authors concluded that bardoxolone methyl preserved estimated glomerular filtration rate (eGFR) relative to placebo at 48 and 100 weeks after randomization. However, exactly the same number of patients (n=3) in each group developed kidney failure. Second opinion. Despite alarming safety signals from previous trials in type 2 diabetics with CKD (increased hospitalizations for heart failure, and fatal and non-fatal cardiovascular events, liver toxicity, and increased blood pressure and albuminuria), major marketing interests encouraged ...
Source: Nephron - Category: Urology & Nephrology Source Type: research