Figure 1.

Contrasting short-term effects of bardoxolone and renin-angiotensin-aldosterone system (RAAS) blockers on eGFR and albumin excretion may lead to contrasting long-term effects on renal function. In progressive CKD (e.g., diabetic nephropathy), eGFR declines in the absence of treatment (black line). Randomized trials have shown that inhibition of the RAAS reduces eGFR in the short term and reduces albuminuria, but then, it slows progressive loss of eGFR. By contrast, bardoxolone increases eGFR (through unknown mechanisms) and also increases albuminuria. Because higher levels of albuminuria are associated with faster decline in eGFR, this raises the hypothesis that bardoxolone may have the opposite effect of RAAS inhibitors and that it may accelerate long-term decline of eGFR.