TNF-α blockade is ineffective in animal models of established polycystic kidney disease.

Abstract

Given the large medical burden of polycystic kidney disease (PKD) and recent clinical trial failures, there is a need for novel, safe and effective treatments for the disorder. In PCK rat and PKD2(ws25/w183) mouse models, entanercept was administered once every three days at 5 or 10 mg/kg, once daily. Mozavaptan was administered as a pilot control, provided continuously via milled chow at 0.1%. Animals were assessed for measures of pharmacodynamic response, and improvements in measures of polycystic kidney disease. Entanercept treatment modulated inflammatory markers, but provided limited therapeutic benefit in multiple animal models of established polycystic kidney disease. Kidney weight, cyst burden and renal function markers remained unchanged following administration of etanercept at various dose levels and multiple treatment durations. While it remains possible that TNF-α inhibition may be effective in truly preventative settings, our observations suggest this pathway is less likely to exhibit therapeutic or disease-modifying efficacy following the standard clinical diagnosis of disease.