Drug discovery for diabetic nephropathy: trying the leap from mouse to man

Abstract

Diabetic nephropathy is the single major cause of kidney failure in the industrialized world and given the emerging global pandemic of diabetes mellitus, its prevalence is expected to only increase. Because of the lack of dynamic biomarkers that define the rate of kidney function loss, there are few proof-of-concept clinical trials for new therapeutics to treat diabetic nephropathy. A molecular understanding of the pathogenesis of diabetic nephropathy also is lacking. These deficiencies are magnified by the fact that most mouse models of diabetic nephropathy fail to show progressive kidney disease. Recently, some mouse models that showed requisite phenotypic changes of diabetic nephropathy have been identified. Validation of results obtained in these experimental models, and showing whether they accurately can predict clinical response to therapeutics in human diabetic nephropathy, must now be established.