Novel avenues for drug discovery in diabetic kidney disease.

INTRODUCTION: Diabetic kidney disease (DKD) has emerged as major cause of morbidity and mortality. After progressing to renal failure, over 70% of DKD patients are dead with five years. New treatments to slow this progression are desperately needed. Areas covered: This review highlights the current treatment options for people with DKD with a particular focus on angiotensin pathway blockade and the potential use of sodium glucose linked transporter 2 (SGLT2) inhibitors. These treatments are associated with an initial decrease in glomerular filtration rate (GFR) and albuminuria; there is also attention on renal hyperfiltration as therapeutic target. Both clinical and preclinical testing are facilitated by leveraging albuminuria reduction as a dynamic biomarker of drug effect linked to renal failure. It is critical to ensure that animal models exhibit both albuminuria and progressive loss of renal function so drug effects can be established in both. Expert opinion: New pathways and potential drug targets are emerging from gene expression profiling of human kidney biopsies and genome wide association studies. By harmonizing animal experimentation endpoints with clinical outcomes, focusing on disease pathophysiology and incorporating novel gene expression and biomarker changes, therapeutics can be advanced into clinical testing with greater confidence.