Endothelial-Podocyte Crosstalk: The Missing Link Between Endothelial Dysfunction and Albuminuria in Diabetes

Although diabetes is the most common cause of end-stage renal disease (ESRD) worldwide, most people with diabetic nephrop-athy will never develop ESRD but will instead die of cardiovas-cular (CV) disease (CVD). The first evidence of kidney injury in diabetes is often microalbuminuria, itself also an independent risk marker for CVD. Although the two processes are closely associated, the recent failure of antialbuminuric therapies to affect CV outcomes has encouraged a reconsideration of how albuminuria may occur in diabetes and how increased urinary albumin excretion may be indicative of CV risk. The relationship between CVD and urinary albumin content (even within the normal range) is widely considered to reflect the common underlying pathology of endo-thelial dysfunction. At the same time, recent years have witnessed a growing appreciation that diabetic albuminuria commonly arises from damage to glomerular podocytes, specialized epithelial cell