Targeting the Pathobiology of Diabetic Kidney Disease.

The pathobiology of diabetic kidney disease (DKD) involves an interplay between all the many different cell types that exist within the kidney and their shared and cumulative dysfunction in response to chronic hyperglycemia. DKD is characteriszed by morphological changes including tubular hypertrophy, podocyte dysfunction, mesangial expansion and mesangiolysis, endothelitis and capillary rarefaction, arteriolar hyalinosis, basement membrane thickening, and ultimately nephron dropout and tubulointerstitial fibrosis. These adaptive but ultimately maladaptive changes accelerate the progression of lesions in the diabetic kidney by increasing mechanical and oxidative stress, hypoxia, fibrogenesis, inflammation, senescence, and apoptosis. In particular, atrophy at the critical junction between Bowman's capsule and the proximal tubule likely represent the leading cause of nephron dropout and kidney function decline in DKD. Preventing, slowing, or reversing these changes should be the target of future "smart" therapies for patients with DKD, many of which are now under development.