A Paradigm Shift for the Concept of Diabetic Nephropathy

Abstract

Diabetic nephropathy (DN) is increasing rapidly worldwide. In Japan, over the past two decades, the proportion of DN in patients with new-onset hemodialysis induction dramatically increased along with an exponential increase in the number of diabetic patients. Regarding the pathophysiology of DN, it was previously thought to be very simple, i.e. the development/progression of DN was able to be explained only in terms of hyperglycemia, genetic factors, and so on. However, it has become evident that many factors, such as advanced glycation end-products (AGEs), oxidative stress, and chronic inflammation, are involved in the pathogenesis of DN. With respect to progression process of DN, we thought it to be very difficult to halt the progression of this disease if the urinary excretion of albumin increased up to the level of macroalbuminuria (an albuminuria of more than 300 mg/g·Cr), a stage which has been called “the point of no return”. Now even diabetic patients with a nephrotic range of proteinuria sometimes regress to levels of normo- or microalbuminuria with the benefit of advances in diabetic treatment.
This review article describes some of the knowledge that has been gained from our previous studies and also reviews advances in clinical and basic research in DN based on published literature over the past decades.