Emerging therapeutic strategies in diabetic nephropathy

Diabetic nephropathy is one of the main causes of end-stage renal disease (ESRD) and is associated with elevated cardiovascular morbidity and mortality. Current renoprotective treatment for diabetic nephropathy includes strict glycemic and optimal blood pressure control, proteinuria/albuminuria reduction and the use of renin-angiotensin-aldosterone system (RAAS) blocking agents. However, the renoprotection provided by these treatments is only partial, and many patients still have progressive disease, thus suggesting that a more effective approach is urgently needed. This review examines emerging strategies for the treatment of diabetic nephropathy, including aggressive RAAS blockade, statins, pentoxifylline, glitazones, ruboxistaurin, as well as sulodexide. Pilot studies that used surrogate end points, mainly albuminuria, will be discussed. New insights suggest that treating microalbum in uric diabetic patients with statins, pentoxifylline, glitazones and sulodexide could be a new approach for reducing the incidence of clinical proteinuria. In diabetic patients with overt nephropathy, the administration of statins, pentoxifylline, sulodexide or aggressive RAAS inhibition, including RAAS dual blockade (i.e., angiotensin-converting enzyme [ACE] inhibitors plus angiotensin receptor blockers or aldosterone antagonists plus ACE inhibitors or angiotensin receptor blockers), seems to be a promising way to preserve renal function and to prevent progression to ESRD. Results of ongoing, long-term trials on major renal and cardiovascular clinical outcomes, as well as on mortality are needed to establish whether the current standard of care of diabetic nephropathy might be improved with these new strategies.