Inflammation in Diabetic Kidney Disease: Focus on New Therapeutic Considerations

Abstract

Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) in the U.S. and worldwide. A role of chronic low-grade inflammation in the microvascular complications in diabetic patients has now been widely accepted, and anti-inflammatory therapies for DKD are being actively pursued. Such therapies may be especially useful in the treatment of patients with chronic kidney disease (CKD) with normal to only moderately increased albuminuria, a DKD phenotype which is becoming more frequent. Current pharmacologic treatment for DKD includes inhibitors of the renin-angiotensin-aldosterone system (RAAS) and the sodium-glucose co-transporter 2 (SGLT2) in the proximal tubule. Both classes of agents are known to reduce blood pressure but also are thought to have anti-inflammatory, antioxidant, and anti-fibrotic effects independent of their hemodynamic actions. Large clinical trials with experimental agents such as bardoxolone and selonsertib that target inflammation and oxidative stress in DKD have been carried out or are in progress. The non-specific phosphodiesterase inhibitor pentoxifylline (PTX) is also being studied in a large US trial to see if this FDA-approved drug may be able to be repurposed to treat DKD. Other agents have also shown promising effects in small clinical trials but require further large-scale investigation.