The Role of Autophagy in Type 2 Diabetic Kidney Disease Management

Abstract

Diabetic kidney disease (DKD), or diabetic nephropathy (DN), is one of the most prevalent complications of type 2 diabetes mellitus (T2DM) and causes severe burden on the general welfare of T2DM patients around the world. While several new agents have shown promise in treating this condition and potentially halting the progression of the disease, more work is needed to understand the complex regulatory network involved in the disorder. Recent studies have provided new insights into the connection between autophagy, a physiological metabolic process known to maintain cellular homeostasis, and the pathophysiological pathways of DKD. Typically, autophagic activity plays a role in DKD progression mainly by promoting an inflammatory response to tissue damage, while both overactivated and downregulated autophagy worsen disease outcomes in different stages of DKD. This correlation demonstrates the potential of autophagy as a novel therapeutic target for the disease, and also highlights new possibilities for utilizing already available DN-related medications. In this review, we summarize findings on the relationship between autophagy and DKD, and the impact of these results on clinical management strategies.

Keywords: autophagy; diabetic kidney disease; diabetic nephropathy.

Figure 1

Summary of the correlation between common pharmacological agents and autophagy reactivation. Oral hypoglycemic agents (OHAs) and renin-angiotensin-aldosterone system (RAAS) blockade agents were found to regulate autophagy reactivation in DKD, while reports on the direct impact of RAAS-blockade agents on autophagy in DKD are still lacking. EMT, epithelial—mesenchymal transition; SGLT2i, sodium–glucose cotransporter 2 inhibitors; DPP4i, dipeptidyl peptidase-4 inhibitors; GLP-1 RA, glucagon-like peptide-1 receptor analogs; AMPK, AMP-activated protein kinase; Sirt1, Sirtuin-1; FOXO1, Forkhead box protein O1; mTOR, mechanistic target of rapamycin.