Molecular Therapeutics for Diabetic Kidney Disease: An Update

Abstract

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes mellitus (DM). With the increasing prevalence of DM worldwide, the incidence of DKD remains high. If DKD is not well controlled, it can develop into chronic kidney disease or end-stage renal disease (ESRD), which places considerable economic pressure on society. Traditional therapies, including glycemic control, blood pressure control, blood lipid control, the use of renin-angiotensin system blockers and novel drugs, such as sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor inhibitors and glucagon-like peptide-1 receptor agonists, have been used in DKD patients. Although the above treatment strategies can delay the progression of DKD, most DKD patients still ultimately progress to ESRD. Therefore, new and multimodal treatment methods need to be explored. In recent years, researchers have continuously developed new treatment methods and targets to delay the progression of DKD, including miRNA therapy, stem cell therapy, gene therapy, gut microbiota-targeted therapy and lifestyle intervention. These new molecular therapy methods constitute opportunities to better understand and treat DKD. In this review, we summarize the progress of molecular therapeutics for DKD, leading to new treatment strategies.

Keywords: diabetic kidney disease; gene therapy; gut microbiota; miRNA; stem cell; therapeutics.

Figure 1

Current and potential targets for therapeutic interventions of DKD. Abbreviations: RAS: renin–angiotensin–aldosterone system; MRAs: mineralocorticoid system; SGLT2: sodium–glucose cotransporter 2; GLP-1R: glucagon-like peptide 1 receptor; JAK/STAT: Janus kinase/signal transducer and activator of transcription; NOX: nicotinamide adenine dinucleotide phosphate oxidases; AGE: advanced glycation end product; Nrf2: nuclear factor erythroid 2-related factor 2; IPSC: induced pluripotent stem cells; ESC: embryonic stem cell; FMT: fecal microbiota transplantation.