Novel Insights into Diabetic Kidney Disease

Abstract

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM), affecting over one-third of type 1 and nearly half of type 2 diabetes patients. As the leading cause of end-stage renal disease (ESRD) globally, DKD develops through a complex interplay of chronic hyperglycemia, oxidative stress, and inflammation. Early detection is crucial, with diagnosis based on persistent albuminuria and reduced estimated glomerular filtration rate (eGFR). Treatment strategies emphasize comprehensive management, including glycemic control, blood pressure regulation, and the use of nephroprotective agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists. Ongoing research explores novel therapies targeting molecular pathways and non-coding RNAs. Preventive measures focus on rigorous control of hyperglycemia and hypertension, aiming to mitigate disease progression. Despite therapeutic advances, DKD remains a leading cause of ESRD, highlighting the need for continued research to identify new biomarkers and innovative treatments.

Keywords: chronic kidney disease; diabetic kidney disease; end-stage renal disease; molecular mechanisms; pathogenesis; treatment.

Figure 1

Structural changes in the diabetic kidney. GBM—glomerular basement membrane; TEC—renal tubular epithelial cells; TBM—tubular basement membrane.

Figure 2

Mechanisms of hyperglycemia in diabetic kidney disease. VEGF—vascular endothelial growth factor; PTEN K27-polyUb—phosphatase and tensin homolog (PTEN) K27-polyubiquitinated; TGF-β—transforming growth factor β; NLRP3—NLR family pyrin domain containing 3; MAPK—mitogen-activated protein kinases; JAK/STAT—Janus kinase/signal transducers and activators of transcription; NFκB—nuclear factor kappa-light-chain-enhancer of activated B cells; NETs—neutrophil extracellular traps; EMT—epithelial–mesenchymal transition; ROS—reactive oxygen species; NO—nitric oxide; ECM—extracellular matrix; STING/PINK1—stimulator of interferon genes/PTEN-induced kinase 1; ABCA1—ATP-binding cassette sub-family A member 1; SIRT1—sirtuin 1; PPARγ—peroxisome proliferators-activated receptor γ; Nrf2—nuclear factor erythroid 2-related factor 2.