Nephroprotective Strategies and Metabolic Control in the Treatment of Diabetic Nephropathy

Diabetic nephropathy, or diabetic kidney disease (DKD), is the primary microvascular complication of diabetes mellitus and often progresses to end-stage kidney disease. This narrative review explores advances in pathophysiology, phenotypic heterogeneity, and current renoprotective and metabolic strategies for the treatment of DKD. The study covers everything from the molecular mechanisms of oxidative stress, inflammation via NF-κB/NLRP3, and single-cell transcriptomic changes (such as the modulation of Srsf7 and Spp1) to the paradigm shift from sequential monotherapy to multipillar combination therapy (ACEI/ARB, iSGLT2, finerenone, and GLP-1RA). It highlights the distinction between albuminuric and non-albuminuric phenotypes, as well as the emerging role of Nrf2/SIRT1-modulating phytochemicals and intervention in the gut-kidney axis. It is concluded that optimal management of diabetic kidney disease requires early intervention, precise risk stratification, and accelerated implementation of multipillar, multipathway therapy to halt renal functional decline and reduce associated cardiorenal risk.