Translational advances in diabetic nephropathy management: integrating nanoformulation-based drug delivery systems

The incidence of diabetes mellitus (DM) is increasing worldwide, especially for its major renal complications, diabetic nephropathy (DN) and chronic kidney disease (CKD). These are caused by chronic hyperglycemia, oxidative stress, hemodynamics, inflammation, and profibrotic signaling, which result in progressive renal structural damage and functional decline. All these mechanisms contribute to podocyte injury, thickening of the glomerular basement membrane, interstitial fibrosis, and progressive loss of renal function. While traditional diagnostic markers like albuminuria or estimated glomerular filtration rate (eGFR) aid in tracking disease with imaging, and emerging markers like neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin C can help, none can detect early, subclinical kidney damage. A comprehensive literature review was conducted in PubMed, Google Scholar, Scopus, Web of Science, and ScienceDirect using keywords related to DN pathophysiology, diagnosis, nanomedicine, renal targeting, and nanoformulations, with publications between 2015 and 2026. Intensive glycemic and blood pressure control, inhibition of the renin-angiotensin-aldosterone system, and lipid-lowering therapy are currently used as therapeutic interventions. Poor bioavailability, off-target toxicity, complex dosing regimens, and variable renal drug handling are often responsible for their limited effectiveness. One approach to circumventing these limitations is with nanotechnology-based drug delivery systems. In preclinical studies, the antioxidant, anti-inflammatory, and antifibrotic effects have consistently been reported to be superior, with reduced systemic toxicity, while clinical translation remains in its early stages. This review discusses current knowledge on DN and critically evaluates the pros, cons, and future of nanotechnology-based approaches for delivering targeted nanomedicines to the kidney.