Diabetic kidney disease (DKD) is one of the most common causes of end-stage renal disease worldwide. The treatment of DKD is strongly associated with clinical outcomes in patients with diabetes mellitus. Traditional therapeutic strategies focus on the control of major risk factors, such as blood glucose, blood lipids, and blood pressure. Renin–angiotensin–aldosterone system inhibitors have been the main therapeutic measures in the past, but the emergence of sodium–glucose cotransporter 2 inhibitors, incretin mimetics, and endothelin-1 receptor antagonists has provided more options for the management of DKD. Simultaneously, with advances in research on the pathogenesis of DKD, some new therapies targeting renal inflammation, fibrosis, and oxidative stress have gradually entered clinical application. In addition, some recently discovered therapeutic targets and signaling pathways, mainly in preclinical and early clinical trial stages, are expected to provide benefits for patients with DKD in the future. This review summarizes the traditional treatments and emerging management options for DKD, demonstrating recent advances in the therapeutic strategies for DKD.

Mechanical stress on the glomerular filtration barrier (GFB) exposes podocytes to hydrostatic pressure. Their mechanosensitivity is established, yet the underlying mechanotransduction pathways and responses under hypertension remain unclear. This review examines the mechanical stresses experienced by podocytes in both physiologic and hypertensive conditions and updates the latest extracorporeal techniques used to simulate these forces. Additionally, this review discusses how podocytes respond to these mechanical forces and elucidates the detailed molecular mechanisms involved. Furthermore, we summarize potential protective mechanisms that enable podocytes to withstand mechanical challenges and propose novel therapeutic strategies to delay the progression of hypertensive nephropathy. This review uniquely underscores the importance of biomechanical factors in disease progression and integrates emerging therapeutic strategies targeting podocyte mechanotransduction, offering a novel biomechanical framework for delaying hypertensive nephropathy progression.

In addition to apoptosis, inflammatory cell death modalities—including pyroptosis, necroptosis, ferroptosis, NETosis, and the integrated paradigm of PANoptosis—are now established as critical drivers of diabetic kidney disease (DKD) pathogenesis. This review summarizes how key inflammatory cell death molecular mediators—such as the NLRP3 inflammasome, the RIPK1/RIPK3/MLKL axis, executioner caspases, and gasdermin-D (GSDMD)—orchestrate the death of renal cells (podocytes, tubular cells, mesangial cells, endothelium), thereby propagating inflammation and fibrosis. Preclinical studies have demonstrated the efficacy of agents targeting these pathways, highlighting their therapeutic potential. Key challenges include achieving cell type-specific targeting, overcoming redundancy among cell death pathways, and improving the translational applicability of current models. Emerging solutions include the development of precise biomarkers, kidney-targeted delivery systems, and combination therapies that concurrently target multiple cell death axes. This review synthesizes evidence establishing inflammatory cell death as a cornerstone of DKD pathology and provides a conceptual framework to guide future research and therapeutic innovation.