Ectopic lipid deposition in kidney diseases: mechanisms in specific cell types and therapeutic strategies

Kidney diseases represent a major global health burden and arise from complex interactions among multiple cellular and molecular processes. Ectopic lipid deposition (ELD), defined as the accumulation of excess lipids in non-adipose tissues when lipid supply exceeds adipose storage capacity, has emerged as a key contributor to the initiation and progression of renal injury. ELD occurs across multiple renal cell types, including proximal tubular epithelial cells, podocytes, mesangial cells, glomerular endothelial cells, as well as interstitial fibroblasts and macrophages. Owing to differences in metabolic profiles and lipid-handling capacity, these cells exhibit distinct susceptibilities and pathological responses to lipid accumulation. This review summarizes the major sources and underlying mechanisms of renal ELD, with particular emphasis on cell-specific injury pathways driven by different lipid subtypes. It further discusses how these divergent responses collectively contribute to renal dysfunction and structural damage. We also outline current approaches for the clinical assessment and diagnosis of renal ELD, and highlight the relevance of age stratification in improving diagnostic precision. Recent advances in therapeutic strategies targeting renal ELD are also reviewed, including evidence from diabetic kidney disease, obesity-related kidney disease, acute kidney injury, and Alport syndrome. Overall, this review provides a systematic overview of the molecular mechanisms and therapeutic implications of ELD in kidney diseases from a cell-specific perspective, and highlights its potential as a target for improved prevention and treatment strategies.