Targeting renal lipotoxicity with natural products in chronic kidney disease: mechanisms, molecular targets, and translational prospects.

BACKGROUND

Renal lipotoxicity is increasingly recognized as a metabolic driver of chronic kidney disease (CKD), linking excessive lipid delivery, impaired fatty acid oxidation, defective cholesterol handling, and insufficient lysosomal clearance to inflammation, ferroptosis, and fibrosis.

PURPOSE: This review evaluates evidence on the effects of natural products on impaired renal lipid handling and downstream pathways of lipotoxic injury in CKD.

STUDY

DESIGN

A structured, mechanism-oriented narrative review.

METHODS

PubMed/MEDLINE and Web of Science Core Collection were searched for experimental, translational, and clinical studies related to CKD, renal lipotoxicity, lipid metabolism, organelle stress, and natural products or phytochemicals. Database searching was complemented by reference-list screening, citation tracking, and targeted searches for relevant mechanistic and translational evidence. Evidence was synthesized narratively and evaluated according to mechanistic directness and translational relevance.

RESULTS

Renal lipotoxicity is best understood as an imbalance among lipid uptake, synthesis, fatty acid oxidation, cholesterol efflux, and autophagic-lysosomal clearance rather than lipid accumulation alone. Natural products have been reported to modulate these processes and downstream inflammatory, ferroptotic, and fibrotic responses. However, most intervention studies were preclinical, concentrated in diabetic kidney disease models, and based on renal lipid burden or pathway-associated markers rather than direct measurements of lipid flux.

CONCLUSION

Natural products provide useful pharmacological probes and candidate leads for renal lipotoxicity, but translation requires chemically defined preparations, reproducible exposure, renal target engagement, mechanism-matched pharmacodynamic biomarkers, dose-response data, and CKD-relevant safety assessment.