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Global Journal of Urology and Kidney Research

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Mechanisms of Renoprotection Induced by Omega-3 Fatty Acids: Implications for Diabetic Nephropathy, Acute and Chronic Kidney Disease Management

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Graphical Abstract:

Mechanisms of renoprotection induced by omega-3 fatty acids: implications for diabetic nephropathy, acute kidney injury, and chronic kidney disease management. Dietary alpha-linolenic acid and preformed EPA/DHA sources contribute to systemic and renal omega-3 availability, membrane remodeling, and displacement of arachidonic acid-derived inflammatory lipid signaling. EPA- and DHA-derived metabolites generate specialized pro-resolving mediators, including E-series resolvins, D-series resolvins, protectins, and maresins, which act through defined GPCR pathways to suppress neutrophil recruitment, enhance efferocytosis, promote macrophage reprogramming, and support tissue repair. In the kidney, these actions preserve podocyte structure, improve proximal tubular mitochondrial and metabolic homeostasis, reduce mesangial and endothelial injury, and limit interstitial fibroblast activation and fibrosis. These effects converge on inhibition of NF-κB/NLRP3 signaling, activation of NRF2-dependent antioxidant defenses, preservation of mitochondrial function, and regulation of apoptosis, autophagy, and ferroptosis, thereby supporting improved renal and cardiometabolic outcomes across diabetic and non-diabetic kidney disease contexts

 Abstract

Background:

Chronic kidney disease (CKD) affects >10% of adults worldwide, diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease, and acute kidney injury (AKI) complicates 10–15% of hospitalizations, often progressing to CKD. Persistent inflammation, oxidative stress, lipotoxicity, podocyte loss and tubulointerstitial fibrosis drive progression across aetiologies, yet current renin–angiotensin blockade, SGLT2 inhibitors and finerenone only partially attenuate risk. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and their specialized pro-resolving mediators (SPMs) offer multitargeted, low-toxicity renoprotection.

Objective:

 This narrative review explored cellular and molecular mechanisms of omega-3-induced renoprotection and evaluates implications for diabetic nephropathy, AKI and CKD management.

Methods:

 A structured narrative search of PubMed/MEDLINE, Scopus and Web of Science (2000–2026) was performed for omega-3, EPA/DHA, resolvins, protectins, maresins, DKD, AKI, CKD, proteinuria, fibrosis and clinical trials. Mechanistic, preclinical and clinical studies, meta-analyses and guidelines were critically appraised.

Results:

EPA/DHA incorporate into renal membranes, activate GPR120, PPARs and NRF2, suppress NF-κB, TLRs and NLRP3 inflammasome, attenuate SREBP-1-driven lipotoxicity, stabilize podocytes, and inhibit TGF-β/Smad fibrosis, apoptosis and ferroptosis. DHA-derived resolvins D1/D2, protectin D1 and maresin 1, and EPA-derived resolvin E1 actively resolve neutrophil/macrophage inflammation, promote M2 polarization, enhance efferocytosis and heme oxygenase-1, and reduce albuminuria, glomerulosclerosis and AKI-to-CKD transition in rodents.

Conclusion:

 Omega-3 fatty acids act as nutrient-derived resolution agonists with coherent mechanistic rationale for adjunctive renoprotection. Optimizing formulation (EPA+DHA vs. pure EPA), dose, Omega-3 Index targeting and SPM-based drugs, and testing in biomarker-enriched DKD/AKI trials, are priorities.

Keywords:

Omega-3 fatty acids; EPA; DHA; Resolvins; Diabetic nephropathy; Acute kidney injury; chronic kidney disease; Glomerulosclerosis

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