Impact of tumor immunotherapy on kidney injury and multi-organ outcomes: a mechanistic and clinical perspective.

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer therapeutics yet frequently induce renal injury and multi-organ immune-related adverse events (irAEs) that present substantial clinical management challenges. Critical evidence gaps persist regarding dynamic immune microenvironment interactions and optimal organ-protective strategies. Objective: We systematically evaluated ICI efficacy and safety profiles concerning renal and multi-organ outcomes in cancer patients, with particular focus on underlying mechanisms and protective interventional approaches. Methods: We conducted a comprehensive, systematic literature search across PubMed, Cochrane Library, Embase, Web of Science, and Scopus (January 2000-December 2025) to inform a narrative synthesis. This narrative review approach integrates evidence from diverse study designs (experimental, observational, and clinical) to generate mechanistic hypotheses and clinical insights, rather than to estimate pooled effect sizes. Two independent reviewers performed structured study selection and quality appraisal using established tools (Cochrane RoB 2.0, ROBINS-I, GRADE) to enhance transparency and evaluate evidence certainty, acknowledging that formal meta-analysis was precluded by methodological heterogeneity. We employed narrative synthesis methodologies organized around mechanistic themes (PD-1/PD-L1 signaling, mTORC1-autophagy, cGAS-STING) to integrate translational and clinical evidence. Results: Our analysis of 68 included studies (n=15,392 participants) establishes that ICIs associate with acute kidney injury manifestations-notably tubulointerstitial nephritis-and multi-organ irAEs including myocarditis. Mechanistic investigations reveal PD-1/PD-L1 pathway disruption, metabolic dysregulation, and immune cell heterogeneity as central pathways, though quantitative effect estimates demonstrated significant interstudy variability. Conclusions: Tumor immunotherapy substantially impacts renal and multi-organ homeostasis, supported by moderate-certainty evidence. Immune microenvironment-targeted protective strategies emerge as crucial for optimizing therapeutic outcomes, while future investigations should prioritize biomarker-guided precision approaches to balance efficacy and safety considerations. The observed heterogeneity in nephrotoxicity patterns suggests tissue-specific immune microenvironment interactions warranting single-cell resolution analysis.