Objectives: Immune checkpoint inhibitors (ICIs) have become a standard therapy for various cancers. Although ICIs improve survival, they may cause immune-related adverse events, including acute kidney injury. However, their long-term renal outcomes compared with conventional chemotherapy remain unclear. Methods: Data were obtained from the electronic health records of two tertiary referral centers (2015–2024). Among 19,668 patients initiating first-line systemic anticancer therapy, propensity score matching on 12 covariates was performed, yielding a matched cohort (N=2,172; 1,086 pairs). Results: In the matched cohort, the mean age was 65.5 years, 70.8% were male, and the mean baseline eGFR was 93.3 mL/min/1.73 m²; The median follow-up was 11.1 months (IQR 4.7–21.0) in the ICI group and 10.4 months (IQR 4.7–22.2) in the non-ICI group. The ICI group experienced a significant early decline within the first 6 months (Δslope −0.352 mL/min/1.73 m²/month, p<0.001), followed by a significant attenuation in the rate of decline during months 6–12 (Δslope +0.227, p=0.002), after which no between-group difference remained (Δslope +0.028, p=0.22). The risk of ≥30% eGFR decline showed a statistically significant but modest association with ICI therapy (HR 1.16, 95% CI 1.02–1.31, p=0.019), which was attenuated after competing risk adjustment. In contrast, de novo overt proteinuria was consistently associated with ICI: stratified Cox HR 1.84 (95% CI 1.37–2.47, p<0.001). Subgroup analysis by ICI class revealed that anti-PD-1 therapy was associated with both eGFR decline and proteinuria, whereas anti-PD-L1 therapy showed no eGFR decline but a markedly elevated risk of proteinuria (HR 3.12, 95% CI 1.66–5.89, p<0.001). All-cause mortality was higher in the ICI group (HR 1.49, 95% CI 1.30–1.70, p<0.001). Conclusion: ICI therapy was associated with an early decline in eGFR followed by partial recovery and an increased risk of proteinuria.