Immune checkpoint inhibitors and acute kidney injury in melanoma: An Australian retrospective cohort study

Background: Immune checkpoint inhibitors (ICI) have transformed outcomes for patients with advanced melanoma but are associated with acute kidney injury (AKI), including immune-related (IR) nephritis, which may lead to treatment interruption, immunosuppression, and adverse kidney and oncological outcomes. Objective: To describe incidence, clinical characteristics, management, and outcomes of AKI, including IR nephritis, in patients with melanoma treated with ICIs in an Australian cancer centre. Design: Retrospective single-centre cohort study. Setting: Melbourne, Australia. Participants: All adults (⩾18 years) with stage II–IV melanoma who received ⩾1cycle of ICI therapy between 1 August 2020 and 1 November 2024. Main outcomes: Incidence of AKI and IR nephritis; clinical characteristics; management; kidney recovery; treatment interruption; rechallenge; overall survival. Results: Among 633 patients with melanoma receiving ICIs, 86 (13.6%) developed AKI. Fifteen (2.4%) were classified as IR nephritis (seven biopsy-confirmed). Compared with non-immune AKI ( n = 71), IR nephritis occurred earlier after ICI initiation (median 43 vs 192 days; p = 0.009) and with more severe AKI (IR nephritis Stage 3 = 53%, versus non-immune AKI Stage 3 = 15%, p = 0.003). Concurrent IR-adverse events were common in both groups (64% vs 45%). Systemic corticosteroids were administered in all IR nephritis cases, and additional immunosuppression in 26%. Complete kidney recovery occurred in 80% of IR nephritis cases and 75% of non-immune AKI ( p = 0.92). Among patients with metastatic or unresectable melanoma ( n = 407), in a multivariate time-dependent Cox regression analysis, AKI was independently associated with a 2.71 fold higher hazard of death (adjusted hazard ratio 2.71, 95% CI 1.72–4.26; p < 0.001). Seven patients were rechallenged with ICIs after IR nephritis; none developed recurrent nephritis (median follow-up 13.9 months, IQR 7. 2–22.9 months). Conclusions: In this Australian study of patients with melanoma, AKI occurred in 13.6% treated with ICIs. IR nephritis was uncommon but often severe; however, kidney recovery was frequent with immunosuppression. AKI of any cause was associated with worse survival, and disrupted cancer treatment. Selected patients with IR nephritis may be safely rechallenged, highlighting the importance for individualised, multidisciplinary patient care.