{"doi":"10.1016/j.ekir.2022.08.030","title":"Effect of Cancer Stage on Adverse Kidney Outcomes in Patients Receiving Immune Checkpoint Inhibitors for Melanoma","abstract":"IntroductionImmune checkpoint inhibitors (ICIs) have transformed the treatment of melanoma. Since the approval of ipilimumab, a humanized cytotoxic T-lymphocyte associated antigen 4 antibody (anti-CTLA-4) in 2011, pembrolizumab and nivolumab (both targeting programmed cell death protein 1 [anti-PD-1]), as well as combination therapy (ipilimumab/nivolumab) have been shown to prolong progression-free survival and were approved for treatment of stage 4 melanoma. 1Larkin J. Chiarion-Sileni V. Gonzalez R. et al.Combined nivolumab and ipilimumab or monotherapy in untreated melanoma.N Engl J Med. 2015; 373: 23-34https://doi.org/10.1056/NEJMoa1504030Crossref PubMed Scopus (4932) Google Scholar,S1,S2 Most recently, ICIs have been approved as adjuvant therapy for surgically resected stage 3 melanoma. S3,S4 Nevertheless, their success in cancer response comes with the cost of immune-related adverse events. ICI-associated acute kidney injury (AKI), characterized by acute tubulointerstitial nephritis on pathology, was estimated to have an incidence of 2% to 5%.2Seethapathy H. Zhao S. Chute D.F. et al.The incidence, causes, and risk factors of acute kidney injury in patients receiving immune checkpoint inhibitors.Clin J Am Soc Nephrol. 2019; 14: 1692-1700https://doi.org/10.2215/CJN.00990119Crossref PubMed Scopus (83) Google Scholar, 3Cortazar F.B. Marrone K.A. Troxell M.L. et al.Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors.Kidney Int. 2016; 90: 638-647https://doi.org/10.1016/j.kint.2016.04.008Abstract Full Text Full Text PDF PubMed Scopus (312) Google Scholar, 4Stein C. Burtey S. Mancini J. et al.Acute kidney injury in patients treated with anti-programmed death receptor-1 for advanced melanoma: a real-life study in a single-centre cohort.Nephrol Dial Transplant. 2021; 36: 1664-1674https://doi.org/10.1093/ndt/gfaa137Crossref PubMed Scopus (14) Google Scholar,S6,S5 Differentiating between ICI-associated AKI and other causes of AKI is important.2Seethapathy H. Zhao S. Chute D.F. et al.The incidence, causes, and risk factors of acute kidney injury in patients receiving immune checkpoint inhibitors.Clin J Am Soc Nephrol. 2019; 14: 1692-1700https://doi.org/10.2215/CJN.00990119Crossref PubMed Scopus (83) Google Scholar, 3Cortazar F.B. Marrone K.A. Troxell M.L. et al.Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors.Kidney Int. 2016; 90: 638-647https://doi.org/10.1016/j.kint.2016.04.008Abstract Full Text Full Text PDF PubMed Scopus (312) Google Scholar, 4Stein C. Burtey S. Mancini J. et al.Acute kidney injury in patients treated with anti-programmed death receptor-1 for advanced melanoma: a real-life study in a single-centre cohort.Nephrol Dial Transplant. 2021; 36: 1664-1674https://doi.org/10.1093/ndt/gfaa137Crossref PubMed Scopus (14) Google Scholar,S7–S12To better understand the effect of cancer stage on adverse kidney outcomes, we retrospectively evaluated the incidence and etiology of AKI and long-term kidney function decline in a large cohort of patients with stage 3 and stage 4 melanoma treated with ICIs.ResultsAmong the 848 ICI-treated patients with advanced melanoma included in the study, 640 patients were treated with anti-PD-1 monotherapy (N = 251 stage 3, N = 389 stage 4) and 208 patients were treated with combination anti-CTLA-4/PD-1 therapy (all stage 4) (Supplementary Figure S1). The average age was 63.6 years (SD 13.8), 60% were men, and 97% were White. The mean baseline estimated glomerular filtration rate was 87 ml/min per 1.73 m2. The distributions of sex, race, and comorbidities were similar across the 3 groups (Supplementary Table S1).Incidence of All-cause AKI and Comparison of EtiologiesThe incidence of all-cause AKI was 16.7%, sustained AKI 6.6%, and ICI-associated AKI 2.6% within 1-year follow-up of the entire cohort. AKI rates were significantly higher among patients with stage 4 melanoma (27.4% in patients treated with anti","journal":"Kidney International Reports","year":2022,"id":290389,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9469,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":268728,"name":"Ian A. Strohbehn","orcid":"0000-0003-2167-2896","position":1,"is_corresponding":false},{"id":471053,"name":"Sophia Zhao","orcid":"0009-0008-6914-3583","position":2,"is_corresponding":false},{"id":268727,"name":"Harish Seethapathy","orcid":"0000-0002-1171-1022","position":3,"is_corresponding":false},{"id":973315,"name":"Samuel D. Strohbehn","orcid":null,"position":4,"is_corresponding":false},{"id":972784,"name":"Paul Hanna","orcid":"0000-0003-4976-9104","position":5,"is_corresponding":false},{"id":321297,"name":"Meghan Lee","orcid":"0000-0002-6895-5968","position":6,"is_corresponding":false},{"id":365632,"name":"Riley Fadden","orcid":null,"position":7,"is_corresponding":false},{"id":412,"name":"Ryan J. Sullivan","orcid":"0000-0001-5344-6645","position":8,"is_corresponding":false},{"id":411,"name":"Genevieve M. Boland","orcid":"0000-0002-7522-6173","position":9,"is_corresponding":false},{"id":105169,"name":"Kerry L. Reynolds","orcid":"0000-0002-7793-654X","position":10,"is_corresponding":false},{"id":263649,"name":"Meghan E. Sise","orcid":"0000-0002-4327-9713","position":11,"is_corresponding":false},{"id":972783,"name":"Qiyu Wang","orcid":"0000-0003-4959-7437","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T00:30:30.639224Z","pmid":"36531890","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}