{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:23:47Z","timestamp":1783488227767,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K18603"],"award-info":[{"award-number":["19K18603"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the effects of renal impairment at the time of second\u2010line tyrosine kinase inhibitor (TKI) therapy initiation and rapid renal function decline during first\u2010line immuno\u2010oncology (IO) combination therapy on metastatic renal cell carcinoma (mRCC) patients treated with second\u2010line TKIs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This multicenter retrospective study included 243 mRCC patients treated with first\u2010line IO combination therapy, followed by second\u2010line TKI therapy. Patients were divided into three groups using the estimated glomerular filtration rate (eGFR; mL\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      ) at the time of second\u2010line TKI therapy initiation: eGFR\u2009\u2265\u200960, 30\u2009\u2264\u2009eGFR\u2009&lt;\u200960, and eGFR\u2009&lt;\u200930. The eGFR slope during first\u2010line IO combination therapy was calculated using eGFR measurements when initiating first\u2010line and second\u2010line therapies. Multivariable Cox proportional hazards regression analyses were performed to evaluate the effects of renal impairment and eGFR slope on progression\u2010free survival (PFS) and overall survival (OS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The incidence rates of any grade and grade \u2265\u20093 adverse events were not significantly different among the three groups. Univariable analyses indicated that eGFR slope was not significantly associated with PFS or OS. Multivariable analyses suggested that moderate (30\u2009\u2264\u2009eGFR\u2009&lt;\u200960\u2009mL\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      ) and severe (eGFR\u2009&lt;\u200930\u2009mL\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      ) renal impairment had no effects on shorter PFS, whereas severe renal impairment was independently and significantly associated with shorter OS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TKIs can be safely used as a second\u2010line treatment after first\u2010line IO combination therapy in mRCC patients with renal impairment without sacrificing oncological outcomes, except for in patients with severe renal impairment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iju.70172","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T07:44:46Z","timestamp":1751615086000},"page":"1506-1517","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Impaired Renal Function on the Efficacy and Safety of Second\u2010Line Tyrosine Kinase Inhibitor Therapy After First\u2010Line Immuno\u2010Oncology Combination Therapy in Metastatic Renal Cell Carcinoma: A Japanese Multicenter Retrospective Study"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8284-9582","authenticated-orcid":false,"given":"Naoki","family":"Fujita","sequence":"first","affiliation":[{"name":"Department of Urology Hirosaki University Graduate School of Medicine  Hirosaki 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