{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:42:04Z","timestamp":1791297724334,"version":"4.1.0"},"reference-count":39,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"2","license":[{"start":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T00:00:00Z","timestamp":1671235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2020AAA0109500"],"award-info":[{"award-number":["2020AAA0109500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030025"],"award-info":[{"award-number":["82030025"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32100631"],"award-info":[{"award-number":["32100631"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003269"],"award-info":[{"award-number":["82003269"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82122053"],"award-info":[{"award-number":["82122053"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Commun"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p xml:lang=\"en\">With the development and introduction of immune checkpoint inhibitors (ICIs) in cancer patients, immune\u2010related side effects have increasingly attracted attention. However, the risks of immune\u2010related renal toxicity are poorly characterized. In this study, we performed a network meta\u2010analysis (NMA) of ICI\u2010related randomized clinical trials (RCTs) to elucidate the comparative risk of acute kidney injury (AKI) in cancer patients receiving different ICIs. We also sought to identify other factors potentially affecting the risk of AKI. PubMed and EMBASE were searched for peer\u2010reviewed trial reports published between January 2000 and May 2021. Eligible studies were RCTs studying ICIs in cancer patients and reporting AKI data. We performed a frequentist NMA to evaluate the risk ratios for grade 1\u20105 and grade 3\u20105 AKI between the treatment groups. We also assessed the absolute incidence of AKI in the ICI\u2010containing arm using traditional direct meta\u2010analysis. Once significant heterogeneity was detected in a traditional direct meta\u2010analysis, multivariable meta\u2010regression analysis was applied to identify factors that significantly affected the absolute incidence of AKI. A total of 85 RCTs were included in this study. In the NMA for the risk of grade 1\u20105 and 3\u20105 AKI, ipilimumab showed a significantly higher risk than avelumab and durvalumab, whereas 1 mg\/kg nivolumab plus 3 mg\/kg ipilimumab (N1I3) showed a significantly higher risk than other groups. In terms of treatment ranking, durvalumab \u00b1 low\u2010dose tremelimumab and avelumab were consistently among the top three safest treatments for grade 1\u20105 or 3\u20105 AKI, whereas N1I3, ipilimumab and tremelimumab were consistently among the top three treatments with the highest risk for grade 1\u20105 or 3\u20105 AKI. Compared with other cancers, renal cell carcinoma and urothelial carcinoma showed a significantly higher risk of AKI. The incidence of AKI was significantly higher with ICI+chemotherapy than with ICI monotherapy. In this NMA involving large\u2010scale up\u2010to\u2010date ICI trials, we demonstrated the comparative safety of existing ICI drugs for grade 1\u20105 and grade 3\u20105 AKI. Based on data from the ICI arms of these trials, we also revealed several potential risk factors for immune\u2010related AKI, including tumor type and treatment paradigm.<\/jats:p>","DOI":"10.1002\/cac2.12396","type":"journal-article","created":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T21:55:00Z","timestamp":1671314100000},"page":"214-224","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Comparative risk of acute kidney injury among cancer patients treated with immune checkpoint inhibitors"],"prefix":"10.34133","volume":"43","author":[{"given":"Fei","family":"Liu","sequence":"first","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital","place":["Beijing, P. R. China"]},{"name":"Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, P. R. China"]},{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital","place":["Beijing, P. R. China"]},{"name":"Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, P. R. China"]},{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital","place":["Beijing, P. R. China"]},{"name":"Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixian","family":"Wang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofan","family":"Li","sequence":"additional","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital","place":["Beijing, P. R. China"]},{"name":"Nephrology Institute of the Chinese People's Liberation Army","place":["Beijing, P. R. China"]},{"name":"State Key Laboratory of Kidney Diseases","place":["Beijing, P. R. China"]},{"name":"National Clinical Research Center for Kidney Diseases","place":["Beijing, P. R. China"]},{"name":"Beijing Key Laboratory of Kidney Disease Research","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yang","sequence":"additional","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital","place":["Beijing, P. R. China"]},{"name":"Nephrology Institute of the Chinese People's Liberation Army","place":["Beijing, P. R. China"]},{"name":"State Key Laboratory of Kidney Diseases","place":["Beijing, P. R. China"]},{"name":"National Clinical Research Center for Kidney Diseases","place":["Beijing, P. R. China"]},{"name":"Beijing Key Laboratory of Kidney Disease Research","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junquan","family":"Chen","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinghua","family":"Chen","sequence":"additional","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital","place":["Beijing, P. R. China"]},{"name":"Nephrology Institute of the Chinese People's Liberation Army","place":["Beijing, P. R. China"]},{"name":"State Key Laboratory of Kidney Diseases","place":["Beijing, P. R. China"]},{"name":"National Clinical Research Center for Kidney Diseases","place":["Beijing, P. R. China"]},{"name":"Beijing Key Laboratory of Kidney Disease Research","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Wu","sequence":"additional","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital","place":["Beijing, P. R. China"]},{"name":"Nephrology Institute of the Chinese People's Liberation Army","place":["Beijing, P. R. China"]},{"name":"State Key Laboratory of Kidney Diseases","place":["Beijing, P. R. China"]},{"name":"National Clinical Research Center for Kidney Diseases","place":["Beijing, P. R. China"]},{"name":"Beijing Key Laboratory of Kidney Disease Research","place":["Beijing, P. R. 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasilijiang","family":"Wahafu","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital","place":["Beijing, P. R. China"]},{"name":"Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Gao","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital","place":["Beijing, P. R. China"]},{"name":"Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, P. R. China"]},{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital","place":["Beijing, P. R. China"]},{"name":"Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, P. R. China"]},{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital","place":["Beijing, P. R. China"]},{"name":"Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, P. R. China"]},{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital & Shenzhen Hospital","place":["Shenzhen, P. R. China"]},{"name":"Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Shenzhen, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shancheng","family":"Ren","sequence":"additional","affiliation":[{"name":"Shanghai Changzheng Hospital","place":["Shanghai, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nianzeng","family":"Xing","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital","place":["Beijing, P. R. China"]},{"name":"Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, P. R. China"]},{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital","place":["Beijing, P. R. China"]},{"name":"Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyan","family":"Cai","sequence":"additional","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital","place":["Beijing, P. R. China"]},{"name":"Nephrology Institute of the Chinese People's Liberation Army","place":["Beijing, P. R. China"]},{"name":"State Key Laboratory of Kidney Diseases","place":["Beijing, P. R. China"]},{"name":"National Clinical Research Center for Kidney Diseases","place":["Beijing, P. R. China"]},{"name":"Beijing Key Laboratory of Kidney Disease Research","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangmei","family":"Chen","sequence":"additional","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital","place":["Beijing, P. R. China"]},{"name":"Nephrology Institute of the Chinese People's Liberation Army","place":["Beijing, P. R. China"]},{"name":"State Key Laboratory of Kidney Diseases","place":["Beijing, P. R. China"]},{"name":"National Clinical Research Center for Kidney Diseases","place":["Beijing, P. R. China"]},{"name":"Beijing Key Laboratory of Kidney Disease Research","place":["Beijing, P. R. 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Clinical Features and Outcomes of Immune Checkpoint Inhibitor\u2010Associated AKI: A Multicenter Study. J Am Soc Nephrol. 2020;31((2)):435\u201046.","journal-title":"J Am Soc Nephrol"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80089-8"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609214"},{"issue":"1","key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40425-018-0478-8","article-title":"Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: single\u2010center experience","volume":"7","author":"Mamlouk O","year":"2019","unstructured":"Mamlouk O, Selamet U, Machado S, Abdelrahim M, Glass WF, Tchakarov A, et\u00a0al. Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: single\u2010center experience. J Immunother Cancer. 2019;7((1)):2.","journal-title":"J Immunother Cancer"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-004421"},{"issue":"10","key":"e_1_3_2_12_2","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-003467","article-title":"Acute kidney injury in patients treated with immune checkpoint inhibitors","volume":"9","author":"Gupta S","year":"2021","unstructured":"Gupta S, Short S, Sise ME, Prosek JM, Madhavan SM, Soler MJ, et\u00a0al. Acute kidney injury in patients treated with immune checkpoint inhibitors. 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