{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T19:55:13Z","timestamp":1778788513875,"version":"3.51.4"},"reference-count":9,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T00:00:00Z","timestamp":1675036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005795","name":"Chang-Gung Medical Research Project","doi-asserted-by":"publisher","award":["CMRPG3G1661"],"award-info":[{"award-number":["CMRPG3G1661"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005795","name":"Chang-Gung Medical Research Project","doi-asserted-by":"publisher","award":["111-2628-B-182A-003"],"award-info":[{"award-number":["111-2628-B-182A-003"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005795","name":"Chang-Gung Medical Research Project","doi-asserted-by":"publisher","award":["110-2628-B-182A-019"],"award-info":[{"award-number":["110-2628-B-182A-019"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Taiwan Ministry of Science and Technology (MOST)","award":["CMRPG3G1661"],"award-info":[{"award-number":["CMRPG3G1661"]}]},{"name":"Taiwan Ministry of Science and Technology (MOST)","award":["111-2628-B-182A-003"],"award-info":[{"award-number":["111-2628-B-182A-003"]}]},{"name":"Taiwan Ministry of Science and Technology (MOST)","award":["110-2628-B-182A-019"],"award-info":[{"award-number":["110-2628-B-182A-019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinics and Practice"],"abstract":"<jats:p>Anti-programmed death-1 (PD-1)\/programmed death ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs), combined with bevacizumab and platinum-based chemotherapy, have shown promising efficacy in treating metastatic non-squamous cell lung cancer in phase 3 clinical trials. However, drug-induced nephrotoxicity is an uncommon but threatening adverse effect when using this combination therapy, and should be evaluated and managed carefully. Here, we present two patients experiencing late-onset asymptomatic heavy proteinuria during the clinical trial. Kidney biopsies performed finally identified bevacizumab-induced thrombotic microangiopathy (TMA), and the proteinuria was decreased after discontinuing bevacizumab permanently. Our report suggests that a kidney biopsy is needed for those receiving ICIs in combination with bevacizumab and chemotherapy and experiencing nephrotoxicity such as heavy proteinuria.<\/jats:p>","DOI":"10.3390\/clinpract13010018","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T11:25:47Z","timestamp":1675077947000},"page":"200-205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bevacizumab-Induced Thrombotic Microangiopathy (TMA) in Metastatic Lung Adenocarcinoma Patients Receiving Nivolumab Combined with Bevacizumab, Carboplatin and Paclitaxel: Two Case Reports"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0173-7509","authenticated-orcid":false,"given":"Ping-Chih","family":"Hsu","sequence":"first","affiliation":[{"name":"Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan"},{"name":"Department of Medicine, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4231-7677","authenticated-orcid":false,"given":"Tai-Di","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan"},{"name":"Department of Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsung-Yu","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan"},{"name":"Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1846-1027","authenticated-orcid":false,"given":"Cheng-Ta","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan"},{"name":"Department of Internal Medicine, Taoyuan Chang Gung Memorial Hospital, Taoyuan City 33378, Taiwan"},{"name":"Department of Respiratory Therapy, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.annonc.2021.06.004","article-title":"Nivolumab with carboplatin, paclitaxel, and bevacizumab for first-line treatment of advanced nonsquamous non-small-cell lung cancer","volume":"32","author":"Sugawara","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1758835920980546","DOI":"10.1177\/1758835920980546","article-title":"The association between immune-related adverse events and the prognosis of solid cancer patients treated with immunotherapy: A systematic review and meta-analysis","volume":"12","author":"Xu","year":"2020","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1056\/NEJMoa1716948","article-title":"Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC","volume":"378","author":"Socinski","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1056\/NEJMoa0707330","article-title":"VEGF inhibition and renal thrombotic microangiopathy","volume":"358","author":"Eremina","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/ki.2015.30","article-title":"New drug toxicities in the onco-nephrology world","volume":"87","author":"Perazella","year":"2015","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.kint.2016.04.008","article-title":"Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors","volume":"90","author":"Cortazar","year":"2016","journal-title":"Kidney Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e000467","DOI":"10.1136\/jitc-2019-000467","article-title":"Acute kidney injury associated with immune checkpoint inhibitor therapy: Incidence, risk factors and outcomes","volume":"8","author":"Amir","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1159\/000455014","article-title":"Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors. Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review","volume":"45","author":"Wanchoo","year":"2017","journal-title":"Am. J. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17588359221113278","DOI":"10.1177\/17588359221113278","article-title":"Comparison of afatinib and erlotinib combined with bevacizumab in untreated stage IIIB\/IV epidermal growth factor receptor-mutated lung adenocarcinoma patients: A multicenter clinical analysis study","volume":"14","author":"Lee","year":"2022","journal-title":"Ther. Adv. Med. Oncol."}],"container-title":["Clinics and Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-7283\/13\/1\/18\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:19:59Z","timestamp":1760120399000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-7283\/13\/1\/18"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,30]]},"references-count":9,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["clinpract13010018"],"URL":"https:\/\/doi.org\/10.3390\/clinpract13010018","relation":{},"ISSN":["2039-7283"],"issn-type":[{"value":"2039-7283","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,30]]}}}