{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:42:54Z","timestamp":1792712574003,"version":"4.5.0"},"reference-count":35,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Checkpoint inhibitors are a standard of care in the treatment of advanced renal cell carcinoma (RCC) and urothelial carcinoma (UC). Patients with these tumors often suffer from concomitant chronic kidney disease (CKD). Limited data are available on the efficacy and toxicity of checkpoint inhibitors in patients with CKD. Methods: We retrospectively analyzed 126 patients who received checkpoint inhibitors for RCC (n = 85) or UC (n = 41) and analyzed the frequency of treatment- and immune-related adverse events (AEs). We performed a multivariate analysis to determine progression-free survival (PFS) and overall survival (OS). Results: A total of 38.9% of patients had CKD. Frequencies of general AEs (49.0% in CKD vs. 48.1%, p &gt; 0.99999) and immune-related AEs (28.6 vs. 24.7%, p \u2265 0.9999) did not significantly differ between the groups. There was no difference in PFS for patients with RCC or UC and CKD or without CKD (RCC: 6.81 vs. 7.54 months, HR 1.000 (95%CI 0.548\u201301.822), p = 0.999; UC:2.33 vs. 3.67 months, HR 01.492 (95%CI 0.686\u20133.247), p = 0.431). CKD appeared to be a potential effect modifier for OS in both RCC and UC (RCC: NR vs. 23.9 months, HR 0.502 (95%CI 0.219\u20131.152), p = 0.104; UC:18.84 vs. 15.42 months, HR 0.656 (95%CI 0.296\u20131.454), p = 0.299). Conclusions: Checkpoint inhibitor treatment in our cohort of patients with CKD was as safe and efficient as in the cohort of patients without CKD.<\/jats:p>","DOI":"10.3390\/cancers13071623","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T21:37:03Z","timestamp":1617226623000},"page":"1623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Efficacy and Safety of Checkpoint Inhibitor Treatment in Patients with Advanced Renal or Urothelial Cell Carcinoma and Concomitant Chronic Kidney Disease: A Retrospective Cohort Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Florian","family":"Seydel","sequence":"first","affiliation":[{"name":"Department of Nephrology, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Delecluse","sequence":"additional","affiliation":[{"name":"Department of Nephrology, University Hospital Heidelberg, 69120 Heidelberg, Germany"},{"name":"German Center for Infection Research (DZIF), 69120 Heidelberg, Germany"},{"name":"German Cancer Research Centre (DKFZ) Unit F100, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Zeier","sequence":"additional","affiliation":[{"name":"Department of Nephrology, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Holland-Letz","sequence":"additional","affiliation":[{"name":"German Cancer Research Centre (DKFZ) Unit C060, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg Martin","family":"Haag","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Center of Tumor Diseases (NCT), University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Katrin","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Center of Tumor Diseases (NCT), University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara Christine","family":"Gr\u00fcn","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Center of Tumor Diseases (NCT), University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0718-7360","authenticated-orcid":false,"given":"Nina","family":"Bougatf","sequence":"additional","affiliation":[{"name":"Cancer Registry, National Center of Tumor Diseases (NCT), University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hohenfellner","sequence":"additional","affiliation":[{"name":"Department of Urology, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Duensing","sequence":"additional","affiliation":[{"name":"Department of Urology, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"J\u00e4ger","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Center of Tumor Diseases (NCT), University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Zsch\u00e4bitz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Center of Tumor Diseases (NCT), University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1056\/NEJMoa1712126","article-title":"Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma","volume":"378","author":"Motzer","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1056\/NEJMoa1816714","article-title":"Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma","volume":"380","author":"Rini","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1056\/NEJMoa1816047","article-title":"Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma","volume":"380","author":"Motzer","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S1159","DOI":"10.1016\/j.annonc.2020.08.2257","article-title":"696O_PR Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: First results from the randomized phase III CheckMate 9ER trial","volume":"31","author":"Choueiri","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1056\/NEJMoa1510665","article-title":"Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma","volume":"373","author":"Motzer","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"LBA1","DOI":"10.1200\/JCO.2020.38.18_suppl.LBA1","article-title":"Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis","volume":"38","author":"Powles","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1056\/NEJMoa1613683","article-title":"Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma","volume":"376","author":"Bellmunt","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1001\/jamaoncol.2019.0393","article-title":"Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-analysis","volume":"5","author":"Wang","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e201611","DOI":"10.1001\/jamanetworkopen.2020.1611","article-title":"Immune Checkpoint Inhibitors and Immune-Related Adverse Events in Patients With Advanced Melanoma: A Systematic Review and Network Meta-analysis","volume":"3","author":"Chang","year":"2020","journal-title":"JAMA Netw. Open."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S1470-2045(06)70803-8","article-title":"Chronic kidney disease after nephrectomy in patients with renal cortical tumours: A retrospective cohort study","volume":"7","author":"Huang","year":"2006","journal-title":"Lancet Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.1093\/ndt\/gfp331","article-title":"The pattern of excess cancer in dialysis and transplantation","volume":"24","author":"Stewart","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1681\/ASN.2007090971","article-title":"Impaired immune responses and antigen-specific memory CD4+ T cells in hemodialysis patients","volume":"19","author":"Litjens","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/j.1525-139X.2007.00283.x","article-title":"Basic Science and Dialysis: Disturbances of Acquired Immunity in Hemodialysis Patients","volume":"20","author":"Eleftheriadis","year":"2007","journal-title":"Semin. Dial."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.eururo.2019.03.015","article-title":"Primary Results from SAUL, a Multinational Single-arm Safety Study of Atezolizumab Therapy for Locally Advanced or Metastatic Urothelial or Nonurothelial Carcinoma of the Urinary Tract","volume":"76","author":"Sternberg","year":"2019","journal-title":"Eur. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hoffman-Censits, J., Pal, S., Kaiser, C., Ding, B., and Bellmunt, J. (2020). Atezolizumab in patients with renal insufficiency and mixed variant histology: Analyses from an expanded access program in platinum-treated locally advanced or metastatic urothelial carcinoma. J. Immunother. Cancer, 8.","DOI":"10.1136\/jitc-2019-000419"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"825","DOI":"10.7326\/0003-4819-158-11-201306040-00007","article-title":"Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group, Evaluation and management of chronic kidney disease: Synopsis of the kidney disease: Improving global outcomes 2012 clinical practice guideline","volume":"158","author":"Stevens","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"v58","DOI":"10.1093\/annonc\/mdw328","article-title":"Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"27","author":"Escudier","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"iii40","DOI":"10.1093\/annonc\/mdu223","article-title":"Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up","volume":"25","author":"Bellmunt","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_19","unstructured":"(2021, March 29). Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0, Available online: https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/docs\/ctcae_v5_quick_reference_5x7.pdf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ejca.2015.11.016","article-title":"Immune-related adverse events with immune checkpoint blockade: A comprehensive review","volume":"54","author":"Michot","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/S0140-6736(17)33297-X","article-title":"Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): A multicentre, open-label, phase 3 randomised controlled trial","volume":"391","author":"Powles","year":"2018","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e172411","DOI":"10.1001\/jamaoncol.2017.2411","article-title":"Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: Updated results from a phase 1\/2 open-label study","volume":"3","author":"Powles","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1016\/S0140-6736(16)00561-4","article-title":"Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial","volume":"387","author":"Rosenberg","year":"2016","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S1470-2045(17)30900-2","article-title":"Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): Pooled results from two expansion cohorts of an open-label, phase 1 trial","volume":"19","author":"Patel","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Siefker-Radtke, A.O., Baron, A.D., Necchi, A., Plimack, E.R., Pal, S.K., Bedke, J., Zakharia, Y., Grimm, M.O., Bracarda, S., and Retz, M. (2019). Nivolumab monotherapy in patients with advanced platinum-resistant urothelial carcinoma: Efficacy and safety update from CheckMate 275. J. Clin. Oncol., 4524.","DOI":"10.1200\/JCO.2019.37.15_suppl.4524"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Elias, R., Yan, F., Singla, N., Levonyack, N., Formella, J., Christie, A., Kapur, P., Bowman, A.I., Hammers, H.J., and Hannan, R. (2019). Immune-related adverse events are associated with improved outcomes in ICI-treated renal cell carcinoma patients. J. Clin. Oncol., 37.","DOI":"10.1200\/JCO.2019.37.7_suppl.645"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s40425-019-0579-z","article-title":"Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: The Italian expanded access program","volume":"7","author":"Verzoni","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Morales-Barrera, R., Rodriguez, C.S., Gonzalez, M., Ros, J., Semidey, M.E., Hernandez, E.S., Mateo, J., S\u00e1ez, C.F., Lozano, F., and Mast, R. (2019). Impact of immune-related adverse events on survival in patients with metastastic urothelial carcinoma treated with immune-checkpoint inhibitors. J. Clin. Oncol., 37.","DOI":"10.1200\/JCO.2019.37.15_suppl.4531"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1186\/s40425-019-0805-8","article-title":"Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors","volume":"7","author":"Das","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1093\/ndt\/gfy105","article-title":"Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: Meta-analysis","volume":"34","author":"Manohar","year":"2019","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.currproblcancer.2016.12.004","article-title":"Renal complications of immune checkpoint blockade","volume":"41","author":"Murakami","year":"2017","journal-title":"Curr. Probl. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"808","DOI":"10.3389\/fonc.2020.00808","article-title":"Checkpoint Inhibition for Metastatic Urothelial Carcinoma After Chemotherapy\u2014Real-World Clinical Impressions and Comparative Review of the Literature","volume":"10","author":"Fuhrmann","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.eururo.2013.08.033","article-title":"Adjuvant Chemotherapy for Invasive Bladder Cancer: A 2013 Updated Systematic Review and Meta-Analysis of Randomized Trials","volume":"66","author":"Leow","year":"2014","journal-title":"Eur. Urol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tsai, T.F., Lin, J.F., Lin, Y.C., Chou, K.Y., Chen, H.E., Ho, C.Y., Chen, P.C., and Hwang, T.I. (2019). Cisplatin contributes to programmed death-ligand 1 expression in bladder cancer through ERK1\/2-AP-1 signaling pathway. Biosci. Rep., 39.","DOI":"10.1042\/BSR20190362"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"R\u00e9b\u00e9, C., Demontoux, L., Pilot, T., and Ghiringhelli, F. (2019). Platinum Derivatives Effects on Anticancer Immune Response. Biomolecules, 10.","DOI":"10.3390\/biom10010013"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/7\/1623\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:55:53Z","timestamp":1760363753000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/7\/1623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,1]]},"references-count":35,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["cancers13071623"],"URL":"https:\/\/doi.org\/10.3390\/cancers13071623","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,1]]}}}