{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T02:16:56Z","timestamp":1774577816947,"version":"3.50.1"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T00:00:00Z","timestamp":1617408000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T00:00:00Z","timestamp":1617408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Med Case Reports"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Immune checkpoint inhibitors and mitogen-activated protein kinase inhibitors have become the standard of care in patients with advanced melanoma bearing V600 mutations. However, little is known about their nephrotoxicity. To date, only two cases of anti-glomerular basement membrane glomerulonephritis after exposure to checkpoint inhibitors have been documented. Herein, we report the first case of a patient with metastatic melanoma who developed linear Immunoglobulin G  3+,  Immunoglobulin A 2+, kappa 2+, lambda 1+ anti-glomerular basement membrane glomerulonephritis with negative serology following treatment with checkpoint inhibitors and subsequently mitogen-activated protein kinase inhibitors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>A 58-year-old Caucasian male was referred to our outpatient nephrology clinic with acute kidney injury and proteinuria. He had received three cycles of ipilimumab and nivolumab for recurrent melanoma positive for the BRAF V600E mutation with metastasis to the lungs. Immunotherapy had been discontinued in the setting of severe adverse effects including dermatitis, colitis, and hepatitis. Because of persistent bilateral lung metastases and left pleural metastases, the patient had been initiated on dabrafenib and trametinib until his presentation to our clinic 6 months later. On presentation, his blood pressure was 172\/89\u00a0mm\/Hg and had 2+ edema bilaterally. His creatinine level was 2.4 mg\/dL from a previous normal baseline with a urinary protein-to-creatinine ratio of 2 g\/g. His urinalysis showed dysmorphic erythrocytes and red blood cell casts. Serologic testing was negative for antineutrophilic cytoplasmic antibodies, proteinase 3 antigen, myeloperoxidase, and anti-glomerular basement membrane antibody. Complement levels were normal. A renal biopsy showed focal crescentic (2 of 15 glomeruli with cellular crescents), proliferative, and sclerosing glomerulonephritis with diffuse linear staining of glomerular capillary loops dominant for IgG (3+), IgA (2+), kappa (2+), and lambda (1+) minimal changes. He was initiated on oral cyclophosphamide and pulse intravenous methylprednisolone followed by oral prednisone for 6 months, which stabilized his renal function until reinitiation of immunotherapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Acute kidney injury is an increasingly reported adverse effect of both drug classes, mostly affecting the tubulointerstitial compartment and infrequently the glomerulus. Although the biologic effect of these drugs on immune cells is not entirely understood, it is possible that BRAF-induced podocyte injury in combination with direct T-cell-mediated glomerular injury facilitated by checkpoint inhibitors led to the unmasking of cryptic antigens, loss of self-tolerance, and autoimmunity. More importantly, we show that treatment with corticosteroids and cyclophosphamide was able to improve and stabilize our patient\u2019s renal function until the reinitiation of immunotherapy.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13256-021-02766-w","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T19:04:59Z","timestamp":1617390299000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Atypical anti-glomerular basement membrane glomerulonephritis in a patient with metastatic melanoma treated with mitogen-activated protein kinase and immune checkpoint inhibitors: a case report"],"prefix":"10.1186","volume":"15","author":[{"given":"Periklis","family":"Kyriazis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhinav","family":"Tiwary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Landry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Braden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,4,3]]},"reference":[{"key":"2766_CR1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1517\/13543784.2013.748032","volume":"22","author":"M Mackiewicz-Wysocka","year":"2013","unstructured":"Mackiewicz-Wysocka M, Zolnierek J, Wysocki PJ. New therapeutic options in systemic treatment of advanced cutaneous melanoma. Expert Opin Investig Drugs. 2013;22:181\u201390.","journal-title":"Expert Opin Investig Drugs"},{"key":"2766_CR2","doi-asserted-by":"publisher","first-page":"2769","DOI":"10.1158\/1535-7163.MCT-14-0290","volume":"13","author":"KM Ilieva","year":"2014","unstructured":"Ilieva KM, Correa I, Josephs DH, Karagiannis P, Egbuniwe IU, Cafferkey MJ, et\u00a0al. Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma. Mol Cancer Ther. 2014;13:2769\u201383.","journal-title":"Mol Cancer Ther"},{"key":"2766_CR3","doi-asserted-by":"publisher","first-page":"990","DOI":"10.3389\/fimmu.2019.00990","volume":"10","author":"C Yu","year":"2019","unstructured":"Yu C, Liu X, Yang J, Zhang M, Jin H, Ma X, et\u00a0al. Combination of immunotherapy with targeted therapy: theory and practice in metastatic melanoma. Front Immunol. 2019;10:990.","journal-title":"Front Immunol"},{"key":"2766_CR4","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.kint.2016.04.008","volume":"90","author":"FB Cortazar","year":"2016","unstructured":"Cortazar FB, Marrone KA, Troxell ML, Ralto KM, Hoenig MP, Brahmer JR, et\u00a0al. Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors. Kidney Int. 2016;90:638\u201347.","journal-title":"Kidney Int"},{"key":"2766_CR5","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1158\/2159-8290.CD-18-0367","volume":"8","author":"SC Wei","year":"2018","unstructured":"Wei SC, Duffy CR, Allison JP. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 2018;8:1069\u201386.","journal-title":"Cancer Discov"},{"key":"2766_CR6","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1093\/ckj\/sfv149","volume":"9","author":"R Wanchoo","year":"2016","unstructured":"Wanchoo R, Jhaveri KD, Deray G, Launay-Vacher V. Renal effects of BRAF inhibitors: a systematic review by the Cancer and the Kidney International Network. Clin Kidney J. 2016;9:245\u201351.","journal-title":"Clin Kidney J"},{"key":"2766_CR7","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1053\/j.ajkd.2016.12.013","volume":"70","author":"L Perico","year":"2017","unstructured":"Perico L, Mandal\u00e0 M, Schieppati A, Carrara C, Rizzo P, Conti S, et\u00a0al. BRAF signaling pathway inhibition, podocyte injury, and nephrotic syndrome. Am J Kidney Dis. 2017;70:145\u201350.","journal-title":"Am J Kidney Dis"},{"key":"2766_CR8","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1159\/000455014","volume":"45","author":"R Wanchoo","year":"2017","unstructured":"Wanchoo R, Karam S, Uppal NN, Barta VS, Deray G, Devoe C, et\u00a0al. Adverse renal effects of immune checkpoint inhibitors: a narrative review. Am J Nephrol. 2017;45:160\u20139.","journal-title":"Am J Nephrol"},{"key":"2766_CR9","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.2215\/CJN.01380217","volume":"12","author":"SP McAdoo","year":"2017","unstructured":"McAdoo SP, Pusey CD. Anti-glomerular basement membrane disease. CJASN. 2017;12:1162\u201372.","journal-title":"CJASN"},{"key":"2766_CR10","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1016\/j.autrev.2013.06.014","volume":"12","author":"F Dammacco","year":"2013","unstructured":"Dammacco F, Battaglia S, Gesualdo L, Racanelli V. Goodpasture\u2019s disease: a report of ten cases and a review of the literature. Autoimmun Rev. 2013;12:1101\u20138.","journal-title":"Autoimmun Rev"},{"key":"2766_CR11","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.kint.2016.02.001","volume":"89","author":"SH Nasr","year":"2016","unstructured":"Nasr SH, Collins AB, Alexander MP, Schraith DF, Herrera Hernandez L, Fidler ME, et\u00a0al. The clinicopathologic characteristics and outcome of atypical anti-glomerular basement membrane nephritis. Kidney Int. 2016;89:897\u2013908.","journal-title":"Kidney Int"},{"key":"2766_CR12","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1093\/ckj\/sfw068","volume":"9","author":"RJ Glassock","year":"2016","unstructured":"Glassock RJ. Atypical anti-glomerular basement membrane disease: lessons learned. Clin Kidney J. 2016;9:653\u20136.","journal-title":"Clin Kidney J"},{"key":"2766_CR13","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1093\/ndtplus\/sfp177","volume":"3","author":"C Sammartino","year":"2010","unstructured":"Sammartino C, Goodman D, Flanagan G, Hill P. Anti-GBM disease following CTLA4 blockade in a patient with metastatic melanoma. Clin Kidney J. 2010;3:135\u20137.","journal-title":"Clin Kidney J"},{"key":"2766_CR14","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.lungcan.2018.05.015","volume":"122","author":"N Takahashi","year":"2018","unstructured":"Takahashi N, Tsuji K, Tamiya H, Shinohara T, Kuroda N, Takeuchi E. Goodpasture\u2019s disease in a patient with advanced lung cancer treated with nivolumab: an autopsy case report. Lung Cancer. 2018;122:22\u20134.","journal-title":"Lung Cancer"},{"key":"2766_CR15","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1016\/j.cell.2017.07.024","volume":"170","author":"SC Wei","year":"2017","unstructured":"Wei SC, Levine JH, Cogdill AP, Zhao Y, Anang N, Andrews MC, et\u00a0al. Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade. Cell. 2017;170:1120\u201333.","journal-title":"Cell."},{"key":"2766_CR16","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1084\/jem.20130579","volume":"210","author":"TR Simpson","year":"2013","unstructured":"Simpson TR, Li F, Montalvo-Ortiz W, Sepulveda MA, Bergerhoff K, Arce F, et\u00a0al. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med. 2013;210:1695\u2013710.","journal-title":"J Exp Med"},{"key":"2766_CR17","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1158\/2326-6066.CIR-13-0013","volume":"1","author":"MJ Selby","year":"2013","unstructured":"Selby MJ, Engelhardt JJ, Quigley M, Henning KA, Chen T, Srinivasan M, et\u00a0al. Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Cancer Immunol Res. 2013;1:32\u201342.","journal-title":"Cancer Immunol Res"},{"key":"2766_CR18","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1172\/JCI6710","volume":"105","author":"J Reynolds","year":"2000","unstructured":"Reynolds J, Tam FWK, Chandraker A, Smith J, Karkar AM, Cross J, et\u00a0al. CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis. J Clin Invest. 2000;105:643\u201351.","journal-title":"J Clin Invest"},{"key":"2766_CR19","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1046\/j.1365-2249.2002.01859.x","volume":"128","author":"AR Kitching","year":"2002","unstructured":"Kitching AR, Huang XR, Ruth A-J, Tipping PG, Holdsworth SR. Effects of CTLA4-Fc on glomerular injury in humorally-mediated glomerulonephritis in BALB\/c mice. Clin Exp Immunol. 2002;128:429\u201335.","journal-title":"Clin Exp Immunol"},{"key":"2766_CR20","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1172\/JCI13876","volume":"109","author":"J Wu","year":"2002","unstructured":"Wu J, Hicks J, Borillo J, Glass WF, Lou Y-H. CD4+ T cells specific to a glomerular basement membrane antigen mediate glomerulonephritis. J Clin Invest. 2002;109:517\u201324.","journal-title":"J Clin Invest"},{"key":"2766_CR21","doi-asserted-by":"publisher","first-page":"3256","DOI":"10.1681\/ASN.2005040421","volume":"16","author":"J Robertson","year":"2005","unstructured":"Robertson J, Wu J, Arends J, Zhou C, McMahon J, Torres L, et\u00a0al. Activation of glomerular basement membrane-specific B cells in the renal draining lymph node after T cell-mediated glomerular injury. JASN. 2005;16:3256\u201363.","journal-title":"JASN"},{"key":"2766_CR22","doi-asserted-by":"publisher","first-page":"F93","DOI":"10.1152\/ajprenal.00345.2007","volume":"294","author":"H Chaib","year":"2008","unstructured":"Chaib H, Hoskins BE, Ashraf S, Goyal M, Wiggins RC, Hildebrandt F. Identification of BRAF as a new interactor of PLC\u03b51, the protein mutated in nephrotic syndrome type 3. Am J Physiol Renal Physiol. 2008;294:F93\u20139.","journal-title":"Am J Physiol Renal Physiol"}],"container-title":["Journal of Medical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13256-021-02766-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13256-021-02766-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13256-021-02766-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T19:34:19Z","timestamp":1617392059000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmedicalcasereports.biomedcentral.com\/articles\/10.1186\/s13256-021-02766-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,3]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2766"],"URL":"https:\/\/doi.org\/10.1186\/s13256-021-02766-w","relation":{},"ISSN":["1752-1947"],"issn-type":[{"value":"1752-1947","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,3]]},"assertion":[{"value":"12 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The Ethics Advisory Committee at Baystate Health reviewed the consent documentation, the involvement of human subjects, and the data collection and monitoring in this study and found it to be without ethical violation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent form"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"186"}}