Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: single-center experience

Journal for ImmunoTherapy of Cancer - Tập 7 Số 1 - Trang 1-13 - 2019
Mamlouk, Omar1, Selamet, Umut2, Machado, Shana1, Abdelrahim, Maen3, Glass, William F.4, Tchakarov, Amanda4, Gaber, Lillian5, Lahoti, Amit6, Workeneh, Biruh6, Chen, Sheldon6, Lin, Jamie6, Abdel-Wahab, Noha7,8, Tayar, Jean8, Lu, Huifang8, Suarez-Almazor, Maria8, Tannir, Nizar9, Yee, Cassian10, Diab, Adi10, Abudayyeh, Ala6
1Department of Nephrology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA
2Division of Nephrology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA
3Institute for Academic Medicine and Weill Cornell Medical College, Houston Methodist Cancer Center, Houston, USA
4Department of Pathology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA
5Department of Pathology, Houston Methodist Hospital, Houston, USA
6Division of Internal Medicine, Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, USA
7Rheumatology and Rehabilitation Department, Assiut University Hospitals, Faculty of Medicine, Assiut, Egypt
8Department of General Internal Medicine, Section of Rheumatology and Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston, USA
9Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
10Department of Melanoma, The University of Texas MD Anderson Cancer Center, Houston, USA

Tóm tắt

The approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding including treatment in the adjuvant setting, the immune related toxicities associated with CPI can limit the efficacy of these agents. The literature on the nephrotoxicity of CPI is limited. Here, we present cases of biopsy proven acute tubulointerstitial nephritis (ATIN) and glomerulonephritis (GN) induced by CPIs and discuss potential mechanisms of these adverse effects. We retrospectively reviewed all cancer patients from 2008 to 2018 who were treated with a CPI and subsequently underwent a kidney biopsy at The University of Texas MD Anderson Cancer Center. We identified 16 cases diagnosed with advanced solid or hematologic malignancy; 12 patients were male, and the median age was 64 (range 38 to 77 years). The median time to developing acute kidney injury (AKI) from starting CPIs was 14 weeks (range 6–56 weeks). The average time from AKI diagnosis to obtaining renal biopsy was 16 days (range from 1 to 46 days). Fifteen cases occurred post anti-PD-1based therapy. ATIN was the most common pathologic finding on biopsy (14 of 16) and presented in almost all cases as either the major microscopic finding or as a mild form of interstitial inflammation in association with other glomerular pathologies (pauci-immune glomerulonephritis, membranous glomerulonephritis, C3 glomerulonephritis, immunoglobulin A (IgA) nephropathy, or amyloid A (AA) amyloidosis). CPIs were discontinued in 15 out of 16 cases. Steroids and further immunosuppression were used in most cases as indicated for treatment of ATIN and glomerulonephritis (14 of 16), with the majority achieving complete to partial renal recovery. Our data demonstrate that CPI related AKI occurs relatively late after CPI therapy. Our biopsy data demonstrate that ATIN is the most common pathological finding; however it can frequently co-occur with other glomerular pathologies, which may require immune suppressive therapy beyond corticosteroids. In the lack of predictive blood or urine biomarker, we recommend obtaining kidney biopsy for CPI related AKI.

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citation_journal_title=Lancet Oncol; citation_title=Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial; citation_author=AM Eggermont, V Chiarion-Sileni, JJ Grob; citation_volume=16; citation_publication_date=2015; citation_pages=522-530; citation_doi=10.1016/S1470-2045(15)70122-1; citation_id=CR1 citation_journal_title=N Engl J Med; citation_title=Adjuvant Nivolumab versus Ipilimumab in resected stage III or IV melanoma; citation_author=J Weber, M Mandala, M Vecchio; citation_volume=377; citation_publication_date=2017; citation_pages=1824-1835; citation_doi=10.1056/NEJMoa1709030; citation_id=CR2 citation_journal_title=N Engl J Med; citation_title=Durvalumab after Chemoradiotherapy in stage III non-small-cell lung Cancer; citation_author=SJ Antonia, A Villegas, D Daniel; citation_volume=377; citation_publication_date=2017; citation_pages=1919-1929; citation_doi=10.1056/NEJMoa1709937; citation_id=CR3 Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018. https://doi.org/10.1200/JCO.2017.77.6385 . citation_journal_title=J Clin Oncol; citation_title=Pooled analysis safety profile of Nivolumab and Ipilimumab combination therapy in patients with advanced melanoma; citation_author=M Sznol, PF Ferrucci, D Hogg; citation_volume=35; citation_publication_date=2017; citation_pages=3815-3822; citation_doi=10.1200/JCO.2016.72.1167; citation_id=CR5 citation_journal_title=J Clin Oncol; citation_title=Safety profile of Nivolumab monotherapy: a pooled analysis of patients with advanced melanoma; citation_author=JS Weber, FS Hodi, JD Wolchok; citation_volume=35; citation_publication_date=2017; citation_pages=785-792; citation_doi=10.1200/JCO.2015.66.1389; citation_id=CR6 citation_journal_title=J Immunother Cancer; citation_title=Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) toxicity management working group; citation_author=I Puzanov, A Diab, K Abdallah; citation_volume=5; citation_publication_date=2017; citation_pages=95; citation_doi=10.1186/s40425-017-0300-z; citation_id=CR7 Postow MA. Managing immune checkpoint-blocking antibody side effects. Am Soc Clin Oncol Educ Book. 2015:76–83. https://doi.org/10.14694/EdBook_AM.2015.35.76 . citation_journal_title=J Am Soc Nephrol; citation_title=Membranous Nephropathy Related to the Checkpoint Inhibitor Nivolumab; citation_author=T Jonathan, MS Lin, S Salvatore, AN Shoushtari, I Glezerman; citation_volume=27; citation_publication_date=2016; citation_pages=102A; citation_id=CR9 Ina Cusnir KS, Yacyshyn E. Granulomatosis with Polyangitis Assosciated with Immune Checkpoint Blockade: Case report and Literature Review. J Rheumatol. 2017:950–A247. citation_journal_title=N Engl J Med; citation_title=Anti-CTLA4 antibody-induced lupus nephritis; citation_author=F Fadel, K Karoui, B Knebelmann; citation_volume=361; citation_publication_date=2009; citation_pages=211-212; citation_doi=10.1056/NEJMc0904283; citation_id=CR11 citation_journal_title=Rheumatology (Oxford); citation_title=Rapid granulomatosis with polyangiitis induced by immune checkpoint inhibition; citation_author=RR Brom, WH Abdulahad, A Rutgers; citation_volume=55; citation_publication_date=2016; citation_pages=1143-1145; citation_doi=10.1093/rheumatology/kew063; citation_id=CR12 citation_journal_title=J Immunother; citation_title=Nivolumab-associated nephrotic syndrome in a patient with renal cell carcinoma: a case report; citation_author=RA Daanen, RJH Maas, RHT Koornstra, EJ Steenbergen, CML Herpen, A Willemsen; citation_volume=40; citation_publication_date=2017; citation_pages=345-348; citation_doi=10.1097/CJI.0000000000000189; citation_id=CR13 citation_journal_title=Am J Kidney Dis; citation_title=Nephrotic syndrome with Cancer immunotherapies: a report of 2 cases; citation_author=A Kitchlu, W Fingrut, C Avila-Casado; citation_volume=70; citation_publication_date=2017; citation_pages=581-585; citation_doi=10.1053/j.ajkd.2017.04.026; citation_id=CR14 Kishi S, Minato M, Saijo A, et al. A case of IgA nephropathy after nivolumab therapy for postoperative recurrence of lung squamous cell carcinoma. Intern Med. 2018;57(9):1259-63. citation_journal_title=BMC Nephrol; citation_title=Nivolumab-associated acute glomerulonephritis: a case report and literature review; citation_author=K Jung, X Zeng, M Bilusic; citation_volume=17; citation_publication_date=2016; citation_pages=188; citation_doi=10.1186/s12882-016-0408-2; citation_id=CR16 citation_journal_title=Crit Care; citation_title=Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury; citation_author=RL Mehta, JA Kellum, SV Shah; citation_volume=11; citation_publication_date=2007; citation_pages=R31; citation_doi=10.1186/cc5713; citation_id=CR17 citation_journal_title=Kidney Int; citation_title=Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors; citation_author=FB Cortazar, KA Marrone, ML Troxell; citation_volume=90; citation_publication_date=2016; citation_pages=638-647; citation_doi=10.1016/j.kint.2016.04.008; citation_id=CR18 citation_journal_title=J Am Soc Nephrol; citation_title=A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy; citation_author=V Jha, A Ganguli, TK Saha; citation_volume=18; citation_publication_date=2007; citation_pages=1899-1904; citation_doi=10.1681/ASN.2007020166; citation_id=CR19 citation_journal_title=Nephrol Dial Transplant; citation_title=The association between proton pump inhibitor use and the risk of adverse kidney outcomes: a systematic review and meta-analysis; citation_author=S Nochaiwong, C Ruengorn, R Awiphan; citation_volume=33; citation_publication_date=2018; citation_pages=331-342; citation_doi=10.1093/ndt/gfw470; citation_id=CR20 citation_journal_title=Am J Nephrol; citation_title=Adverse renal effects of immune checkpoint inhibitors: a narrative review; citation_author=R Wanchoo, S Karam, NN Uppal; citation_volume=45; citation_publication_date=2017; citation_pages=160-169; citation_doi=10.1159/000455014; citation_id=CR21 citation_journal_title=Am J Kidney Dis; citation_title=Association of Acute Interstitial Nephritis with Programmed Cell Death 1 inhibitor therapy in lung Cancer patients; citation_author=AC Shirali, MA Perazella, S Gettinger; citation_volume=68; citation_publication_date=2016; citation_pages=287-291; citation_doi=10.1053/j.ajkd.2016.02.057; citation_id=CR22 citation_journal_title=Clin Kidney J; citation_title=Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma; citation_author=N Murakami, TJ Borges, M Yamashita, LV Riella; citation_volume=9; citation_publication_date=2016; citation_pages=411-417; citation_doi=10.1093/ckj/sfw024; citation_id=CR23 citation_journal_title=Immunol Rev; citation_title=The PD-1 pathway in tolerance and autoimmunity; citation_author=LM Francisco, PT Sage, AH Sharpe; citation_volume=236; citation_publication_date=2010; citation_pages=219-242; citation_doi=10.1111/j.1600-065X.2010.00923.x; citation_id=CR24 citation_journal_title=N Engl J Med; citation_title=Immune-related adverse events associated with immune checkpoint blockade; citation_author=MA Postow, R Sidlow, MD Hellmann; citation_volume=378; citation_publication_date=2018; citation_pages=158-168; citation_doi=10.1056/NEJMra1703481; citation_id=CR25 citation_journal_title=N Engl J Med; citation_title=Adverse events associated with immune checkpoint blockade; citation_author=JW Cohen Tervaert, C Ye, E Yacyshyn; citation_volume=378; citation_publication_date=2018; citation_pages=1164-1165; citation_id=CR26 citation_journal_title=Eur J Cancer; citation_title=Immune-related adverse events with immune checkpoint blockade: a comprehensive review; citation_author=JM Michot, C Bigenwald, S Champiat; citation_volume=54; citation_publication_date=2016; citation_pages=139-148; citation_doi=10.1016/j.ejca.2015.11.016; citation_id=CR27 citation_journal_title=JAMA Oncol; citation_title=Treatment of the immune-related adverse effects of immune checkpoint inhibitors: a review; citation_author=CF Friedman, TA Proverbs-Singh, MA Postow; citation_volume=2; citation_publication_date=2016; citation_pages=1346-1353; citation_doi=10.1001/jamaoncol.2016.1051; citation_id=CR28
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Journal for ImmunoTherapy of Cancer

Tập 7 Số 1

1-13

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