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      Renal Tubular Acidosis an Adverse Effect of PD-1 Inhibitor Immunotherapy

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          Abstract

          Immune checkpoint blockade therapy is gaining popularity among oncologists for treatment of solid and hematologic malignancies. The widespread use of these agents resulted in increasing incidence of renal immune-related adverse events. Reported renal toxicity described so far includes acute interstitial nephritis, minimal change disease, and immune complex glomerulonephritis. We report the case of a 79-year-old female with metastatic non-small cell lung cancer on anti-PD-1 therapy nivolumab. After the 4th administration of nivolumab, the treatment course was complicated with normal anion gap metabolic acidosis. Urine and blood studies were in favor of distal renal tubular acidosis (RTA). Following a negative workup for an underlying etiology, immunotherapy-induced RTA was suspected. Withholding of the offending agent and initiation of steroid therapy resulted in adequate response. The present report provides the first presentation of RTA as a renal immune-related adverse event secondary to nivolumab. Nephrologists and oncologists should be familiar with potentially life-threatening renal side effects induced by immune checkpoint inhibitors.

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          Most cited references7

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          Tumor immunotherapy directed at PD-1.

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            Immune Checkpoint Inhibitors: New Insights and Current Place in Cancer Therapy.

            The treatment of cancer has largely relied on killing tumor cells with nonspecific cytotoxic therapies and radiotherapy. This approach, however, has limitations including severe systemic toxicities, bystander effects on normal cells, recurrence of drug-resistant tumor cells, and the inability to target micrometastases or subclinical disease. An increased understanding of the critical role of the immune system in cancer development and progression has led to new treatment strategies using various immunotherapies. It is now recognized that established tumors have numerous mechanisms of suppressing the antitumor immune response including production of inhibitory cytokines, recruitment of immunosuppressive immune cells, and upregulation of coinhibitory receptors known as immune checkpoints. This review focuses on the immune checkpoint inhibitors, a novel class of immunotherapy first approved in 2011. Our objective is to highlight similarities and differences among the three immune checkpoint inhibitors approved by the U.S. Food and Drug Administration-ipilimumab, pembrolizumab, and nivolumab-to facilitate therapeutic decision making. We conducted a review of the published literature and conference proceedings and present a critical appraisal of the clinical evidence supporting their use in the treatment of metastatic melanoma and advanced squamous non-small cell lung cancer (NSCLC). We also compare and contrast their current place in cancer therapy and patterns of immune-related toxicities, and discuss the role of dual immune checkpoint inhibition and strategies for the management of immune-related adverse events. The immune checkpoint inhibitors have demonstrated a dramatic improvement in overall survival in patients with advanced melanoma and squamous NSCLC, along with acceptable toxicity profiles. These agents have a clear role in the first-line treatment of advanced melanoma and in the second-line treatment of advanced squamous NSCLC.
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              Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma

              Immune-checkpoint inhibitors are emerging as revolutionary drugs for certain malignancies. However, blocking the co-inhibitory signals may lead to immune-related adverse events, mainly in the spectrum of autoimmune diseases including colitis, endocrinopathies and nephritis. Here, we report a case of a 75-year-old man with metastatic malignant melanoma treated with a combination of nivolumab (anti-PD1-antibody) and ipilimumab (anti-CTLA-4 antibody) who developed systemic rash along with severe acute tubulointerstitial nephritis after two doses of combination therapy. Kidney biopsy and peripheral blood immune profile revealed highly proliferative and cytotoxic T cell features. Herein, we discuss the pathophysiology and management of immune checkpoint blockade-related adverse events.
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                Author and article information

                Contributors
                Journal
                Case Rep Oncol Med
                Case Rep Oncol Med
                CRIONM
                Case Reports in Oncological Medicine
                Hindawi
                2090-6706
                2090-6714
                2018
                31 January 2018
                : 2018
                : 8408015
                Affiliations
                1Department of Internal Medicine, Northwell Health Staten Island University Hospital, Staten Island, NY, USA
                2Department of Hematology and Oncology, Northwell Health Staten Island University Hospital, Staten Island, NY, USA
                3Department of Nephrology, Northwell Health Staten Island University Hospital, Staten Island, NY, USA
                Author notes

                Academic Editor: Raffaele Palmirotta

                Author information
                http://orcid.org/0000-0002-2625-9171
                http://orcid.org/0000-0002-3244-1957
                Article
                10.1155/2018/8408015
                5831873
                29666732
                eb6f5e3c-4861-4cf2-a026-911e683e9b55
                Copyright © 2018 Sandy El Bitar et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 October 2017
                : 18 January 2018
                Categories
                Case Report

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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