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      A new expression of immune checkpoint inhibitors’ renal toxicity: when distal tubular acidosis precedes creatinine elevation

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          Abstract

          The main manifestation of acute interstitial nephritis (AIN) due to immune checkpoint inhibitors is acute kidney injury. We report here a biopsy-proven AIN revealed by tubular acidosis. This case highlights that immune checkpoint inhibitor prescribers must be aware of electrolytic disorders since tubular dysfunction can precede serum creatinine increase and reveal renal toxicity.

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          Most cited references 3

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          Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review

          Background: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers. Summary: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity. In addition, primary data from the initial clinical trials of these agents and the FDA adverse reporting system database were also reviewed to determine renal adverse events. Acute interstitial nephritis (AIN), podocytopathy, and hyponatremia were toxicities caused by ipilimumab. The main adverse effect associated with both the PD-1 inhibitors was AIN. The onset of kidney injury seen with PD-1 inhibitors is usually late (3-10 months) compared to CTLA-4 antagonists related renal injury, which happens earlier (2-3 months). PD-1 as opposed to CTLA-4 inhibitors has been associated with kidney rejection in transplantation. Steroids appear to be effective in treating the immune-related adverse effects noted with these agents. Key Message: Although initially thought to be rare, the incidence rates of renal toxicities might be higher (9.9-29%) as identified by recent studies. As a result, obtaining knowledge about renal toxicities of immune checkpoint inhibitors is extremely important.
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            Renal Tubular Acidosis an Adverse Effect of PD-1 Inhibitor Immunotherapy

            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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              Autoantibodies against intercalated cells in Sjögren's syndrome

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                Author and article information

                Journal
                Clin Kidney J
                Clin Kidney J
                ckj
                Clinical Kidney Journal
                Oxford University Press
                2048-8505
                2048-8513
                February 2020
                14 May 2019
                14 May 2019
                : 13
                : 1
                : 42-45
                Affiliations
                [1 ] Department of Nephrology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud , Pierre-Bénite, France
                [2 ] Immunology Cancer Research (ImmuCare), Institut de Cancérologie des Hospices Civils de Lyon , Lyon, France
                [3 ] Institute of Physiology, University of Zurich , Zürich, Switzerland
                [4 ] Department of Pathology, Groupement Hospitalier Est, Hospices Civils de Lyon , Bron, France
                [5 ] Department of Physiology, Hôpital Tenon, APHP , Paris Cedex 20, France
                Author notes
                Correspondence and offprint requests to: Xavier Charmetant; E-mail: xaviercharmetant@ 123456hotmail.com
                Article
                sfz051
                10.1093/ckj/sfz051
                7025331
                © The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                Page count
                Pages: 4
                Product
                Categories
                Onconephrology

                Nephrology

                distal tubular acidosis, immune checkpoint inhibitors, nephrotoxicity

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