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      A Case of Myeloma Kidney with Perinuclear Anti-Neutrophil Cytoplasmic Antibody and Anti-Myeloperoxidase Positivity: The Importance of Determining the True Cause of Renal Impairment

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          Abstract

          Acute kidney injury (AKI) is a common presentation which can result from a number of different underlying pathological processes. Haematological malignancies, particularly multiple myeloma (MM), are known to frequently present with AKI. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare condition which can cause crescentic glomerulonephritis (GN), resulting in AKI. We present the case of a 60-year-old man who presented with clinical features suggestive of AAV in the context of blood tests which demonstrated AKI and positive perinuclear ANCA (p-ANCA) and anti-myeloperoxidase (anti-MPO) titres. Further investigations demonstrated an underlying diagnosis of MM. A renal biopsy was ultimately required to determine the cause of AKI, a cast nephropathy. This case is the first to our knowledge which demonstrates a rare situation in which myeloma kidney is associated with positive p-ANCA and anti-MPO titres, without any evidence of a crescentic GN. It highlights the importance of following up on all investigations sent in the context of AKI, even when a potential diagnosis seems evident. Furthermore, it demonstrates the role of renal biopsy in confirming a diagnosis in the context of AKI with multiple differential diagnoses.

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          Most cited references13

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          The pathogenesis and diagnosis of acute kidney injury in multiple myeloma.

          Renal failure remains a principal cause of morbidity for patients with multiple myeloma. Once reversible factors such as hypercalcemia have been corrected, the most common cause of severe renal failure in these patients is a tubulointerstitial pathology that results from the very high circulating concentrations of monoclonal immunoglobulin free light chains. These endogenous proteins can result in isolated proximal tubule cell cytotoxicity, tubulointerstitial nephritis and cast nephropathy (myeloma kidney). Less frequently, high levels of free light chains can lead to immunoglobulin light chain amyloidosis and light chain deposition disease, although these conditions are usually associated with insidious progression of renal failure rather than acute kidney injury. Unless there is rapid intervention, progressive and irreversible damage occurs, particularly interstitial fibrosis and tubular atrophy. Despite advances in our understanding of the pathogenesis of these processes there has been a gap in translating these achievements into improved patient outcomes. The International Kidney and Monoclonal Gammopathy Research Group was formed to address this need. In this Review, we discuss the mechanisms of disease and diagnostic approaches to patients with acute kidney injury complicating multiple myeloma.
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            ANCA-associated vasculitis with renal involvement.

            Systemic vasculitis is a rare but severe group of diseases characterized by inflammation and necrosis of blood vessels. The size of the vessel affected varies among the different forms of vasculitis and there are three main subgroups: large, medium and small vessel vasculitis. Among small vessel vasculitis, the antineutrophil cytoplasmic antibody (ANCA)-associated forms are of particular importance. This subgroup includes: microscopic polyangiitis, granulomatosis with polyangiitis (Wegener's), eosinophilic granulomatosis with polyangiitis (Churg-Strauss) and the form limited to the kidney. ANCA are serum autoantibodies directed against proteins present in the cytoplasmic granules of neutrophils and represent the serological markers of small vessel vasculitis. Renal involvement is present in the majority of patients with ANCA-associated vasculitis (AAV) and the consequences of a missed or delayed diagnosis of renal vasculitis are potentially life threatening. Patient survival and the risk of end-stage renal disease are closely associated with renal function at presentation. The gold standard for diagnosis remains renal biopsy. In 2010, a new histopathological classification based on the percent of normal glomeruli, cellular crescent or global sclerotic glomeruli was proposed. The aim of this classification was to predict the renal prognosis. Nowadays, remission can be achieved and maintained in most cases with a combination of high-dose steroid and immunosuppressive drugs. This therapy has to be continued for at least 24 months after a substantial remission has been obtained because early cessation of treatment is associated with an increased risk of relapse. For this reason, patients should be regularly monitored in order to promptly diagnose and treat a possible recurrence of AAV. This review will focus on kidney involvement in AAV with an overview of the clinical-pathological characteristics and therapeutic strategy for these conditions.
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              Primary dexamethasone treatment of multiple myeloma.

              Intermittent courses of dexamethasone (DEX) were administered to 112 consecutive, previously untreated patients with multiple myeloma (MM). Using criteria based on a 75% or greater reduction of calculated tumor mass, the overall response rate was 43%. Among comparable patients, response rate were approximately 15% less than those observed previously with vincristine-doxorubicin by continuous infusion with intermittent DEX (VAD) and similar to those with melphalan-prednisone. The projected survival times with VAD or DEX were similar. Results indicated that DEX accounted for most of the plasma cell reduction achieved with VAD. Serious complications occurred in 27% of patients treated with VAD, but in only 4% of those who received DEX. In view of the similar outcome with fewer serious complications, DEX provided a simple, effective, and safe primary treatment for a large fraction of patients with MM. Patients who appear most likely to benefit include those with hypercalcemia or pancytopenia, or who require simultaneous radiotherapy for a pathologic fracture.
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                Author and article information

                Journal
                CND
                CND
                10.1159/issn.2296-9705
                Case Reports in Nephrology and Dialysis
                S. Karger AG
                2296-9705
                2020
                May – August 2020
                29 July 2020
                : 10
                : 2
                : 79-85
                Affiliations
                [_a] aNephrology Department, Guy’s & St Thomas’ NHS Foundation Trust, London, United Kingdom
                [_b] bNephrology Department, King’s College Hospital NHS Foundation Trust, London, United Kingdom
                Author notes
                *Tayeba Roper, Nephrology Department, Guy’s & St Thomas’ NHS Foundation Trust, Great Maze Pond, London SE1 9RT (UK), t.roper@nhs.net
                Article
                509099 PMC7443628 Case Rep Nephrol Dial 2020;10:79–85
                10.1159/000509099
                PMC7443628
                32884934
                e8127dd6-098f-4469-9c90-02a140845a29
                © 2020 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 14 November 2019
                : 31 May 2020
                Page count
                Tables: 1, Pages: 7
                Categories
                Case Report

                Cardiovascular Medicine,Nephrology
                Histopathology,Myeloma kidney,Vasculitis,Glomerulonephritis,Acute kidney injury,Kidney biopsy

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