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      Monoclonal gammopathy of renal significance (MGRS) increases the risk for progression to multiple myeloma: an observational study of 2935 MGUS patients

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          Abstract

          Purpose

          Monoclonal gammopathy of undetermined significance (MGUS) is a premalignancy preceding multiple myeloma (MM) or related disorders. In MGUS, renal impairment caused by deposition of the monoclonal immunoglobulins or free light-chains monoclonal gammopathy of renal significance (MGRS) is often associated with high morbidity and mortality. We analysed the prevalence of renal impairment, clinical features and the long-term outcome in 2935 patients with MGUS.

          Methods

          Between 1/2000 and 8/2016, 2935 adult patients with MGUS were identified in our database.

          Results

          In 44/2935 (1.5%) patients MGRS was diagnosed. In MGRS patients, significantly more progressions to MM were observed than in MGUS patients (18% vs. 3%; P<0.001). MGRS patients showed a higher risk for progression (HR 3.3 [1.5-7.4]) in the Cox model. Median time to progression was 23 years for MGUS and 18.8 years for MGRS patients. Corresponding progression rate was 8.8 [7.2-10.7] per 1000 patient-years (py) for MGUS patients and 30.6 [15.3–61] for the MGRS group. Risk for progression within the first year after diagnosis was 1% [0.6-1.4] in the MGUS group and 10% [4-29] among MGRS patients.

          Conclusion

          The significantly higher risk for progression to MM means MGRS patients should be monitored carefully and treated in a specialized centre.

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          Proliferative glomerulonephritis with monoclonal IgG deposits.

          G. Markowitz, D A Valeri, Anjali Satoskar … (2009)
          Dysproteinemias that result in monoclonal glomerular deposits of IgG are relatively uncommon. Here, we report the largest series of proliferative glomerulonephritis with monoclonal IgG deposits, a form of renal involvement by monoclonal gammopathy that mimics immune-complex glomerulonephritis. We retrospectively identified 37 patients, most of whom were white (81%), female (62%), or older than 50 yr (65%). At presentation, 49% had nephrotic syndrome, 68% had renal insufficiency, and 77% had hematuria. In 30% of the patients, we identified a monoclonal serum protein with the same heavy- and light-chain isotypes as the glomerular deposits (mostly IgG1 or IgG2), but only one patient had myeloma. Histologic patterns were predominantly membranoproliferative (57%) or endocapillary proliferative (35%) with membranous features. Electron microscopy revealed granular, nonorganized deposits, and immunofluorescence demonstrated glomerular deposits that stained for a single light-chain isotype and a single heavy-chain subtype, most commonly IgG3kappa (53%). During an average of 30.3 mo of follow-up for 32 patients with available data, 38% had complete or partial recovery, 38% had persistent renal dysfunction, and 22% progressed to ESRD. Correlates of ESRD on univariate analysis were higher creatinine at biopsy, percentage of glomerulosclerosis, and degree of interstitial fibrosis but not immunomodulatory treatment or presence of a monoclonal spike. On multivariate analysis, higher percentage of glomerulosclerosis was the only independent predictor of ESRD. Only one patient lacking a monoclonal spike at presentation subsequently developed a monoclonal spike and no patient with a monoclonal spike at presentation subsequently developed a hematologic malignancy. We conclude that proliferative glomerulonephritis with monoclonal IgG deposits does not seem to be a precursor of myeloma in the vast majority of patients.
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            Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the International Myeloma Working Group.

            S Rajkumar, Antonio Palumbo, Chris G Richardson … (2010)
            Renal impairment is a common complication of multiple myeloma (MM). The estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula is the recommended method for the assessment of renal function in patients with MM with stabilized serum creatinine. In acute renal injury, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment. Novel criteria based on eGFR measurements are recommended for the definition of the reversibility of renal impairment. Rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light chain cast nephropathy. Bortezomib with high-dose dexamethasone is considered as the treatment of choice for such patients. There is limited experience with thalidomide in patients with myeloma with renal impairment. Thus, thalidomide can be carefully administered, mainly in the context of well-designed clinical trials, to evaluate if it can improve the rapidity and probability of response that is produced by the combination with bortezomib and high-dose dexamethasone. Lenalidomide is effective in this setting and can reverse renal insufficiency in a significant subset of patients, when it is given at reduced doses, according to renal function. The role of plasma exchange in patients with suspected light chain cast nephropathy and renal impairment is controversial. High-dose melphalan (140 mg/m(2)) and autologous stem-cell transplantation should be limited to younger patients with chemosensitive disease.
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              How I treat monoclonal gammopathy of renal significance (MGRS).

              Jean-Paul Fermand, Frank Bridoux, Robert A Kyle … (2013)
              Recently, the term monoclonal gammopathy of renal significance (MGRS) was introduced to distinguish monoclonal gammopathies that result in the development of kidney disease from those that are benign. By definition, patients with MGRS have B-cell clones that do not meet the definition of multiple myeloma or lymphoma. Nevertheless, these clones produce monoclonal proteins that are capable of injuring the kidney resulting in permanent damage. Except for immunoglobulin light chain amyloidosis with heart involvement in which death can be rapid, treatment of MGRS is often indicated more to preserve kidney function and prevent recurrence after kidney transplantation rather than the prolongation of life. Clinical trials are rare for MGRS-related kidney diseases, except in immunoglobulin light chain amyloidosis. Treatment recommendations are therefore based on the clinical data obtained from treatment of the clonal disorder in its malignant state. The establishment of these treatment recommendations is important until data can be obtained by clinical trials of MGRS-related kidney diseases.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Oncotarget
                Journal ID (iso-abbrev): Oncotarget
                Journal ID (publisher-id): Oncotarget
                Journal ID (publisher-id): ImpactJ
                Title: Oncotarget
                Publisher: Impact Journals LLC
                ISSN (Electronic): 1949-2553
                Publication date Collection: 5 January 2018
                Publication date (Electronic): 18 December 2017
                Volume: 9
                Issue: 2
                Pages: 2344-2356
                Affiliations
                1 Department of Internal Medicine V (Haematology and Medical Oncology), Medical University of Innsbruck, A-6020 Innsbruck, Austria
                2 Department of Internal Medicine IV Nephrology and Hypertension, Medical University of Innsbruck, A-6020 Innsbruck, Austria
                3 Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, A-6020 Innsbruck, Austria
                4 Central Institute for Medical and Chemical Laboratory Diagnosis, Innsbruck Medical University Hospital, Medical University of Innsbruck, A-6020 Innsbruck, Austria
                Author notes
                Correspondence to: Normann Steiner, normann.steiner@ 123456i-med.ac.at
                Article
                Publisher ID: 23412
                DOI: 10.18632/oncotarget.23412
                PMC ID: 5788644
                PubMed ID: 29416776
                SO-VID: ca167cb5-18ca-4bb7-b675-b47cbed93d1b
                Copyright © Copyright: © 2018 Steiner et al.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 23 August 2017
                Date accepted : 5 December 2017
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: monoclonal gammopathy of undetermined significance,mgus,monoclonal gammopathy of renal significance,mgrs,multiple myeloma
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: monoclonal gammopathy of undetermined significance, mgus, monoclonal gammopathy of renal significance, mgrs, multiple myeloma

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