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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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          Most cited references 27

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          Prevalence of monoclonal gammopathy of undetermined significance.

          The prevalence of monoclonal gammopathy of undetermined significance (MGUS), a premalignant plasma-cell disorder, among persons 50 years of age or older has not been accurately determined. We used sensitive laboratory techniques to ascertain the prevalence of MGUS in a large population in a well-defined geographic area. We identified all living residents of Olmsted County, Minnesota, as of January 1, 1995. We obtained serum that remained after the performance of routine clinical tests at Mayo Clinic or asked subjects for whom such serum was unavailable to provide a sample. Agarose-gel electrophoresis was performed on all serum samples, and any serum sample with a discrete band of monoclonal protein or thought to have a localized band was subjected to immunofixation. Serum samples were obtained from 21,463 of the 28,038 enumerated residents 50 years of age or older (76.6 percent). MGUS was identified in 694 (3.2 percent) of these persons. Age-adjusted rates were higher in men than in women (4.0 percent vs. 2.7 percent, P<0.001). The prevalence of MGUS was 5.3 percent among persons 70 years of age or older and 7.5 percent among those 85 years of age or older. The concentration of monoclonal immunoglobulin was less than 1.0 g per deciliter in 63.5 percent and at least 2.0 g per deciliter in only 4.5 percent of 694 persons. The concentration of uninvolved immunoglobulins was reduced in 27.7 percent of 447 persons tested, and 21.5 percent of 79 tested had a monoclonal urinary light chain. Among residents of Olmsted County, Minnesota, MGUS was found in 3.2 percent of persons 50 years of age or older and 5.3 percent of persons 70 years of age or older. Copyright 2006 Massachusetts Medical Society.
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            Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management.

            Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is approximately 1% per year. Low-risk MGUS is characterized by having an M protein <15 g/l, IgG type and a normal free light chain (FLC) ratio. Patients should be followed with serum protein electrophoresis at six months and, if stable, can be followed every 2-3 years or when symptoms suggestive of a plasma cell malignancy arise. Patients with intermediate and high-risk MGUS should be followed in 6 months and then annually for life. The risk of smoldering (asymptomatic) multiple myeloma (SMM) progressing to multiple myeloma or a related disorder is 10% per year for the first 5 years, 3% per year for the next 5 years and 1-2% per year for the next 10 years. Testing should be done 2-3 months after the initial recognition of SMM. If the results are stable, the patient should be followed every 4-6 months for 1 year and, if stable, every 6-12 months.
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              Monoclonal gammopathy of renal significance: when MGUS is no longer undetermined or insignificant.

              Multiple myeloma is the most frequent monoclonal gammopathy to involve the kidney; however, a growing number of kidney diseases associated with other monoclonal gammopathies are being recognized. Although many histopathologic patterns exist, they are all distinguished by the monoclonal immunoglobulin (or component) deposits. The hematologic disorder in these patients is more consistent with monoclonal gammopathy of undetermined significance (MGUS) than with multiple myeloma. Unfortunately, due to the limitations of the current diagnostic schema, they are frequently diagnosed as MGUS. Because treatment is not recommended for MGUS, appropriate therapy is commonly withheld. In addition to end-stage renal disease, the persistence of the monoclonal gammopathy is associated with high rates of recurrence after kidney transplantation. Preservation and restoration of kidney function are possible with successful treatment targeting the responsible clone. Achievement of hematologic complete response has been shown to prevent recurrence after kidney transplantation. There is a need for a term that properly conveys the pathologic nature of these diseases. We think the term monoclonal gammopathy of renal significance is most helpful to indicate a causal relationship between the monoclonal gammopathy and the renal damage and because the significance of the monoclonal gammopathy is no longer undetermined.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                5 January 2018
                18 December 2017
                : 9
                : 2
                : 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
                23412
                10.18632/oncotarget.23412
                5788644
                Copyright: © 2018 Steiner et al.

                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.

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                Research Paper

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