New nosology in nephrology: monoclonal gammopathy of renal significance


DOI: https://dx.doi.org/10.18565/therapy.2019.6.57-65

Khrabrova M.S., Smirnov A.V., Dobronravov V.A.

1) Department of propaedeutics of internal medicine with the Clinic of I.P. Pavlov First St. Petersburg State medical University of the Ministry of Healthcare of Russia; 2) Research Institute of neprolology of I.P. Pavlov First St. Petersburg State medical University of the Ministry of Healthcare of Russia
Monoclonal gammopathy of renal significance (MGRS) associated with kidney injury due to nephrotoxic protein which is produced by B-cell clonal line is a new nosology in the field of internal disease. Prevalence, spectrum and renal prognosis in MGRS still remain unclear, particularly in Russian population.
Aim of the study was to analyze the prevalence, spectrum and renal prognosis in patients with MGRS based on the data of Nephrology Department of First Saint-Petersburg State Medical University.
Material and methods. Cases met the criteria of MGRS (presence of B-cell line clone which does not meet haematological criteria for specific treatment and morphologically proved kidney injury related to produced monoclonal immunoglobulin) were enrolled from 1580 patients with kidney biopsy performed from 2011 till 2018. Treatment, haematological and renal responses (RR) were analyzed. RR was determined as: i) no RR - reduction of eGFR>25 % from initial value (IV)/initiation of renal replacement treatment (RRT); ii) presence of RR - eGFR increase>25 % from IV/ discontinuation of RRT; iii) other cases were considered as stable kidney disease. Additionally RR based on 24h proteinuria reduction>30% from IV in stable eGFR was calculated. Combined renal outcome endpoint was defined as RRT initiation or eGFR <15 ml/min/1,73m² at follow-up. The Kaplan-Meier death-censored survival plots were used to analyze long-term renal survival. The median follow-up period was 12 (2; 22) months.
Results. Prevalence of MGRS was 4,5% (n=72) including AL-amyloidosis (n=55) and IgM-related monoclonal gammopathy of undetermined significance (n=3). Prevalence of different MGRS types was the following: AL-amyloidosis (n=54), light chain deposition disease (n=5), proliferative glomerulonephritis with monoclonal immunoglobulin deposits (n=3), thrombotic microangiopathy (n=3), cryoglobulinemic glomerulonephritis (n=2), C3-glomerulopathy (n=2), fibrillary glomerulonephritis (n=1). Combination of two types of kidney injury was diagnosed in two cases. Almost all patients were treated with chemotherapy including bortesomib, cyclophosphamide, melphalan, dexamethasone or rituximab in the case of lymphoplasmacytic clone. In 9 patients autologous stem cell transplantation was performed. 8 patients fell out the follow-up, 6 patients died. Haematological response was achieved in 60% of cases including 38% of patients with complete response. In AL-amyloidosis RR response was achieved in 63%. RR and stable kidney function were registered in 20% and 80% of patients with other types of MGRS. RR based on 24-proteinuria was determined in AL-amyloidosis (57%) and other MGRS (50%). Five-year cumulative renal survival was 51% and did not differ between patients with AL-amyloidosis and other MGRS.
Conclusion. MGRS is not a rare pathological entity which is characterized by different clinical and morphological presentation and associated with inferior renal prognosis that requires multidisciplinary approach for appropriate diagnostics and treatment of such patients. The alertness of primary care doctors regarding this new nosology, especially among elderlies, will lead to effective identification of this pathology and prompt initiation of clone-specific treatment.
Keywords: AL-amyloidosis, clone-specific treatment, onconephrology, monoclonal gammopathy of renal significance, kidney injury, kidney biopsy
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About the Autors

Maria S. Khrabrova, PhD, associate professor of the Department of propaedeutics of internal medicine with the Clinic of I.P. Pavlov First St. Petersburg State medical University of the Ministry of Healthcare of Russia. Address: 197022, St. Petersburg, 17/54 Leo Tolstoy Str. Tel.: +7 (812) 338-69-01. E-mail: hrabrovamc@gmail.com
Alexey V. Smirnov, MD, professor, Director of Research Institute of neprolology of I.P. Pavlov First St. Petersburg State medical University of the Ministry of Healthcare of Russia. Address: 197022, St. Petersburg, 17/54 Leo Tolstoy Str. Tel.: +7 (812) 338-69-01. E-mail: smirnov@nephrolog.ru
Vladimir A. Dobronravov, MD, professor, Deputy Director of studies of Research Institute of neprolology of I.P. Pavlov First St. Petersburg State medical University of the Ministry of Healthcare of Russia. Address: 197022, St. Petersburg, 17/54 Leo Tolstoy Str. Tel.: +7 (812) 338-69-16. E-mail: dobronravov@nephrolog.ru


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