Clinical and morphological spectrum and long-term outcome in monoclonal gammopathy of renal significance: one center study

INTRODUCTION AND AIM. Monoclonal gammopathy of renal significance (MGRS), heterogeneous nosological entity, is caused by monoclonal immunoglobulin (IG) produced by a "small" B-cell lineage clone. The analysis of long-term renal prognosis in various clinical and morphological types of disease and in different degrees of hematological response (HR) in the Russian patient cohort became the goal of this study. PATIENTS AND METHODS. Patients met the criteria of MGRS (morphologically verified monoclonal IG related kidney damage, an aberrant clone in the bone marrow and/or the level of serum/urine paraprotein not met the oncohematological criteria for treatment initiation) were enrolled in this one-center prospective study from 01.01.2011 till 01.03.2020. The morphological spectrum of MGRS, types of therapy, hematological and renal responses (RR) were analyzed. HR was assessed depending on the type of monoclonal IG according to the accepted criteria. The presence of RR was considered as a decrease in daily proteinuria> 30 % from the initial level or less than 0.5 g in the absence of a decrease in eGFR> 25 % at the time of the end of follow-up. The progression of renal dysfunction was documented with a decrease in eGFR> 25 % from baseline. Renal outcome (initiation of renal replacement therapy or eGFR <15 ml/min/1.73m2  at the end of follow-up) and death were determined. Long-term renal survival was assessed by the Kaplan-Meier method. The median follow-up period was 18 (4; 38) months. RESULTS. The incidence of MGRS was 4.9 % (n = 102) of all performed kidney biopsies (n = 2042), the majority of cases represented with AL amyloidosis (AL, n = 73; 71.6 %). In cases of non-amyloid variant of MGRS (non-AL MGRS, n=29, 28.4 %) the most common types of renal injury were light chain deposition disease (27,6 %) and proliferative glomerulonephritis with deposition of monoclonal IG (27.6 %). The majority of patients (80.4 %) was treated with clone-specific agents, autologous bone marrow transplantation was performed in 13 cases. HR was achieved in 74 % and 80 % of the treated patients with AL and non-AL MGRS, respectively. RR was obtained in 42 % of patients with AL and in 62 % of patients with non-AL MGRS. The five-year cumulative renal survival did not differ significantly between the groups: 66 % in AL and 44 % in non-AL MGRS (р=0,78). Cumulative renal survival in patients who did not achieve HR was significantly lower (42 %) than in cases with complete HR (86 %), p=0.0014. CONCLUSION. MGRS is a clinically and morphologically heterogeneous nosological entity characterized by a poor renal prognosis, especially in the absence of clone-specific therapy. Treatment in MGRS should be carried out in a timely manner with the participation of a hematologist and nephrologist in order to prevent loss of kidney function and increase life expectancy.

AL-amyloidosis, non-amyloid types of monoclonal gammopathy of renal significance, monoclonal immunoglobulin, renal response, hematological response, clone-specific treatment

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