#2284 Clinical characteristics and renal survival of patients with monoclonal gammopathy of renal significance (MGRS)

Abstract

Abstract Background and Aims Monoclonal gammopathy of renal significance (MGRS) comprises a diverse group of renal disorders related to a nephrotoxic monoclonal immunoglobulin. Due to the rarity of the disease and the recent definition of MGRS-associated kidney lesions, data about long-term clinical outcomes remain limited. Method A single-center, retrospective cohort study was conducted including data of all patients with biopsy-proven MGRS who were followed at our center between 2005 and 2023. We examined the clinicopathologic characteristics and renal survival of the patients. Disease progression was defined as an eGFR decline >30% or end-stage kidney disease (ESKD). Univariate Cox regression analysis was used to assess the relationship between clinical features and disease progression. Results A total of 23 adults (males 43.5%) with a median age of 65 years (IQR 55-70) were included in our study. At presentation, median eGFR was 51 ml/min/1.73 m2 (IQR 40-80) and proteinuria 3.94 g/24 h (IQR 2.00-6.26). Serum or urine monoclonal protein was not detected in 4 patients (18.2%). MGRS-associated renal lesions included Ig-related amyloidosis (n = 8), monoclonal immunoglobulin deposition disease (n = 7), cryoglobulinemic glomerulonephritis (n = 2), C3 glomerulopathy (n = 2), proliferative glomerulonephritis with monoclonal IgG deposits (n = 1), immunotactoid glomerulopathy (n = 1) and miscellaneous (n = 2). Most patients were treated with a plasma cell-directed regimen (77.3%) and the rest with B-cell-directed (13.6%) or conservative therapy (9.1%). Median follow-up for the cohort was 45 months (IQR 27-67). Thirteen patients responded to treatment (52.1%), achieving a reduction in proteinuria (0.44 vs 3.94 g/24 h, p:001) and maintenance of eGFR (60 vs 56 ml/min, p:0.363) at the last follow-up visit. All responders had received clone-directed therapy. Disease progression occurred in 8 patients (34.8%), three of whom reached ESKD (13.0%). Renal survival, defined as survival without ESKD, was 84.6% at 48 months (CI 73.3-101.7). Factors that were associated with disease progression were Ig-related amyloidosis (HR: 6.94, CI: 1.30-36.84, p:0.023) and eGFR < 45 ml/min at diagnosis (HR: 14.73, CI: 1.62-132.95, p:0.017). Conclusion MGRS is a heterogeneous clinical entity manifesting with varying degrees of proteinuria and kidney injury. Impaired kidney function at diagnosis and Ig-related amyloidosis correlated with worse renal prognosis in our cohort. Early identification and clone-directed treatment of MGRS may improve long-term renal survival.