Comparative Kidney and Clinical Outcomes in Monoclonal Gammopathy of Renal Significance vs. Other Glomerulopathies: Propensity-Matched Real-World Analysis

Background: Monoclonal gammopathy of renal significance (MGRS) is a rare and heterogeneous cause of glomerular disease, associated with distinct risks from both its hematologic and renal components. However, real-world comparative outcome data for MGRS versus other primary glomerulopathies are lacking. We aimed to evaluate renal and clinical outcomes in MGRS compared to other glomerular diseases using a large, multi-institutional electronic health record network. Methods: We conducted a retrospective cohort study in the TriNetX Global Network. MGRS patients were identified by the presence of both monoclonal gammopathy and glomerular disease diagnosis codes. The comparator cohort included patients with glomerulopathy ICD codes but no monoclonal gammopathy. In both groups, individuals with diabetic nephropathy, hereditary nephropathy, or lupus nephritis were excluded. Each MGRS patient was 1:1 propensity score–matched to a control with another primary glomerulopathy using demographics, baseline kidney function, comorbidities, and diagnosis year. Covariate balance was confirmed. Outcomes were compared using standardized analytic methods. Results: The matched analysis included 1,236 patients per group. There were no significant differences in acute kidney injury (3.6% vs. 3.3%, p=0.753), new dialysis initiation (1.9% vs. 1.7%, p=0.812), CKD stage 4/5 (6.6% vs. 5.7%, p=0.456), or progression to dialysis (1.9% vs. 1.7%, p=0.812). MGRS patients had higher rates of pneumonia (17.5% vs. 12.8%, p=0.003), blood transfusion (10.8% vs. 6.6%, p<0.001), neutropenia (9.3% vs. 3.3%, p<0.001), and CRP ≥30 mg/L (mean 4.7 vs. 2.6, p=0.005). No differences were observed in cardiac arrest (1.9% vs. 1.8%, p=0.872), septic shock (0.6% vs. 0.6%, p=0.987), hospitalization (37.1% vs. 33.6%, p=0.098), outpatient visits (mean 4.97 vs. 3.39, p=0.313), or all-cause mortality (5.9% vs. 5.0%, p=0.388). Conclusion: In this large, matched real-world study, MGRS was associated with higher risks of infection, cytopenia, transfusion, and inflammation compared to other glomerulopathies, while rates of renal progression and mortality were similar. These findings support enhanced supportive care strategies in MGRS management.