Monoclonal gammopathy is present in one fourth of patients undergoing renal biopsy but is pathogenic only in half of them

About 4-7% of renal biopsies show a monoclonal gammopathy-related nephropathy, such as AL amyloidosis, cast nephropathy, or light chain deposition disease. Both a high prevalence and a causal role of monoclonal gammopathy have been observed in patients with C3 glomerulopathy or thrombotic microangiopathy, although a definitive causative role cannot be established in most cases (potentially monoclonal gammopathy-related nephropathies). A coexisting monoclonal gammopathy has been identified in many cases of nephropathy without a defined causative role (monoclonal gammopathy-unrelated nephropathies). The aim of this study was to investigate the prevalence and distribution of monoclonal gammopathy in patients who underwent a renal biopsy and assess its possible causal role in nephropathies not ordinarily related to monoclonal gammopathy. In our single-center retrospective observational study, we considered patients who underwent native kidney biopsy from 2009 to 2023 at the Nephrology Unit, Careggi University Hospital, Florence (Italy) and for whom a complete monoclonal gammopathy workup (serum electrophoresis, serum and urinary immunofixation, serum free light chains) was available. Overall, 827 patients were included: 208 (25%) had a monoclonal gammopathy: in 104 cases the monoclonal gammopathy was unrelated to the kidney disease; 87 subjects showed renal pathology related to monoclonal gammopathy (monoclonal gammopathy-related nephropathies). Patients with thrombotic microangiopathy and C3 glomerulopathy (potentially monoclonal gammopathy-related nephropathies) exhibited a prevalence of monoclonal gammopathy > 30%. In a subgroup of diagnoses (e.g. tubulointerstitial nephritis, membranoproliferative glomerulonephritis) a possible causal and/or prognostic role of a concomitant monoclonal gammopathy may be hypothesized. In our cohort, one fourth of patients undergoing a renal biopsy had a monoclonal gammopathy, although in half of them the monoclonal gammopathy did not have a causative role in the kidney disease. Hence, it is impossible to conclude that a monoclonal gammopathy in the context of renal disease equates to a causal association without performing a renal biopsy because of the high frequency of monoclonal gammopathy in patients undergoing a kidney biopsy.