Spectrum of renal diseases caused by monoclonal immunoglobulin: experience from an Australian tertiary referral centre over a 10-year period.

Abstract

Monoclonal immunoglobulin (MIg)-associated renal diseases are caused by nephrotoxic MIg originating from underlying plasma cell or lymphoid clone. The present study is an analysis of patient demographics, pathological characteristics, haematological and renal biomarkers of 83 biopsy-proven cases of diseases mediated by MIg, accrued from 6196 renal biopsies in a single Australian tertiary referral centre, over a decade. Older patients were more commonly affected with 89.2% of patients over the age of 50 years, with a male predominance. The spectrum consisted of direct MIg deposition diseases with organised and non-organised deposits, immunoglobulin light-chain amyloidosis +/- light chain cast nephropathy (AL amyloidosis +/- LCCN; 60.2%), cryoglobulinaemic glomerulonephritis types I and II (6%), monoclonal immunoglobulin deposition disease +/- light-chain cast nephropathy (MIDD +/- LCCN; 14.4%), proliferative glomerulonephritis with monoclonal immunoglobulin deposition disease (PGNMID; 13.3%), light-chain proximal tubulopathy (LCPT; 1.2%), light-chain cast nephropathy (LCCN; 2.4%), and indirect complement-mediated lesions including monoclonal thrombotic microangiopathy (TMA; 1.2%) and C3 glomerulopathy (1.2%). PGNMID was the only type of lesion seen with post-transplant graft recurrences (3.6%). Tissue clonality was reliably established by immunofluorescence (IF) on frozen tissue, with paraffin IF and immunohistochemistry as useful salvage procedures. An underlying plasma cell clone was identified in 80.3% cases and a lymphoid clone in 19.7% cases. An overt haematological malignancy was seen in 39.8% of cases. A confirmed diagnosis of monoclonal gammopathy of renal significance (MGRS) was made in 70.5% of cases and renal biopsy preceded haematological investigations in 65.8% of cases, emphasising the significant role of the pathologist in the accurate diagnosis and classification of these lesions. MIg-mediated renal diseases can be accurately diagnosed and classified on renal biopsies. The presence of LCCN was associated with adverse renal outcome and overall survival. Future studies with a larger sample size are necessary to determine individual parameters that affect renal and overall survival.