A FLAVELL1, S HOLT1,R FULLINFAW2, M FINLAY3,T BARBOUR1
1Department of Nephrology, Royal Melbourne Hospital,, Australia, 2Department of Chemical Pathology, Royal Melbourne Hospital,, Australia, 3Department of Anatomical Pathology, Royal Melbourne Hospital, Australia
Aim: To assess coincident monoclonal gammopathy (MG) in patients with noninfectious cryoglobulinaemic glomerulonephritis (CGN).
Background: Increasing recognition that monoclonal immunoglobulin (mIg) including free light chain (LC) causes certain types of glomerulonephritis has led to the term monoclonal gammopathy of renal significance (MGRS). MGRS implies a need for clonally directed therapy where this would otherwise be considered unnecessary (i.e. for monoclonal gammopathy of unknown significance). MGRS is exemplified by (Brouet) type I CGN, in which the cryoglobulin is composed of mIg. By contrast, mixed CGN (type II/III, polyclonal immunoglobulin with or without mIg) is not specifically associated with MG.
Methods: A single-centre, retrospective review of clinical and pathological data from 2002 onwards for noninfectious CGN with accompanying MG excluding myeloma, Waldenstrom’s macroglobulinaemia and lymphoma.
Results: 5 cases included 3 with membranoproliferative glomerulonephritis, 2 with crescents, 4 with intracapillary hyaline microthrombi and 1 with necrotising arteritis; 0/2 assessed by immunoperoxidase showed LC restriction; 0/3 assessed by electron microscopy showed organised deposits. MG (median 2g/L) included 2 IgG-lambda, 1 IgM-kappa, 2 faint/untyped, with 1/5 Bence Jones positive. Cryoglobulinaemia (median 0.4g/L) was type II or III in all cases (no type I). 4/5 had rheumatoid factor positivity and 3/5 had low complements. 2 patients had primary Sjögrens syndrome, 1 subsequently undergoing surgery for cholangiocarcinoma, with no other systemic illnesses identified.
Conclusions: In patients with noninfectious CGN, coincident MG necessitates testing and surveillance for malignant B cell disorders. Where these are excluded, the renal lesion may in fact be unrelated to the MG, as (cautiously) appears to be the case in our small series. Here, renal immunostaining for LC restriction and careful typing of the cryoglobulin provide valuable information.
Advanced Trainee in Nephrology