SUN-007 MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE AND MONOCLONAL IMMUNOGLOBULIN RENAL DAMAGE IN MALIGNANT B-CELL DISORDERS: REAL CLINICAL PRACTICE – WHAT IS BEYOND MONOCLONAL IMMUNOGLOBULIN AMYLOIDOSIS?

Abstract

Monoclonal gammopathy of renal significance (MGRS) merges paraprotein-mediated renal disorders in patients who do not meet criteria for multiple myeloma (MM) and systemic lymphoma (SL). MGRS is driven by monoclonal immunoglobulin (MIg), secreted by small non-malignant B-cell clone. By definition, diagnosis of MGRS requires identification of MIg deposition on kidney biopsy. Spectrum of MGRS, beyond MIg related amyloidosis, includes various types of tubular and glomerular disorders with organized and non-organized MIg or fragments thereof deposition: light chain proximal tubulopathy (LCPT), crystal-storing histiocytosis, fibrillary glomerulonephritis (GN), type I cryoglobulinemic (Cryo) GN, immunotactiod GN, monoclonal immunoglobulin deposition disease (MIDD), proliferative GN with monoclonal Ig deposits (PGNMID), and C3 GN. Membranous nephropathy (MN) and anti-glomerular basement (anti-GBM) GN have also been described. Same lesions may occur during symptomatic B-cell proliferation, however high tumor mass with massive paraprotein precipitation more often results in cast-nephropathy (CN) in MM, or in glomerular intracapillary deposition of MIgM in Waldenström’s macroglobulinemia (WM). We aimed to evaluate the spectrum of MGRS versus MM/SL associated paraprotein-induced renal damage in patients, treated in our unit in 1997-2017. We identified 168 patients with biopsy-proven paraprotein-induced kidney damage, underwent advanced hematologic evaluation. Patients with MIg amyloidosis were excluded from further analysis. Pathology study included light microscopy and immune staining in all cases, and electron microscopy in 19% of cases. Study group included 41 patients, M/F 20/21, median age 61 [30; 76] years. Indications for kidney biopsy were nephrotic syndrome in 6 (14.6%), decline of kidney function in 17 (41.4%), or both in 18 (43.9%) of cases. Clinical diagnosis and pathology are shown in the Table 1. Tabled 1Clinical setting/Pathology patternMGRS 14 (34.1%)MM 20 (48.7%)WM 6 (14.6%)B-cell lymphoma 1 (2.4%)TotalMIDD10818PGNMID213MN22CN77LCPT33CN+LCPT11CN+MIDD22LCPT+MIDD11Anti-GBM GN11Cryo GN11C3 GN112Intracapillary deposition of MIgM44Total14246145 Open table in a new tab Patients with MGRS presented mainly with MIDD with few cases of PGNMID and MN. Patients with MM demonstrated not only CN, but also LCPT and MIDD, and various combinations of these patterns, single cases of PGNMID and anti-GBM GN were also observed in the setting of MM. Patients with WM presented mainly, but not exclusively, with glomerular intracapillary deposition of MIgM, with single cases of Cryo GN and C3 GN. The only case of B-cell lymphoma showed C3 GN. And vice versa, LCDD and PGNMID patterns were found both in MGRS and MM, and only MN was found exclusively in MGRS setting. CN and LCPT or both and in combination with LCDD were characteristic for MM. C3 GN was found in WM and B-cell lymphoma, single cases of anti-GBM GN and Cryo GN were found in MM and WM respectively. We did not find fibrillary and immunotactoid GN in our case series, most likely because of lack of electron microscopy studies. Conditions like LCPT, LCDD, PGNMID, C3 GN and anti-GBM GN, attributed in the literature mostly to MGRS, are also seen in patients with overt malignant B-cell disorders, demanding advanced henatology evaluation. Dual patterns of renal damage are not that rare, reflecting biclonal nature of B-cell proliferation.