POS-499 CLINICAL AND PATHOLOGY SPECTRUM OF NON-AMYLOID MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE – ONE CENTER EXPERIENCE

Abstract

In 2012, the International Kidney and Monoclonal Gammopathy Research Group (IKMG) introduced the term monoclonal gammopathy of renal significance (MGRS) to highlight causal relationship between gammopathy and monoclonal immunoglobulin (MIg)-mediated renal damage in cases, which do not meet criteria for B-cell malignancies. MGRS spectrum included various patterns with organized and non-organized paraprotein deposition: light chain proximal tubulopathy (LCPT), crystal-storing histiocytosis, MIg related amyloidosis, monoclonal fibrillary glomerulonephritis (GN), immunotactiod GN, type I cryoglobulinemic glomerulonephritis (cryo-GN), MIg deposition disease (MIDD), proliferative GN with MIg deposits (PGNMID), and C3-glomerulonephritis (C3-GN). According to the IKMG 2019 Consensus report, MGRS in addition to the above listed variants now merges type II cryo-GN, (cryo)-crystalglobulin GN, thrombotic microangiopathy associated with monoclonal gammopathy, monotypic membranous nephropathy (MN), monotypic anti-glomerular basement (anti-GBM) GN, smoldering myeloma (SM), smoldering Waldenström’s macroglobulinemia (SWM), and low-grade B-cell non-Hodgkin lymphoma (B-cell NHL) associated with renal lesions. Cast-nephropathy (CN) regarded as myeloma-defining event, and as such - does not belong to the MGRS, even though it is not exclusive to multiple myeloma. Same, intracapillary MIgM deposits, traditionally attributed to overt Waldenström’s macroglobulinemia, not included into MGRS list For this retrospective study, we evaluated 87 cases matching the updated MGRS criteria and followed in our unit in 2002-2020. The main data collected were clinical diagnosis, proteinuria, eGFR (CKD-EPI equation), need for dialysis at the time of kidney biopsy, and pathology pattern. Pathology evaluation of kidney tissue per protocol included light microscopy and immune staining; with the electron microscopy additionally performed 9% of cases. MGRS diagnosis based on evaluation of kidney pathology findings, serum and urine immunochemistry, and bone marrow biopsy. For this particular study, we evaluated non-amyloid variants of MGRS and non-amyloid patterns presenting in combination with MIg amyloidosis, and excluded from further analysis cases of “pure” MIg related amyloidosis. Study group included 29 patents - 9 males and 20 females of mean age 64 [53; 82] years; 8 patients were ultimately diagnosed with SM, 6 - with SWM, 2- with low-grade B-cell NHL, the rest 13 had no underlying hematological disease. At the time of kidney biopsy nephrotic syndrome presented in 16 (55%) of cases; 6 patients had CKD stage G2, 4 - stage G3a, 5 - stage G3b, 10 - stage G4, and 4 - stage 5, two of the latter required dialysis at the time of biopsy. Pathology patterns shown in the Table 1 Patterns with the organized MIg deposits presented mostly in SM cases, whereas non-organized deposits, mainly MIDD, dominated in patients without underlying hematological condition and in cases of SWM. The combination of organized and non-organized MIg deposits found rarely - both in SM and in cases without underlying hematological condition. Amyloidosis was combined with other patterns in 4 cases. Single cases of C3-GN alone and in combination with LCPT revealed only in SM and SWM. Importantly, we found 3 cases of SM with CN and 2 cases of SWM with intracapillary deposits MIgM, which complement the MGRS spectrum