P0415MONOCLONAL GAMMOPATHY-RELATED RENAL DISEASES: NEW CLINICAL AND HISTOLOGICAL PATTERNS

Abstract

Abstract Background and Aims In the last few years new clinical-histopathological forms of paraproteinemia associated kidney disease have emerged: light chain proximal tubulopathies, proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) and C3-glomerulopathy. It is now widely recognized that the pathogenic role of the monoclonal protein depends on the free light chain chemical-physical features, even in the case of “dangerous small B cell clones”. Thus MGRS (monoclonal gammopathy of renal significance) associated disease is now considered a different entity from monoclonal gammopathy of undetermined significance (MGUS). Method We retrospectively evaluated the clinical-histopathological features of the biopsies performed in our Nephrological Unit on patients with MGUS in 2008-2018, in order to re-classify them in accordance with the recent scientific literature. Results Nine patients (7 M/2 F; age 46-77 y) were analyzed: five of them suffering from CKD stage 2, four of them with AKI or rapidly progressive CKD, 7 with proteinuria > 1 g/day, 2 with physiological proteinuria. Bone marrow biopsy: 7 patients with MGUS, 2 with smoldering multiple myeloma. Renal biopsy: 4 glomerulopathies (monoclonal fibrillary glomerulonephritis, cryoglobulinaemic (type I) glomerulonephritis, C3 glomerulonephritis, PGNMID), 5 proximal tubulopathies (2 LCPT with Fanconi syndrome, 1 LCPT without cytoplasmic inclusions and with interstitial inflammatory reaction, 2 LCPT with acute tubular necrosis) Table 1, Table 2, Light microscopy and IF of PGNMID. Conclusion MGRS is responsible for the pathogenesis of new histopathological renal lesions, based on new pathogenetic pathways. The clinical and histological features of the different disease states are dependent on the structure of FLCs. Our retrospective analysis of MGRS biopsies confirms how difficult and complex the diagnostic challenge of monoclonal renal injury really is. The differentiation between MGUS and MGRS is based on renal biopsy and demonstration of monoclonality on kidney tissue even if serum/urine immunofixation is negative. Early biomarkers of the pathogenetic role of monoclonal FLC should be identified both for diagnosis and therapeutical monitoring.