#5430 ANTI-PLA2R ASSOCIATED MEMBRANOUS NEPHROPATHY AND CHRONIC LYMPHOCYTIC LEUKAEMIA, IS THERE A LINK?

Abstract

Abstract Background and Aims The spectrum of glomerular lesion that occurs in the context of plasma cell dyscrasias (PCD) is wide, including type I and type II membranoproliferative glomerulonephritis (MPGN), focal proliferative GN, membranous nephropathy (MN), minimal change disease and amyloidosis. A clear-cut link between hematological dyscrasias and glomerulopathy is often offered by the finding of paraproteins in the kidney or by kidney leucocytic infiltration and, in these scenarios, malignancy treatment is often found to be also effective towards the glomerulopathy. In the context of PCD in which proliferation of the B-cell clone does not lead to plasma-cell terminal differentiation such as chronic lymphocytic leukemia (LLC) the physiopathological link with glomerulonephritis is not well established and it's hard to determine whether the combination of these two disorders is fortuitous. With regarding to MN, it's now well established that this histopathological pattern must be related to the presence of circulating autoantibodies, where anti-PLA2R auto-antibodies usually been associated with primary MN. To our knowledge association between LLC and anti-PLA2R associated MN has not been described. Case report We report the case of a 76-year-old man who was admitted in February 2022 with anasarca and acute kidney injury. He had recently been evaluated by a hematologist in the context of suspected chronic lymphocytic leukemia (CLL). Laboratory findings, along with typical CLL white blood cell count, showed decreased kidney function from baseline and were compatible with nephrotic syndrome, with proteinuria progressively increasing up to 27 gr/24 h in the following weeks. CLL was confirmed by lymphocyte typing. A total body CT scan showed mediastinal, abdominal and inguinal lymphadenopathies, but no suspected neoplastic lesions. Screening for autoimmunity tested completely negative, as well as infectious screening for common hepatic viruses (HBV, HAV, HCV), EBV, CMV, HIV, Parvovirus B19. Lymph node biopsy showed no aspects of aggressive lymphoproliferative disease and hematological consultation only indicated clinical and laboratory follow-up of LLC, with no further indication to specific therapies. A kidney biopsy was performed showing diffuse thickening of the basement membrane (Fig. 1) with granular deposition of IgG (+++) and C3 (++) along the glomerular capillary walls at immunofluorescence. Electron microscopy revealed subepithelial immune deposits (Fig. 2) with initial incorporation from the glomerular basement membrane (GBM). Anti PLA2R antibodies, found negative at first determination, subsequently tested positive at high titre (ELISA 1356.4 U/ml). A diagnosis of stage two membranous nephropathy was made, and the patient was treated with Rituximab 375 mg/m2 every week for four weeks. Clinical stability was obtained with repeated intravenous administration of diuretics (furosemide 60 mg + canrenone 200 mg) along with albumin. Nevertheless, nephrotic syndrome persisted, and kidney function progressively decreased with serum creatinine up to 2.8 mg/dL. Immunophenotype, which showed reduction but no suppression of CD19+ lymphocytes, was again repeated on November 2022 and showed typical LLC findings (CD 19+, CD 20+, CD 23+, CD 5+) with repopulation of CD19+ lymphocytes. Anti PLA2R antibodies gradually decreased instead, reaching a value of ELISA 1.8 U/ml in November 2022 and persisted negative until present. The patient recovered from nephrotic syndrome in Autumn 2022 and is currently on stage G3B chronic kidney disease with persistent sub-nephrotic proteinuria in supportive treatment. Conclusion Simultaneous diagnosis of primary MN and LLC led us to ask ourselves whether this patient could benefit from LLC-specific chemotherapy, even though there were no signs of aggressive hematological disease and no clear link with the nephropathy. We think that further investigations are required to deeply understand the connection between hematological and renal disorders, in order to identify whether there are two diseases to treat separately or two sides of the same disease to treat as one.