P0478CLINICOPATHOLOGICAL CHARACTERISTICS AND TREATMENT OUTCOMES OF IGM NEPHROPATHY

Abstract

Abstract Background and Aims IgM nephropathy (IgMN) is a controversial clinicopathological entity that is characterized by the presence of dominant diffuse mesangial IgM deposits, with diverse clinical presentations and varying response to supportive or immunosuppressive treatment. The aim of our study was to determine the clinical features, histopathological characteristics and treatment outcomes in patients with IgMN. Method We conducted a multicenter retrospective observational study that included patients that had undergone a kidney biopsy between January 1990 and December 2018. We identified 40 patients with mesangial proliferative glomerulopathy with dominant IgM deposits. Patients with the presence of systemic diseases (systemic lupus erythematosus, rheumatoid arthritis, diabetes mellitus or paraproteinemia) were excluded, as well as those with incomplete histological or follow-up data. Demographic, clinical, analytical, and histological data were collected, and the different treatment regimens were compared for achieving clinical remission and prevention of kidney disease progression. Results 33 patients were identified with primary mesangial IgM nephropathy, with a median post-biopsy follow-up of 7.3 (2.8-11.1) years. Mean age of presentation was 34.9±19.0 years, 51.5% were females. The most frequent initial manifestation was nephrotic syndrome in 54.5% of cases, followed by proteinuria with microscopic hematuria in 21.2%, proteinuria in 19.1%, and isolated microhematuria in 3% of patients. On presentation, mean eGFR measured by CKD-EPI was 102.9±38.9 ml/min, median proteinuria was 3.3 g/24h (IQR 1.13-4.88), 69.7% had microscopic hematuria and 27.3% presented with hypertension. Light microscopy revealed mesangial hypercellularity and expansion in 81.8% and 78.8% respectively, 6.6% showed extracapillary proliferation, 33.3% showed segmental sclerosis, 39.4% had mild to moderate interstitial fibrosis, and 46.9% had vascular hyaline deposits. On immunofluorescence all patients showed diffuse mesangial IgM deposits, along with subdominant mesangial deposits of IgG (6.1%), IgA (6%), C3 (39.4%), C1q (27.3%) and Lambda (3%). In nephrotic patients, 16.7% were steroid-resistant, whereas 40% of steroid-sensitive patients were steroid-dependent. 41.7% of steroid-sensitive and nondependent IgMN patients developed a median 3.5 relapses during follow-up. 12 nephrotic patients (3 steroid-resistant and 9 steroid-dependent) received immunosuppressive treatment; 5 patients were initially treated with oral cyclophosphamide, 5 with a calcineurin inhibitor (CNI) and 2 with chlorambucil. All steroid-dependent or resistant patients treated with cyclophosphamide or chlorambucil achieved partial or complete clinical remission. Out of the five patients treated with a CNI, 3 attained remission whereas the other two were switched to cyclophosphamide and chlorambucil respectively after which remission was obtained. No patients progressed to end-stage kidney disease. Conclusion IgMN is a rare mesangial proliferative glomerulopathy with a varying clinical and morphological spectrum. It commonly presents as nephrotic syndrome, and is frequently associated with microscopic hematuria. Clinical course is variable, with frequent relapses and a high prevalence of steroid dependence. Complete remission can be achieved with immunosuppressive therapy in cases of steroid-dependent or resistant IgMN, particularly with cytotoxic agents.