Membranous Nephropathy With Monoclonal IgM Lambda Deposits in a Patient With IgM Monoclonal Gammopathy: A Case Report

We report a case of membranous nephropathy with monoclonal immunoglobulin (Ig)M lambda deposits in a patient with IgM monoclonal gammopathy, in whom histological changes were observed on repeat renal biopsy. A 72-year-old Japanese woman was referred to our hospital because of massive proteinuria. A prominent increase in monoclonal IgM lambda level was identified, and she was diagnosed as having IgM monoclonal gammopathy of undetermined significance. Renal biopsy showed glomerular subepithelial electron-dense deposits that were found to be granular deposits of IgM lambda but not kappa or IgG by immunofluorescence staining, resulting in a diagnosis of membranous nephropathy with monoclonal IgM deposits. The second biopsy, which was performed 2 years later because of exacerbation of her nephrotic syndrome, demonstrated less immunofluorescence staining of IgM, and dominant IgG2 deposition without light chain restriction. Interestingly, immunostaining for thrombospondin-type-1-domain-containing-7A was positive in both renal biopsy tissues, although the second biopsy showed clearly stronger immunoreactivity. The effect of steroid therapy was limited; however, rituximab treatment improved both the hematological and renal abnormalities. Solitary deposition of IgM in membranous nephropathy is a quite rare condition. To our knowledge, this is the first case of monoclonal gammopathy of renal significance presenting as membranous nephropathy with monoclonal IgM deposits, in which chronological immunohistochemical changes were observed and rituximab therapy was effective.

Successful treatment of a rare variant of mesangioproliferative glomerulonephritis with IgM deposits with Cyclosporin A

We present a case with a rare variant of glomerulonephritis, IgM nephropathy, which occurs mainly with nephrotic syndrome. The clinical features of this variant of kidney damage are characterized; the pathogenetic and the transformation of this form of nephritis into focal segmental glomerulosclerosis are discussed. The development of severe nephrotic syndrome at the beginning of the disease, the formation of secondary steroid resistance have confirmed this hypothesis and have justified the treatment with cyclosporin A aimed at the recovery of the function of the podocyte with remission of nephritis.

P0478CLINICOPATHOLOGICAL CHARACTERISTICS AND TREATMENT OUTCOMES OF IGM NEPHROPATHY

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.

Acute tubulointerstitial nephritis and IgM deposits on glomerular capillary walls after immunotherapy with nivolumab for metastatic renal cell carcinoma

Nivolumab is an anti-programmed cell death-1 antibody that is utilized as an immune checkpoint inhibitor for several malignancies. However, this agent is associated with immune-related adverse events (irAEs), mainly in the spectrum of autoimmune disease including interstitial pneumonia, colitis, type 1 diabetes, and renal impairment. We herein present the case of a 59-year-old man with renal cell carcinoma who developed worsening renal function approximately 4 months after initiation of nivolumab. Urinalysis showed proteinuria and microscopic hematuria along with increase levels of N-acetyl-β-d-glucosaminidase. Renal biopsy revealed acute tubulointerstitial nephritis and thickening of the glomerular basement membranes. Immunofluorescence showed granular IgM deposits in capillary loops. We initiated high-dose prednisolone therapy with nivolumab, which improved renal function and achieved complete remission of proteinuria. Although renal irAEs are considered to be rare and glomerulonephropathy is not typical presentation, physicians need the close monitoring of renal function and urinalysis in patients under immunotherapy with this agents. In addition, our case provides a possible link between nivolumab and immune-mediated glomerulonephropathy.

Immunofluorescent microscopy in patients with IgA nephropathy

The aim of the study was to evaluate relations between the deposition of IgA, IgG, IgM, C3, C1q and baseline clinical features and pathological findings.According to exclusion criteria, 72 patients with diagnosed primary IgAN who were biopsied from 2015 to 2017 in the district of the Minsk city, Belarus were included for retrospective analysis. All biopsy had to be reviewed according to the Oxford classification (MEST-C). We examined the immunofluorescence staining with antibodies against IgG, IgA, IgM, C3, C1q.Mean age was 32 (26; 42.5) years, 72.2% was men, 48.6% of the patients had arterial hypertension. Median of proteinuria was 870 (355; 1420) mg/day, 8.4% of the patients had isolated hematuria, serum creatinine – 104 (89; 126.5) µmol/l.The patients with 3+ IgA deposits showed a significantly higher percentage of crescents (C1-2) than those with 2+ IgA deposits (p = 0.028). The presence of C3 deposits showed a gradual increase in the percentage of endothelial proliferation (E1) (p = 0.007). The degree of IgA deposits showed a significant negative relation to the IgM deposits (p = 0.01) and a positive relation to the C3 deposits (p = 0.001).We found that the intensity of IgA and C3 deposits is associated with histopathology markers of the acute reaction (C1-2 and E1) according to the Oxford classification. At the same time, the appearance of the IgM deposits testifies the acute phase of the disease as well as the advanced sclerotic stage in some patients.