Rituximab Treatment of Fibrillary Glomerulonephritis

Ohio State University College of Medicine, Columbus, OH 43210, USA.
American Journal of Kidney Diseases (Impact Factor: 5.9). 10/2008; 52(6):1158-62. DOI: 10.1053/j.ajkd.2008.07.011
Source: PubMed


Fibrillary glomerulonephritis belongs to a group of disorders characterized by pathogenic deposition of fibrils in glomeruli. This glomerulopathy tends to progress to end-stage kidney disease, and there currently are no treatments of proven benefit, including corticosteroids and cytotoxic agents. Because the glomerular deposits contain an immunoglobulin component, it was postulated that anti-B-cell therapy with rituximab, an anti-CD20 monoclonal antibody, may be effective in the treatment of patients with fibrillary glomerulonephritis. We describe 3 patients with fibrillary glomerulonephritis who were treated with rituximab for nephrotic-range proteinuria. Each patient also received standard antiproteinuria therapy, including blockade of the renin-angiotensin system and strict blood pressure control. All patients showed a decrease in proteinuria to less than 1.5 g/d of protein by 27 months, and kidney function was preserved throughout the duration of therapy and follow-up. No adverse effects were seen with rituximab. These outcomes suggest that treatment with rituximab may be a promising approach to the management of fibrillary glomerulonephritis, an entity previously considered refractory to therapy.

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    • "There have been no controlled trials that agree on recommending an ideal therapy, and most reports choose the treatment according to light microscopy findings. Different agents have been proposed as treatment of this rare entity: corticosteroid or cytotoxic agents have been used with limited effectiveness [19]; some groups have published their successful experience using mycophenolate mofetil, rituximab concomitantly with corticosteroids, immunoglobulin, or calcineurin inhibitors [4, 20, 21]. There is controversy in relation to the use of plasmapheresis as a therapy. "
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    ABSTRACT: Although clinical presentation of fibrillary glomerulonephritis is similar to most forms of glomerulonephritis, it is usually difficult to make the diagnosis. Clinical manifestations include proteinuria, microscopic haematuria, nephrotic syndrome, and impairment of renal function. A diagnosis of fibrillary glomerulonephritis is only confirmed by renal biopsy and it must comprise electronmicroscopy-verified ultrastructural findings. We report four cases between 45-50 years old with documented type 2 diabetes mellitus (T2DM) and arterial hypertension. All patients were found to have fibrils on kidney biopsy. The differential diagnosis of fibrils in the setting of diabetes mellitus is also discussed.
    Case Reports in Medicine 05/2013; 2013:935172. DOI:10.1155/2013/935172
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    • "Early on after diagnosis, FibGN is likely to be steroid-sensitive [4]. For steroid-refractory cases, rituximab [5] or cyclophosphamide [6] is a therapy alternative. Rituximab has yielded a partial reduction in nephrotic-range proteinuria due to FibGN [5], whereas cyclophosphamide has been reported to have an effect on nephrotic-range proteinuria in a case report only [7]. "
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    ABSTRACT: Fibrillary glomerulonephritis (FibGN) is characterized by extracellular deposition of Congo red-negative microfibrils within the glomerular mesangium and leads to gross proteinuria or nephrotic syndrome. After diagnosis of FibGN, end-stage renal disease occurs within four years in 50% of patients. A 36-year-old Caucasian woman with proteinuria and intermittent nephrotic syndrome due to FibGN intermittently received immunosuppressive therapies, including glucocorticoids, mycophenolate mofetil, and rituximab, for 10 years. However, disease remission was not achieved and progressive kidney injury developed. Ultimately, in stage IV of chronic kidney disease (Kidney Disease: Improving Global Outcomes), three cycles of plasmapheresis of five to seven sessions each were performed every three to four months, reducing steady-state proteinuria from 7 to less than 1 g/day. Here, plasmapheresis led to a remission of nephrotic syndrome associated with FibGN. Plasmapheresis therapy is proposed as a further option for immunosuppressant-refractory FibGN.
    Journal of Medical Case Reports 04/2012; 6(1):116. DOI:10.1186/1752-1947-6-116
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    ABSTRACT: Dysproteinemias that result in monoclonal glomerular deposits of IgG are relatively uncommon. Here, we report the largest series of proliferative glomerulonephritis with monoclonal IgG deposits, a form of renal involvement by monoclonal gammopathy that mimics immune-complex glomerulonephritis. We retrospectively identified 37 patients, most of whom were white (81%), female (62%), or older than 50 yr (65%). At presentation, 49% had nephrotic syndrome, 68% had renal insufficiency, and 77% had hematuria. In 30% of the patients, we identified a monoclonal serum protein with the same heavy- and light-chain isotypes as the glomerular deposits (mostly IgG1 or IgG2), but only one patient had myeloma. Histologic patterns were predominantly membranoproliferative (57%) or endocapillary proliferative (35%) with membranous features. Electron microscopy revealed granular, nonorganized deposits, and immunofluorescence demonstrated glomerular deposits that stained for a single light-chain isotype and a single heavy-chain subtype, most commonly IgG3kappa (53%). During an average of 30.3 mo of follow-up for 32 patients with available data, 38% had complete or partial recovery, 38% had persistent renal dysfunction, and 22% progressed to ESRD. Correlates of ESRD on univariate analysis were higher creatinine at biopsy, percentage of glomerulosclerosis, and degree of interstitial fibrosis but not immunomodulatory treatment or presence of a monoclonal spike. On multivariate analysis, higher percentage of glomerulosclerosis was the only independent predictor of ESRD. Only one patient lacking a monoclonal spike at presentation subsequently developed a monoclonal spike and no patient with a monoclonal spike at presentation subsequently developed a hematologic malignancy. We conclude that proliferative glomerulonephritis with monoclonal IgG deposits does not seem to be a precursor of myeloma in the vast majority of patients.
    Journal of the American Society of Nephrology 06/2009; 20(9):2055-64. DOI:10.1681/ASN.2009010110 · 9.34 Impact Factor
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