IgG4-related kidney disease: The effects of a Rituximab-based immunosuppressive therapy

// Giacomo Quattrocchio 1 , Antonella Barreca 2 , Andrea Demarchi 3 , Laura Solfietti 4 , Giulietta Beltrame 1 , Roberta Fenoglio 1 , Michela Ferro 1 , Paola Mesiano 1 , Stefano Murgia 1 , Giulio Del Vecchio 1 , Carlo Massara 1 , Cristiana Rollino 1 and Dario Roccatello 1, 4 1 Nephrology and Dialysis Unit, San Giovanni Bosco Hospital, and University of Turin, Italy 2 Department of Biomedical Sciences, University of Turin, Turin, Italy 3 Surgical Pathology Unit, San Giovanni Bosco Hospital, Turin, Italy 4 Center of Research of Immunopathology and Rare Diseases (CMID), Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, San Giovanni Bosco Hospital, Turin, and University of Turin, Turin, Italy Correspondence to: Giacomo Quattrocchio, email: g.quattrocchio@libero.it Keywords: IgG4-related disease; IgG4-related kidney disease; tubulointerstitial nephritis; retroperitoneal fibrosis; Rituximab Received: August 03, 2017      Accepted: March 24, 2018      Published: April 20, 2018 ABSTRACT IgG4-related disease (IgG4-RD) is a recently recognized disorder, characterized by elevated serum IgG4 concentrations, dense tissue infiltration of IgG4-positive plasma cells and storiform fibrosis. Treatment is usually based on steroids, however, relapses and long-term adverse effects are frequent. We prospectively studied 5 consecutive patients with histologically-proven IgG4-RD and renal involvement, treated with an extended Rituximab protocol combined with steroids. Two doses of intravenous cyclophosphamide were added in 4 patients. Five patients with IgG-RD were investigated: three had tubulointerstitial nephritis (TIN), while two had retroperitoneal fibrosis (RPF). In the patients with TIN, renal biospy was repeated after 1 year. In the patients with TIN, estimated glomerular filtration rate (eGFR) at 12 months increased from 9 to 24 ml/min per 1.73 m 2 ; IgG/IgG4 decreased from 3,236/665 to 706/51 mg/dl; C3/C4 increased from 49/6 to 99/27 mg/dl; CD20 + B-cells decreased from 8.7% to 0.5%; Regulatory T-cells decreased from 7.2% to 2.5%. These functional and immunologic changes persisted at 24 months and in two patients at 36 months. A repeat renal biopsy in the patients with TIN showed a dramatic decrease in interstitial plasma cell infiltrate with normalization of IgG4/IgG positive plasma cells. The patients with RPF showed a huge regression of retroperitoneal tissue. In this sample of patients with aggressive IgG4-RD and renal involvement, treatment aimed at depleting B cells and decreasing antibody and cytokine production was associated with a substantial, persistent increase in eGFR, and a definite improvement in immunologic, radiologic and histological parameters.