IgG4-Mediated Interstitial Nephritis Treated with Inebilizumab

Introduction: Tubulointerstitial nephritis (TIN) is the most common renal manifestation of IgG4-mediated disease and is characterized by IgG4-positive plasma cells and storiform fibrosis in the interstitium. Commonly, IgG4-mediated TIN is treated with steroids; however, long term use of steroids has negative consequences. Thus, inebilizumab, which targets and depletes plasma cells, has been studied as a treatment for IgG4-mediated disease. Case Description: A 71-year-old Caucasian male was sent to the emergency department from his primary care physician due to a creatinine of 4.3 mg/dl without prior history of renal disease. He had recently developed unilateral gynecomastia that had been evaluated by mammogram and was negative for malignancy. On presentation, blood pressure was 127/80 mmHg, and he had no peripheral edema. Pertinent labs revealed a urine protein to creatinine ratio of 0.96 g/g without hematuria. Subsequent evaluation of his proteinuria was unremarkable aside from polyclonal hypergammaglobulinemia with a prominent increase in polytypic IgG in the near gamma region. A kidney biopsy was performed that revealed chronic tubulointerstitial nephritis with increased IgG4-positive plasma cells. Prednisone was initiated and tapered, and the patient transitioned to inebilizumab infusions. Kidney function continues to improve with the most recent serum creatinine of 1.9 mg/dl. Further evaluation is planned with MRI to assess for extra-renal manifestations including gynecomastia, a rare manifestation of IgG4 disease. Discussion: IgG4-related disease (RD) affects many organs and can manifest as IgG4-TIN in the kidneys. Though the pathogenesis is not fully understood, B cells are thought to play a central role in IgG4-RD and are the targets of new therapies. While glucocorticoids may be effective in IgG4-RD, they have harmful side effects, and most patients flare within 3 years of discontinuation. Steroid sparing regimens are desirable to mitigate these consequences. Promising new drugs, such as inebilizumab which targets CD19 cells, have been shown to reduce flares in IgG4-RD and increase the chance of flare-free remission at one year.