Breakthrough IgG4 Disease-Related Tubulointerstitial Nephritis Treated with Rituximab as Maintenance Therapy

Introduction: IgG4-related disease (IgG4-RD) is a systemic immune-mediated condition that can affect almost any organ system. In the kidneys, the most common manifestation is IgG4-related tubulointerstitial nephritis (IgG4-TIN), characterized by fibrosis and IgG4-positive plasma cell infiltrates in the interstitium. IgG4-RD is typically treated with immunosuppressives, including steroids and rituximab (RTX), which have demonstrated efficacy in achieving disease remission. We present a case of a patient with recurrent IgG4-RD manifesting as IgG4-TIN despite successful treatment of autoimmune pancreatitis and cholangitis. Case Description: A 69-year-old male with a history of IgG4-RD treated with two courses of prednisone and four infusions of RTX for flares presented with non-oliguric acute kidney injury (AKI) (serum creatinine (sCr) of 2.1 mg/dL (baseline 1.1 mg/dL)). AKI was associated with hypertension, proteinuria (urine protein/creatinine ratio of 0.41 g/g), and hypocomplementemia consistent with IgG4-TIN. Kidney biopsy was also consistent and demonstrated diffuse “bird’s eye” fibrosis in the cortex and medulla, extensive tubular destruction, and numerous IgG4-positive plasma cells (Fig 1). IgG4-TIN was treated with pulsed steroids and maintenance remission therapy of RTX 1 gm every 14 days for two doses every six months. At one year, sCr improved to 1.1 mg/dL and urine protein/creatinine ratio improved to 0.08g/g (normal ≤ 0.15g/g), and he remained relapse free. Discussion: This case has three main teaching points: 1) It is important to maintain a high index of suspicion for IgG4-TIN when AKI is superimposed on IgG4-RD and ensure close follow-up for refractory cases. 2) IgG4-TIN can develop despite appropriate steroid therapy and remission in other involved organs with RTX. 3) Maintenance therapy with RTX retreatment was associated with longer relapse-free survival at 12 months of follow up in this case. Our patient had no severe infections or hypogammaglobulinemia ≤5 g/l with RTX, confirming RTX's safety and efficacy in maintenance remission therapy for recurrent IgG4-TIN.