Is It Time to Crown Steroid and Rituximab Therapy as Standard of Care for IgG4-Related Tubulointerstitial Nephritis (IgG4 TIN)? A Case of IgG4 TIN in a Patient with Diabetes Causing Decline in Kidney Function with Sustained Response to Dual Therapy

Introduction: IgG4 related disease (IgG4 RD) is a rare immune mediated, multiorgan fibroinflammatory disorder with renal manifestations to include tubulointerstitial nephritis (IgG4 TIN). Rituximab (RTX) is increasingly recognized as an effective treatment for IgG4 RD, although current consensus guidelines only recognize RTX as adjunctive or alternative therapy to steroids. Case Description: A 67 year old man with hypertension, coronary artery disease, insulin-dependent type 2 diabetes, chronic pancreatitis, hepatitis C (post interferon), and compensated cirrhosis presented with a one year unexplained decline in estimated glomerular filtration rate (eGFR) from 48mL/min/1.73 m2 to 18mL/min/1.73 m2. Urine studies showed minimal albuminuria (20mg) and elevated proteinuria (760mg). Kidney biopsy demonstrated plasma cell rich interstitial nephritis, severe tubular atrophy with tubulitis, and moderate arterial intimal fibrosis. Serum IgG4 (2007mg/dL) was elevated; complement levels were within normal limits. PET/CT showed increased renal cortical activity, hypermetabolic hilar/retroperitoneal lymphadenopathy (without evidence of retroperitoneal fibrosis), and sialadenitis. Given the patient’s comorbid diabetes, the decision was made to treat with dual steroid/RTX therapy and subsequent maintenance RTX to limit the duration of steroid treatment. At 12 weeks, improvement was seen in eGFR (28mL/min/1.73 m2), proteinuria (100mg) and serum IgG4 level (336mg/dL). At 6 months, PET/CT showed resolution of hypermetabolic renal cortical activity, sialadenitis, and mediastinal/retroperitoneal lymphadenopathy. At 6 months, further improvements in eGFR (38mL/min/1.73 m2), proteinuria (90mg) and serum IgG4 level (231mg/dL) was seen. At 12 months, eGFR was stable (38mL/min/1.73 m2) and serum IgG4 level continued to improve (151mg/dL). Patient remains on maintenance RTX every six months without flare to date. Discussion: This case lends additional support to the growing body of evidence of the efficacy of combination steroid/RTX therapy in IgG4 TIN. As IgG4 RD is a rare condition, randomized clinical trials would be difficult to perform. We therefore recommend increasing utilization of RTX in combination with steroids as first-line treatment for IgG4 RD.