Rare case report: a man with rheumatoid arthritis developed membranous nephropathy and ANCA-associated vasculitis successively

Renal involvement in rheumatoid arthritis (RA) is relatively common, which may be due to the RA itself or may be associated with the use of nephrotoxic drugs. The widespread use of biological agents has led to an increasing number of reports of RA-related nephropathy. We report a rare case of sequential membranous nephropathy (MN) and ANCA-associated vasculitis (AAV) in a 74-year-old male with seropositive RA (RF 389 IU/mL, anti-CCP 360 U/mL). One month after initiating etanercept (25 mg twice weekly), he developed nephrotic syndrome (proteinuria 5.42 g/24 h, albumin 19.9 g/L) and elevated anti-PLA2R (33.78 RU/mL). Renal biopsy revealed stage I MN with granular IgG/C3 deposits. After rituximab therapy (1600 mg cumulative dose) proteinuria decreased to 1.6 g/24 h; yet after six months the patient presented with acute kidney injury (serum creatinine [SCr] 11.87 mg/dL), hematuria, and positive MPO-ANCA (169.8 RU/mL), which was consistent with AAV. Immunosuppression with methylprednisolone and cyclophosphamide reduced the SCr level to 6.60 mg/dL, although dialysis dependence persisted. To our knowledge, this represents the first documented case of sequential MN and AAV in an RA patient who received etanercept and rituximab therapy during the clinical course. While lacking definitive proof of causality, this case emphasizes that clinicians must be vigilant for complex renal complications in biologic-treated RA patients, irrespective of the underlying cause.