Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? PRO.

Abstract

For decades, plasma exchange (PLEX) has been advocated for patients with rapidly progressive GN and diffuse alveolar hemorrhage due to ANCA (1 ⇓–3). Autoantibodies in ANCA vasculitis are typically directed to one of two proteins, myeloperoxidase or proteinase-3 (PR3). These autoantibodies are pathogenic and trigger disease activity, activating primed neutrophils and monocytes, leading to vessel injury, and activation of the alternative complement pathway (4). PLEX can rapidly clear these pathogenic autoantibodies, potentially abolishing the inciting cause of ANCA vasculitis. An early controlled study of PLEX for small-vessel vasculitis included 23 patients treated with standardized immunosuppression and 25 who received PLEX in addition (1). Among those who were dialysis dependent at presentation, 91% (10 out of 11) who received PLEX had improvement in kidney function at 1 month, compared with 38% (three out of eight) of those in the group who did not receive PLEX. The subsequent Randomized Trial of Plasma Exchange or High-dosage Methylprednisolone as Adjunctive Therapy for Severe Renal Vasculitis (MEPEX) study included patients with ANCA vasculitis and severe renal failure, defined as a serum creatinine above 5.8 mg/dl (500 μmol/L) randomized to receive PLEX or pulse intravenous (IV) methylprednisolone (5). A renal biopsy was required for inclusion. Among the 137 patients randomized, 67 received IV methylprednisolone and 70 received PLEX administered as a total of seven exchanges within 14 days of enrollment. The primary outcome was renal recovery at 3 months, defined as dialysis independence and serum creatinine <5.8 mg/dl (500 μmol/L). At 3 months, 49% of the IV methylprednisolone group achieved renal recovery compared with 69% ( P =0.02) of the PLEX group. At 12 months, each group had 51 surviving participants, and 59% (29 out of 51) in the IV methylprednisolone arm remained dialysis independent, compared with 80% (41 out of 51) who received PLEX …