Phospholipase A2 receptor autoantibodies and clinical outcome in patients with primary membranous nephropathy.

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, with an uncertain clinical outcome. The characterization of the phospholipase A(2) receptor (PLA(2)R) as the major target antigen in primary MN and the detection of circulating autoantibodies in these patients is a major advance in understanding this disease. To test whether PLA(2)R antibody levels reflect disease activity or clinical outcome, we performed a prospective multicenter study of 133 adult patients with primary MN and detectable serum PLA(2)R antibodies who had not received immunosuppressive therapy. Patients were followed <= 24 months. PLA(2)R antibody levels associated with clinical disease activity (proteinuria) in patients with immunosuppressive therapy (n=101) or supportive care (n=32). Within 3 months, immunosuppressive therapy led to a sustained 81% reduction in PLA(2)R antibody levels paralleled by a 39% reduction in proteinuria. Patients who experienced remission of proteinuria after 12 months had significantly lower PLA(2)R antibody levels at the time of study inclusion compared with patients with no remission. Patients with high PLA(2)R antibody levels achieved remission of proteinuria significantly later than patients with low PLA(2)R antibody levels. PLA(2)R antibody levels fell over time in patients with spontaneous remission but remained elevated in patients who did not show a reduction in proteinuria. Multivariable Cox regression analysis confirmed PLA(2)R antibody level as an independent risk factor for not achieving remission of proteinuria. We conclude that a decrease in PLA(2)R antibody level is associated with a decrease of proteinuria in patients with primary MN.