Anti-phospholipase A2 receptor antibody levels at diagnosis predicts spontaneous remission of idiopathic membranous nephropathy

Abstract

Background: The diagnostic role of circulating anti-phospholipase A2 receptor antibodies (anti-PLA2R Abs) is now well recognized in idiopathic membranous nephropathy (iMN). These Abs could also be interesting as predictors of clinical outcome. In this study, we explored the prognostic value of anti-PLA2R Abs measured in a cohort of iMN patients, with a special focus on their ability to detect patients achieving spontaneous remission. Methods: All adult patients with biopsy-proven iMN diagnosed between 1978 and 2007 were retrospectively screened in our centre. Using a validated enzyme-linked immunosorbent assay, levels of anti-PLA2R Abs were measured from serum samples obtained at the time of renal biopsy and stored at -80°C until processing. Clinical data on disease activity, treatments and outcomes were collected by reviewing patients' medical records. The association between anti-PLA2R Ab titres and clinical activity/outcome was assessed by Cox proportional hazard and Kaplan-Meier methods. Results: In this retrospective study, 68 patients were included in the final analysis (median follow-up of 81 months). No significant association was found between anti-PLA2R Ab titres at diagnosis with baseline proteinuria, baseline estimated glomerular filtration rate or chronic kidney disease progression. Spontaneous remission was observed in 22% of patients. Ab titres were significantly and gradually correlated in a dose-response manner with the likelihood of spontaneous remission. Conclusions: While Ab titres measured at diagnosis were not found to predict the activity of iMN, evaluation of anti-PLA2R Ab titres might prove useful in the early identification of patients likely to achieve spontaneous remission.

Keywords: antibody; disease activity; idiopathic membranous nephropathy; phospholipase A2 receptor; spontaneous remission.

Fig. 1

(A and B) Association between anti-PLA2R antibody levels and disease activity at diagnosis (A = urinary protein excretion, Kruskal–Wallis test, P = 0.64; B = glomerular filtration rate, Kruskal–Wallis test, P = 0.99). (C and D) Association between anti-PLA2R antibody levels and the development of stage 3 (C) and stage 5 (D) CKD (log rank test, P = 0.68 and P = 0.83, respectively). T1, T2 and T3, tertiles 1, 2 and 3.

Fig. 2

Incidence of spontaneous remission according to the tertile of anti-PLA2R antibody titre. Log rank test, P-value = 0.048 for comparison between all tertiles. Log rank tests for comparison between each tertile: tertile 1 versus tertile 3, P = 0.0167; tertile 1 versus tertile 2, P = 0.38; and tertile 2 versus tertile 3, P = 0.129. *P  < 0.05. T1, T2 and T3, tertiles 1, 2 and 3.