Effects of phospholipase A receptor and thrombospondin type-1 domain-containing 7A expression in glomerular basement membranes on treatment response and renal outcome in membranous nephropathy.

Background: The aim of this study was to define the clinicopathologic features of phospholipase A receptor (PLAR) and/or thrombospondin type-1 domain-containing 7A (THSD7A) associated membranous nephropathy(MN) focusing on their impact to disease relapse and response to treatment.

Methods: A total of 201 patients were enrolled for baseline clinical and histopathological features and 102 patients with a clinical follow-up for more than 1 year were evaluated for outcomes. Immunohistochemical staining was performed with PLAR and THSD7A antibodies on kidney biopsies and glomerular staining was evaluated.

Results: PLAR expression was observed in 75% of the patients' biopsies; however, THSD7A expression was present only in 7 patients' biopsies (3.5%). No significant difference was found between histopathological and clinical features of PLAR positive and negative patients, collectively. Glomerular PLAR expression was significantly associated with complete and complete/partial remission with first-line treatment; however, overall complete, and complete/partial remission rates did not differ from PLAR negative patients (p = 0.2 and p = 0.8). Male gender, the presence of IgG4 staining and a necessity of immunosuppressive treatment were significantly associated with glomerular PLAR expression. One patient, who developed end-stage renal disease, had glomerular expression for both PLAR and THSD7A. Three patients with THSD7A-positive MN achieved complete remission.

Conclusions: The probability of achieving complete remission is high in patients with PLAR-positive MN for whom the relapse rate was also higher. The overall renal outcome did not differ from PLAR negative cases. Low incidence of THSD7A-positive MN reduces the possibility of future randomized controlled trials.