Effects of phospholipase A2 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 2 receptor (PLA 2 R) 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 PLA 2 R and THSD7A antibodies on kidney biopsies and glomerular staining was evaluated. Results PLA 2 R 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 PLA 2 R positive and negative patients, collectively. Glomerular PLA 2 R 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 PLA 2 R 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 PLA 2 R expression. One patient, who developed end-stage renal disease, had glomerular expression for both PLA 2 R and THSD7A. Three patients with THSD7A-positive MN achieved complete remission. Conclusions The probability of achieving complete remission is high in patients with PLA 2 R-positive MN for whom the relapse rate was also higher. The overall renal outcome did not differ from PLA 2 R negative cases. Low incidence of THSD7A-positive MN reduces the possibility of future randomized controlled trials.