Open AccessRole of phospholipase A2 receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy
Author(s) -
Maida Mahmud,
Hans O. Pinnschmidt,
Linda Reinhard,
Sigrid Harendza,
Thorsten Wiech,
Rolf A.K. Stahl,
Elion Hoxha
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0221293
Subject(s) - membranous nephropathy , medicine , proteinuria , hazard ratio , gastroenterology , renal biopsy , creatinine , prospective cohort study , renal function , kidney , confidence interval
Background Membranous nephropathy (MN) is an autoimmune disease induced by circulating antibodies against the podocyte protein phospholipase A 2 receptor 1 (PLA 2 R1-ab) in 80% of patients and represents the leading cause of nephrotic syndrome in adults. PLA 2 R1-ab levels correlate with disease activity and treatment response. However, their predictive role for long-term renal outcome is not clear. Methods The aim of this prospective observational multicenter study was to investigate the predictive role of PLA 2 R1-ab levels at the time of diagnosis for long-term outcome in a cohort of 243 patients with newly diagnosed biopsy-proven PLA 2 R1-associated MN. Statistical analyses included Cox proportional hazard models. The primary study endpoint was defined prior to data collection as doubling of serum creatinine or development of end-stage renal disease. Results During the median follow-up time of 48 months, 36 (15%) patients reached the study endpoint. Independent predictors for reaching the study endpoint were baseline PLA 2 R1-ab levels (HR = 1.36, 95%CI 1.11–1.66, p = 0.01), percentage of tubular atrophy and interstitial fibrosis (HR = 1.32, 95%CI 1.03–1.68, p = 0.03), PLA 2 R1-ab relapse during follow-up (HR = 3.22, 95%CI 1.36–7.60, p = 0.01), and relapse of proteinuria (HR = 2.60, 95%CI 1.17–5.79, p = 0.02). Fifty-four (22%) patients received no immunosuppressive treatment during the study, in 41 (76%) of them PLA 2 R1-ab spontaneously disappeared during follow-up, 29 (54%) patients had a complete remission of proteinuria, and 19 (35%) had a partial remission. Patients not treated with immunosuppression were more often females and had lower PLA 2 R1-ab levels, proteinuria, and serum creatinine at baseline compared to patients receiving immunosuppression. However, no conclusion on the efficacy of immunosuppressive therapies can be made, since this was not a randomized controlled study and treatment decisions were not made per-protocol. Conclusions PLA 2 R1-ab levels are, in addition to pre-existing renal damage, predictive factors for long-term outcome and should therefore be considered when deciding the treatment of patients with MN.