Role of phospholipase A2 receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy
Autoři:
Maida Mahmud aff001; Hans O. Pinnschmidt aff002; Linda Reinhard aff001; Sigrid Harendza aff001; Thorsten Wiech aff003; Rolf A. K. Stahl aff001; Elion Hoxha aff001
Působiště autorů:
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
aff001; Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
aff002; Division of Nephropathology, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
aff003
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0221293
Souhrn
Background
Membranous nephropathy (MN) is an autoimmune disease induced by circulating antibodies against the podocyte protein phospholipase A2 receptor 1 (PLA2R1-ab) in 80% of patients and represents the leading cause of nephrotic syndrome in adults. PLA2R1-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 PLA2R1-ab levels at the time of diagnosis for long-term outcome in a cohort of 243 patients with newly diagnosed biopsy-proven PLA2R1-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 PLA2R1-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), PLA2R1-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 PLA2R1-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 PLA2R1-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
PLA2R1-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.
Klíčová slova:
Medicine and health sciences – Diagnostic medicine – Signs and symptoms – Proteinuria – Immune suppression – Pathology and laboratory medicine – Pharmacology – Drugs – Immunosuppressives – Cyclophosphamide – Immunology – Pharmaceutics – Drug therapy – Biology and life sciences – Biochemistry – Biomarkers – Creatinine – Developmental biology – Fibrosis – Research and analysis methods – Mathematical and statistical techniques – Statistical methods – Regression analysis – Physical sciences – Mathematics – Statistics
Zdroje
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