PLA2R Antibody Does Not Outperform Conventional Clinical Markers in Predicting Outcomes in Membranous Nephropathy

Omar Ragy; Sebastian Bate; Samar Bukhari; Mrityunjay Hiremath; Syazril Samani; Arif Khwaja; Anirudh Rao; Durga Anil K Kanigicherla

doi:10.1016/j.ekir.2023.05.019

PLA2R Antibody Does Not Outperform Conventional Clinical Markers in Predicting Outcomes in Membranous Nephropathy

Kidney Int Rep. 2023 May 26;8(8):1605-1615. doi: 10.1016/j.ekir.2023.05.019. eCollection 2023 Aug.

Authors

Omar Ragy^{1

2}, Sebastian Bate^{3

4}, Samar Bukhari⁵, Mrityunjay Hiremath⁶, Syazril Samani⁶, Arif Khwaja⁵, Anirudh Rao⁶, Durga Anil K Kanigicherla^{1

2}

Affiliations

¹ Manchester Institute of Nephrology and Transplantation, Manchester University NHS Foundation Trust, Manchester, UK.
² Division of Cardiovascular Sciences, University of Manchester, Manchester, UK.
³ Manchester Academic Health Science Centre, Research and Innovation, Manchester University NHS Foundation Trust, Manchester, UK.
⁴ Centre for Biostatistics, Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, UK.
⁵ Sheffield Kidney Institute, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
⁶ Nephrology Department, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.

Abstract

Introduction: The prognostic value of PLA2R antibody (Ab) test in clinical practice remains unclear. We aimed to evaluate its ability in predicting hard outcomes in primary membranous nephropathy (PMN) after adjustments to conventional markers of disease activity.

Methods: A total of 222 patients diagnosed with PMN from January 2003 to July 2019 having had a serum PLA2R Ab test, were included from 3 centers in the north of England. Baseline conventional markers, PLA2R-Ab-status (positive vs. negative), Ab-titer (high vs. low), and time of testing (pre-PLA2R era vs. PLA2R era) were evaluated for association with outcomes. Primary outcome was time to progression (composite of doubling of creatinine, stage 5 chronic kidney disease, or death). Secondary outcomes were time to partial remission (PR) and time to immunosuppression. Cox proportional hazard testing was used.

Results: During a median follow-up of 5.26 years, progression was seen in 65 (29.3%) and PR in 179 of 222 patients (80.6%). There was a clear association of estimated glomerular filtration rate (eGFR) (standardized hazard ratio [HR_Z] = 0.767, P < 0.05) and urine protein-to-creatinine ratio (uPCR) (HR_Z = 1.44, P < 0.005) with time to progression among all patients, and eGFR (HR_Z = 0.606, P < 0.005) in Ab-positive patients. Baseline Ab-positivity was not associated with time to progression (adjusted hazard ratio [aHR] = 0.93, P = 0.71) or time to PR (aHR = 0.84, P = 0.13). Similarly, baseline high Ab-titer was not associated with time to progression (aHR = 1.07, P = 0.77) or time to PR (aHR = 0.794, P = 0.08).

Conclusion: Once adjusted to conventional markers of disease activity, baseline PLA2R Ab-positivity or Ab-titer do not predict disease progression or time to PR. Further studies are needed to harness the utility of PLA2R Ab test in prognostication in PMN.

Keywords: anti-PLA2R ab-status; anti-PLA2R ab-titers; conventional markers of disease activity; partial remission; primary membranous nephropathy; progression.