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PLA2R Antibody Does Not Outperform Conventional Clinical Markers in Predicting Outcomes in Membranous Nephropathy
Omar Ragy1,2, Sebastian Bate3,4, Samar Bukhari5
1Manchester Institute of Nephrology and Transplantation, Manchester University NHS Foundation Trust, Manchester, UK.
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 [HRZ] = 0.767, P < 0.05) and urine protein-to-creatinine ratio (uPCR) (HRZ = 1.44, P < 0.005) with time to progression among all patients, and eGFR (HRZ = 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.
Insights
The phospholipase A2 receptor antibody (Ab) test does not predict disease progression or remission in primary membranous nephropathy (PMN) when adjusted for conventional markers. Further research is needed to clarify the PLA2R Ab test
Area of Science:
- Nephrology
- Immunology
- Clinical Diagnostics
Background:
- Primary membranous nephropathy (PMN) is a leading cause of nephrotic syndrome in adults.
- The prognostic value of phospholipase A2 receptor antibody (PLA2R Ab) testing in PMN remains uncertain.
- Conventional markers of disease activity are established predictors of PMN outcomes.
Purpose of the Study:
- To evaluate the prognostic ability of the PLA2R Ab test in predicting hard clinical outcomes in PMN.
- To assess the PLA2R Ab test's predictive value after adjusting for conventional markers of disease activity.
- To determine if baseline PLA2R Ab status or titer predicts disease progression or remission.
Main Methods:
- A cohort of 222 PMN patients with available serum PLA2R Ab tests was analyzed.
- Baseline conventional markers, PLA2R Ab status (positive/negative), and Ab titer (high/low) were assessed.
- Cox proportional hazard modeling was used to evaluate associations with time to progression and partial remission (PR).
Main Results:
- Estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio (uPCR) were associated with time to progression.
- Baseline PLA2R Ab positivity was not significantly associated with time to progression (aHR=0.93, P=0.71) or time to PR (aHR=0.84, P=0.13).
- Baseline high PLA2R Ab titer was not significantly associated with time to progression (aHR=1.07, P=0.77) or time to PR (aHR=0.794, P=0.08).
Conclusions:
- Adjusted for conventional markers, baseline PLA2R Ab status and titer do not predict disease progression or remission in PMN.
- The utility of the PLA2R Ab test in PMN prognostication requires further investigation.
- Conventional markers remain crucial for assessing PMN disease activity and predicting outcomes.
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