Abstract

Abstract BACKGROUND AND AIMS PLA2R antibody level could be used in the risk stratification for patients with Membranous Nephrology (MN). However, the association of PLA2R antibody level and glomerular filtration rate slope in PLA2R-related MN and what specific PLA2R antibody level should be used to predict the risk of disease progression remains unclear. METHOD A total of 11 628 patients who had at least one positive serum PLA2R antibody test (>20 RU/mL) were screened from July 2016 through June 2021 in our kidney center. The baseline was defined as the first time of PLA2R antibody test. PLA2R exposure level was defined as area under the curve of the antibodies divided by the time of follow-up. The eGFR slope for each individual was calculated using mixed-effects models. The association between PLA2R exposure level and eGFR slope was analyzed using locally weighted linear regression. The candidate cutoff level of PLA2R antibody used to predict the risk of disease progression were defined as the value corresponding to the lower quartile (25th percentile) of the eGFR slope. RESULTS A total of 3982 PLA2R-related MN patients were finally included in this study. The median follow-up (IQR) was 3.7 (2.7–4.6) years. The participants had a median (IQR) proteinuria exposure of 1.7 (0.94–3.4) g/24 h and a median (IQR) PLA2R antibodies exposure level of 27.7 (11.9–67.0) RU/mL during follow-up. The median eGFR slope (IQR) was –1.5 (–5.2 to –0.02) mL/min/1.73 m2 per year in the mixed model. The relationship between eGFR slope and PLA2R antibody exposure is linear in the square root scale of PLA2R antibodies, but is obvious non-linear in the linear scale and in the log scale of PLA2R antibodies. One unit increase of PLA2R antibodies exposure in square root scale is associated with a –0.61 ± 0.02 mL/min/1.73 m2 per year faster decline in eGFR (P < 0.001). The level of PLA2R antibody exposure corresponding to the lower quartile of the eGFR slope (–5.2 ml/min/1.73 m2 per year) is 8.7 RU/mL in square root scale (75 RU/mL in linear scale). CONCLUSION A linear relationship was observed between eGFR slope and PLA2R antibodies exposure in square root scale. It would be more helpful to report PLA2R antibodies test in square root scale than in linear scale. Our data suggest that 8.7 RU/mL in square root scale (75 RU/mL in linear scale) could be used as one of the candidate cutoff values of PLA2R antibody level to predict the risk of MN progression.

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