Anti-phospholipase A2 Receptor Antibody Levels At Diagnosis Predicts Outcome Of Tacrolimus Treatment For Idiopathic Membranous Nephropathy Patients

ObjectiveThis study assessed the relationship between the serum anti-phospholipase A2receptor(anti-PLA2R)antibody level at diagnosis and the response to tacrolimus(TAC)-based treatment in idiopathic membranous nephropathy(MN)patients,and aimed to identify patients who will benefit from TAC-based immunosuppressive treatment according to their anti-PLA2 R antibody titer.MethodsThis is a single center,retrospective study.We selected patients with membranous nephropathy confirmed by renal biopsy,whose serum anti-PLA2 R antibody were positive at diagnosis.All patients were diagnosed in the Department of Nephrology,the First Affiliated Hospital of Nanchang University,and were followed up from May 2017 to September 2020.And all patients received tacrolimus-based regimen as the initial immunosuppressive treatment.According to the anti-PLA2 R antibody titer at diagnosis,all patients were divided into two groups,namely high-level group(>150RU/ml)and low-level group(≤150RU/ml).According to the therapeutic regime,the group was divided into two subgroups: TAC subgroup and TAC + hormone subgroup.The clinical data of patients were collected and followed up until September 30,2021.SPSS 21.0was used to statistically analyze the collected clinical data.Kaplan Meier method was used to describe the cumulative remission curve of the two groups during follow-up.Results1.94 patients were included in this study,including 42 cases in the high-level(>150RU/ml)group,52 cases in the low-level(≤ 150RU/ml)group.At diagnosis,the serum albumin in the high-level group was significantly lower than low-level group(P=0.005),and the low-density lipoprotein was significantly higher than low-level group(P=0.029).However,there was no significant difference in the 24-hour proteinuria,hemoglobin,total cholesterol,triglyceride,creatinine and e GFR levels at diagnosis between two groups.2.The total and complete remission rates were significantly higher in the lowlevel group than high-level group after treatment with TAC for 6,12,18,or 24 months(all P<0.05).After 12 months of treatment with TAC,82.7% of the patients in the lowlevel group achieved remission(mean,6.52±0.53 months.However,38.1% of the patients in high-level group achieved CR or PR(mean,9.86±0.51 months).In the highlevel group,only 2 cases achieved complete remission after tacrolimus treatment for12 months,and the complete remission rate was only 4.7%(the average remission time was 11.88 ± 0.63 months).3.According to the therapeutic regime,the group was divided into two subgroups:TAC subgroup and TAC + hormone subgroup.The remission rate of TAC + hormone subgroup was higher than that of TAC subgroup,but there was no significant difference.For patients with anti-PLA2 R antibody≤150RU/ml at diagnosis,the total remission rates of TAC and TAC + hormone treatment were 85.7% and 91.7% respectively.For patients with anti-PLA2 R antibody>150 RU/ml at diagnosis,the total remission rates of two years after TAC and TAC + hormone treatment were 39.1% and 47.4%respectively.4.The infection frequency in the high-level group(35.6%)was higher than the low-level group(20%)during the TAC treatment,there was no significant difference.During the follow-up period,19%(8/42)of the patients in the high-level group progressed to end-stage renal disease,while only 1 case(1.9%)in the low-level group progressed to end-stage renal disease,the difference between the two groups was statistically significant.There were 7.1%(3/42)patients in the high-level group died of ESRD during the follow-up period,and there was no death in the low-level group.13patients(13.8%)developed steroid diabetes or impaired glucose tolerance during the follow-up period,6 in the low-level group,and 7 in the high-level group,there was no significant difference in the elevation of blood glucose between the two groups.No thromboembolic events were observed in both groups during follow-up.ConclusionsThe high level of anti PLA2 R antibody at diagnosis can predict the adverse reactions and prognosis of patients with idiopathic membranous nephropathy,but tacrolimus cannot reduce this adverse prognosis.IMN patients with anti-PLA2 R antibody titer > 150 RU/ml at diagnosis who used tacrolimus as the initial immunosuppressive therapy had poor response,low remission rate and high rate of progression to end-stage renal disease.