Evaluation Of Tacrolimus Combined With Corticosteroids Therapy In Patients With Anti-M-Type Phospholipase A2 Receptor Antibody Positive Nephrotic Syndrome

Objective:To retrospectively analyze the efficacy and drug safety of corticosteroids combined with Tacrolimus(TAC)and Cyclophosphamide(CTX)in patients with nephrotic syndrome who had positive serum anti-M-type phospholipase A2receptor(PLA2R)antibody but without renal biopsy.Methods:A total of 63 patients with nephrotic syndrome who were diagnosed and treated in the Department of Nephrology of China-Japan Friendship Hospital of Jilin University from September 2018 to March 2020.They were selected by the inclusion and exclusion criteria,including 46 males and 17 females,with an average age of49.57±7.32 years.All the patients were divided into 2 groups,group A was TAC combined with glucocorticoid group,a total of 32 patients;Group B was CTX combined with glucocorticoid group,including 31 cases.General and laboratory data were collected before the start of tacrolimus or cyclophosphamide combined with glucocorticoid therapy,and laboratory data and adverse drug reactions were recorded at 3 and 6 months after treatment.SPSS21.0 statistical software was used for data analysis.Result:1.A total of 63 patients with a clear diagnosis of nephrotic syndrome who did not undergo renal biopsy were divided into two groups.The general information such as gender,age,body mass index,etc.and baseline data in serum albumin,24h-urinary protein excretion,serum anti-PLA2 R antibody titer,serum creatinine,glomerular filtration rate,cholesterol,triglycerides and white blood cell count in TAC combined glucocorticoid group(32 cases)and the CTX combined glucocorticoid group(31cases)was no significant differences(P>0.05).2.At 3 months of treatment,the 24h-urinary protein excretion,anti-PLA2 R antibody titer and cholesterol of TAC group and CTX group were significantly lower than prior treatment,while the serum albumin of the two groups was significantly higher than that before treatment.The above differences are all significantly different(P<0.05);while the above-mentioned indicators were not significantly different between the two groups(P>0.05);there was no statistically significant difference in serum creatinine,urea nitrogen and triglycerides between the two groups before and after treatment(P> 0.05).3.At 6 months of treatment,the 24h-urinary protein excretion,anti-PLA2 R antibody titer and cholesterol of TAC group and CTX group were significantly lower than prior treatment,and triglycerides of TAC group were also significantly lower than prior treatment.Serum albumin in two groups were significantly increased compared to prior treatment,and the above differences were significantly different(P<0.05);the anti-PLA2 R antibody titer of TAC group was lower than that of CTX group,and the difference was significantly different(P<0.05).There was no significant difference in 24h-urinary protein excretion,serum albumin,triglyceride and cholesterol between two groups(P>0.05);there was also no significant difference in serum creatinine and urea nitrogen between the two groups before and after treatment(P>0.05).4.After 3 months of treatment,the total remission rates of the TAC combined with glucocorticoid group and CTX combined with glucocorticoid group were 87.5%(28/32)and 61.3%(19/31),respectively.The difference between the two groups was significantly different(P<0.05).After 6 months of treatment,the total remission rates of the TAC combined with glucocorticoid group and CTX combined with glucocorticoid group were 93.2%(30/32)and 74.2%(23/31),respectively,there was no difference between the two groups(P>0.05).It shows that the TAC combined with glucocorticoid group has a relatively rapid effect than the CTX combined with glucocorticoid group.5.Spearman analysis of 63 patients showed that serum anti-PLA2 R antibody titers were correlated with 24h-urinary protein excretion,serum albumin and the remission rate,respectively.With the gradual increase of serum albumin or the gradual decrease of 24h-urinary protein excretion or the improvement of the remission rate,the patient’s serum anti-PLA2 R antibody titer level also decreased,indicating that the serum anti-PLA2 R antibody and serum albumin and the remission rate were negative respectively correlation,and positive correlation with 24-hour urine protein quantification.The correlation coefficients were-0.748,-0.779 and 0.705(P<0.01),respectively.6.Adverse events during the follow-up period were mainly elevated fasting blood glucose,gastrointestinal reactions,upper respiratory infections and liver function abnormalities.The incidence of adverse events during the follow-up period in the TAC combined with glucocorticoid group was lower than that in the CTX combined with glucocorticoid group,but there was no significant difference in the incidence of adverse events between the two groups(P>0.05).Conclusion:1.The detection of serum anti-PLA2 R antibodies is helpful in the diagnosis of idiopathic membranous nephropathy,and helps patients with nephrotic syndrome who have not undergone a renal biopsy to choose an immunomodulatory therapy.2.Dynamic monitoring of anti-PLA2 R antibody levels can be used to determine the efficacy of patients with nephrotic syndrome who have positive antibodies but have not undergone renal biopsy.3.Tacrolimus combined corticosteroids and cyclophosphamide combined corticosteroids are effective for treating patients with nephrotic syndrome who have positive serum anti-PLA2 R antibodies but have not undergone renal biopsy.However,tacrolimus has a relatively rapid effect than cyclophosphamide.