Clinical Efficacy And Safety Of Different Tacrolimus Levels For Idiopathic Membranous Nephropathy

Background:There are many treatment programs for IMN patients,such as glucocorticoid（GC）combined with cyclophosphamide（CTX）GC combined with tacrolimus（TAC）,and rituximab,etc.However,due to the efficiency and side effects,views on IMN of treatment vary across races.2020 KDIGO guidelines recommend TAC for the treatment of IMN.In comparison with no immunosuppressant therapy in subjects,TAC monotherapy was recently suggested to be a useful therapeutic option for patients with IMN in a placebo-controlled,randomized trial.The immunosuppressant TAC（3～8ng/ml）is used as a first-line treatment for MN according to the 2020 KDIGO.However,the definite relationship between TAC levels and drug efficacy was not clear.It is uncertain that adverse reactions of TAC increase with TAC concentration.We believe that our study is important in so far as it represents the first clinical trial to explore the effectiveness and safety of TAC in the treatment of IMN patients at different levels.Methods:260 IMN patients were recruited with nephrotic syndrome（NS）.125 patients had TAC concentrations are no greater than 5ng/ml(C_TAC≤5ng/ml),and 135 patients had TAC concentrations are more than 5ng/ml(C_TAC>5ng/ml).Complete remission rates（CRR）and overall response rates（ORR）were included in the primary outcome.The secondary outcomes included 24-hour urinary protein（24h UP）,serum albumin（ALB）and serum creatinine（Scr）,and adverse events（AEs）.Results:During the 12 months follow-up,the overall response rates were statistically significantly different between C_TAC≤5ng/ml group and C_TAC>5ng/ml group（P<0.0001）.However,at 12 months,there was no significant difference in the CRR between the two groups（chi-square,62%vs 63%,P=0.852）.Compared with the C_TAC≤5ng/ml group,the C_TAC>5ng/ml group could effectively improve the level of 24h UTP（P=0.017）,Scr（P=0.010）.Meanwhile,the incidences of acute reversible nephrotoxicity（P<0.001）,hepatotoxicity（P=0.036）and New-onset diabetes mellitus（P=0.036）,Glucose intolerance（P=0.005）,were lower in the C_TAC≤5ng/ml group than the C_TAC>5ng/ml group.Conclusion:The C_TAC>5ng/ml group was more effective than the C_TAC≤5ng/ml group in terms of PR and CR at 6 months,but there is no difference in the CR between the two groups at 12 months.