| Purpose:IgA(immunoglobulin A)nephropathy is the most common primary glomerulonephritis in the world,the most common chronic kidney disease in our country,and the leading primary renal disease in uremia.With the development of various clinical researches,the diagnosis and treatment of IgA nephropathy are gradually understood.It is found that the clinical manifestations of IgA nephropathy are diverse and the pathological types are complex,about 50% of patients with IgA nephropathy may develop stage 5 chronic kidney disease 25-30 years after the onset of the disease.It is suggested that the immune disorder plays a key role in the pathogenesis of IgA nephropathy.Tacrolimus,one of the classic immunosuppressants,is a Calcineurin that has potent immunosuppressive properties,the mechanism of immunosuppression is mainly through inhibiting the activity of Calcineurin,blocking the activation of T cells and transcription of various cytokines.In addition,it plays an important role in enhancing the stability of podocyte cytoskeleton and reducing urinary protein.At present,there are few reports about tacrolimus in the treatment of IgA nephropathy at home and abroad.In this paper,a randomized controlled study was conducted to investigate the safety and efficacy of tacrolimus in the treatment of IgA nephropathy,objective analysis of the treatment results will provide new ideas and methods for the treatment of IgA nephropathy in the future.Method:Fifty patients with IgA nephropathy admitted to the Second Affiliated Hospital of Nanchang University from July 1,2019 to December 31,2019 and diagnosed by renal pathology within 4 weeks were included.All patients’ 24-hour urinary protein excretion was ≥ 2.0g/24 h,and the estimated glomerular filtration rate was ≥50ml/min/1.73m2..According to the distribution ratio of 1:1.5,they were randomly divided into observation group(tacrolimus group)with 20 cases and control group(glucocorticoid group)with 30 cases,in which treatment for ≥2 weeks,observation for ≥6 weeks or termination of treatment earlier were all included in the safety analysis.Patients in the observation group were treated with tacrolimus orally at a dose of 0.05mg/kg(not more than 0.15mg/kg/d)every day,with the same dose twice every 12 hours,and the target concentration of tacrolimus was adjusted at a dose of 3～ 6 ng/ml during the treatment for 6 months.In addition,the tacrolimus group was given oral glucocorticoid 15-20 mg every day for 4 months,and then every day.Patients in the control group received adequate oral glucocorticoid at a dose of0.8-1.0 mg/kg per day for the first 2 months,and then decreased by 20% every month for the next 4 months.During the six-month treatment period,RAS inhibitors were allowed as the basic treatment of the two groups.The main goal was to evaluate the remission(complete remission and partial remission),the number of recurrent patients,biochemical indicators and adverse drug reactions of the two groups after six months of treatment.The complete remission rate,remission rate,24-hour urine protein,estimated glomerular filtration rate and adverse reaction were analyzed by Rev Man 5.2 software.Result:1,Clinical efficacy:(1)Complete remission and remission: a total of 50 cases were included in this study.During the trial,there was no significant difference in the complete remission rate(CR)between tacrolimus(TAC)group(n = 20)and glucocorticoid(GC)group(n= 30)(P > 0.05).There was no significant difference in the response rate(RE)between the two groups(65% vs 70%,P >0.05).(2)Recurrence: No patient in the tacrolimus group relapsed,while 3 patients in the glucocorticoid group relapsed,but there was no significant difference in the recurrence rate between the two groups(P >0.05).2,Clinical indicators:(1)Compared with the situation before treatment,after two,four and six months of treatment in tacrolimus treatment group and glucocorticoid control group,the serum creatinine level of tacrolimus group increased slightly,while that of glucocorticoid group was relatively stable.Before treatment,there was no significant difference in serum creatinine between the two groups(P >0.05).After two,four and six months of treatment,there was a significant difference in serum creatinine between the two groups(P <0.05).However,we found that creatinine levels in patients in the tacrolimus group significantly decreased to almost original levels 3months after stopping tacrolimus treatment.(2)Before treatment,there was no significant difference in estimated GFR between tacrolimus treatment group and glucocorticoid control group(P >0.05).Six months after treatment,there was a significant difference in estimated GFR between the two groups(P <0.05).However,after follow-up visit,the estimated GFR of tacrolimus group significantly increased to almost the original level 3 months after drug discontinuation.(3)Before treatment and two,four,and six months after treatment,the systolic blood pressure of the glucocorticoid control group was higher than that of the tacrolimus treatment group,but there was no significant difference between the two groups(P >0.05).The diastolic blood pressure of the two groups tended to be stable,and there was no significant difference between the two groups(P >0.05).3.Adverse reactions: The total number of adverse events showed that the incidence rate of tacrolimus group was 35%(7 cases),while that of glucocorticoid group was 46.7%(14 cases).Among them,in the serious adverse events,a large amount of gastrorrhagia occurred in one case in the glucocorticoid group,but was not found in the tacrolimus group.The most frequently reported event was infection,which occurred in 3 cases(15%)in the tacrolimus group and 7 cases(23.3%)in the glucocorticoid group(P >0.05).Abnormal liver function occurred in 1 case(5%)in the tacrolimus group and 4 cases(13.3%)in the glucocorticoid group.For abnormal renal function,five cases(25%)and one case(3.3%)in tacrolimus group and glucocorticoid group respectively showed statistical significance(P <0.05).Gastrointestinal symptoms occurred in 1 case(5%)in the tacrolimus group and 4cases(13.3%)in the glucocorticoid group.Dermatologic symptoms occurred in 1case(5%)in the tacrolimus group and 3 cases(10%)in the glucocorticoid group.The glucocorticoid group also bled in 1 case of vascular disease(3.3%),1 case of obvious fatigue(3.3%),1 case of anemia(3.3%)and 1 case of subclinical hyperthyroidism(3.3%).These adverse events were not found in the tacrolimus group,but there was no statistically significant difference between the two groups(P >0.05).Conclusion:When tacrolimus is used for 6 months,the effect of reducing urinary protein is not inferior to that of adequate glucocorticoid,and it has good safety.Therefore,tacrolimus can be used as an alternative for IgA nephropathy patients treated with adequate glucocorticoid. |
