| Objective To evaluate the efficacy and safety of immunosuppressive agents in the treatment of Ig A nephropathy(Ig AN)nephropathy by meta-analysis.Method We systematically searched the Pub Med,Embase,The Cochrane Library,China National Knowledge Infrastructure(CNKI)and Wan Fang Data Knowledge Service Platform and the Chinese Biomedical Literature(CBM)for RCTs of immunosuppressive therapies up to 1,December,2019.The RCT quality assessment was completed by using risk of bias tool.Two authors(HWJ and SM)independently extracted and assessed the date of included trials.We using the Review Manager 3.0software to finish the meta-analysis.We use RR and 95% CI or WMD and 95% CI as the analysis statistic.ResultPart 1.Meta-analysis of the efficacy and safety of immunosuppressive agents versus supportive therapy for Ig A nephropathyA total of 5,963 relevant literatures were obtained in the initial examinations(Pub Med 1597,Embase 2165,and The Cochrane Library 2201).After layer-by-layer screening,29 articles and 25 RCTs were finally included,including 1968 patients.(1)The results of meta-analysis show that compared with intensive supportive therapy,immunosuppressive therapy can significantly reduce urinary protein(WMD=-0.29,95%CI :-0.34~-0.23;random effect model,I2=83%,p<0.01),and has a reduced risk of creatinine doubling or ESRD in patients with Ig AN(RR=0.40,95%CI:0.27~0.60;fixed effect model,I2=35%,P=0.12);but there was no statistical difference of SCr,e GFR and clinical response between the two group.The results also shows that the incidence of adverse events was higher in the immunosuppressant group(RR=2.23,95%CI:1.75~2.85;fixed effect model,I2=32%,P=0.08).The results of the subgroup analysis suggested that compared with the support therapy,theimmunosuppressive ahents group had higher incidence of infection(RR=2.59,95%CI:1.29~5.20),diabetes or impaired glucose tolerance(RR=3.20,95%CI:1.31~7.83),acne(RR=5.40,95%CI:1.46~19.99),gastrointestinal symptoms(RR=2.49,95%CI:1.07~5.80),but there were no statistically significant differences in the incidence of other adverse events such as cough,hyperkalemia,leucopenia,abnormal bone metabolism,cardiovascular events,and abnormal liver function.(2)We use different therapeutic schemes to conduct subgroup analysis(steroids(S),non-steroidal immunosuppressive agents(NSI),glucocorticoids combined with non-glucocorticoid immunosuppressive agents(S & NSI).The results showed that compared with supportive treatment,S or NSI alone can significantly reduce urinary protein(WMD =-0.43,95%CI:-0.64~-0.23;WMD =-0.25,95%CI:-0.45~-0.06).But there was no statistical difference in the combination group(WMD =-0.73,95%CI:-1.61~-0.15);at the same time,the analysis found that the S group had a higher clinical response rate(RR=2.40,95%CI : 1.39~4.14)and smaller risk of creatinine doubling and ESRD(RR=0.28,95%CI:0.12~0.36).(3)According to the follow-up time we conducted subgroup analysis to evaluate the long-term efficacy of immunosuppressive therapy.The results showed that regardless of whether the follow-up time was longer than 5 years,the immunosuppressive group could significantly reduce the risk of creatinine doubling or ESRD(RR=0.26,95%CI:0.13~0.51;RR=0.53,95%CI:0.32~0.89);However,when analyzing the effect of lowering urine protein,immunosuppressive agents have a significant effect within 5 years of treatment(WMD =-0.33,95%CI:-0.49~-0.18),but when the follow-up period exceeds 5 years,there was no significant difference in urinary protein levels between the immunosuppressive group and the supportive treatment group.(4)Patients were divided into Asian,American or European based on the skin color of the included patients.Subgroup analysis showed that immunosuppressants can significantly reduce urine protein(WMD =-0.37,95%CI:-0.49~-0.26),and delay the risk of creatinine doubling or ESRD(RR=0.35,95%CI:0.17~0.7)of Asian patients.But the above treatment effect is not significant in the white people.We also find that the rate of clinical response of Ig AN in the immunosuppressive group was higher in the Caucasian(RR=2.8,95%CI:1.1.3~6.9)?Part 2.Meta-analysis of the efficacy and safety of combined immunosuppressant therapy versus glucocorticoid alone for Ig A nephropathyA total of 7,298 related literatures were obtained in the preliminary inspection(Pub Med 1597,Embase 2165,The Cochrane Library 2201,Wanfang 769,CNKI 277,CBM 289).After layer-by-layer screening,13 articles and 1054 patients were finally included.The meta-analysis results showed no statistical significance of the level of urinary protein(WMD= 0,95%CI :-0.21~-0.21;random effect model,I2=91%,p<0.01),SCr(WMD =-0.97,95%CI:-4.46~2.52;fixed effect model,I2=0%,p=0.43),e GFR(WMD= 2.15,95%CI:-1.49~5.79;fixed effect Model,I2=0%,p=0.47),and clinical remission rate(RR=1.10,95%CI:0.93~1.30;random effect model,I2=19%,P=0.23),doubling of creatinine or ESRD risk(RR=1.36,95%CI:0.72~2.56;fixed effect model,I2=27%,P=0.24)in the immunosuppressant combined therapy and glucocorticoid alone group.Moreover,there were no significant difference in the incidence of adverse events between the two groups(RR=0.97,95%CI:0.76~1.23;random effect model,I2=5%,P=0.38).The subgroup analysis showed that the incidence of diabetes or impaired glucose tolerance was higher in the glucocorticoid monotherapy group(RR=0.49,95%CI:0.31~0.76),but the incidence of adverse events of leukopenia was higher in the immunosuppressant combination treatment group(RR=4.62,95%CI:1.23~17.35).Conclusion1.Compared with supportive therapy,glucocorticoids or nonsteroidal immuneosuppressants alone have significant benefits for proteinuria and delay ESRD in Asian Ig AN patients,but due to side effects such as infection,diabetes or impaired glucose tolerance,acne,stomach intestinal symptoms,the clinician should be cautions when making dicisions.2.There is no significant difference of the level of urinary protein,SCr,e GFR,clinical remission,and population of ESRD of the combined immunosuppressive therapy or glucocorticoid alone.Clinician can make decisions based on clinical manifestation and pathological type. |
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