| Objectives:The clinical course and prognosis of patients withIdiopathic membranous nephropathy have large differences,which can also be spontaneous remission or expressed asnephrotic syndrome with persistent worsening of renalfunction. Its treatment has been controversial, yet no acceptedbest treatment options. Leflunomide is a new kind ofimmunosuppressant, which in recent years has been widelyused in the treatment of kidney diseases. Due to the majoritysize of the study samples, the results of leflunomide treatmentfor idiopathic membranous nephropathy are not consistent.While its efficacy and adverse effects are still inconclusive.Through the integration of small studies, a meta-analysiscan draw reliable conclusions of this analysis. A systematicreview and meta-analysis was in order to evaluate the efficacyand safety of leflunomide for patients with idiopathicmembranous nephropathy comparing with cyclophosphamide,tacrolimus, mycophenolate mofetil and tripterygium wilfordii, and to provide a basis for the rational use of the drugtreatment for patients with idiopathic membranousnephropathy.Methods:A systematic literature search was performed forpublished randomized controlled trials about treatingidiopathic membranous nephropathy with leflunomide in theCochrane Library, Medline, EMBASE, Science Citation Index(SCI), WanFang database, VIP and CNKI-China AcademicJournal from the construction of the library to December,2014.We use ’leflunomide’,’immunosuppressant’,’idiopathic’,’glomerulonephritis’,’membranous’,’membranousnephropathy’,’membranous glomerulopathy’,’membranousglomerulonephropathy’,’idiopathic membranous nephropathy’,’idiopathic membranous glomerulonephritis’,’nephriticsyndrome’ as a search term among English databases. Whilewe use "LEF","immunosuppressive","membranousnephropathy,""idiopathic","primary","membranousglomerulonephritis" as a search term among Chinesedatabases. Literature search language is limited to English orChinese. We do an artificial retrieval among the related kidneymagazines, including "Chinese Journal of Nephrology", "Chinese Integrative Medicine","International Journal ofTransplantation and blood purification","Chinese Medicine"and unpublished research data or conference data.We retrieved the initial335Chinese literatures and10English literatures. By browsing the titles, abstracts, fulltexts,and strictly controlling inclusion and exclusion criteria, weremoved duplicate documents, non-clinical documents orliteratures of which research purposes inconsistent with thisresearch literature.We conducted a meta-analysis with thirteen Chineseliteratures, a total of583cases of patients, which were in linewith the inclusion criteria, observing total remission, completeremission and adverse drug reactions at the end of follow-up,using relative risk (RR) to assess the outcome measures. Andthe outcomes were evaluated by the software “Reviewmanager5.2” offered by the Cochrane web．Results:Meta-analysis showed: Between the treatment group withleflunomide and the control group, there was no significantdifference in total remission rate (RR=1.04,95%CI0.89-1.22,P value=0.60). Excluding the study with mere application ofleflunomide, which was not combined hormone therapy for idiopathic membranous nephropathy, the outcome of themeta-analysis showed that the effect size was no significantchange compared with the previous. Excluding the studieswhich the test groups were with application of leflunomidecombined with CTX or TW and hormone therapy for idiopathicmembranous nephropathy, the meta-analysis showed that theeffect size was no significant change compared with theformer either. Excluding these three studies for meta-analysis,the effect was still no significant change in value.Subgroup analysis showed that:1. Comparing with thecyclophosphamide group, the complete remission rate andoverall response rate was not statistically different.2.Compared with tacrolimus treatment for idiopathicmembranous nephropathy, there was no significant differencein the rate of complete remission (RR=0.55,95%CI0.29-1.04,P value=0.06). Therefore, the overall response rate oftacrolimus group was higher than the leflunomide group (RR=0.73,95%CI0.55-0.96, P value=0.02).3. Comparing with theCTX or TW combined hormone group, there was no differencein the rate of complete remission (RR=1.60,95%CI0.71-3.64,P value=0.26), while the addition of leflunomide treatmentcould increase the overall response rate (RR=1.44,95%CI 1.07-1.96, P value=0.02).Adverse reactions:1. The adverse reactions caused byleflunomide were less than the cyclophosphamide group, RR0.41,95%CI0.25-0.68, effect size test Z=3.52, P value=0.0004.Otherwise, respectively, adverse reactions from four areas, thegastrointestinal tract, liver dysfunction, leukopenia andinfection, comparing CTX and leflunomide treatment group,the difference was not statistically significant.2. Leflunomidegroup and the tacrolimus group, especially in the treatment ofadverse reactions in patients with idiopathic membranousnephropathy caused no significant difference (RR1.66,95%CI0.90-3.06, effect size test Z=1.62, P value=0.11).3. Theadditional use of LEF based on CTX or TW combined hormonetherapy, did not increase the risk of adverse events (RR0.77,95%CI0.48-1.22, effect size test Z=1.12, P value=0.26).Conclusion:Present evidence indicated that compared with the controlgroup, treatment with LEF had equal efficacy which could playa role in remission of proteinuria for patients with IMN.Furthermore, treatment with LEF caused fewer adversereactions compared with cyclophosphamide, while with nosignificant differences to the tacrolimus group, CTX or TW combined with hormone group, and could be much cheaperthan other immunosuppressants. Consequently, leflunomidecan be used as one of IMN treatment., but the evidence doesnot yet support LEF as a first-line therapy for IMN. |
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