Comparison of different therapies in high-risk patients with idiopathic membranous nephropathy

Peng, Lei; Wei, Shih-Chung; Li, Leiting; He, Yizhu; Li, Bing

doi:10.1016/j.jfma.2015.07.021

Cited by 34 publications

(37 citation statements)

References 36 publications

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“…We further analyzed the association between treatment options and clinical outcome, and found no significant difference between variety of therapeutic regimens and outcome ( fig. 4 d), consistent with other research [14] and our previous study [22] . Same results were also confirmed by multivariable analyses ( table 3 ).…”

Section: Spla 2 R-ab Is a Promising Indicator Of Prognosis Assessmentsupporting

confidence: 93%

Serum Anti-PLA<sub>2</sub>R Antibody Predicts Treatment Outcome in Idiopathic Membranous Nephropathy

Wei

Wang

et al. 2016

Am J Nephrol

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Background: M-type phospholipase A₂ receptor (PLA₂R) has been identified as the major target antigen in idiopathic membranous nephropathy (IMN). However, the role of glomerular PLA₂R (gPLA₂R) and the associations of serum anti-PLA₂R antibody (sPLA₂R-Ab) titre with diagnosis, treatment and prognosis in IMN need to be further investigated. Methods: We screened 148 consecutive patients with biopsy-proven membranous nephropathy (MN; 113 with IMN and 35 with secondary MN (SMN)) who were followed up for ≤20 months. Serum and urine samples were simultaneously collected at different time points. The levels of sPLA₂R-Ab were detected using immunofluorescence and enzyme-linked immunosorbent assay. gPLA₂R was assessed by immunofluorescence. Results: Most patients with IMN displayed both gPLA₂R and sPLA₂R-Ab positive (85.8 and 82.3%, respectively). In contrast, very few patients with SMN showed either gPLA₂R or sPLA₂R-Ab positive. The sPLA₂R-Ab titre, not gPLA₂R, was significantly correlated with proteinuria. Surprisingly, changes in sPLA₂R-Ab titre occurred earlier and faster than proteinuria in patients who were followed up for ≤20 months during the whole period of observation. Survival analysis of IMN patients indicated a significant association between sPLA₂R-Ab titre and outcome, whereas, no significant difference was observed between the gPLA₂R intensity and outcome. Conclusions: These data indicate that sPLA₂R-Ab might be a better biomarker for IMN diagnosis and treatment outcome. In addition, monitoring sPLA₂R-Ab titre may assist in determining when to initiate the administration of immunosuppressive agents and in evaluating treatment efficacy.

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Section: Spla 2 R-ab Is a Promising Indicator Of Prognosis Assessmentsupporting

confidence: 93%

Serum Anti-PLA<sub>2</sub>R Antibody Predicts Treatment Outcome in Idiopathic Membranous Nephropathy

Wei

Wang

et al. 2016

Am J Nephrol

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“…A total of 1829 citations were retrieved based on electronic searches, and 12 additional studies were retrieved after checking the references of relevant reviews and guidelines. Ultimately, 48 studies21–68 including 2736 adults were available for network meta-analysis. These trials evaluated 13 different immunosuppressive treatment regimens, including ACTH, AZA, chlorambucil (CH), cyclophosphamide (CTX), cyclosporine (CsA), leflunomide (LEF), MMF, MZB, rituximab (RIT), steroids (STE), tacrolimus (TAC), tacrolimus+tripterygiumwilfordii (TAC+TW) and TW for patients with IMN.…”

Section: Resultsmentioning

confidence: 99%

Comparative efficacy of 13 immunosuppressive agents for idiopathic membranous nephropathy in adults with nephrotic syndrome: a systematic review and network meta-analysis

et al. 2019

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ObjectivesThis study aimed to compare the effectiveness of 13 types of immunosuppressive agents used to treat idiopathic membranous nephropathy (IMN) in adults with nephrotic syndrome.DesignSystematic review and network meta-analysis.Data sourcesPubMed, EMbase, Cochrane Library, Web of Science, Clinical trials, SinoMed, Chinese Biomedicine, CNKI, WanFang and Chongqing VIP Information databases were comprehensively searched until February 2018.Eligibility criteriaRandomised clinical trials (RCTs) comparing the effects of different immunosuppressive treatments in adult patients with IMN and nephrotic syndrome were included, and all included RCTs had a study-duration of at least 6 months.Data extraction and synthesisTwo reviewers independently screened articles, extracted data and assessed study quality. Standard pairwise meta-analysis was performed using DerSimonian-Laird random-effects model.ResultsThis study ultimately included 48 RCTs with 2736 patients and 13 immunosuppressive agents. The network meta-analysis results showed that most regimens, except for leflunomide (LEF), mizoribine (MZB) and steroids (STE), showed significantly higher probabilities of total remission (TR) when compared with non-immunosuppressive therapies (the control group),with risk ratios (RRs) of 2.71 (95% CI) 1.81 to 4.06)for tacrolimus+tripterygium wilfordii (TAC+TW), 2.16 (1.27 to 3.69) foradrenocorticotropic hormone, 2.02 (1.64 to 2.49) for TAC, 2.03 (1.13 to3.64) for azathioprine (AZA), 1.91 (1.46 to 2.50) for cyclosporine (CsA), 1.86 (1.44 to2.42) for mycophenolate mofetil (MMF), 1.85 (1.52 to 2.25) for cyclophosphamide (CTX),1.81 (1.10 to 2.98) for rituximab (RIT), 1.80 (1.38 to 2.33) for TW, 1.72 (1.35 to 2.19) for chlorambucil. As for 24 hours UTP, the direct andindirect comparisons showed that AZA (standard mean difference (SMD), −1.02(95% CI −1.90 to −0.15)), CsA (SMD, −0.70 (95% CI −1.33 to −0.08)),CTX (SMD, −1.01 (95% CI −1.44 to -0.58)), MMF (SMD, −0.98 (95% CI −1.64 to −0.32)), MZB (SMD, −0.97 (95% CI −1.90 to−0.04]), TAC (SMD, −1.16 (95% CI −1.72 to −0.60)) and TAC+TW(SMD, −2.03 (95% CI −2.94 to −1.12)) could significantly superior thancontrol, except for chlorambucil, LEF, RIT and STE. Thechanges of serum creatinine (Scr) was not significantly different between eachtreatments of immunosuppressive agents and the control, except for STE whichhas the possibility of increasing Scr (SMD, 1.00 (95% CI 0.36 to 1.64)).Comparisons among all treatments of immunosuppressive agents showed nostatistical significance in the outcome of relapse. A drenocorticotropichormone (85.1%) showed the lowest probability of relapse under the cumulativeranking curve values among all immunosuppressants. Infection,gastrointestinal symptoms, and bone marrow suppression were the common adverseevents associated with most of the immunosuppressive therapies.ConclusionsThis study demonstrates that TAC+TW, TAC and CTX are superior to other immunosuppressive agents in terms of TR and 24 hours UTP. Moreover, they are all at risk of infection, gastrointestinal symptoms, and myelosuppression. Furthermore, TAC could increase the risk of glucose intolerance or new-onset diabetes mellitus. Conversely, STE alone, LEF and MZB seem to have little advantage in clinical treatment of IMN.PROSPERO registration numberCRD42018094228.

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“…Few studies have compared the effect of alkylating agents with that of CNIs, in the treatment of PMN and initially showed a comparable efficacy in proteinuria reduction and rate of relapse [8][9][10][11]. However, all had a short term period, not exceeding 12 months, and they did not refer to outcome after discontinuation of treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Both treatment options have their own side effects and both have undergone alterations and improvements in order to minimize complications [1,4]. Although Cyclo and CNIs have been used in the treatment of PMN for more than twenty years, there are not enough data to support one against the other, and the few prospective studies have only a short term follow up, up to 12 months, which is not a long enough period to come to confident conclusion [8][9][10][11][12]. Aim of the present retrospective multicenter study, was to evaluate the long term effects of Cyclo and CNI treatments in a large cohort of PMN patients.…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressive regimens based on Cyclophospamide or Calcineurin inhibitors: Comparison of their effect in the long term outcome of Primary Membranous Nephropathy

Stangou

Marinaki

Papachristou

et al. 2019

Preprint

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Management of the Primary Membranous Nephropathy (PMN) usually involves administration of immunosuppressives. Cyclophosphamide (Cyclo) and Calcineurin Inhibitors (CNIs) are both widely used but only limited data exist to compare their efficacy in long term follow-up.Aim of the present study was to estimate and compare long term effects of Cyclo and CNIs in patients with PMN.Patients-Methods. Clinical data, histologic findings and long term outcome were retrospectively studied. The response to treatment and rate of relapse was compared between patients treated with CNIs or Cyclo based immunosuppressive regimens.Results. Twenty three centers participated in the study, with 752 PMN patients (Mean age 53.4(14-87)yrs, M/F 467/285), followed for 10.1±5.7 years. All patients were initially treated with Renin Angiotensin Aldosterone System inhibitors (RAASi) for at least 6 months. Based on their response and tolerance to initial treatment, patients were divided into 3 groups, group I with spontaneous remission, who had no further treatment, group II, continued on RAASi only, and group III on RAASi+immunosuppression. Immunosuppressive regimes were mainly based on CNIs or Cyclo. Frequent relapses and failure to treatment were more common between patients who had started on CNIs (n=381) compared to those initially treated with Cyclo (n=110), relapse rate: 25.2% vs. 6.4%, p<0.0001, and no response rate: 22.5% vs. 13.6%, p=0.04, respectively. Conclusions.Long term follow up showed that administration of Cyclo in PMN is followed by better preservation of renal function, increased response rate and less frequent relapses, compared to CNIs.

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Comparison of different therapies in high-risk patients with idiopathic membranous nephropathy

Cited by 34 publications

References 36 publications

Serum Anti-PLA<sub>2</sub>R Antibody Predicts Treatment Outcome in Idiopathic Membranous Nephropathy

Serum Anti-PLA<sub>2</sub>R Antibody Predicts Treatment Outcome in Idiopathic Membranous Nephropathy

Comparative efficacy of 13 immunosuppressive agents for idiopathic membranous nephropathy in adults with nephrotic syndrome: a systematic review and network meta-analysis

Immunosuppressive regimens based on Cyclophospamide or Calcineurin inhibitors: Comparison of their effect in the long term outcome of Primary Membranous Nephropathy

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