Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors versus erythropoiesis-stimulating agents on iron metabolism and inflammation in patients undergoing dialysis: A systematic review and meta-analysis.

Aims: This study aimed to evaluate the effects of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) on iron metabolism and inflammation in dialysis-dependent chronic kidney disease (DD-CKD) patients. Methods: PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov websites were searched for randomized controlled trials (RCTs) investigating HIF-PHIs versus ESAs for DD-CKD patients. Key findings: Twenty studies with 14,737 participants were included in the meta-analysis, which demonstrated no significant difference in the effect of transferrin saturation and ferritin between HIF-PHIs and the ESAs group (MD, 0.65; 95%CI, -0.45 to 1.75; very low certainty; SMD, -0.03; 95% CI, -0.13 to 0.07; low certainty). However, HIF-PHIs significantly increased the iron (MD, 2.30; 95% CI, 1.40 to 3.20; low certainty), total iron-binding capacity (SMD, 0.82; 95% CI, 0.66 to 0.98; low certainty), and transferrin (SMD, 0.90; 95%CI, 0.74 to 1.05; moderate certainty) levels when compared with the ESAs group. In contrast, the hepcidin level and dosage of intravenous iron were significantly decreased in the HIF-PHIs group compared with the ESAs group (MD, -15.06, 95%CI, -21.96 to -8.16; low certainty; MD, -18.07; 95% CI, -30.05 to -6.09; low certainty). The maintenance dose requirements of roxadustat were independent of baseline CRP or hsCRP levels with respect to the effect on inflammation. Significance: HIF-PHIs promote iron utilization and reduce the use of intravenous iron therapy. Furthermore, HIF-PHIs, such as roxadustat, maintain the erythropoietic response independent of the inflammatory state. Thus, HIF-PHIs may be an alternative treatment strategy for anemia in DD-CKD patients, where ESA is hyporesponsive due to iron deficiency and inflammation.

Cardiac and Kidney Adverse Effects of HIF Prolyl-Hydroxylase Inhibitors for Anemia in Patients With CKD Not Receiving Dialysis: A Systematic Review and Meta-analysis.

RATIONALE & OBJECTIVE: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel, orally administered agents for anemia management in chronic kidney disease (CKD). We evaluated the cardiac and kidney-related adverse effects of HIF-PHIs among patients with CKD and anemia. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING & STUDY POPULATIONS: Patients with anemia and CKD not receiving maintenance dialysis. SELECTION CRITERIA FOR STUDIES: RCTs comparing HIF-PHIs to placebo or an erythropoiesis-stimulating agent (ESA) with primary outcomes of cardiac and kidney-related adverse events (AEs). DATA EXTRACTION: Two independent reviewers evaluated RCTs for eligibility and extracted relevant data. ANALYTICAL APPROACH: Dichotomous variables were pooled using the Mantel-Haenszel method and presented as risk ratios (RRs). Subgroup analyses evaluated different intervention times and HIF-PHIs, as well as phase 2 versus phase 3 trials. The certainty of findings was rated according to GRADE criteria. RESULTS: Twenty-three studies with 15,144 participants were included. No significant difference in the risk of cardiac AEs was observed between the HIF-PHIs group and the placebo (RR, 1.02 [95% CI, 0.89-1.16]; moderate certainty) or ESA (RR, 1.06 [95% CI, 0.98-1.14]; low certainty) groups. No significant difference in the risk of kidney-related AEs was observed between the HIF-PHIs group and the placebo (RR, 1.09 [95% CI, 0.98-1.20]; moderate certainty) or ESA (RR, 1.00 [95% CI, 0.94-1.06]; low certainty) groups. The occurrence of hypertension and hyperkalemia was higher in the HIF-PHIs group than in the placebo group (RRs of 1.35 [95% CI, 1.14-1.60] and 1.25 [95% CI, 1.03-1.51], respectively; both findings had high certainty). The occurrence of hypertension was lower in the HIF-PHIs group than in the ESA group (RR, 0.89 [95% CI, 0.81-0.98]; moderate certainty). LIMITATIONS: The reporting criteria of cardiac and kidney-related AEs and dosage of HIF-PHIs were inconsistent across trials. CONCLUSIONS: The occurrence of cardiac or kidney-related AEs in the HIF-PHI groups were not different compared with placebo or ESA groups. REGISTRATION: Registered at PROSPERO with registration number CRD42021228243.

Efficacy and Safety of Finerenone in Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: Chronic kidney disease (CKD) is a global public health issue. In recent years, the effectiveness of finerenone for treatment of CKD has been the subject of considerable debate. The main objective of the current meta-analysis was to validate the clinical efficacy and safety of finerenone in patients with CKD. Methods: Seven databases were searched for randomized controlled trials (RCTs) comparing finerenone with placebo in patients with CKD. Data from eligible studies were extracted, and the Cochrane risk of bias tool utilized for evaluating the methodological quality of RCTs. The effect size was estimated using the risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI). Results: Five trials (n = 13,078) were included. Compared to placebo groups, the urinary albumin-to-creatinine ratio (UACR) mean from the baseline was significantly lower [MD -0.30 (95% CI -0.32, -0.28), p < 0.00001], while a decrease in the estimated glomerular filtration rate (eGFR) from baseline was significantly higher [MD -2.44 (95% CI -2.82, -2.05), p < 0.00001] for the finerenone groups. Furthermore, the proportion of patients with decreased eGFR (≥40%) post-baseline was significantly lower [RR 0.85 (95% CI 0.78, 0.93), p = 0.0002], along with end-stage kidney disease (ESKD) [RR 0.80 (95% CI 0.65, 0.99), p = 0.04] and cardiovascular events (CVs) [RR 0.88 (95% CI 0.80, 0.95), p < 0.003] in the finerenone groups. In terms of safety, the increase in the serum potassium concentration and incidence of hyperkalemia was significantly higher for the finerenone groups [MD 0.17 (95% CI 0.10, 0.24), p < 0.00001; RR 2.03 (95% CI 1.83, 2.26), p < 0.00001, respectively], but the incidence of adverse events (AEs) was similar to placebo [RR 1.00 (95% CI 0.98-1.01), p = 0.67]. In all cases, the results were rated as providing moderate-quality or high-quality evidence. Conclusion: Data from our meta-analysis suggest that finerenone confers significant renal and cardiovascular benefits in patients with CKD. While higher risk of hyperkalemia was observed with finerenone than placebo, differences in AEs were not significant. Finerenone may therefore present a novel promising therapeutic agent for patients with CKD. Systematic Review Registration: [https://inplasy.com/inplasy-2021-9-0020/], identifier [INPLASY202190020].

A Novel Insight into the Role of PLA2R and THSD7A in Membranous Nephropathy.

Membranous nephropathy (MN) is an organ-restricted autoimmune disease mainly caused by circulating autoantibodies against podocyte antigens, including the M-type phospholipase A2 receptor (PLA2R) and thrombospondin domain-containing 7A (THSD7A). Antibodies against PLA2R are present in 70%-80% and against THSD7A in 2% of adult patients, which provides a paradigm shift in molecular diagnosis and management monitoring. Both antigens share some similar characteristics: they are expressed by podocytes and have wide tissue distributions; they are bound by autoantibodies only under nonreducing conditions, and the subtype of most autoantibodies is IgG4. However, the factors triggering autoantibody production as well as the association among air pollution, malignancy, and the pathogenesis of MN remain unclear. In this review, we discuss the similarity between the pathological mechanisms triggered by disparate antigens and their associated diseases. Furthermore, we demonstrated the possibility that PM2.5, malignancy, and gene expression specifically induce exposure of these antigens through conformational changes, molecular mimicry, or increased expression eliciting autoimmune responses. Thus, this review provides novel insights into the pathological mechanism of MN.

Controlled ovarian hyperstimulation for poor ovarian responders undergoing in vitro fertilisation/intracytoplasmic sperm injection: a protocol for systematic review and Bayesian network meta-analysis.

INTRODUCTION: Controlled ovarian hyperstimulation (COH) is the routine regimen used to generate a sufficient number of follicles during in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Poor ovarian response is a challenge encountered by many clinicians during COH and poor ovarian responders (PORs) usually have higher follicle stimulating hormone levels, lower levels of anti-Mullerian hormone and few oocytes retrieved, which have been attributed mainly to advanced maternal age and poor follicle reserve or other reasons that could impair ovarian response during ovarian stimulation. Over the last few decades, researchers have proposed a series of strategies and ovarian stimulation protocols to improve pregnancy outcomes in patients with POR during their IVF/ICSI treatment. However, clinical decisions regarding COH protocols in PORs during IVF/ICSI treatment remain controversial. Traditional pairwise meta-analysis only allows the direct comparison of two protocols in COH for patients with POR. However, many of these COH protocols have not been compared directly in randomised controlled trials (RCTs). Thus, we aim to use network meta-analysis (NMA) to assess the clinical effectiveness and safety of COH protocols and to generate treatment rankings of these COH protocols for the most clinically important and commonly reported outcomes events. METHODS AND ANALYSIS: The PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, WanFang database and Chongqing VIP information databases will be searched for all RCTs of COH for POR women during IVF/ICSI from inception to 31 March 2020. Primary outcomes will include live birth rate and number of oocytes retrieved. Secondary outcomes will include ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, ovarian hyperstimulation syndrome rate, multiple pregnancy rate and cycle cancellation rate. Pairwise meta-analysis and Bayesian NMA will be conducted for each outcome. Subgroup analysis, meta-regression, and sensitivity analysis will be performed to assess the robustness of the findings. The generation of NMA plots and subsequent results will be performed by using R V.4.0.1. The assessment of confidence in network estimates will use the Confidence in Network Meta-Analysis)web application (see https://cinema.ispm.unibe.ch/). ETHICS AND DISSEMINATION: This review does not require ethics approval and the results of the NMA will be submitted to a peer-review journal.

The efficacy and safety of roxadustat for anemia in patients with chronic kidney disease: a meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) is an increasing public health issue. Anemia, which is a complication of CKD, is associated with reduced quality of life and increased morbidity and mortality. Currently quite a few clinical studies have been conducted to compare roxadustat with epoetin alfa [all for dialysis-dependent (DD) patients] or placebo [all for nondialysis-dependent (NDD) patients]. Our meta-analysis aimed to investigate the efficacy and safety of roxadustat for anemia in patients with CKD. METHODS: We thoroughly searched eight electronic resource databases for randomized controlled trials (RCTs) comparing the efficacy and safety between roxadustat versus epoetin alfa or placebo for the treatment of anemia in patients with CKD. RESULTS: Four Phase 2 and two Phase 3 studies with 1010 participants were included. Hemoglobin (Hb) and transferrin levels were increased significantly in the roxadustat group versus those in the placebo {standard mean difference [SMD] 1.57 [95% confidence interval (CI) 1.17-1.98]; SMD 1.81 [95% CI 1.53-2.08]; respectively, both low-quality evidence} or epoetin alfa group [SMD 0.47 (95% CI 0.02-0.93), very low-quality evidence; SMD 1.05 (95% CI 0.81-1.29), low-quality evidence; respectively]. Hepcidin levels were reduced significantly in the roxadustat group versus those in the placebo [SMD -1.72 (95% CI -3.03 to -0.41), very low-quality evidence] or epoetin alfa group [SMD -0.23 (95% CI -0.43 to -0.02), low-quality evidence]. Ferritin and serum transferrin saturation (TSAT) levels were reduced significantly in the roxadustat group versus those in the placebo group [SMD -0.82 (95% CI -1.31 to -0.33); SMD -0.54 (95% CI -0.76 to -0.32), respectively; both low-quality evidence] and ferritin and TSAT levels in the roxadustat group were comparable to those in the epoetin alfa group [SMD 0.02 (95% CI -0.18-0.21); SMD 0.15 (95% CI -0.04-0.35), respectively, both low-quality evidence]. As for safety, the incidence of adverse events (AEs) in the roxadustat group was insignificantly different from that of the placebo group [risk ratio (RR) 0.99 (95% CI 0.83-1.18); P = 0.89, very low-quality evidence]. But the incidence of AEs in the roxadustat group was significantly higher than that in the epoetin alfa group [RR 1.25 (95% CI 1.01-1.54); P = 0.04, low-quality evidence]. There was no significant association between roxadustat and the incidence of serious AEs (SAEs) for both NDD and DD patients [RR 1.08 (95% CI 0.51-2.28) and RR 1.43 (95% CI 0.85-2.40), respectively, both very low-quality evidence]. CONCLUSION: In this meta-analysis of RCTs, we found evidence that after the oral administration of roxadustat, NDD patients' Hb levels were increased effectively and DD patients' Hb levels were maintained effectively. The risk of SAEs was not observed with the short-term use of roxadustat. These findings support roxadustat for the treatment of anemia in patients with CKD.

Efficacy and safety of HIF prolyl-hydroxylase inhibitor vs epoetin and darbepoetin for anemia in chronic kidney disease patients not undergoing dialysis: A network meta-analysis.

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of oral medicines being developed for the treatment of anemia in chronic kidney disease (CKD) patients. This study aimed to compare the efficacy and safety of HIF-PHI vs epoetin and darbepoetin in CKD patients with anemia not undergoing dialysis. The PubMed, Embase, Cochrane Library, Web of Science, and clinicaltrials.gov databases were searched from inception to October 2019 for randomized controlled trials investigating different agents (six HIF-PHIs, epoetin, darbepoetin, and placebo) for treating CKD patients with anemia that did not undergo dialysis. The outcomes included a change in hemoglobin (Hb) levels and all-cause mortality. A total of 19 studies were included. Compared with the placebo, except for vadadustat (mean differences: 1.12, 95 % confidence interval [CI]: ‒0.11-2.35), the other drugs significantly increased Hb levels, with mean differences of 2.46 (95 % CI: 0.93-3.99) for desidustat, 1.81 (0.87-2.75) for enarodustat, 1.68 (0.64-2.72) for molidustat, 1.66 (0.89-2.44) for epoetin, 1.63 (0.69-2.56) for darbepoetin, 1.61 (0.99-2.22) for roxadustat, and 1.55 (0.74-2.36) for daprodustat. No differences were found in the Hb level elevations among these eight drugs. Compared with the placebo, there also was no significant association between the drugs and all-cause mortality (molidustat of RR, 0.39 [95 % CI, 0.06-2.59]; roxadustat, 0.40 (0.06-2.84); enarodustat, 0.33 (0.01-16.25); desidustat, 0.34 (0.01-17.00); epoetin, 0.50 (0.18-1.42); daprodustat, 0.54 (0.09-3.31); darbepoetin, 1.03 (0.65-1.65); and vadadustat, 1.43 (0.15-13.27)). No differences were observed in the all-cause mortality among the drugs. In conclusion, these HIF-PHIs are effective and relatively tolerant for treating anemia patients with CKD not undergoing dialysis. Further research should consider the limitations of our study to evaluate the value of these HIF-PHIs in clinical settings.

Full-Spectrum Analysis of Perovskite-Based Surface Plasmon Nanolasers.

We systematically studied the characteristics of hybrid perovskite-based surface plasmon nanolasers. If one changes the anion composition of perovskites, the emission wavelength can be easily tuned. We conducted in full-spectrum modeling that featured hybrid perovskite nanowires placed on different SiO2-coated metallic (Au, Ag, and Al) plates. The proposed nanocavities that supported plasmonic gap modes exhibited distinguished properties of nanolasers, such as low-transparency threshold-gain and low lasing threshold. The corresponding experimental results for the MAPbBr3 nanolaser on Ag revealed the low-threshold operation. These superior features were attributed to enhanced light-matter interaction with strong coupling. Therefore, the proposed scheme, integrated with hybrid perovskite as gain material, provides an excellent platform for nanoscale plasmon lasing in the visible to near-infrared spectra.

Efficacy of Intermittent or Continuous Very Low-Energy Diets in Overweight and Obese Individuals with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analyses.

OBJECTIVE: This study is aimed at investigating the efficacy of a very low-energy diet (VLED) in overweight and obese individuals with type 2 diabetes mellitus (T2DM). METHODS: We thoroughly searched eight electronic resource databases of controlled studies concerning the efficacy and acceptability of intermittent or continuous VLEDs in patients with T2DM compared with other energy restriction interventions. RESULTS: Eighteen studies (11 randomized and seven nonrandomized controlled trials) with 911 participants were included. The meta-analyses showed that compared with a low-energy diet (LED) and mild energy restriction (MER), VLED is superior in the reduction of body weight (mean difference (MD) MDLED = -2.77, 95% confidence interval (CI) CILED = -4.81 to - 0.72, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, I 2 = 0%) and TG level (MD = -0.25, 95%CI = -0.55 to 0.06, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, I 2 = 0%) and TG level (MD = -0.25, 95%CI = -0.55 to 0.06, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39, P LED = 0.008; MDMER = -6.72, 95%CIMER = -10.05 to - 3.39. CONCLUSION: Dietary intervention through VLEDs is an effective therapy for rapid weight loss, glycemic control, and improved lipid metabolism in overweight and obese individuals with T2DM. Thus, VLEDs should be encouraged in overweight and obese individuals with T2DM who urgently need weight loss and are unsuitable or unwilling to undergo surgery. As all outcome indicators have low or extremely low quality after GRADE evaluation, further clinical trials that focus on the remission effect of VLEDs on T2DM are needed.

Efficacy and Safety of Daprodustat for Anemia Therapy in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis.

Objective: Daprodustat is a novel oral agent in treating anemia of chronic kidney disease (CKD), and several clinical trials have been conducted to compare daprodustat with recombinant human erythropoietin (rhEPO) or placebo. Our systematic review aimed to investigate the efficacy and safety of daprodustat for anemia treatment in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients. Methods: Six databases were searched for randomized controlled trials (RCTs) reporting daprodustat vs. rhEPO or placebo for anemia patients in CKD. The outcome indicators were focused on hemoglobin (Hb), ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), vascular endothelial growth factor (VEGF), and serious adverse events (SAEs). Results: Eight eligible studies with 1,516 participants were included. For both NDD and DD patients, changes in Hb levels from baseline were significantly higher in daprodustat group than that in the placebo (mean difference (MD) = 1.73, [95% confidence interval (CI), 0.34 to 3.12], p = 0.01; MD = 1.88, [95% CI, 0.68 to 3.09], p = 0.002; respectively), and there was no significant difference between daprodustat and rhEPO group (MD = 0.05, [95% CI, -0.49 to 0.59], p = 0.86; MD = 0.12, [95% CI, -0.28 to 0.52], p = 0.55; respectively). The indexes of iron metabolism were improved significantly in the daprodustat group compared to placebo- or rhEPO-treated patients, while there was no similar change in terms of TSAT for DD patients. Furthermore, no trend of increasing plasma VEGF was observed in daprodustat-treated subjects. As for safety, there was no significant difference in the incidence of SAEs between daprodustat and placebo treatment, while the incidence of SAEs in the daprodustat group was significantly lower than that in the rhEPO group. Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs. And daprodustat may become an effective alternative for treatment of anemia with CKD. Since the application of daprodustat is still under exploration, future researches should consider the limitations of our study to evaluate the value of daprodustat.

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

OBJECTIVES: This study aimed to compare the effectiveness of 13 types of immunosuppressive agents used to treat idiopathic membranous nephropathy (IMN) in adults with nephrotic syndrome. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: PubMed, 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 CRITERIA: Randomised 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 SYNTHESIS: Two reviewers independently screened articles, extracted data and assessed study quality. Standard pairwise meta-analysis was performed using DerSimonian-Laird random-effects model. RESULTS: This 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. CONCLUSIONS: This 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 NUMBER: CRD42018094228.

[Meta-analysis of Yiqi Huoxue method in treating idiopathic membranous nephropathy].

The incidence of idiopathic membranous nephropathy (IMN) is increasing year by year, and the clinical research on Chinese medicine treatment of INM is also growing. This study aims to evaluate the efficiency and safety of Yiqi Huoxue method for IMN. Data sources used were from PubMed, EMbase, the Cochrane Library, CBM, CNKI, Wanfang and VIP database. Two researchers independently screened the literature and extracted data. RevMan 5.3 software was used for Meta analysis, and the evidences were graded for the outcomes according to GRADE system by using GRADEprofiler 3.6. Eventually, eleven trials (725 participants) were included in the Meta-analyses. There was statistically significant difference between Yiqi Huoxue method and controls when combining all trials in 24 h UTP [RR=-1.23, 95%CI=(-1.94,-0.53), P=0.000 6] or when combining all trials in ALB [RR=3.56, 95%CI=(1.64, 5.47), P=0.000 3]. Meanwhile, there was statistically significant difference between Yiqi Huoxue method and controls when combining all trials in TC [RR=-0.39, 95%CI=(-0.57, -0.20), P<0.000 1] or when combining all trials in TG [RR=-0.49, 95%CI=(-0.82, -0.15), P=0.004]. However, there was no statistically significant difference between Yiqi Huoxue method and controls when combining all trials in Scr [RR=-3.25, 95%CI=(-9.35, 2.84), P=0.30] or when combining all trials in BUN [RR=-0.81,95%CI=(-2.29, 0.66), P=0.28]. In the statistics, the most frequently used Chinese medicines in clinical application were Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma, Codonopsis Radix, Atractylodis Macrocephalae Rhizome and Salvia Miltiorrhiza. The present evidences suggested that Yiqi Huoxue method should be thought highly of in the treatment of IMN, and at the same time, the rational use of traditional Chinese medicine, such as Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma also should be paid attention to. However, due to the GRADE evidence grading of the primary outcome measure of 24 h UTP had very low quality, this review can not provide high-quality evidence to prove the clinical efficacy of this method. More well-designed and large-scale multi-center randomized controlled trials should be conducted in the future for verification.