Efficacy of Combined Abelmoschus manihot and Irbesartan for Reduction of Albuminuria in Patients With Type 2 Diabetes and Diabetic Kidney Disease: A Multicenter Randomized Double-Blind Parallel Controlled Clinical Trial.
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SUBMITTER: Zhao J
PROVIDER: S-EPMC9274216 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
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Efficacy of Combined Abelmoschus manihot and Irbesartan for Reduction of Albuminuria in Patients With Type 2 Diabetes and Diabetic Kidney Disease: A Multicenter Randomized Double-Blind Parallel Controlled Clinical Trial.
Zhao Jing J Tostivint Isabelle I Xu Lingdong L Huang Jihan J Gambotti Laetitia L Boffa Jean-Jacques JJ Yang Min M Wang Ling L Sun Zhuxing Z Chen Xiaolan X Liou-Schischmanoff Amélie A Baumelou Alain A Ma Teng T Lu Guoyuan G Li Ling L Chen Dai D Piéroni Laurence L Liu Bingkai B Qin Xiao X He Weiming W Wang Yuejuan Y Gu Harvest F HF Sun Wei W
Diabetes care 20220701 7
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Project description:Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). Many trials have shown that Abelmoschus manihot could further improve proteinuria and protect kidney function in patients with DN when added to a renin-angiotensin system (RAS) blocker. A systematic assessment of the efficacy and safety of A. manihot in DN is essential. Eight electronic databases were searched to identify eligible trials published from inception to December 2017. The Cochrane Risk of Bias Tool was used to evaluate the methodological quality of eligible studies. Seventy-two studies with 5,895 participants were identified. The methodological quality of included studies was generally low. The results indicated that, compared to a RAS blocker, combined treatment of A. manihot with a RAS blocker was more effective for 24h urinary protein (24h UP) (mean difference [MD], -0.39 [95% confidence interval [CI], -0.46 to -0.33] g/d; P<0.00001), urinary albumin excretion rate (UAER)(MD, -19.90 [95% CI, -22.62 to -17.18] μg/min; P<0.00001), 24h UP reduction rate (risk ratio [RR], 1.43; 95% CI, 1.26-1.63; P<0.00001), normalization of UAER (RR, 1.48; 95% CI, 1.29-1.70; P<0.00001), and serum creatinine (SCr) (MD, -7.35 [95% CI, -9.95 to -4.76] umol/L; P<0.00001). None of these trials reported the ESRD rate. No statistically significant difference occurred between A. manihot combined with a RAS blocker and a RAS blocker alone in estimated glomerular filtration rate (eGFR) (MD, 4.43 [95% CI, -1.68 to 10.54] mL/min; P=0.16). A. manihot did not increase the rates of adverse drug events. A. manihot in addition to a RAS blocker was effective and safe to further improve proteinuria and protect kidney function in patients with DN. However, due to the generally low methodological quality, significant heterogeneity, and publication bias, high-quality randomized controlled trials are required to confirm these findings before the routine use of A. manihot can be recommended.
| S-EPMC6500631 | biostudies-literature
Project description:BackgroundClinical observations have recently shown that Abelmoschus manihot (L.) in the form of Huangkui capsule (HKC) and in combination with irbesartan (EB) is an effective therapy for diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). The present study aims to explore the mechanisms underlying the therapeutic efficacies of HKC and its combination with EB in DN via the gut-kidney axis.MethodsHKC, EB, and their combination or vehicle were administered in db/db mice, which is an animal model for the study of T2D and DN. Comparative analyses of the gut microbiota, serum metabolites, and kidney transcriptomics before and after drug administration were performed.ResultsAfter treatment with HKC, EB, and their combination for 4 weeks, the urinary albumin-to-creatinine ratios decreased significantly in the db/db mice with DN. In terms of the gut microbiota, the abundances of Faecalitalea, Blautia, and Streptococcus increased but those of Bacteroidetes, Firmicutes, Enterobacteriaceae, and Desulfovibrio decreased. Parallelly, serum metabolites, mainly including quercetin 3'-glucuronide and L-dopa, were elevated while cortisol and cytochalasin B were reduced. Furthermore, the S100a8, S100a9, Trem1, and Mmp7 genes in the kidneys were downregulated. These altered elements were associated with proteinuria/albuminuria reduction. However, EB had no effects on the changes in blood pressure and specific differentially expressed genes in the kidneys.ConclusionThe present study provides experimental evidence that HKC regulates the gut microbiota, circulating metabolites, and renal gene activities, which are useful for better understanding of the action mechanisms of A. manihot in the treatment of DN through the gut-kidney axis.
| S-EPMC11550981 | biostudies-literature
Project description:ObjectiveTo determine whether the use of herbal medicines combined with conventional treatment is more effective than conventional medication alone in improving clinical symptoms in patients with diabetic distal symmetric polyneuropathy (DSPN).MethodsThis multicenter, placebo-controlled, double-blind, randomized controlled clinical trial recruited patients from 6 clinical centers in mainland China. A total of 188 patients were randomly assigned in a 1:1 ratio to the treatment group (Tangbi Formula plus methylcobalamin) and the control group (placebo plus methylcobalamin). Subjects were reassessed after the 24-week intervention. The primary outcomes were differences in changes in clinical signs and symptoms and changes in the Michigan Diabetic Neuropathy Score (MDNS) between the two groups before and after treatment. Secondary outcomes were changes in nerve conduction velocity (NCV) and single clinical signs and symptoms as measured by the visual-analogue scale (VAS) and Toronto clinical scoring system (TCSS).ResultsCompared with the placebo group, after 24 weeks of treatment, the MDNS score of TangBi Formula group was significantly reduced (p < 0.001). There were no significant changes in NCV results in either group before or after treatment. Compared with baseline, the difference in the change value of VAS score between the two groups after treatment was statistically significant (p = 0.031). A statistically significant difference in the change value of TCSS after treatment compared to baseline was found between the two groups (p = 0.033 at 12 weeks and p = 0.030 at 24 weeks). No severe adverse events due to study participation or study intervention were reported.Conclusions and relevanceThis trial demonstrated that combining Tangbi Formula with basal therapy can be safer and more effective in improving the symptoms of DSPN patients.
| S-EPMC11702395 | biostudies-literature
Project description:Abelmoschus manihot Genome sequencing and assembly
| PRJNA926783 | ENA
Project description:BackgroundIrbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome.MethodsWe did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6-40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794.FindingsBetween March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12-28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of -0·22 mm per year (-0·41 to -0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means -0·10 per year, 95% CI -0·19 to -0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events.InterpretationIrbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications.FundingBritish Heart Foundation, the UK Marfan Trust, the UK Marfan Association.
| S-EPMC6934233 | biostudies-literature
Project description:Prior research has shown that in experimental diabetes mellitus, green tea reduces albuminuria by decreasing podocyte apoptosis through activation of the WNT pathway. We investigated the effect of green tea polyphenols (GTP) on residual albuminuria of diabetic subjects with nephropathy. We conducted a randomised, double-blind study in 42 diabetic subjects with a urinary albumin-creatinine ratio (UACR) >30 mg/g, despite administration of the maximum recommended dose of renin-angiotensin (RAS) inhibition. Patients were randomly assigned to two equal groups to receive either GTP (containing 800 mg of epigallocatechin gallate, 17 with type 2 diabetes and 4 with type 1 diabetes) or placebo (21 with type 2 diabetes) for 12 weeks. Treatment with GTP reduced UACR by 41%, while the placebo group saw a 2% increase in UACR (p = 0.019). Podocyte apoptosis (p = 0.001) and in vitro albumin permeability (p < 0.001) were higher in immortalized human podocytes exposed to plasma from diabetic subjects compared to podocytes treated with plasma from normal individuals. In conclusion, GTP administration reduces albuminuria in diabetic patients receiving the maximum recommended dose of RAS. Reduction in podocyte apoptosis by activation of the WNT pathway may have contributed to this effect.
| S-EPMC4913255 | biostudies-literature
Project description:Huangkui capsule (HKC), a traditional Chinese medicine, has been used for medication of kidney diseases, including diabetic nephropathy (DN). The current study aimed to evaluate the effects of HKC in the modulation of gut microbiota and the amelioration of metabolite levels by using non-obese diabetes (NOD) mice with DN. The microbiota from three parts of intestines (duodenum, ileum and colon) in NOD mice with and without HKC treatment were analysed using 16S rDNA sequencing techniques. Untargeted metabolomics in plasma of NOD mice were analysed with liquid mass spectrometry. Results showed that HKC administration ameliorated DN in NOD mice and the flora in duodenum were more sensitive to HKC intervention, while the flora in colon had more effects on metabolism. The bacterial genera such as Faecalitalea and Muribaculum significantly increased and negatively correlated with most of the altered metabolites after HKC treatment, while Phyllobacterium, Weissella and Akkermansia showed an opposite trend. The plasma metabolites, mainly including amino acids and fatty acids such as methionine sulfoxide, BCAAs and cis-7-Hexadecenoic acid, exhibited a distinct return to normal after HKC treatment. The current study thereby provides experimental evidence suggesting that HKC may modulate gut microbiota and subsequently ameliorate the metabolite levels in DN.
| S-EPMC10034626 | biostudies-literature
Project description:BackgroundCardiovascular complications are the leading cause of mortality and morbidity in Marfan syndrome (MFS), a dominantly inherited disorder caused by mutations in the gene that encodes fibrillin-1. There are approximately 18,000 patients in the UK with MFS. Current treatment includes careful follow-up, beta blockers, and prophylactic surgical intervention; however, there is no known treatment which effectively prevents the rate of aortic dilatation in MFS. Preclinical, neonatal, and pediatric studies have indicated that angiotensin receptor blockers (ARBs) may reduce the rate of aortic dilatation. This trial will investigate the effects of irbesartan on aortic dilatation in Marfan syndrome.Methods/designThe Aortic Irbesartan Marfan Study (AIMS) is an investigator-led, prospective, randomized, placebo-controlled, double-blind, phase III, multicenter trial. Currently, 26 centers in the UK will recruit 490 clinically confirmed MFS patients (aged ≥6 to ≤40 years) using the revised Ghent diagnostic criteria. Patients will be randomized to irbesartan or placebo. Aortic root dilatation will be measured by transthoracic echocardiography at baseline and annually thereafter. The primary outcome is the absolute change in aortic root diameter per year measured by echocardiography. The follow-up period will be a minimum of 36 months with an expected mean follow-up period of 48 months.DiscussionThis is the first clinical trial to evaluate the ARB irbesartan versus placebo in reducing the rate of aortic root dilatation in MFS. Not only will this provide useful information on the safety and efficacy of ARBs in MFS, it will also provide a rationale basis for potentially lifesaving therapy for MFS patients.Trial registrationISRCTN, 90011794.
| S-EPMC4220813 | biostudies-literature
Project description:Background: Diabetic kidney disease (DKD) is one of the most serious microvascular complications of diabetes, with the incidence rate increasing yearly, which is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease. Abelmoschus Manihot capsule, as a proprietary Chinese patent medicine, is widely used for treating CKD in China. Currently, the combination of Abelmoschus Manihot (AM) capsule and renin-angiotensin-aldosterone system inhibitor (RASI) has gained popularity as a treatment option for DKD, with more and more randomized control trials (RCTs) in progress. However, the high-quality clinical evidence supporting its application in DKD is still insufficient. Aim of the study: To comprehensively and systematically evaluate the efficacy and safety of AM capsule combined with RASI in the treatment of DKD. Materials and methods: English and Chinese databases such as Pubmed, Cochrane Library, Embase, CNKI, SinoMed, WF, and VIP were searched to collect the RCTs of AM capsule in treatment of DKD. Then Two investigators independently reviewed and extracted data from the RCTs which met the inclusion criteria. The quality of the data was assessed using the Cochrane risk of bias assessment tool, and meta-analysis was performed using RevMan 5.4 software. Results: 32 RCTs with a total of 2,881 DKD patients (1,442 in the treatment group and 1,439 in the control group) were included. The study results showed that AM capsule combined with RASI could be more effective in decreasing 24h-UTP [MD = -442.05, 95% CI (-609.72, -274.38), p < 0.00001], UAER [MD = -30.53, 95% CI (-39.10, -21.96), p < 0.00001], UACR [MD = -157.93, 95% CI (-288.60, -27.25), p < 0.00001], Scr [MD = -6.80, 95% CI (-9.85, -3.74), p < 0.0001], and BUN [MD = -0.59, 95% CI (-1.07, -0.12), p = 0.01], compared to using RASI alone. According to the subgroup analyses, the combination of AM and ARB seems to be more effective in reducing UAER than the combination of ACEI, and the addition of AM may achieve a more significant clinical effect on decreasing Scr for DKD patients with 24h-UTP>2 g or Scr>110-133 μmol/L and >133 μmol/L. Furthermore, no additional adverse reactions were observed in the combination group [OR = 1.06; 95%CI: (0.66, 1.69), p = 0.82]. Conclusion: Combining AM with RASI may be a superior strategy for DKD treatment compared to RASI monotherapy. However, due to significant heterogeneity, the results should be interpreted with great caution, and more high-quality RCTs with multi-centers, different stages of DKD, large sample sizes, and long follow-up periods are still needed to improve the evidence quality of AM for DKD in the future. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails; Identifier CRD42022351422.
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