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Frontiers in Pharmacology 2020Astragaloside IV (AS-IV) has a variety of biological activities and is widely used to treat kidney diseases. We conducted a systematic review of 24 animal studies...
Astragaloside IV (AS-IV) has a variety of biological activities and is widely used to treat kidney diseases. We conducted a systematic review of 24 animal studies including 424 animals to evaluate the efficacy of AS-IV for diabetic nephropathy (DN); all current possible mechanisms were summarized. A search strategy was applied to eight databases from inception to June 2020. The CAMARADES 10-item quality checklist and Rev-Man 5.3 software were used to analyze the risks of bias of each study and data regarding outcome measures, respectively. The mean study quality score was 5.4 points (range 3-8 points). Meta-analyses data and comparisons between groups showed that AS-IV significantly slowed the progression of pathological signs in the kidney including glomeruli and tubules, increasing creatinine clearance rate, decreasing blood urea nitrogen, serum creatinine, 24-h urinary neutrophil gelatinase-associated lipocalin and N-acetyl--D-glucosaminidase, 24-h urinary albumin, 24-h urinary microalbumin and HbA1c. There were no significant differences between experimental and control groups with respect to mortality or levels of alanine aminotransferase and aspartate aminotransferase. In terms of the possible mechanisms of treatment of DN, AS-IV acts through antifibrotic, antioxidant, and antiapoptotic mechanisms, thereby alleviating endoplasmic reticulum stress, inhibiting mitochondrial fission, and increasing autophagic activity. Taken together, our findings suggest that AS-IV is a multifaceted renoprotective candidate drug for DN.
PubMed: 32695006
DOI: 10.3389/fphar.2020.00988 -
Therapeutic Apheresis and Dialysis :... Aug 2022Medium cut-off (MCO) dialyzers were designed to provide better clearance of uremic toxins. We conducted a meta-analysis comparing MCO with high-flux (HF) dialyzers for... (Meta-Analysis)
Meta-Analysis
Medium cut-off (MCO) dialyzers were designed to provide better clearance of uremic toxins. We conducted a meta-analysis comparing MCO with high-flux (HF) dialyzers for the effect on uremic toxins in maintenance hemodialysis (HD) patients. Five databases were systematically searched for relevant studies and nine studies were identified finally. Reduction ratio (RR) of urea, urea, creatinine, β2-macroglobulin (β2-MG), kappa free light chain (κFLC), and lambda FLC (λFLC) levels were not significantly different between MCO and HF dialyzers. But RR of β2-MG, κFLC, and λFLC were greater for MCO than HF dialyzers. MCO dialyzers could better reduce tumor necrosis factor-α (TNF-α) levels. Subgroup analysis stratified by study design indicated that in randomized controlled trial (RCT) studies, albumin levels was lower in MCO than HF dialyzers group, but the two dialyzers treatments were equivalent in non-RCT subgroup. Compared with HF dialyzers, MCO dialyzers provided higher middle-molecules uremic toxins clearance and obviously reduced TNF-α levels.
Topics: Creatinine; Hemodiafiltration; Humans; Immunoglobulin Light Chains; Membranes, Artificial; Renal Dialysis; Tumor Necrosis Factor-alpha; Urea
PubMed: 34773675
DOI: 10.1111/1744-9987.13755 -
Frontiers in Pharmacology 2022To evaluate and compare the efficacy, safety, and cost of nine Chinese patent medicines (CPMs) combined with angiotensin-converting enzyme inhibitor (ACEI) or...
To evaluate and compare the efficacy, safety, and cost of nine Chinese patent medicines (CPMs) combined with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in treating early diabetic kidney disease (DKD). Systematic review and network meta-analysis. PubMed, Embase, Cochrane Library, Web of Science, clinicaltrials.gov, SinoMed, Chinese Biomedicine, China National Knowledge Infrastructure, WanFang, and Chongqing VIP Information databases were comprehensively searched from the beginning to February 2022. Randomized controlled trials (RCTs) including Bailing capsule (BLC); Jinshuibao capsule (JSB); Huangkui capsule (HKC); Compound Xueshuantong capsule (CXC); uremic clearance granule (UCG); Shenyan Kangfu tablet (SYKFT); tripterygium glycosides (TG); Keluoxin capsule (KLX), and Shenshuaining tablet (SSNT) combined with ACEI/ARB for patients with early DKD were reviewed. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. Risk ratios (RRs) and mean difference (MD) were reckoned to assess dichotomous variable quantities and continuous variable quantities, respectively. Using the surface under the cumulative ranking curve (SUCRA), we then ranked each therapeutic regime. Ultimately, 160 RCTs involving 13,365 patients and nine CPMs were included. UCG showed significantly higher probabilities on urinary albumin excretion rate (UAER) when compared with ACEI/ARB group, with MD of -47 (95%CI) (-57, -37) and SUCRA 98.0%. The CXC group achieved a remarkable improvement in overall response rate (ORR) compared with ACEI/ARB (RR, 1.3, 95%CI (1.2, 1.5)) with SUCRA 91.9%. SSNT could be significantly superior to ACEI/ARB group in terms of serum creatinine (Scr) (-19 (-26, -12), SUCRA 99.3%) and adverse effects (AEs) (0.46 (0.17, 1.1), SUCRA 82.9%). BLC showed the greatest effectiveness on 24 h urinary total protein (24 h UTP) (-170 (-260, -83), SUCRA 78.5%) and triglyceride (Trig) (-0.89 (-1.2, -0.53), SUCRA 97.0%). From the cost-effectiveness analysis of CPMs in China, the cost of TG, SYKFT and CXC was 108, 600, and 648 RMB, respectively, per 3 months and were ranked in the top three. UCG and CXC might be the optimum selection for improving UAER and ORR, and SSNT could be significantly superior to ACEI/ARB group in terms of Scr and AEs. BLC shows the best curative effect on 24 h UTP and Trig. TG shows the highest cost-effectiveness among the nine CPMs.
PubMed: 36071841
DOI: 10.3389/fphar.2022.939488 -
Frontiers in Endocrinology 2024To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN).
METHODS
We conducted an umbrella review of existing meta-analyses of randomized controlled trials (RCTs) that focused on the effects of dietary intervention on DN incidence. The literature was searched via PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. According to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE), evidence of each outcome was evaluated and graded as "high", "moderate", "low" or "very low" quality to draw conclusions. Additionally, we classified evidence of outcomes into 4 categories.
RESULTS
We identified 36 meta-analyses of RCTs and 55 clinical outcomes of DN from 395 unique articles. Moderate-quality evidence suggested that probiotic supplementation could significantly improve blood urea nitrogen (BUN), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in DN patients. Low-quality evidence indicated that probiotic supplementation significantly improved the serum creatinine concentration, urinary albumin-creatinine ratio (UACR), fasting blood glucose (FBG), HbA1c and high-density lipoprotein cholesterol (HDL-C) in DN patients. In addition, low-quality evidence suggested that a salt restriction diet could significantly improve the creatinine clearance rate (CrCl) in patients with DN. Low-quality evidence suggested that vitamin D supplementation could significantly improve the UACR in patients with DN. In addition, low-quality evidence has indicated that soy isoflavone supplementation could significantly improve BUN, FBG, total cholesterol (TC), triglyceride (TG) and LDL-C levels in patients with DN. Furthermore, low-quality evidence suggested that coenzyme Q10 supplementation could significantly improve HbA1c, TC and HDL-C in patients with DN, and dietary polyphenols also significantly improved HbA1c in patients with DN. Finally, low-quality evidence suggested that supplementation with antioxidant vitamins could significantly improve the serum creatinine concentration, systolic blood pressure, and HbA1c level in patients with DN. Given the small sample size, all significantly associated outcomes were evaluated as class IV evidence.
CONCLUSION
Moderate to low amounts of evidence suggest that supplementation with probiotics, vitamin D, soy isoflavones, coenzyme Q10, dietary polyphenols, antioxidant vitamins, or salt-restricted diets may significantly improve clinical outcomes in patients with DN.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024512670.
Topics: Humans; Diabetic Nephropathies; Dietary Supplements; Meta-Analysis as Topic; Probiotics; Randomized Controlled Trials as Topic; Systematic Reviews as Topic
PubMed: 38742202
DOI: 10.3389/fendo.2024.1385872 -
Systematic Reviews May 2015It is known that risk of chronic kidney disease (CKD) is elevated in patients with diabetes mellitus but it is not clear whether the risk is also elevated with impaired... (Review)
Review
BACKGROUND
It is known that risk of chronic kidney disease (CKD) is elevated in patients with diabetes mellitus but it is not clear whether the risk is also elevated with impaired glucose tolerance (IGT). If the risk is increased, it is not known if this is confined to people with IGT who progress to type 2 diabetes (T2DM). The purpose of this systematic review is to determine the relative risk of CKD in young adults (aged 18 to 40 years) with IGT (exposed group) compared to those without glycaemic abnormality (comparator group).
METHODS/DESIGN
The following electronic databases will be systematically searched from inception to January 2015 for relevant studies: CINAHL, EMBASE, MEDLINE, PubMed, Cochrane libraries and grey literature. Two independent reviewers will screen search results, extract data, select studies for inclusion and assess their quality. Studies including young adults (aged 18 to 40 years) with IGT containing any of the following CKD markers will be included: estimated glomerular filtration rate (eGFR), albumin creatinine ratio (ACR), protein creatinine ratio (PCR), serum creatinine (SCr) and creatinine clearance (CrCl) levels. Studies at any time period after diagnosis of IGT and with any length of follow-up will be included. The proportion of IGT participants reporting each outcome will be documented. Relative risks (RR) and odds ratios (OR) will be extracted or calculated from raw data. If possible, study results will be combined in a meta-analysis.
DISCUSSION
The results of this comprehensive review will establish the evidence for the association between IGT and the risk of developing CKD in young adults (aged 18 to 40 years).
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42014007081.
Topics: Adolescent; Adult; Comorbidity; Glucose Intolerance; Humans; Incidence; Renal Insufficiency, Chronic; Young Adult
PubMed: 25968063
DOI: 10.1186/s13643-015-0059-6 -
Frontiers in Immunology 2022A number of population pharmacokinetic (PPK) models of anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) in multiple tumor types have been published to...
AIMS AND BACKGROUND
A number of population pharmacokinetic (PPK) models of anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) in multiple tumor types have been published to characterize the influencing factors of their pharmacokinetics. This review described PPK models of anti-PD-1 mAbs that investigate the magnitude and types of covariate effects in PK parameters, provide a reference for building PPK models of other anti-PD-1 mAbs, and identify areas requiring additional research to facilitate the application of PPK models.
METHODS
A systematic search for analyses of PPK models of eleven anti-PD-1 mAbs on the market that were carried out in humans was conducted using PubMed, Embase, and the Cochrane Library. The search covered the period from the inception of the databases to April 2022.
RESULTS
Currently, there are fourteen analyses on PPK models of anti-PD-1 mAbs summarized in this review, including seven models that refer to nivolumab, four referring to pembrolizumab, one referring to cemiplimab, one referring to camrelizumab, and one referred to dostarlimab. Most analyses described the pharmacokinetics of anti-PD-1 mAbs with a two-compartment model with time-varying clearance (CL) and a sigmoidal maximum effect. The estimated CL and volume of distribution in the central (V) ranged from 0.179 to 0.290 L/day and 2.98 to 4.46 L, respectively. The median (range) of interindividual variability (IIV) for CL and V was 30.9% (8.7%-50.8%) and 29.0% (4.32%-40.7%), respectively. The commonly identified significant covariates were body weight (BW) on CL and V, and albumin (ALB), tumor type, sex, and performance status (PS) on CL. Other less assessed significant covariates included lactate dehydrogenase (LDH), immunoglobulin G (IgG), ipilimumab coadministration (IPICO) on CL, and body mass index (BMI), malignant pleural mesothelioma (MESO) on V.
CONCLUSION
This review provides detailed information about the characteristics of PPK models of anti-PD-1 mAbs, the effects of covariates on PK parameters, and the current status of the application of the models. ALB, BW, specific tumor type, sex, and PS should be considered for the future development of the PPK model of anti-PD-1 mAbs. Other potential covariates that were assessed less frequently but still have significance (e.g., LDH, IgG, and IPICO) should not be ignored. Thus, further research and thorough investigation are needed to assess new or potential covariates, which will pave the way for personalized anti-PD-1 mAbs therapy.
Topics: Antibodies, Monoclonal, Humanized; Body Weight; Humans; Immunoglobulin G; Ipilimumab; Neoplasms; Nivolumab
PubMed: 35983041
DOI: 10.3389/fimmu.2022.871372 -
BMC Anesthesiology Mar 2024Animal experiments have confirmed that remote ischemic preconditioning (RIPC) can reduce hepatic ischemia-reperfusion injuries (HIRIs), significantly improving early... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Animal experiments have confirmed that remote ischemic preconditioning (RIPC) can reduce hepatic ischemia-reperfusion injuries (HIRIs), significantly improving early tissue perfusion and oxygenation of the residual liver after resections, accelerating surgical prognoses, and improving survival rates. However, there is still controversy over the role of RIPC in relieving HIRI in clinical studies, which warrants clarification. This study aimed to evaluate the beneficial effects and applicability of RIPC in hepatectomy and to provide evidence-based information for clinical decision-making.
METHODS
Randomized controlled trials (RCTs) evaluating the efficacy and safety of RIPC interventions were collected, comparing RIPC to no preconditioning in patients undergoing hepatectomies. This search spanned from database inception to January 2024. Data were extracted independently by two researchers according to the PRISMA guidelines. The primary outcomes assessed were postoperative alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) levels. The secondary outcomes assessed included duration of surgery and Pringle, length of postoperative hospital stay, intraoperative blood loss and transfusion, indocyanine green (ICG) clearance, hepatocyte apoptosis index, postoperative complications, and others.
RESULTS
Ten RCTs were included in this meta-analysis, with a total of 865 patients (428 in the RIPC group and 437 in the control group). ALT levels in the RIPC group were lower than those in the control group on postoperative day (POD) 1 (WMD = - 59.24, 95% CI: - 115.04 to - 3.45; P = 0.04) and POD 3 (WMD = - 27.47, 95% CI: - 52.26 to - 2.68; P = 0.03). However, heterogeneities were significant (I = 89% and I = 78%), and ALT levels on POD 3 were unstable based on a sensitivity analysis. AST levels on POD 1 in the RIPC group were lower than those in the control group (WMD = - 50.03, 95% CI: - 94.35 to - 5.71; P = 0.03), but heterogeneity was also significant (I = 81%). A subgroup analysis showed no significant differences in ALT and AST levels on POD 1 between groups, regardless of whether the Pringle maneuver or propofol was used for anesthesia (induction only or induction and maintenance, P > 0.05). The remaining outcome indicators were not statistically significant or could not be analyzed due to lack of sufficient data.
CONCLUSION
RIPC has some short-term liver protective effects on HIRIs during hepatectomies. However, there is still insufficient evidence to encourage its routine use to improve clinical outcomes.
TRIAL REGISTRATION
The protocol of this study was registered with PROSPERO (CRD42022333383).
Topics: Animals; Humans; Hepatectomy; Ischemic Preconditioning; Liver; Reperfusion Injury; Postoperative Complications; Alanine Transaminase
PubMed: 38532332
DOI: 10.1186/s12871-024-02506-9 -
Renal Failure Dec 2021Studies have shown that the use of statins could significantly improve lipid profiles; however, it remains controversial whether the use of statins could improve renal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies have shown that the use of statins could significantly improve lipid profiles; however, it remains controversial whether the use of statins could improve renal function in patients with chronic kidney disease (CKD). Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of statins on renal function in patients with CKD.
METHODS
We systematically searched PubMed, EMBASE, and the Cochrane Library databases for eligible RCTs from inception to October 2020. Pooled effect estimates were assigned as weighted mean differences (WMDs) with 95% confidence intervals (CIs) using the random-effects model.
RESULTS
We selected 33 RCTs that recruited 37,391 patients with CKD patients. The summary results suggested that statin use significantly reduced urinary albumin (WMD: -2.04; 95%CI: -3.53 to -0.56; = .007) and protein (WMD: -0.58; 95%CI: -0.95 to -0.21; = .002) excretions and increased creatinine clearance (WMD: 0.86; 95%CI: 0.32-1.41; = .002). However, there were no significant differences between statin and control groups in terms of changes in estimated glomerular filtration rate (WMD: 0.38; 95%CI: -0.04 to 0.79; = .075), and serum creatinine levels (WMD: -0.07; 95%CI: -0.25, 0.12; = .475).
CONCLUSIONS
We found that statin use in patients with CKD may slow CKD progression by lowering urinary albumin and protein excretions or increasing creatinine clearance. Further large-scale RCTs should be conducted to evaluate the long-term effects of statins on renal outcomes. CKD: chronic kidney disease; RCT: randomized controlled trials; WMD: weighted mean differences; CI: confidence intervals; ACEI: angiotensin-converting enzyme inhibitors; eGFR: estimated glomerular filtration rate.
Topics: Disease Progression; Glomerular Filtration Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic
PubMed: 33926359
DOI: 10.1080/0886022X.2021.1915799 -
Frontiers in Immunology 2024Liver failure represents a critical medical condition with a traditionally grim prognosis, where treatment options have been notably limited. Historically, liver...
Liver failure represents a critical medical condition with a traditionally grim prognosis, where treatment options have been notably limited. Historically, liver transplantation has stood as the sole definitive cure, yet the stark disparity between the limited availability of liver donations and the high demand for such organs has significantly hampered its feasibility. This discrepancy has necessitated the exploration of hepatocyte transplantation as a temporary, supportive intervention. In light of this, our review delves into the burgeoning field of hepatocyte transplantation, with a focus on the latest advancements in maintaining hepatocyte function, co-microencapsulation techniques, xenogeneic hepatocyte transplantation, and the selection of materials for microencapsulation. Our examination of hepatocyte microencapsulation research highlights that, to date, most studies have been conducted or using liver failure mouse models, with a notable paucity of experiments on larger mammals. The functionality of microencapsulated hepatocytes is primarily inferred through indirect measures such as urea and albumin production and the rate of ammonia clearance. Furthermore, research on the mechanisms underlying hepatocyte co-microencapsulation remains limited, and the practicality of xenogeneic hepatocyte transplantation requires further validation. The potential of hepatocyte microencapsulation extends beyond the current scope of application, suggesting a promising horizon for liver failure treatment modalities. Innovations in encapsulation materials and techniques aim to enhance cell viability and function, indicating a need for comprehensive studies that bridge the gap between small-scale laboratory success and clinical applicability. Moreover, the integration of bioengineering and regenerative medicine offers novel pathways to refine hepatocyte transplantation, potentially overcoming the challenges of immune rejection and ensuring the long-term functionality of transplanted cells. In conclusion, while hepatocyte microencapsulation and transplantation herald a new era in liver failure therapy, significant strides must be made to translate these experimental approaches into viable clinical solutions. Future research should aim to expand the experimental models to include larger mammals, thereby providing a clearer understanding of the clinical potential of these therapies. Additionally, a deeper exploration into the mechanisms of cell survival and function within microcapsules, alongside the development of innovative encapsulation materials, will be critical in advancing the field and offering new hope to patients with liver failure.
Topics: Animals; Humans; Cell Encapsulation; Cell Survival; Hepatocytes; Liver Failure; Transplantation, Heterologous
PubMed: 38694507
DOI: 10.3389/fimmu.2024.1385022