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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 -
Canadian Journal of Kidney Health and... 2022Medium cut-off (MCO) membranes enhance large middle-molecule clearance while selectively retaining molecules >45 000 Da.
BACKGROUND
Medium cut-off (MCO) membranes enhance large middle-molecule clearance while selectively retaining molecules >45 000 Da.
OBJECTIVES
We undertook a systematic review and meta-analysis comparing the effects of MCO versus high-flux membranes on biomarkers.
METHODS
We searched MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science from January 2015 to July 2020, and gray literature sources from 2017. We included randomized (RS) and nonrandomized studies (NRS) comparing MCO and high-flux membranes in adults (>18 years) receiving maintenance hemodialysis. We performed study selection, data extraction, and quality appraisals in duplicate and used the Grading of Recommendations Assessment, Development, and Evaluation framework. Outcomes included solute removal (plasma clearance or dialysate quantitation), reduction ratios, and predialysis serum concentrations for a range of prespecified large middle molecules.
RESULTS
We identified 26 eligible studies (10 RS and 16 NRS; N = 1883 patients; patient-years = 1366.3). The mean difference (MD) for albumin removal was 2.31 g per session (95% confidence interval [CI], 2.79 to 1.83; high certainty), with a reduction in predialysis albumin of -0.12 g/dl (95% CI, -0.16 to -0.07; = 0%; high certainty) in the first 24 weeks, returning to normal (MD = -0.02 g/dl, 95% CI, -0.07 to -0.03; = 56%; high certainty) after 24 weeks. We also found with high certainty that MCO dialysis resulted in a large increase (standardized mean difference [SMD]> 2.0 for all) in β2-microglobulin, κ- and λ-free light chains, and myoglobin removal, resulting in moderate (SMD > 0.5) to large (SMD > 0.8) reductions in predialysis concentrations for all of these solutes. Medium cut-off dialysis increased the reduction ratio for tumor necrosis factor-alpha (TNF-α) by 7.7% (95% CI, 4.7 to 10.6; moderate certainty), and reduced predialysis TNF-α by SMD -0.48 (95% CI, -0.91 to -0.04; moderate certainty). We found with moderate certainty that MCO dialysis had little to no effect on predialysis interleukin-6 (IL-6) plasma concentrations. Medium cut-off dialysis reduced mRNA expression of TNF-α and IL-6 in peripheral leukocytes by MD -15% (95% CI, -19.6 to -10.4; moderate certainty) and -8.8% (95% CI, -10.2 to -7.4; moderate certainty), respectively.
CONCLUSION
Medium cut-off dialysis increases the clearance of a wide range of large middle molecules and likely reduces inflammatory mediators with a concomitant transient reduction in serum albumin concentration. The net effect of MCO dialysis on large middle molecules could translate into important clinical effects.
PubMed: 35070336
DOI: 10.1177/20543581211067090 -
Current Medicinal Chemistry Oct 2023Early diagnosis of renal dysfunction in β-thalassemia major (β- TM) may help take specific measures to delay irreversible damage and renal failure. Therefore, the...
BACKGROUND
Early diagnosis of renal dysfunction in β-thalassemia major (β- TM) may help take specific measures to delay irreversible damage and renal failure. Therefore, the present meta-analysis aimed to compare biochemical markers of premature renal dysfunction between β-TM and healthy subjects and identify renal issues' prevalence in patients with β-TM.
METHODS
We searched PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Medline, Scopus, Web of Science, ScienceDirect, ProQuest, Google Scholar, and State Inpatient Databases (SIDs) without any language constraints for all relevant articles published up to April 2019.
RESULTS
Out of 1458 articles published up to April 2019, 24 case-control and 22 crosssectional studies were investigated. The investigated levels of serum phosphorus, uric acid (UA), cystatin C, and ferritin were significantly different between β-TM patients and controls. The albumin/creatinine ratio (ACR), N-acetyl-β-D-glucosaminidase/creatinine (NAG/Cr) ratio, urinary and serum β2 microglobulin (β2MG), and serum ferritin levels were significantly higher in β-TM patients than in healthy individuals. However, glomerular filtration rate, creatinine clearance, and pretransfusion hemoglobin indicated a significantly lower rate. The general prevalence of renal glomerular and/or tubular defects in patients with β-TM was 50.22%.
CONCLUSION
Urinary NAG, β2MG, ACR, and Scys-C may be early markers of renal dysfunction in patients with β-thalassemia major. An observation of elevated levels of these markers despite normal levels of other markers of renal dysfunction may indicate primary, subclinical injury to the renal tubules and glomeruli.
PubMed: 37921173
DOI: 10.2174/0109298673250805230922054406 -
Journal of Ethnopharmacology Apr 2020Ligusticum wallichii has been used to treat renal diseases for thousands of years in China. Ligustrazine (Lig) is the active ingredient of Ligusticum wallichii that... (Meta-Analysis)
Meta-Analysis
Protective effect and possible mechanisms of ligustrazine isolated from Ligusticum wallichii on nephropathy in rats with diabetes: A preclinical systematic review and meta-analysis.
ETHNOPHARMACOLOGICAL RELEVANCE
Ligusticum wallichii has been used to treat renal diseases for thousands of years in China. Ligustrazine (Lig) is the active ingredient of Ligusticum wallichii that possesses a variety of biological activities against kidney disease.
AIM OF THE STUDY
The purpose of this review is to further evaluate whether the supplementation with Lig has an effect on improving renal pathology, renal function indexes and blood glucose levels in animal model of diabetic nephropathy (DN). Potential mechanisms of Lig for DN as well as the existing problems regarding the modeling method and limitations in this area of research were also summarized.
MATERIALS AND METHODS
The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist was used to organize the search of eight databases from inception to June 2019. We used Cochrane Collaboration's 10-item checklist and Rev-Man 5.3 software to analyze the data as well as risk of bias.
RESULTS
The study quality scores ranged from 2 to 6 points with an average of 4.471. Compared with the control group, Lig significantly improved pathological changes of kidney including glomeruli and tubules, and induced significant decreases in levels of blood urea nitrogen, serum creatinine, 24-h urinary albumin and HbA1c, as well as increasing creatinine clearance rates. In subgroup analysis, the groups of high-dose STZ (≥60 mg/kg) and longer period of Lig treatment (>8 w) showed better results than those of the control group. No difference was seen between the high (>150 mg/kg, QD) and low (≤150 mg/kg, QD) dose of Lig treatment groups.
CONCLUSION
Lig exerts renoprotective functions in an animal model of DN mediated by antioxidant action, inhibition of apoptosis, anti-inflammatory action, reduction of renal fibrosis, reduction of the proliferation of mesangial cells, inhibition of endotheliosis, inhibition of atherosclerosis and promotion of renal autophagy. The positive conclusion should be treated cautiously because of various methodological flaws. Further studies are recommended according to ARRIVE guidelines. The method of modeling with high-dose STZ should be avoided and improved STZ modeling schemes are recommended. Considering the large dosage range of Lig used clinically and in animals, the future studies on the basis of animal renal histology are urgently needed to determine the optimal dosages to delay histological changes. Nevertheless, together, our findings suggest that Lig is a renoprotective candidate drug for treatment of DN.
Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Ligusticum; Protective Agents; Pyrazines; Rats
PubMed: 31978520
DOI: 10.1016/j.jep.2020.112568 -
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 -
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 -
Pharmacological Research May 2016Chronic kidney disease (CKD) represents an important health problem worldwide and the search for new therapeutic approaches for retarding CKD progression is a timely... (Meta-Analysis)
Meta-Analysis Review
Chronic kidney disease (CKD) represents an important health problem worldwide and the search for new therapeutic approaches for retarding CKD progression is a timely issue. Recent evidence suggest that the anti-inflammatory and hemorrheologic drug Pentoxifylline (PTX), may produce favorable effects on kidney function. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to ascertain whether PTX derivatives, alone or in combination to other treatments, may be useful in slowing down disease progression in patients with diabetic or non-diabetic CKD. We found 26 studies (1518 subjects) matching our search criteria. Information on the effects of PTX on hard renal outcomes (doubling of serum creatinine or need for chronic dialysis) were lacking in all the reviewed trials. Conversely, PTX was effective in reducing proteinuria compared to control, a benefit that was more evident in patients with type-1 diabetes mellitus, higher proteinuria at baseline and early renal impairment. An improvement in renal function (eGFR/creatinine clearance) was observed particularly in patients with more advanced CKD stage and in studies with longer follow-up. Conversely, cumulative analyses did not reveal any evident reduction in urinary albumin excretion, even in diabetic patients. The use of PTX was relatively safe as most trials recorded only minor gastrointestinal adverse effects. Although these findings point at some reno-protective effects of PTX, there is no conclusive evidence proving the usefulness of this agent for improving renal outcomes in subjects with chronic kidney disease of various etiology. Future trials adequately powered and designed on hard clinical end-points are needed.
Topics: Humans; Kidney; Pentoxifylline; Proteinuria; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic
PubMed: 26995301
DOI: 10.1016/j.phrs.2016.03.001 -
The Journal of Antimicrobial... Feb 2022Fraction unbound has been used as a surrogate for antimicrobial sieving coefficient (SC) to predict extracorporeal clearance in critically ill patients on continuous...
BACKGROUND
Fraction unbound has been used as a surrogate for antimicrobial sieving coefficient (SC) to predict extracorporeal clearance in critically ill patients on continuous renal replacement therapy (CRRT), but this is based largely on expert opinion.
OBJECTIVES
To examine relationships between package insert-derived fraction unbound (Fu-P), study-specific fraction unbound (Fu-S), and SC in critically ill patients receiving CRRT.
METHODS
English-language studies containing patient-specific in vivo pharmacokinetic parameters for antimicrobials in critically ill patients requiring CRRT were included. The primary outcome included correlations between Fu-S, Fu-P, and SC. Secondary outcomes included correlations across protein binding quartiles, serum albumin, and predicted in-hospital mortality, and identification of predictors for SC through multivariable analysis.
RESULTS
Eighty-nine studies including 32 antimicrobials were included for analysis. SC was moderately correlated to Fu-S (R2 = 0.55, P < 0.001) and Fu-P (R2 = 0.41, P < 0.001). SC was best correlated to Fu-S in first (<69%) and fourth (>92%) quartiles of fraction unbound and above median albumin concentrations of 24.5 g/L (R2 = 0.71, P = 0.07). Conversely, correlation was weaker in patients with mortality estimates greater than the median of 55% (R2 = 0.06, P = 0.84). SC and Fu-P were also best correlated in the first quartile of antimicrobial fraction unbound (R2 = 0.66, P < 0.001). Increasing Fu-P, flow rate, membrane surface area, and serum albumin, and decreasing physiologic charge significantly predicted increasing SC.
CONCLUSIONS
Fu-S and Fu-P were both reasonably correlated to SC. Caution should be taken when using Fu-S to calculate extracorporeal clearance in antimicrobials with 69%-92% fraction unbound or with >55% estimated in-hospital patient mortality. Fu-P may serve as a rudimentary surrogate for SC when Fu-S is unavailable.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Continuous Renal Replacement Therapy; Critical Illness; Humans; Renal Replacement Therapy; Serum Albumin
PubMed: 35107138
DOI: 10.1093/jac/dkab396 -
Journal of Population Therapeutics and... 2022Several sirolimus (SRL) population pharmacokinetics (PopPK) were conducted to explain its pharmacokinetic variability, and the results varied across studies. Thus, we... (Review)
Review
Several sirolimus (SRL) population pharmacokinetics (PopPK) were conducted to explain its pharmacokinetic variability, and the results varied across studies. Thus, we conducted a systematic review to summarize significant predictors influencing SRL pharmacokinetic variability. Moreover, discrepancies in model methodologies across studies were also reviewed and discussed. Four databases (PubMed, CINAHL Complete, Science Direct, and Scopus) were systematically searched. The PICO framework was used to identify eligible studies conducted in humans and employ a nonlinear-mixed effects strategy. Based on the inclusion and exclusion criteria, 20 studies were included. SRL pharmacokinetics were explained using 1- or 2-compartment models. Only one study assessed the model using an external approach, while the rest employed basic or advanced internal approaches. Significant covariates influencing SRL pharmacokinetics were bodyweight, age, polymorphism, gender, BSA, height, cyclosporine dose or trough concentration, triglyceride, total cholesterol, hematocrit, albumin, aspartate aminotransferase, alanine aminotransferase, and total bilirubin. Of these, bodyweight, age, and polymorphism were the three most identified significant predictors for SRL clearance. This review summarizes significant predictors to predict SRL clearance, which can subsequently be used to individualize SRL maintenance dose. However, the PopPK model selected for such prediction should be based on the resemblance of population characteristics between the target population and those used to conduct the model. Moreover, the predictability of the models in the target population should be assessed before implementation in clinical practice.
Topics: Humans; Sirolimus; Cytochrome P-450 CYP3A; Immunosuppressive Agents; Kidney Transplantation
PubMed: 36308280
DOI: 10.47750/jptcp.2022.940 -
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