-
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 -
Health Technology Assessment... 2007To assess the clinical effectiveness and cost-effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome (SRNS). (Review)
Review
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome (SRNS).
DATA SOURCES
Electronic databases from inception to February 2006, bibliographies of studies, and experts in the field.
REVIEW METHODS
Studies were selected, quality assessed and data were extracted using recognised methods agreed a priori. Meta-analysis was undertaken where appropriate using the random effects model. Where data allowed, subgroup analysis was undertaken according to renal histopathology.
RESULTS
Two systematic reviews and 11 trials were included in the clinical effectiveness review; however, the quality of reporting and methodology of the included studies was generally poor. No economic evaluations were identified. No statistically significant difference in remission rates was found between cyclophosphamide plus prednisone and prednisone alone for all children or those with focal segmental glomerulosclerosis (FSGS), also the time to response was statistically significantly less with cyclophosphamide (38.4 days versus 95.5 days). Remission rates were not statistically significantly different between intravenous and oral cyclophosphamide. Vomiting was common with intravenous cyclophosphamide, while pneumonia and alopecia occurred in the oral group. Ciclosporin statistically significantly increased the number of children with complete remission compared with placebo or supportive treatment, but not for the FSGS subgroup, adverse effects including infection and hypertension differed little between groups. No differences were found between azathioprine and placebo, with about 13% of each group having remission. Complete or partial remission occurred in six out of seven patients on the 18-month methylprednisolone regimen and three out of five patients on the 6-month regimen, for both groups renal function improved and adverse events such as hypertension and frequent infections occurred. Intravenous dexamethasone and methylprednisolone produced similar complete remission rates, partial remission rates, median time to response (about 10 days) and total number of adverse events, with hypertension as the most common. Six-hour urinary albumin and urinary albumin to creatinine ratio decreased statistically significantly with high-dose but not low-dose enalapril. Tuna fish oil was not associated with any statistically significant improvements in proteinuria, creatinine clearance, serum creatinine or lipid profiles compared with placebo. A very limited literature was found on costs associated with SRNS in children. The pharmaceutical cost of treatment varied considerably: an 8-week course of cyclophosphamide cost less than 6 pounds, while a course of ciclosporin cost almost 900 pounds per year. Treatment with tacrolimus, an alternative to ciclosporin, was estimated to cost in excess of 3400 pounds per year. Healthcare medical management costs were estimated; varying by treatment strategy, they ranged from 250 pounds to 930 pounds per year in patients not experiencing complications. Other longer term costs may also be incurred. Lack of data meant that cost-effectiveness modelling was not feasible.
CONCLUSIONS
The clinical effectiveness literature on treatments for idiopathic SRNS in children is very limited. The available evidence suggests a beneficial effect of ciclosporin on remission rates and of cyclophosphamide on time to remission; however, the strength of the conclusions drawn is limited by the poor quality of the included studies. The other treatments included in this review were each evaluated by only one study, and none found a statistically significant effect. There is insufficient evidence to determine whether or not there is a clinically significant difference. The available data on costs and outcomes are sparse and do not permit the reliable modelling of the cost-effectiveness of treatments for SRNS at present. A modelling framework is suggested, should more relevant data become available. A well-designed adequately powered randomised controlled trial comparing ciclosporin with other treatments in children with SRNS without genetic mutation is required.
Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Cost-Benefit Analysis; Drug Resistance; Humans; Immunosuppressive Agents; Infant; Meta-Analysis as Topic; Nephrotic Syndrome; Treatment Outcome; United Kingdom
PubMed: 17537341
DOI: 10.3310/hta11210 -
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 -
Mayo Clinic Proceedings Mar 2019Serum cystatin C has been proposed as a kidney biomarker to inform drug dosing. We conducted a systematic review to synthesize available data for the association between...
Serum cystatin C has been proposed as a kidney biomarker to inform drug dosing. We conducted a systematic review to synthesize available data for the association between serum cystatin C and drug pharmacokinetics, dosing, and clinical outcomes in adults (≥18 years). PubMed, Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL, and Scopus were systematically searched from 1946 to September 2017 to identify candidate studies. Studies of cystatin C as a predictor for acute kidney injury or for management of contrast-associated acute kidney injury were excluded. Also, studies were excluded if drug concentrations were unavailable and if a reference standard for drug dosing (eg, serum creatinine) was not concurrently reported. The outcomes of interest included drug clearance (L/h), concentrations (mg/L), target level achievement (%), therapeutic failure (%), and drug toxicity (%). We included 28 articles that evaluated 16 different medications in 3455 participants. Vancomycin was the most well-studied drug. Overall, cystatin C-based estimated glomerular filtration rate (eGFR) was more predictive of drug levels and drug clearance than eGFR. In only one study were target attainment and outcomes compared between 2 drug-dosing regimens, one based on eGFR and one dosed with the Cockcroft-Gault creatinine clearance equation. Compared with eGFR, use of eGFR to predict elimination of medications via the kidney was as accurate, if not superior, in most studies, but infrequently were data on target attainment or clinical outcomes reported. Drug-specific dosing protocols that use cystatin C to estimate kidney function should be tested for clinical application.
Topics: Biomarkers; Creatinine; Cystatin C; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Renal Elimination; Serum Albumin
PubMed: 30713050
DOI: 10.1016/j.mayocp.2018.08.002