Non-linear Relationship between Tacrolimus Blood Concentration and Acute Rejection After Kidney Transplantation: A Systematic Review and Dose-Response Meta-Analysis of Cohort Studies

2019 ◽  
Vol 25 (21) ◽  
pp. 2394-2403
Author(s):  
Saifu Yin ◽  
Turun Song ◽  
Xingxing Li ◽  
Hanyue Xu ◽  
Xueling Zhang ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Linear Relationship ◽  
Dose Response ◽  
Blood Concentration ◽  
Meta Analysis ◽  
West China Hospital ◽  
West China ◽  
One Stage ◽  
Non Linear

Background: Maintaining the exposure of tacrolimus (Tac) after kidney transplantation (KT) must be necessary to prevent acute rejection (AR) and improve graft survival，but there is still no clear consensus on the optimal Tac target blood concentration and concentration-effect relationship is poorly defined. Methods: We conducted a dose-response meta-analysis to quantitatively assess the association between Tac blood concentration and (AR) or adverse effects after KT. A comprehensive search of PubMed, Embase and Cochrane library databases was conducted to find eligible studies up to 10th September 2018. Unpublished data from patients receiving KT in West China Hospital (Sichuan University, China) were also collected. Both twostage dose-response and one-stage dose-response meta-analysis models were used to improve the statistical power. Results: A total of 4967 individuals from 10 original studies and 1453 individuals from West China Hospital were eligible for the ultimate analysis. In the two-stage dose-response meta-analysis model, we observed a significant non-linear relationship between Tac blood concentration and AR (P < 0.001) with moderate heterogeneity (I2 = 46.0%, P = 0.08). Tac blood concentration at 8ng/ml was associated with the lowest risk of AR (RR: 0.26, 95%CI: 0.13 - 0.54) by reference to 2ng/ml. Tac concentration at 7.0 - 11.0 ng/ml reduced the risk of AR by at least 70%, 5-14 ng/ml by at least 60%, and 4.5 – 14 ng/ml at least 50%. In the one-stage dose-response model, we also found a strong non-linear relationship between Tac and AR (P < 0.001) with moderate heterogeneity (I2 = 41.2%, P = 0.10). Tac concentration of 7.5 ng/ml was associated with the lowest risk of AR (RR: 0.35, 95%CI: 0.16 - 0.77). The blood concentration at 5.5 - 9.5 ng/ml was associated with the reduced AR by at least 60% and 4.5 - 10.5 ng/ml by at least 50% by reference to 2 ng/ml. Conclusion: Maintaining Tac blood concentration at 5 - 9.5 ng/ml within the first year may prevent AR most effectively.

scholarly journals Sex-Specific Exposure–Effect Relationship Between Physical Activity and Incident Atrial Fibrillation in the General Population: A Dose–Response Meta-Analysis of 16 Prospective Studies

2021 ◽  
Vol 8 ◽  
Author(s):  
Qin Wan ◽  
Yue Zhou ◽  
Wengen Zhu ◽  
Xiao Liu
Keyword(s):  
Physical Activity ◽  
Atrial Fibrillation ◽  
General Population ◽  
Linear Relationship ◽  
Linear Model ◽  
Dose Response ◽  
Prospective Studies ◽  
Meta Analysis ◽  
Exposure Effect ◽  
Non Linear

Background: Since evidence regarding the relationship between physical activity (PA) and atrial fibrillation (AF) incidence is inconsistent among studies, we performed a dose–response meta-analysis to comprehensively evaluate the exposure–effect association between PA and incident AF and the potential sex difference in the general population.Methods: The PubMed and Embase databases were searched for eligible studies published up to July 2020 (PROSPERO: CRD42018091692). The non-linear or linear exposure–effect relationship between PA and AF was examined using the robust error meta-regression method.Results: A total of 16 prospective studies involving 1,449,017 individuals and 39,884 AF cases were included. We observed an inverse non-linear association between PA level and incident AF (I2 = 0%, pnon−linearity &lt; 0.001). In the linear model, a 5 metabolic equivalent of task (MET)-h/week increase in PA was associated with a decreased risk of AF [risk ratio (RR) = 0.992, 95% confidence interval (CI): 0.988–0.996, I2 = 0%]. In the sex-stratified analysis, we observed an inverse non-linear relationship between PA level and AF risk in females (I2 = 90%, pnon−linearity &lt; 0.0001) but not in males (I2 = 0%, pnon−linearity = 0.40). In the linear model, a 5 MET-h/week increase in PA was associated with a reduced risk of AF in females (RR = 0.982, 95% CI: 0.975–0.989, I2 = 71%) but not in males (RR = 0.998, 95% CI: 0.994–1.002, I2 = 0%), with a significant interaction observed between the two groups (pinteraction &lt; 0.0001).Conclusion: There was an inverse non-linear relationship between PA level and incident AF in the general population. The beneficial effect of PA in reducing AF risk might be predominantly observed in females.

One-stage dose–response meta-analysis for aggregated data

2018 ◽  
Vol 28 (5) ◽  
pp. 1579-1596 ◽  
Author(s):  
Alessio Crippa ◽  
Andrea Discacciati ◽  
Matteo Bottai ◽  
Donna Spiegelman ◽  
Nicola Orsini
Keyword(s):  
Dose Response ◽  
Goodness Of Fit ◽  
Linear Mixed Model ◽  
Meta Analysis ◽  
Model Specification ◽  
Two Stage ◽  
Aggregated Data ◽  
One Stage ◽  
Non Linear ◽  
The One

The standard two-stage approach for estimating non-linear dose–response curves based on aggregated data typically excludes those studies with less than three exposure groups. We develop the one-stage method as a linear mixed model and present the main aspects of the methodology, including model specification, estimation, testing, prediction, goodness-of-fit, model comparison, and quantification of between-studies heterogeneity. Using both fictitious and real data from a published meta-analysis, we illustrated the main features of the proposed methodology and compared it to a traditional two-stage analysis. In a one-stage approach, the pooled curve and estimates of the between-studies heterogeneity are based on the whole set of studies without any exclusion. Thus, even complex curves (splines, spike at zero exposure) defined by several parameters can be estimated. We showed how the one-stage method may facilitate several applications, in particular quantification of heterogeneity over the exposure range, prediction of marginal and conditional curves, and comparison of alternative models. The one-stage method for meta-analysis of non-linear curves is implemented in the dosresmeta R package. It is particularly suited for dose–response meta-analyses of aggregated where the complexity of the research question is better addressed by including all the studies.

scholarly journals The association between vitamin D and acute rejection in human kidney transplantation: A systematic review and meta-analysis study

2021 ◽  
pp. 101410
Author(s):  
Mohammad Mirzakhani ◽  
Sheyda Mohammadkhani ◽  
Shirin Hekmatirad ◽  
Soudabeh Aghapour ◽  
Negar Gorjizadeh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Vitamin D ◽  
Kidney Transplantation ◽  
Acute Rejection ◽  
Meta Analysis ◽  
Human Kidney ◽  
Analysis Study

scholarly journals 100% Fruit juice intake and cardiovascular risk: a systematic review and meta-analysis of prospective and randomised controlled studies

2020 ◽  
Author(s):  
Lanfranco D’Elia ◽  
◽  
Monica Dinu ◽  
Francesco Sofi ◽  
Massimo Volpe ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Risk ◽  
Dose Response ◽  
Prospective Studies ◽  
Fruit Juice ◽  
Meta Analysis ◽  
Inverse Association ◽  
Non Linear ◽  
Randomised Controlled ◽  
The Relationship

Abstract Purpose The relationship between 100% fruit juice (100%FJ) consumption and cardiovascular risk is object of debate: indeed, recently published investigations provided new but discrepant evidence on this important question and International dietary guidelines are not in agreement on recommendations about fruit juice consumption. Therefore, we performed a meta-analysis of the prospective studies and the randomised controlled trials (RCTs) that explored the relationship between 100%FJ intake, cardiovascular risk profile and risk of cardiovascular events. Methods We performed a systematic search of publications up to August 2019. Summary relative risks and exploration of linearity of the association were estimated for prospective studies and summary mean differences (MDs) calculated for RCTs. Results A total of 21 prospective studies and 35 RCTs met the inclusion criteria. Dose–response analysis detected a significant inverse association between low-moderate 100%FJ consumption and risk of stroke (up to 200 ml/day) or total CV events (up to 170 ml/day) compared with no consumption, with a non-linear relationship (p for non-linearity < 0.05). No significant association was found for coronary heart disease and diabetes risk. In RCTs, a favorable and significant effect of 100%FJ intake was detected on blood pressure (systolic, MD: − 3.14 mmHg; diastolic, MD: − 1.68 mmHg), arterial compliance (carotid-femoral pulse wave velocity, − 0.38 m/s) and endothelial function (flow-mediated dilation, 2.10%). Neutral effects were found on body weight, blood lipids and glucose metabolism. Conclusions The results of these analyses indicate that 100%FJ consumption is not associated with higher CV risk. A non-linear inverse dose–response relationship occurs between 100%FJ consumption and CV disease, in particular for risk of stroke, probably mediated by the decrease in blood pressure. Trial registration PROSPERO registration number (CRD42019135577).

Association between CTLA4 gene polymorphisms and acute rejection of kidney transplantation: a meta-analysis

2012 ◽  
Vol 25 (6) ◽  
pp. 996-1002 ◽  
Author(s):  
Zhenhua Duan ◽  
Yujing Zhang ◽  
Faming Pan ◽  
Tianchen Zhang ◽  
Zhen Zeng ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Gene Polymorphisms ◽  
Meta Analysis ◽  
Ctla4 Gene

scholarly journals A dose–response meta-analysis reveals an association between vitamin B12 and colorectal cancer risk

2015 ◽  
Vol 19 (8) ◽  
pp. 1446-1456 ◽  
Author(s):  
Nai-Hui Sun ◽  
Xuan-Zhang Huang ◽  
Shuai-Bo Wang ◽  
Yuan Li ◽  
Long-Yi Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dose Response ◽  
Meta Analysis ◽  
Dietary Vitamin ◽  
Vitamin B ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Total Vitamin ◽  
Linear Dose ◽  
Non Linear

AbstractObjectiveThe current meta-analysis evaluated the association between vitamin B12 intake and blood vitamin B12 level and colorectal cancer (CRC) risk.DesignThe PubMed and EMBASE databases were searched. A dose–response analysis was performed with generalized least squares regression, with the relative risk (RR) and 95 % CI as effect values.SettingThe meta-analysis included seventeen studies.SubjectsA total of 10 601 patients.ResultsThe non-linear dose–response relationship between total vitamin B12 intake and CRC risk was insignificant (P=0·690), but the relationship between dietary vitamin B12 intake and CRC risk was significant (P<0·001). Every 4·5 μg/d increment in total and dietary vitamin B12 intake was inversely associated with CRC risk (total intake: RR=0·963; 95 % CI 0·928, 0·999; dietary intake: RR=0·914; 95 % CI 0·856, 0·977). The inverse association between vitamin B12 intake and CRC risk was also significant when vitamin B12 intake was over a dosage threshold, enhancing the non-linear relationship. The non-linear dose–response relationship between blood vitamin B12 level and CRC risk was insignificant (P=0·219). There was an insignificant association between every 150 pmol/l increment in blood vitamin B12 level and CRC risk (RR=1·023; 95 % CI 0·881, 1·187).ConclusionsOur meta-analysis indicates that evidence supports the use of vitamin B12 for cancer prevention, especially among populations with high-dose vitamin B12 intake, and that the association between CRC risk and total vitamin B12 intake is stronger than between CRC risk and dietary vitamin B12 intake only.

scholarly journals Comparison of induction therapy with anti-thymocyte/antilymphocyte globulin or anti-IL-2 receptor antibody in pediatric kidney transplantation: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Xiaohong Lin ◽  
Miaohan Deng ◽  
Xitao Hong ◽  
Weiqiang Ju ◽  
Maogen Chen
Keyword(s):  
Systematic Review ◽  
Kidney Transplantation ◽  
Survival Rate ◽  
Acute Rejection ◽  
Confidence Interval ◽  
Induction Therapy ◽  
Meta Analysis ◽  
Rejection Rate ◽  
Antilymphocyte Globulin ◽  
Pediatric Kidney Transplantation

Abstract BackgroundAnti-IL-2 antibody (basiliximab or daclizumab) and anti-thymocyte globulin (ATG)/antilymphocyte globulin (ALG) are widely used as induction agents in pediatric kidney transplantation. However, which of them benefits patients more remains unknown.MethodsOnline databases were searched to identify controlled clinical studies that compared anti-IL-2 with ATG/ALG for induction therapy in pediatric kidney transplantation. Odds ratios (OR) and 95% confidence interval (CI) were chosen to compare the gathered data. Review Manager 5.4 was applied to identify differences in outcomes between the two agents.ResultsFive retrospective cohort studies were included, enrolling a total of 2510 pediatric patients, 1152 (45.7%) of whom had received ATG/ALG therapy and 1370 (54.3%) of whom received anti-IL-2. According to the pooled results, no differences were seen between anti-IL-2 and ATG/ALG regarding the delayed graft function (DGF) rate (odds ratio (OR) 1.1; 95% confidence interval (CI) 0.36–3.39; P = 0.85), 6-month acute rejection rate (OR 0.80; 95% CI 0.62–1.03; P = 0.09), 1-year acute rejection rate (OR 0.98; 95% CI 0.78–1.24; P = 0.88), 1-year graft survival rate (OR 1.37; 95% CI 0.91–2.06; P = 0.13), 1-year patient survival rate (OR 0.86; 95% CI 0.40–1.86; P = 0.70) and 1-year post-transplantation lymphoproliferative disorder (PTLD) rate (OR 0.30; 95% CI 0.03–3.16; P = 0.32).ConclusionsAnti-IL-2 have the same efficacy and safety as ATG/ALG in transplant induction therapy. However, as most of included studies were small-scale retrospective studies, further studies are needed to identify an optimal choice with certain.The analysis had been registered in PROSPERO and the registration ID is CRD42021237561. Comparison of induction therapy with anti-thymocyte/antilymphocyte globulin or anti-IL-2 receptor antibody in pediatric kidney transplantation: a systematic review and meta-analysis

scholarly journals Flexible piecewise linear model for investigating dose-response relationship in meta-analysis: methodology, examples, and comparison

2018 ◽  
Author(s):  
Chang Xu ◽  
Lehana Thabane ◽  
Tong-Zu Liu ◽  
Ling Li ◽  
Sayem Borhan ◽  
...  
Keyword(s):  
Linear Model ◽  
Dose Response ◽  
Linear Trend ◽  
Piecewise Linear ◽  
Meta Analysis ◽  
Continuous Exposure ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Two Stage ◽  
One Stage

Objectives: Dose-response meta-analysis (DRMA) is widely employed to establishing the potential dose-response relationship between continuous exposures and disease outcomes. However, no method is readily available for exploring the relation between a discrete exposure and a binary or continuous outcome. We proposed a piecewise linear (PL) DRMA model as a solution to this issue. Methods: We illustrated the methodology of PL model in both one-stage DRMA approach and two-stage DRMA approach. The method by testing the equality of slopes of each piecewise was employed to judge if there is “piecewise effect” against simple linear trend. We then used sleep (continuous exposure) and parity (discrete exposure) data as examples to illustrate how to apply PL model in DRMA using the Stata code attached. We also empirically compared the slopes of PL model with simple linear as well as restricted cubic spline (RCS) model. Results: Both one-stage and two-stage PL DRMA model fitted well in our examples, and the results were similar. Obvious “piecewise effects” were detected in both the two examples by the method we used. In our example, the PL model showed better fitting effect and practical reliable results compared to simple linear model, while similar results for to RCS model. Conclusion: Piecewise linear function is a simple and valid method for DRMA and can be used for discrete exposures. It also represents a superior model to linear model in DRMA and may be an alternative model to non-linear model.

Sign in / Sign up

Export Citation Format

Share Document