Comparison of the Predictive Performance of eGFR Formulae for Mortality and Graft Failure in Renal Transplant Recipients

2009 ◽  
Vol 87 (3) ◽  
pp. 384-392 ◽  
Author(s):  
Xiang He ◽  
Jason Moore ◽  
Shazia Shabir ◽  
Mark A. Little ◽  
Paul Cockwell ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Graft Failure ◽  
Predictive Performance ◽  
Renal Transplant Recipients ◽  
Transplant Recipients

scholarly journals HDL Cholesterol Efflux Predicts Graft Failure in Renal Transplant Recipients

2015 ◽  
Vol 27 (2) ◽  
pp. 595-603 ◽  
Author(s):  
Wijtske Annema ◽  
Arne Dikkers ◽  
Jan Freark de Boer ◽  
Robin P. F. Dullaart ◽  
Jan-Stephan F. Sanders ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Graft Failure ◽  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Renal Transplant Recipients ◽  
Transplant Recipients

scholarly journals Incorporating Nonlinear Kinetics to Improve the Predictive Performance of Population Pharmacokinetic Models for Ciclosporin in Adult Renal Transplant Recipients: A Comparison of Modelling Strategies

2020 ◽  
Author(s):  
Jun-Jun Mao ◽  
Zheng Jiao ◽  
Xiao-Yan Qiu ◽  
Ming Zhang ◽  
Ming-Kang Zhong
Keyword(s):  
Renal Transplant ◽  
Predictive Performance ◽  
Population Pharmacokinetic ◽  
List Type ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Inhibitory Effects ◽  
Nonlinear Kinetics ◽  
Nonlinear Properties ◽  
Modelling Strategies

AbstractAimCiclosporin (CsA) has been shown to follow nonlinear pharmacokinetics in renal transplant recipients who received Neoral-based triple immunosuppressive therapy. Some of these nonlinear properties have not been fully considered in population pharmacokinetic (popPK) analysis. Therefore, the aim of this study was to determine the potential influence of nonlinearity and the functional forms of covariates on model predictability.MethodsA total of 2969 CsA whole-blood measurements, including 1328 pre-dose and 1641 2-h post-dose concentrations, were collected from 173 patients who underwent their first renal transplantation. Four popPK models based on different modelling strategies were developed to investigate the discrepancy between empirical and theory-based, linear and nonlinear compartmental kinetic models and empirical formulae on model predictability. Prediction-based and simulation-based diagnostics (prediction-corrected visual predictive checks) were performed to determine the stability and predictive performance of these four models.ResultsModel predictability improved when nonlinearity was considered. The theory-based nonlinear model which incorporated nonlinear property based on known theoretical relationships performed better than the other two compartmental models. The nonlinear Michaelis-Menten model showed a remarkable improvement in predictive performance over that of the other three compartmental models. The saturated binding of CsA to erythrocytes, and auto-inhibition that arose from the inhibitory effects of CsA on CYP3A4/P-gp and CsA-prednisolone drug interaction may have contributed to the nonlinearity.ConclusionsIncorporating nonlinear properties are likely to be a promising approach for improving CsA model predictability. However, CsA nonlinear kinetics resources need further investigation. Until then, Michaelis-Menten empirical model can be used for CsA dose adjustments.What is already known about this subjectCsA in renal transplant recipients receiving Neoral-based triple immunosuppressive therapy followed nonlinear pharmacokinetics.Nonlinearity is rarely incorporated into CsA population pharmacokinetic (popPK) modelling processes.What this study addsFour popPK models based on different modelling strategies were developed to investigate the discrepancy between empirical and theory-based compartmental kinetic models and empirical formulae, as well as the effect of nonlinearity on CsA model predictability.Based on the four models, incorporating nonlinear properties is likely to be a promising approach for improving CsA model predictability.Saturated distribution into red blood cells, and auto-inhibition that arose from the inhibitory effects of CsA on CYP3A4/P-gp and CsA-prednisolone drug interaction may be the main sources of CsA PK nonlinearity.Principal Investigator statementThe authors confirm that the Principal Investigator for this paper is Zheng Jiao and that he had direct clinical responsibility for patients.

scholarly journals Cigarette Smoking in Renal Transplant Recipients

2000 ◽  
Vol 11 (4) ◽  
pp. 753-759 ◽  
Author(s):  
BERTRAM L. KASISKE ◽  
DAGMAR KLINGER
Keyword(s):  
Cardiovascular Disease ◽  
Relative Risk ◽  
Renal Transplant ◽  
General Population ◽  
Cigarette Smoking ◽  
Graft Failure ◽  
Renal Transplant Recipients ◽  
Adjusted Relative Risk ◽  
Transplant Recipients ◽  
Quit Smoking

Abstract. Cigarette smoking increases the risk for cancer and cardiovascular disease in the general population, but the effects of smoking in renal transplant recipients are unknown. The effects of smoking were investigated among patients transplanted at Hennepin County Medical Center between 1963 and 1997. Information on smoking was available in 1334 patients. The 24.7% prevalence of smoking at the time of transplantation was similar to that in the general population. After adjusting for multiple predictors of graft failure, smoking more than 25 pack-years at transplantation (compared to smoking less than 25 pack-years or never having smoked) was associated with a 30% higher risk of graft failure (relative risk 1.30; 95% confidence interval [CI], 1.04 to 1.63;P= 0.021). Having quit smoking more than 5 yr before transplantation reduced the relative risk of graft failure by 34% (relative risk 0.66; 95% CI, 0.52 to 0.85;P< 0.001). The increase in graft failure was due to an increase in deaths (adjusted relative risk 1.42; 95% CI, 1.08 to 1.87;P= 0.012). The relative risk for major cardiovascular disease events with smoking 11 to 25 pack-years at transplant was 1.56 (95% CI, 1.06 to 2.31;P= 0.024), whereas that of smoking more than 25 pack-years was 2.14 (95% CI, 1.49 to 3.08;P< 0.001). The relative risk of invasive malignancies was 1.91 (95% CI, 1.05 to 3.48;P= 0.032). Smoking had no discernible effect on the rate of return to dialysis or on serum creatinine during the first year after transplantation. Thus, cigarette smoking is associated with an increased risk of death after renal transplantation. The effects of smoking appear to dissipate 5 yr after quitting. These results indirectly suggest that greater efforts to encourage patients to quit smoking before transplantation may decrease morbidity and mortality.

scholarly journals NT-PROBNP INDEPENDENTLY PREDICTS CVD AND GRAFT FAILURE IN RENAL TRANSPLANT RECIPIENTS

2008 ◽  
Vol 86 (Supplement) ◽  
pp. 243
Author(s):  
L H. Oterdoom ◽  
R M. van Ree ◽  
A PJ. de Vries ◽  
R T. Gansevoort ◽  
W J. van Son ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Graft Failure ◽  
Renal Transplant Recipients ◽  
Transplant Recipients

scholarly journals MP786ANEMIA, IRRESPECTIVE OF IRON DEFICIENCY, IS ASSOCIATED WITH GRAFT FAILURE IN RENAL TRANSPLANT RECIPIENTS

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii722-iii723
Author(s):  
Michele Eisenga ◽  
Jan-Stephan Sanders ◽  
Martin De Borst ◽  
Stefan Berger ◽  
Stephan Bakker ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Iron Deficiency ◽  
Graft Failure ◽  
Renal Transplant Recipients ◽  
Transplant Recipients

Abstract 326: Group IIA Secretory Phospholipase A 2 Predicts Graft Failure and Cardiovascular Mortality in Renal Transplant Recipients by Mediating Decreased Kidney Function

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Wijtske Annema ◽  
Jan Freark de Boer ◽  
Arne Dikkers ◽  
Stephan J Bakker ◽  
Uwe J Tietge
Keyword(s):  
Renal Transplant ◽  
Transgenic Mice ◽  
Kidney Function ◽  
Graft Failure ◽  
Hazard Ratio ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
All Cause Mortality ◽  
Over Time

The acute phase protein group IIA secretory phospholipase A2 (sPLA2-IIA) has proatherosclerotic properties. The present study prospectively investigated whether plasma sPLA2-IIA levels are associated with graft failure, cardiovascular and all-cause mortality in renal transplant recipients (RTRs), patients known to be susceptible to accelerated atherosclerosis, both in the graft and in the systemic vasculature. In 495 RTRs (median follow-up 7.0 years) sPLA2-IIA was determined at baseline and was significantly higher in RTRs than in healthy controls (median 384 ng/dL [range 86-6951] vs. 185 ng/dL [range 104-271], P<0.001), but lower than in end-stage renal disease patients (median 1053 ng/mL [range 458-2599], P<0.001). Kaplan-Meier analysis demonstrated an increased risk for graft failure (P=0.002), cardiovascular (P<0.001) and all-cause mortality (P<0.001) with increasing gender-stratified quartiles of sPLA2-IIA. Cox regression analyses showed a strong association of sPLA2-IIA with increased risks of graft failure (hazard ratio=1.42[1.11-1.83], P=0.006), cardiovascular (hazard ratio=1.48[1.18-1.85], P=0.001) and all-cause mortality (hazard ratio=1.39[1.17-1.64], P<0.001). However, this association was largely explained by parameters of kidney function. Further analyses in RTRs demonstrated that patients with higher baseline sPLA2-IIA levels showed faster decline in renal function during follow-up. In addition, kidney function in human sPLA2-IIA transgenic mice deteriorated more rapid over time as compared with wild-type controls (urinary albumin:creatinine ratio at 48 weeks of age 774±156 vs. 193±60, P<0.01). In summary, this prospective study demonstrates that sPLA2-IIA is a significant predictive biomarker for the occurrence of chronic graft failure, overall and CVD mortality in RTRs dependent on kidney function. This dependency is explained by sPLA2-IIA impacting negatively on kidney function over time in humans and transgenic mice.

Sign in / Sign up

Export Citation Format

Share Document