Individualization of Immunosuppressive Therapy after Solid Organ Transplantation

__Abstract__ When an individual’s kidneys fail, there are three treatment options: hemodialysis, peritoneal dialysis or kidney transplantation. A successful kidney transplantation results in the best patient survival and a better quality of life compared to the two other treatment modalities. Kidney transplantation is therefore the preferred therapy for renal failure. The first deceased donor kidney transplantation in the United States was performed in 1950 by Lawler and colleagues on Ruth Tucker, a 44-year-old woman with polycystic kidney disease. Although the kidney transplant was rejected ten months later because no immunosuppressive therapy was available at the time, the intervening time allowed Tucker’s remaining native kidney (it was an orthotopic transplantation) to recover and she lived for another five years. At the same time in France, Küss, Hamburger, and others also performed a number of kidney transplantations

Design and Simulation of Temperature Sensor based on Long Period Grating in Liquid Filled Photonic Crystal Fiber

In this paper, a high sensitivity temperature sensor based on photonic crystal fiber long period grating (PCF-LPG) filled with ethanol is proposed and simulated by full vector finite element method. The relationship between the resonant wavelength shift, and the temperature was analyzed. The results show that the resonant wavelength of the ethanol filled photonic crystal fiber long period grating is proportional linearly with temperature and the highest  sensitivity of  was achieved, which is 90 times higher than that of conventional LPG temperature sensors

Concomitant intraperitoneal and systemic chemotherapy for extensive peritoneal metastases of colorectal origin: protocol of the multicentre, open-label, phase I, dose-escalation INTERACT trial

INTRODUCTION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has become standard of care for patients with peritoneal metastases of colorectal origin with a low/moderate abdominal disease load. In case of a peritoneal cancer index (PCI) score >20, CRS-HIPEC is not considered to be beneficial. Patients with a PCI >20 are currently offered palliative systemic chemotherapy. Previous studies have shown that systemic chemotherapy is less effective against peritoneal metastases than it is against haematogenous spread of colorectal cancer. It is suggested that patients with peritoneal metastases may benefit from the addition of intraperitoneal chemotherapy to systemic chemotherapy. Aim of this study is to establish the maximum tolerated dose of intraperitoneal irinotecan, added to standard of care systemic therapy for colorectal cancer. Secondary endpoints are to determine the safety and feasibility of this treatment and to establish the pharmacokinetic profile of intraperitoneally administered irinotecan. METHODS AND ANALYSIS: This phase I, '3+3' dose-escalation, study is performed in two Dutch tertiary referral centres. The study population consists of adult pa

Polymorphisms in CYP3A5, CYP3A4, and ABCB1 are Not Associated With Cyclosporine Pharmacokinetics Nor With Cyclosporine Clinical End Points After Renal Transplantation

Nephrolog

Tacrolimus Predose Concentrations Do Not Predict the Risk of Acute Rejection After Renal Transplantation: A Pooled Analysis From Three Randomized-Controlled Clinical Trials

Therapeutic drug monitoring (TDM) for tacrolimus (Tac) is universally applied. However, the concentrationeffect relationship for Tac is poorly defined. This study investigated whether Tac concentrations are associated with acute rejection in kidney transplant recipients. Data from three large trials were pooled. We used univariate and multivariate analysis to investigate the relationship between biopsy-proven acute rejection (BPAR) and Tac predose concentration at five time points (day 3, 10 and 14, and month 1 and 6 after transplantation). A total of 136/1304 patients experienced BPAR, giving an overall incidence of 10.4%. We did not find any significant correlations between Tac predose concentrations and the incidence of BPAR at the different time points. In the multivariate analysis, only delayed graft function (DGF) and the use of induction therapy were independently correlated with BPAR, with an odds ratio of 2.7 [95% CI: 1.84.0; p < 0.001] for DGF and 0.66 [95% CI: 0.440.99; p = 0.049] for induction therapy. The other variables, including the Tac predose concentrations, were not statistically significantly associated with BPAR. We did not find an association between the Tac predose concentrations measured at five time points after kidney transplantation and the incidence of acute rejection occurring thereafter. Based on this study it is not possible to define the optimal target concentrations for Tac

Impact of POR*28 on the Pharmacokinetics of Tacrolimus and Cyclosporine A in Renal Transplant Patients

Nephrolog

Genetic polymorphisms in IL-2, IL-10, TGF-beta 1, and IL-2RB and acute rejection in renal transplant patients

Nephrolog

A Randomized Controlled Trial Comparing the Efficacy of Cyp3a5 Genotype-Based With Body-Weight-Based Tacrolimus Dosing After Living Donor Kidney Transplantation

Patients expressing the cytochrome P450 (CYP) 3A5 gene require a higher tacrolimus dose to achieve therapeutic exposure compared with nonexpressers. This randomized-controlled study investigated whether adaptation of the tacrolimus starting dose according to CYP3A5 genotype increases the proportion of kidney transplant recipients being within the target tacrolimus predose concentration range (10-15 ng/mL) at first steady-state. Two hundred forty living-donor, renal transplant recipients were assigned to either receive a standard, body-weight-based or a CYP3A5 genotype-based tacrolimus starting dose. At day 3, no difference in the proportion of patients having a tacrolimus exposure within the target range was observed between the standard-dose and genotype-based groups: 37.4% versus 35.6%, respectively; p = 0.79. The proportion of patients with a subtherapeutic (i.e. 15 ng/mL) Tac predose concentration in the two groups was also not significantly different. The incidence of acute rejection was comparable between both groups (p = 0.82). Pharmacogenetic adaptation of the tacrolimus starting dose does not increase the number of patients having therapeutic tacrolimus exposure early after transplantation and does not lead to improved clinical outcome in a low immunological risk populatio