Kidney regeneration and repair after transplantation

PURPOSE OF REVIEW: To briefly show which are the mechanisms and cell types involved in kidney regeneration and describe some of the therapies currently under study in regenerative medicine for kidney transplantation. RECENT FINDINGS: The kidney contains cell progenitors that under specific circumstances have the ability to regenerate specific structures. Apart from the knowledge gained in the self-regenerative properties of the kidney, new concepts in regenerative medicine such as organ engineering and the use of mesenchymal stem cell-based therapies are currently the focus of attention in the field. SUMMARY: Overall, kidney regeneration is a reality and the knowledge on how to control it will be one of the main scopes in the present and future

Datasets for the validation of the "in vivo" siRNA-silencing of CD40 and for the detection of new markers of atherosclerosis progression in ApoE-deficient mice

AbstractData presented in this Data in Brief article correspond to the article "in vivo" silencing of CD40 reduces progression of experimental atherogenesis through a NFκB/miR-125b axis and reveals new potential mediators in the pathogenesis of atherosclerosis" (M. Hueso, L. De Ramon, E. Navarro, E. Ripoll, J.M. Cruzado, J.M. Grinyo, J. Torras, 2016) [1]. Here, we describe the validation of the silencing of CD40 expression with a specific siRNA in ApoE−/− mouse aortas, and its systemic effects on splenic lymphocytic subpopulations as well as on the infiltration of aortic intima by F4/80+, galectin-3+ macrophages or by NF-κB+ cells. We also show the output of a Gene Ontology and TLDA analysis which allowed the detection of potential mediators of atherosclerosis progression. We provide the scientific community with a set of genes whose expression is increased during atherosclerosis progression but downregulated upon CD40 silencing

Decreased Kidney Graft Survival in Low Immunological Risk Patients Showing Inflammation in Normal Protocol Biopsies

Introduction The pros and cons for implementing protocol biopsies (PB) after kidney transplantation are still a matter of debate. We aimed to address the frequency of pathological findings in PB, to analyze their impact on long-term graft survival (GS) and to analyze the risk factors predicting an abnormal histology. Methods We analyzed 946 kidney PB obtained at a median time of 6.5 (+/- 2.9) months after transplantation. Statistics included comparison between groups, Kaplan-Meier and multinomial logistic regression analysis. Results and Discussion PB diagnosis were: 53.4% normal; 46% IFTA; 12.3% borderline and 4.9% had subclinical acute rejection (SCAR). Inflammation had the strongest negative impact on GS. Therefore we split the cases into: "normal without inflammation", "normal with inflammation", "IFTA without inflammation", "IFTA with inflammation" and "rejection" (including SCAR and borderline). 15-year GS in PB diagnosed normal with inflammation was significantly decreased in a similar fashion as in rejection cases. Among normal biopsies, inflammation increased significantly the risk of 15-y graft loss (P = 0.01). Variables that predicted an abnormal biopsy were proteinuria, previous AR and DR-mismatch. Conclusion We conclude that inflammation in normal PB is associated with a significantly lower 15-y GS, comparable to rejection or IFTA with inflammation.Peer reviewe

Investigating the health-economic profiles of biomarker-driven immunosuppresion (BIO-DrIM) following solid organ transplantation

Immunosuppression (IS) following solid organ transplantation is indicated to avoid rejection but puts a sig-nificant burden on patients and healthcare systems due to life-long medication dependency and associated costs. Or-gan-tolerance with low or no IS medication has been observed, and might be forecasted with the help of appropriate biomarkers. Individualized treatments raise the question whether benefits of individualization outweigh the costs of stratification. This article outlines the importance of early economic evaluation in the context of biomarker-guided IS and discusses challenges that an economic evaluation should address, using the BIO-DrIM project as a reference exam-ple. We report on design aspects and health-economic study integration into several newly designed biomarker trials. In these studies, health-economic endpoints were defined to measure benefits of individualization and to compare them to the costs associated with stratification. Key economic outcomes to be collected are resource consumption and patient quality of life. Test accuracy of the biomarker-stratification is critical for the clinical success and the health-economic viability of an individualized reduced IS regime. However, IS regimes are not well standardized, rendering comparator choice difficult. The multi-national character of the trials adds further complexity that needs to be addressed. Develop-ers of biomarker tests should stress the importance of integrating health-economic evaluations early into prod-uct-development

Mycophenolic Acid Exposure after Administration of Mycophenolate Mofetil in the Presence and Absence of Ciclosporin in Renal Transplant Recipients

Background and objective: The pharmacokinetics of mycophenolic acid (MPA) are complex, with large interindividual variability over time. There are also well documented interactions with ciclosporin, and assessment of MPA exposure is therefore necessary when reducing or stopping ciclosporin therapy. Here we report on the pharmacokinetic and pharmacodynamic behaviour of MPA in renal transplant patients on standard dose, reduced dose and no ciclosporin. Study design: The CAESAR study, a prospective 12-month study in primary renal allograft recipients, was designed to determine whether mycophenolate mofetil-based regimens containing either low-dose ciclosporin or low-dose ciclosporin withdrawn by 6 months could minimize nephrotoxicity and improve renal function without an increase in acute rejection compared with a mycophenolate mofetil-based regimen containing standard-dose ciclosporin. Patients and methods: A subset of patients from the CAESAR study contributed to this pharmacokinetic analysis of MPA exposure. Blood samples were taken over one dosing interval on day 7 and at months 3, 7 and 12 post-transplantation. The sampling timepoints were predose, 20, 40 and 75 minutes and 2, 3, 4, 6, 9 and 12 hours after mycophenolate mofetil dosing. Assessments included plasma concentrations of MPA and mycophenolic acid glucuronide (MPAG) and ciclosporin trough concentrations. The area under the plasma concentration-time curve (AUC) from 0 to 12 hours (AUC(12)) for MPA was the primary pharmacokinetic parameter, and the AUC12 for MPAG was the secondary parameter. Results: In total, 536 de novo renal allograft recipients were randomized in the CAESAR study. Of these, 114 patients were entered into the pharmacokinetic substudy and 110 patients contributed to the pharmacokinetic analysis. There was a rapid rise in MPA concentrations (median time to peak concentration 0.72-1.25 hours). At day 7 and month 3, the MPA AUC12 values were similar in the ciclosporin withdrawal and low-dose ciclosporin groups (patients with the same ciclosporin target concentrations to month 6), while at 7 and 12 months, the values in the ciclosporin withdrawal group were higher than in the low-dose group (19.9% and 30.2% higher, respectively). MPA AUC12 values in the standard-dose ciclosporin group were lower than in the other groups at all timepoints and increased over time. At all timepoints, the MPA peak plasma concentration was similar in all groups, and the MPAG concentrations rose more slowly than MPA concentrations. The ratio of the AUC from 6 to 12 hours/AUC(12) suggests that an increasing AUC in the ciclosporin withdrawal group is due to an increase in the enterohepatic recirculation. Conclusion: These findings are consistent with the hypothesis that ciclosporin inhibits the biliary secretion and/or hepatic extraction of MPAG, leading to a reduced rate of enterohepatic recirculation of MPA. Several concurrent mechanisms, such as ciclosporin-induced changes in renal tubular MPAG excretion and enhanced elimination of free MPA through competitive albumin binding with MPAG, can also contribute to the altered MPAG pharmacokinetics observed in the presence and absence of ciclosporin

Cox regression was use for investigating the effect of histological categories diagnosis upon 15-y death censored graft survival.

<p>Cox regression was use for investigating the effect of histological categories diagnosis upon 15-y death censored graft survival.</p

Frequency of the lesions diagnosed in PB.

<p>Frequency of the lesions diagnosed in PB.</p