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

On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes

Complete and high-resolution (HR) HLA typing improves the accurate assessment of donor-recipient compatibility and pre-transplant donor-specific antibodies (DSA). However, the value of this information to identify de novo immune-mediated graft events and its impact on outcomes has not been assessed. In 241 donor/recipient kidney transplant pairs, DNA samples were re-evaluated for six-locus (A/B/C/DRB1/DQB1+A1/DPB1) HR HLA typing. De novo anti-HLA antibodies were assessed using solid-phase assays, and dnDSA were classified either (1) as per current clinical practice according to three-locus (A/B/DRB1) low-resolution (LR) typing, estimating donor HLA-C/DQ typing with frequency tables, or (2) according to complete six-locus HR typing. The impact on graft outcomes was compared between groups. According to LR HLA typing, 36 (15%) patients developed dnDSA (LR_dnDSA+). Twenty-nine out of 36 (80%) were confirmed to have dnDSA by HR typing (LR_dnDSA+/HR_dnDSA+), whereas 7 (20%) did not (LR_dnDSA+/HR_dnDSA-). Out of 49 LR_dnDSA specificities, 34 (69%) were confirmed by HR typing whereas 15 (31%) LR specificities were not confirmed. LR_dnDSA+/HR_dnDSA+ patients were at higher risk of ABMR as compared to dnDSA- and LR_dnDSA+/HR_dnDSA- (logRank < 0.001), and higher risk of death-censored graft loss (logRank = 0.001). Both LR_dnDSA+ (HR: 3.51, 95% CI = 1.25-9.85) and LR_dnDSA+/HR_dnDSA+ (HR: 4.09, 95% CI = 1.45-11.54), but not LR_dnDSA+/HR_dnDSA- independently predicted graft loss. The implementation of HR HLA typing improves the characterization of biologically relevant de novo anti-HLA DSA and discriminates patients with poorer graft outcomes

Rediscovery of Cereopsis studeri Koch, 1891, a forgotten Mediterranean soft coral species, and its inclusion in the genus Nidalia Gray, 1835 (Octocorallia, Alcyonacea, Nidaliidae)

Cereopsis studeri was described by G. von Koch in 1891 with material from Naples. However, it was subsequently synonymized, erroneously identified, and overlooked in subsequent soft coral literature of the twentieth century. After the original description, this species was not recorded or correctly described for 120 years. The study of newly collected material from the North Western Mediterranean permits the re-description of this forgotten species and its assignation to the genus Nidalia in the family Nidaliidae. The main features of Nidalia studeri com. nov. are: colony torch-like, a capitulum light orange in colour, not laterally flattened, dome-shaped and not distinctly projecting beyond the stalk, introvert with sclerites transversally placed in two longitudinal rows per interseptal space, anthocodial crown with 28–38 sclerite rows, points separated from polyps distally, formed by 6–9 pairs of sclerites, and the presence of intermediate points (secondary points) between principal (interseptal) ones. Nidalia studeri is here compared with its closest congeners, especially with the Indonesian species N. simpsoni, species from the West Indian Region N. dissidens, N.occidentalis, N. deichmannae, and the recently described Nidalia aurantia from the Mid-Atlantic Ocean. This is the first time that the genus Nidalia and the family Nidaliidae have been reported with certainty for the Mediterranean Sea

Morphological features of the gorgonian Paramuricea macrospina on the continental shelf and shelf edge (Menorca Channel, Western Mediterranean Sea)

Morphological variability in gorgonians is frequent and commonly associated with habitat variability, often resulting in segregated morphotypes. Paramuricea macrospina is an endemic Mediterranean gorgonian species found on rocky bottoms between 40 and 160 m depth and has recently been reported as one of the most abundant species in continental shelf and shelf edge environments. Three different chromatic forms of P. macrospina were observed in the Menorca Channel: a yellow form and a light purple form occurring on maërl beds of the continental shelf, and a dark purple form occurring on rocky substrates of the shelf edge. The objective of the present work is to verify if these P. macrospina forms may represent distinct taxonomic units by analysing differences in colony morphology and sclerite size and shape of the three chromatic forms. No significant differences were found in colony shape, suggesting that environmental variability between the continental shelf and the shelf edge is not influential enough to significantly alter colony morphology. Significant differences in sclerite size and shape were found amongst all forms, suggesting that sclerites may be influenced by environmental conditions. However, the co-occurrence of the yellow and light purple forms side by side on the continental shelf may indicate a certain degree of genetic differentiation