Evaluación terapéutica, desarrollo y perspectivas del trasplante renal

Las alternativas terapéuticas que se pueden ofrecer a los enfermos afectos de insuficiencia renal terminal son la diálisis, en sus distintas formas, y el trasplante renal. Este último proporciona un grado de rehabilitación superior y, por tanto, es la terapéutica de elección. Tras esta afirmación, se recogen las principales indicaciones del trasplante renal, así como las contraindicaciones del mismo, para adentrarnos, seguidamente, en el campo de la inmunosupresíón y la histocompatibilidad, en donde se han producido los cambios más importantes en los últimos años

La síndrome de descompressió

La síndrome de descompressió és la que sobrevé en el curs o seguint una reducció de pressió a la qual es trobava sotmès l'organisme. Per tant, acostumen a patir-la els bussadors i, generalment, els treballadors sotmesos a hiperpressió. Tot i que l'etiopatogènia no és clara hom considera que la malaltia es produeix a conseqüència de la formació de bombolles intravasculars a càrrec dels gasos dissolts en els teixits i els fluids corporals, sobretot el nitrogen. ..

Chronic allograft nephropathy

Long-term survival of kidney transplants (renal allografts) has changed little during the past decade, despite dramatic improvements in short-term survival. Most late renal allograft loss, other than that associated with the death of the patient, has been attributed to progressive renal dysfunction, termed "chronic allograft nephropathy" (or CAN), a confusing term that lacks a rigorous consensus definition

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

The Costimulatory Pathways And T Regulatory Cells In Ischemia-reperfusion Injury: A Strong Arm In The Inflammatory Response?

Costimulatory molecules have been identified as crucial regulators in the inflammatory response in various immunologic disease models. These molecules are classified into four different families depending on their structure. Here, we will focus on various ischemia studies that use costimulatory molecules as a target to reduce the inherent inflammatory status. Furthermore, we will discuss the relevant role of T regulatory cells in these inflammatory mechanisms and the costimulatory pathways in which they are involved

Macrophage overexpressing NGAL ameliorated kidney fibrosis in the UUO mice model

Background/Aims: Alternatively activated macrophages (AAM) have regenerative and anti-inflammatory characteristics. Here, we sought to evaluate whether AAM cell therapy reduces renal inflammation and fibrosis in the unilateral ureteral obstruction (UUO) mice model. Methods: We stabilized macrophages by adenoviral vector NGAL (Neutrophil gelatinase-associated lipocalin-2) and infused them into UUO mice. To ascertain whether macrophages were capable of reaching the obstructed kidney, macrophages were stained and detected by in vivo cell tracking. Results: We demonstrated that some infused macrophages reached the obstructed kidney and that infusion of macrophages overexpressing NGAL was associated with reduced kidney interstitial fibrosis and inflammation. This therapeutic effect was mainly associated with the phenotype and function preservation of the transferred macrophages isolated from the obstructed kidney Conclusions: Macrophage plasticity is a major hurdle for achieving macrophage therapy success in chronic nephropathies and could be overcome by transferring lipocalin-2

MAG3 renogram deconvolution in kidney transplantation: utility of the measurement of initial tracer uptake

The study of renal retention function by deconvolution analysis of renographic curves is useful to calculate quantitative parameters in renal studies. The aim of the work is to evaluate the usefulness of 99mTc-MAG3 renogram deconvolution in renal function monitoring of kidney graft recipients. Methods: forty-three kidney grafts and 112 renograms were studied: 41 were diagnosed as functioning graft, 35 as acute tubular necrosis, 24 as acute rejection, 8 as obstruction and 4 as cyclosporin toxicity. The parameters calculated were mean transit time (MTT), time at 20% of renal retention function (T20) and initial uptake (IU). Results: MTT and T20 were significantly longer in obstructives than in functioning grafts (p < 0.001). Initial uptake was significantly lower in acute tubular necrosis (ATN) and acute rejection (p < 0.001) and in obstructives (p < 0.05) than in functioning grafts. The joint evaluation of MTT and IU allowed to diagnose cases with graft function severely impaired. Conclusion: initial uptake is useful in evaluating post-transplantation complications and in combination with MTT and T20 reflects renal dysfunction severity

Avances en la inmunosupresión para el trasplante renal. Nuevas estrategias para preservar la función renal y reducir el riesgo cardiovascular

The development of new immunosuppressants for renal transplantation is aimed not only at improving short-term outcomes, but also at achieving better safety, cardiovascular, and metabolic profiles and at decreasing nephrotoxicity. Belatacept is a fusion protein that inhibits T cell activation by binding to CD80 and CD86 antigens. Clinical trials, particularly the BENEFIT and BENEFIT-EXT studies, have shown that belatacept preserves function and structure in renal grafts. The effects of belatacept provide long-term, sustained results, and the safety and efficacy of this drug have been demonstrated in cases of renal transplantation from expanded criteria donors. Compared to calcineurin inhibitors, belatacept is associated with a lower incidence of chronic allograft nephropathy and a more favourable cardiovascular and metabolic profile

Chronic Kidney Disease is associated with an increase of Intimal Dendritic cells in a comparative autopsy study

Background: Chronic Kidney Disease (CKD) and inflammation are risk factors for atherosclerotic vascular disease (ASVD). In inflammatory conditions, Nuclear Factor-kappa B (NF-kappa B) is frequently activated and it has been detected in human ASVD. In this work, we investigated if the degree of inflammation and of NF-kappa B activation were increased in the aorta of patients with CKD. Methods: This is a case-control pilot study performed on 30 abdominal aorta samples from 10 human autopsies. Cases were patients with CKD and controls patients with normal glomerular filtration rate (eGFR). Infiltrating mononuclear cells (S100(+), CD3(+), CD40(+), CD40L(+)) and activation of NF-kappa B were identified by immunohistochemistry. Findings: The number of cells in the intima which showed activated nuclear NF-.B correlated with severity of ASVD lesions (r = 0.56, p = 0.003), with numbers of CD3(+) lymphocytes in adventitia (r = 0.50, p = 0.008), with numbers of CD40(+) cells in the intima (r = 0.59, p = 0.002) or in the adventitia (r = 0.45, p = 0.02), and with numbers of CD40L(+) cells in the intima (r = 0.51, p = 0.011). Increased numbers of S100(+) Intimal Dendritic cells (IDCs) were associated with ASVD (p = 0.03) and CKD (p = 0.01). Conclusions: Number of CD3(+) cells, of CD40(+) cells, of CD40L(+) cells and the degree of NF-kappa B activation were increased in ASVD lesions suggesting a role for the adaptive T cell in the development of ASVD lesions. IDCs were associated both with ASVD and CKD suggesting a role of these cells in the pathogenesis of ASVD in CKD

Description of the ecology of the Gulf of Lions shelf and slope area and identification of the areas that may deserve to be protected

64 pages, 13 figures, 1 tableThe Regional Activity Centre for Specially Protected Areas (UNEP-MAP-RAC/SPA), with support from the European Commission and the Mediterranean Trust Funds, started in 2008 an ambitious project to identify and establish Marine Protected Areas in the open seas, including the deep seas, in order to promote the establishment of a representative ecological network of protected areas in the Mediterranean. The first phase of the project was based on the provisions of the Protocol concerning Specially Protected Areas and Biological Diversity in the Mediterranean (SPA/BD Protocol) and was completed at the end of 2009. Its main result was the identification of twelve areas as priority conservation areas in the open seas, including the deep seas, likely to include sites that could be candidates for inclusion in the SPAMI list. One of these areas is the so-called Gulf of Lions shelf and slope area (Figure 1). [...]This document has been prepared in the framework of the project for supporting the establishment of MPAs in open seas, including deep seas, with financial support of the European CommissionPeer Reviewe