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

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. ..

Early cyclosporine a withdrawal in kidney-transplant recipients receiving sirolimus prevents progression of chronic pathologic allograft lesions

BACKGROUND: Nephrotoxicity of calcineurin inhibitors (CNIs) is partially responsible for the development of chronic allograft nephropathy (CAN). Sirolimus has demonstrated its potential to substitute for CNIs because it lacks significant nephrotoxicity and shows a short-term immunosuppressive capacity comparable with that of cyclosporine. This results in the maintenance of better renal function when cyclosporine is eliminated, but it has not been demonstrated whether this benefit is associated with an improvement in the pathologic substrate and a reduction in CAN. METHODS: We analyzed pretransplant and 1-year renal-allograft biopsies from 64 patients enrolled in a multicenter trial. Patients received cyclosporine and sirolimus during the first 3 months after transplant and were then randomly assigned to continue with cyclosporine or have it withdrawn. Histologic chronic allograft lesions were compared between groups. RESULTS: The percentage of patients in whom chronic pathologic lesions progressed was lower in the group of cyclosporine elimination. Significant differences were observed in chronic interstitial and tubular lesions (70% vs. 40.9% [P<0.05] and 70% vs. 47.8% [P<0.05], respectively), whereas no differences were observed in acute lesions (subclinical rejection). Prevalence of CAN at 1 year was lower in this group, as was the severity and incidence of new cases (P<0.05). CONCLUSIONS: Early cyclosporine withdrawal associated with sirolimus administration is followed by an improvement in renal function, a reduction in the progression of chronic pathologic allograft lesions, and a lower incidence of new cases and severity of CAN during the first year after transplantation. This benefit may result in better long-term graft outcome

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

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

Acute renal failure induced by acute interstitial nephritis secondary to cocaine

Document publicat també en castellàCocaine has been used by 2.6% of the Spanish population aged between 15 and 64 at some point in their life, making it one of the most consumed illegal drugs after cannabis.1 Cocaine use is associated with multiple complications: neurological, cardiovascular, psychiatric, pulmonary, gastrointestinal and nephrological. Renal complications associated with cocaine use have received little attention, despite the existence of several mechanisms, in addition to secondary high blood pressure, that can cause acute renal failure (ARF) or worsen a pre-existing case of chronic renal failure. Drug-induced acute interstitial nephritis (DIAIN) represents a high percentage of acute renal failure in clinical practice. Some studies indicate that DIAIN is the lesion responsible for renal failure in about 15% of biopsies with ARF. Furthermore, in many cases of DIAIN, no biopsy is performed and diagnosis is based on clinical data and recent administration of a new drug which, as described below, is sometimes not very easy to identify

Dual Costimulatory and Coinhibitory Targeting with a Hybrid Fusion Protein as an Immunomodulatory Therapy in Lupus Nephritis Mice Models

Systemic lupus erythematosus is a complex autoimmune disorder mostly mediated by B-cells in which costimulatory signals are involved. This immune dysregulation can cause tissue damage and inflammation of the kidney, resulting in lupus nephritis and chronic renal failure. Given the previous experience reported with CTLA4-Ig as well as recent understanding of the PD-1 pathway in this setting, our group was encouraged to evaluate, in the NZBWF1 model, a human fusion recombinant protein (Hybri) with two domains: CTLA4, blocking the CD28-CD80 costimulatory pathway, and PD-L2, exacerbating the PD-1-PD-L2 coinhibitory pathway. After achieving good results in this model, we decided to validate the therapeutic effect of Hybri in the more severe MRL/lpr model of lupus nephritis. The intraperitoneal administration of Hybri prevented the progression of proteinuria and anti-dsDNA antibodies to levels like those of cyclophosphamide and reduced the histological score, infiltration of B-cells, T-cells, and macrophages and immune deposition in both lupus-prone models. Additionally, Hybri treatment produced changes in both inflammatory-related circulating cytokines and kidney gene expression. To summarize, both in vivo studies revealed that the Hybri effect on costimulatory-coinhibitory pathways may effectively mitigate lupus nephritis, with potential for use as a maintenance therapy

What do glass sponges do when no one is looking? Vazella pourtalesii: Responses to sediment deposition, passive locomotion, and contracting behavior

Behavioral response of deep-sea sponges can provide crucial insights into the mechanisms shaping energy fluxes and ecosystem functioning. Although some advances have been made, the behavior of deep-sea Hexactinellid still remain widely unknown. In the present study we address the glass sponge Vazella pourtalesii behavior. High-temporal resolution imaging and environmental data were acquired with an autonomous lander deployed in the Sambro Bank Sponge Conservation Area (Scotian Shelf) at a depth of 150 m, representing the upper limit of this deep-sea species' distribution and what is commonly regarded as the deep sea. For 94 days, a V. pourtalesii individual was monitored, providing quantitative information on its response to sediment deposition triggered by a storm, as well as on its passive locomotion and contractive behavior. Sediment was cleared from its surface within 72 h, which is highly relevant for its filtering capacity, indicating that this sponge species can cope with high suspended sediment concentrations. This enables it to occur on sedimentary environments like the Scotian Shelf. As observed in other deep-sea hexactinellids, the monitored individual engaged in rhythmic contractions, which appear to be driven by physiological process/es rather than environmental factors. During the study period, strong bottom currents (>37 cm/s) toppled and displaced the monitored individual several times. Despite changes in position and orientation that can negatively impact the filtering capacity of sponges, no signs of deterioration were observed. V. pourtalesii's vase-like body morphology and attachment to cobbles, as a gravitational center, may allow it to have a more homogeneous interaction with currents which may permit them to better cope with positional changes. Overall, this study highlights that deep-sea Porifera display a wide array of phenological changes in response to both biotic and abiotic factors