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

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

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

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

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

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

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

JAK3-STAT pathway blocking benefits in experimental lupus nephritis

Es va publicar un erratum de l'article a: Arthritis Research & Therapy, 2016, vol. 18 , num. 1, p. 152Background: Lupus nephritis (LN) is a complex chronic autoimmune disease of unknown etiology characterized by loss of tolerance against several self-antigens. Cytokines are known to be central players in LN pathogenesis. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is one important pathway that mediates signal transduction of several cytokines. In this study, we examined the pathogenic role of this pathway and how CP-690,550 treatment influences LN outcome. Methods: Six-month-old NZB/NZWF1 mice were divided into two different treatment groups: (1) control animals given vehicle treatment, cyclophosphamide, and mycophenolate mofetil treatment as positive controls of the therapy and (2) mice treated with CP-690,550, a JAK3 inhibitor. Mice were treated for 12 weeks. We evaluated renal function, anti-double-stranded DNA (anti-dsDNA) antibody, renal histology changes, kidney complement and immunoglobulin G (IgG) deposits, T-cell and macrophage infiltration, kidney inflammatory gene expression, and circulating cytokine changes. Results: CP-690,550 treatment significantly reduced proteinuria and improved renal function and histological lesions of the kidney. Compared with vehicle-treated animals, those undergoing CP-690,550 treatment showed significantly diminished anti-dsDNA antibody and complement component C3 and IgG deposition in glomeruli. We also observed a significant reduction of T-cell and macrophage infiltration. Kidney gene expression revealed a reduction in inflammatory cytokines and complement and related macrophage-attracting genes. Circulating inflammatory cytokines were also reduced with treatment. Conclusions: On the basis of our results, we conclude that the JAK-STAT pathway is implicated in the progression of renal inflammation in NZB/WF1 mice and that targeting JAK3 with CP-690,550 is effective in slowing down the course of experimental LN. Thus, CP-690,550 could become a new therapeutic tool in LN and other autoimmune diseases