Pulse wave velocity predicts mortality in renal transplant patients

<p>Abstract</p> <p>Background</p> <p>Measuring arterial stiffness using pulse wave velocity (PWV) has become an important tool to assess vascular function and cardiovascular mortality. For subject with hypertension, end-stage renal disease and diabetes, PWV has been shown to predict cardiovascular and all-cause mortality. We hypothesize that PWV would also predict mortality in subjects who have undergone kidney transplantation.</p> <p>Methods</p> <p>A cohort of 330 patients with renal transplantation was studied with a mean age at entry 51.4 ± 0.75 years. Mean follow-up was 3.8 years (± 0.7 years); 16 deaths occurred during follow-up. At entry, together with standard clinical and biochemical parameters, PWV was determined from pressure tracing over carotid and femoral arteries.</p> <p>Results</p> <p>With increasing PWV, there was a significant increase in age, systolic blood pressure and pulse pressure. In addition, subjects with higher PWV also exhibited more frequently the presence of coronary heart disease. On the basis of Cox analyses, PWV and systolic blood pressure emerged as predictors of all-cause mortality.</p> <p>Conclusion</p> <p>These results provide evidence that PWV is a strong predictor of all-cause mortality in the population of renal transplant recipients.</p

Increased expression of costimulatory markers CD134 and CD80 on interleukin-17 producing T cells in patients with systemic lupus erythematosus

Introduction: There is growing evidence that interleukin 17 (IL-17) producing T cells are involved in the pathogenesis of systemic lupus erythematosus (SLE). Previous studies showed that increased percentages of T-cell subsets expressing the costimulatory molecules CD80 and CD134 are associated with disease activity and renal involvement in SLE. The aim of this study was to investigate the distribution and phenotypical characteristics of IL-17 producing T-cells in SLE, in particular in patients with lupus nephritis, with emphasis on the expression of CD80 and CD134. Methods: Thirty-four patients (3 male, 31 female, mean age 41 +/- 15 years) fulfilling at least four of the American College of Rheumatology (ACR) revised criteria for the diagnosis of SLE and 24 healthy controls were enrolled. T-cells from the peripheral blood were analysed by fluorescence activated cell sorting (FACS) for their expression levels of CD80, CD134 and CCR6. In vitro stimulated CD3(+)IL17(+) cells were also investigated for the expression of these costimulatory markers. Finally, renal biopsies from SLE patients were evaluated for the presence of CD134 expressing T-cells. Results: Percentages of IL-17 expressing T-cells were significantly increased in patients with active disease as compared to healthy controls (1.46 +/- 0.58% versus 0.93 +/- 0.30%, P = 0.007). The percentage of IL-17 producing T-cells was correlated with disease activity as assessed by systemic lupus erythematosus disease activity index (SLEDAI) (r = 0.53, P = 0.003). In patients, most of the IL-17 producing T-cells were confined to the CCR6(+) T-cell subset (80 +/- 13%). Expression of CD80 and CD134 on the IL-17 producing T-cell subset was higher in SLE than in healthy controls (HC) (CD134: 71.78 +/- 14.51% versus 51.45 +/- 16.58%, P = 0.002; CD80: 25.5 +/- 14.99% versus 14.99 +/- 5.74%, P = 0.02). Also, patients with lupus nephritis expressed higher levels of CD134(+) on CD3(+)IL-17(+) cells as compared to HC (72.69 +/- 11.54% versus 51.45 +/- 16.58%, P = 0.006). Furthermore, renal biopsies of lupus nephritis patients showed infiltration of CD134(+) T cells. Conclusions: Percentages of IL-17 expressing T-cells correlate with disease activity. Further, these cells show increased expression of costimulatory markers such as CD134 and CD80. The presence of CD134(+) T-cells in renal biopsies of lupus nephritis patients suggest that these cells migrate to the kidney and might contribute to inflammatory processes through IL-17 secretion

CD107a(+) (LAMP-1) Cytotoxic CD8(+) T-Cells in Lupus Nephritis Patients

Cytotoxic CD8(+) T-cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to investigate the role of CD107a (LAMP-1) on cytotoxic CD8(+) T-cells in SLE-patients in particular with lupus nephritis. Peripheral blood of SLE-patients (n = 31) and healthy controls (n = 21) was analyzed for the expression of CD314 and CD107a by flow cytometry. Kidney biopsies of lupus nephritis patients were investigated for the presence of CD8(+) and C107a(+) cells by immunohistochemistry and immunofluorescence staining. The percentages of CD107a(+) on CD8(+) T-cells were significantly decreased in SLE-patients as compared to healthy controls (40.2 +/- 18.5% vs. 47.9 +/- 15.0%, p = 0.02). This was even more significant in SLE-patients with inactive disease. There was a significant correlation between the percentages of CD107a(+)CD8(+) T-cells and SLEDAI. The evaluation of lupus nephritis biopsies showed a significant number of CD107a(+)CD8(+) T-cells mainly located in the peritubular infiltrates. The intrarenal expression of CD107a(+) was significantly correlated with proteinuria. These results demonstrate that CD8(+) T-cells of patients with systemic lupus erythematosus have an altered expression of CD107a which seems to be associated with disease activity. The proof of intrarenal CD107a(+)CD8(+) suggests a role in the pathogenesis of lupus nephritis

Efectos de la circulación extracorpórea sobre el filtrado glomerular en la cirugía cardiovascular pediátrica

Objetivoconocer como afecta la circulación extracorpórea la función renal tomando como marcador la alteración del filtrado glomerular.Material y métodose realizó un estudio prospectivo, analítico y observacional en 63 pacientes pediátricos sometidos a cirugía cardiaca electiva con circulación extracorpórea en el Cardiocentro Pediátrico «William Soler» entre octubre de 2009 y abril de 2010. Se calcularon las variaciones del filtrado glomerular durante la circulación extracorpórea por el método de Schwartz y se extrajeron muestras de sangre antes y después de la circulación extracorpórea para determinar las cifras de creatinina en el plasma. Los datos se procesaron con el paquete estadístico SPSS versión 11.5.1. Los resultados se expresaron en forma de media, desviación estándar y por cientos. Se consideró que existió diferencia o asociación significativa si la probabilidad asociada al test aplicado era menor que 0,05 (p<0,05). El análisis se realizó por medio de pruebas no paramétricas dado n < 30 y a través de muestras relacionadas.Resultadosla disminución del filtrado glomerular pos-circulación extracorpórea, no se asoció con el tipo de cardiopatía (p<0,056) y sí con el estado previo de éste (p<0,000). El tiempo de duración de la circulación extracorpórea contribuyó significativamente al deterioro del filtrado glomerular (p<0,021); no así el tiempo de pinzamiento aórtico (p<0,06). El volumen de orina obtenido durante el tiempo de la circulación extracorpórea (p<0,051) y en el período trans-operatorio (p<0.056) no fue un índice de buen funcionamiento renal medido a través del filtrado glomerular.Conclusionesla circulación extracorpórea afecta de manera significativa la función renal tomando como marcador la alteración del filtrado glomerular.Objectiveknow how extracorporeal circulation affects renal function taking as marker the impairment of the glomerular filtration rate.Material and methodwe performed a prospective analytical observational study in 63 pediatric patients that underwent elective cardiac surgery with extracorporeal circulation in the Pediatric Cardiac Center ¨William Soler¨ between october 2009 and april 2010. Variations of glomerular filtration rate during extracorporeal circulation were calculated by the Schwartz method and blood samples were taken to determine plasma creatinine values before and after extracorporeal circulation. Data were processed with the SPSS statistical package version 11.5.1. Results were expressed as mean, standard deviation and percentage. We considered that difference or significant association existed if the probability associated to the applied test was less than 0,05 (p<0,05). Analysis was performed by nonparametric testing given n < 30 and through related samples.Resultsthe decline in glomerular filtration rate post extracorporeal circulation was not associated to the type of cardiopathy (p<0,056) but it was associated to its previous state (p<0,000). The duration of extracorporeal circulation contributes significantly to the deterioration of the glomerular filtration rate (p<0,021); this did not happen with the aortic clamping time (p<0,06). The volume of urine obtained during the duration of extracorporeal circulation (p<0,051) and during the trans-operative period (p<0,056) was not an index of appropriate renal function measured by glomerular filtration rate.Conclusionsextracorporeal circulation affects significantly the renal function taking as a marker the impairment of glomerular filtration rate

Transplantation of Renal Allografts From Organ Donors Reactive for HCV Antibodies to HCV-Negative Recipients: Safety and Clinical Outcome

IntroductionBecause of the shortage of available organs for renal transplantation, strategies enabling the safe use of organs from donors with potential chronic infections such as hepatitis C are necessary. The aim of this study was to analyze the outcome of renal transplant donation from hepatitis C virus (HCV)-positive donors.MethodsBetween September 2002 and May 2007, 51 kidneys (34 donors) reactive for HCV antibodies were further evaluated. Six kidneys (5 donors) were transplanted to 6 recipients with known chronic HCV infection. The remaining 29 donors underwent extended virological testing. Nine donors were HCV RNA positive and thus not suitable for HCV-negative patients. Twenty donors (21 kidneys) did not have detectable HCV RNA copies and were transplanted into 21 HCV-negative recipients. Clinical outcomes focusing on safety, allograft function, and de novo HCV infection in the recipient were collected.ResultsThere were no de novo HCV infections detected in recipients who were HCV negative before transplantation. The extended virological donor screening did not have an impact on median cold ischemia time. Five-year graft survival was 75%.DiscussionOrgans from anti-HCV-reactive, nonviremic donors can be transplanted safely to HCV-negative recipients

Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study

Background & AimsIn acute liver failure, severity of liver injury and clinical progression of disease are in part consequent upon activation of the innate immune system. Endotoxaemia contributes to innate immune system activation and the detoxifying function of albumin, critical to recovery from liver injury, is irreversibly destroyed in acute liver failure. University College London-Liver Dialysis Device is a novel artificial extracorporeal liver assist device, which is used with albumin infusion, to achieve removal and replacement of dysfunctional albumin and reduction in endotoxaemia. We aimed to test the effect of this device on survival in a pig model of acetaminophen-induced acute liver failure.MethodsPigs were randomised to three groups: Acetaminophen plus University College London-Liver Dialysis Device (n=9); Acetaminophen plus Control Device (n=7); and Control plus Control Device (n=4). Device treatment was initiated two h after onset of irreversible acute liver failure.ResultsThe Liver Dialysis Device resulted in 67% reduced risk of death in acetaminophen-induced acute liver failure compared to Control Device (hazard ratio=0.33, p=0.0439). This was associated with 27% decrease in circulating irreversibly oxidised human non-mercaptalbumin-2 throughout treatment (p=0.046); 54% reduction in overall severity of endotoxaemia (p=0.024); delay in development of vasoplegia and acute lung injury; and delay in systemic activation of the TLR4 signalling pathway. Liver Dialysis Device-associated adverse clinical effects were not seen.ConclusionsThe survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients

A Case of Severe Acute Kidney Injury by Near-Drowning

Acute kidney injury (AKI) secondary to near-drowning is rarely described and poorly understood. Only few cases of severe isolated AKI resulting from near-drowning exist in the literature. We report a case of near-drowning who developed to isolated AKI due to acute tubular necrosis (ATN) requiring dialysis. A 21-yr-old man who recovered from near-drowning in freshwater 3 days earlier was admitted to our hospital with anuria and elevated level of serum creatinine. He needed five sessions of hemodialysis and then renal function recovered spontaneously. Renal biopsy confirmed ATN. We review the existing literature on near-drowning-induced AKI and discuss the possible pathogenesis