A snapshot of European registries on chronic kidney disease patients not on kidney replacement therapy

Non peer reviewe

Young deceased donor kidneys show a survival benefit over older donor kidneys in transplant recipients aged 20-50 years:a study by the ERA-EDTA Registry

Background: Updated survival outcomes of young recipients receiving young or old deceased donor kidneys are required when considering accepting a deceased donor kidney. Methods: We examined outcomes in 6448 European kidney allografts donated from younger (≥20-<50 years) and older (≥50-<70 years) deceased donors when transplanted into very young (≥20-<35 years) or young (≥35-<50 years) adult recipients. Outcomes of first kidney transplantations during 2000-13 and followed-up to 2015 were determined via competing risk, restricted mean survival and Cox regression methods. Results: The 10-year cumulative incidence of graft failure was lowest in very young {22.0% [95% confidence interval (95% CI) 19.1-24.9]} and young [15.3% (95% CI 13.7-16.9)] recipients of younger donor kidneys and highest in very young [36.7% (95% CI 31.9-41.5)] and young [29.2% (95% CI 25.1-33.2)] recipients of older donor kidneys. At the 10-year follow-up, younger donor kidneys had a 1 year (very young) or 9 months (young) longer mean graft survival time compared with older donor kidneys. Graft failure risk in younger donor kidneys was 45% [very young adjusted hazard ratio (aHR) 0.55 (95% CI 0.44-0.68)] and 40% [young aHR 0.60 (95% CI 0.53-0.67)] lower compared with older donor kidneys. A 1-year increase in donor age resulted in a 2% [very young aHR 1.02 (95% CI 1.00-1.04)] or 1% [young aHR 1.01 (95% CI 1.00-1.01)] increase in the 10-year risk of death. Conclusions: Younger donor kidneys show survival benefits over older donor kidneys in adult recipients ages 20-50 years. Updated survival outcomes from older deceased donors are necessary due to advances in transplantation medicine and the increasing role these donors play in organ transplantation

Bumetanide for autism: more eye contact, less amygdala activation.

We recently showed that constraining eye contact leads to exaggerated increase of amygdala activation in autism. Here, in a proof of concept pilot study, we demonstrate that administration of bumetanide (a NKCC1 chloride importer antagonist that restores GABAergic inhibition) normalizes the level of amygdala activation during constrained eye contact with dynamic emotional face stimuli in autism. In addition, eye-tracking data reveal that bumetanide administration increases the time spent in spontaneous eye gaze during in a free-viewing mode of the same face stimuli. In keeping with clinical trials, our data support the Excitatory/Inhibitory dysfunction hypothesis in autism, and indicate that bumetanide may improve specific aspects of social processing in autism. Future double-blind placebo controlled studies with larger cohorts of participants will help clarify the mechanisms of bumetanide action in autism

Variable viral clearance despite adequate ganciclovir plasma levels during valganciclovir treatment for cytomegalovirus disease in D+/R- transplant recipients

ABSTRACT: BACKGROUND: Valganciclovir, the oral prodrug of ganciclovir, has been demonstrated equivalent to iv ganciclovir for CMV disease treatment in solid organ transplant recipients. Variability in ganciclovir exposure achieved with valganciclovir could be implicated as a contributing factor for explaining variations in the therapeutic response. This prospective observational study aimed to correlate clinical and cytomegalovirus (CMV) viral load response (DNAemia) with ganciclovir plasma concentrations in patients treated with valganciclovir for CMV infection/disease. METHODS: Seven CMV D+/R- transplant recipients (4 kidney, 2 liver and 1 heart) were treated with valganciclovir (initial dose was 900-1800 mg/day for 3-6.5 weeks, followed by 450-900 mg/day for 2-9 weeks). DNAemia was monitored by real time quantitative PCR and ganciclovir plasma concentration was measured at trough (Ctrough) and 3 h after drug administration (C3h) by HPLC. RESULTS: Four patients presented with CMV syndrome, two had CMV tissue-invasive disease after prophylaxis discontinuation, and one liver recipient was treated pre-emptively for asymptomatic rising CMV viral load 5 weeks post-transplantation in the absence of prophylaxis. CMV DNAemia decreased during the first week of treatment in all recipients except in one patient (median decrease: -1.2 log copies/mL, range: -1.8 to 0) despite satisfactory ganciclovir exposure (AUC0-12 = 48 mg.h/L, range for the 7 patients: 40-118 mg.h/L). Viral clearance was obtained in five patients after a median of time of 34 days (range: 28-82 days). Two patients had recurrent CMV disease despite adequate ganciclovir exposure (65 mg.h/L, range: 44-118 mg.h/L). CONCLUSIONS: Valganciclovir treatment for CMV infection/disease in D+/R- transplant recipients can thus result in variable viral clearance despite adequate ganciclovir plasma concentrations, probably correlating inversely with anti-CMV immune responses after primary infection

Hospital and outpatient clinic utilization among older people in the 3-5 years following the initiation of continuing care: a longitudinal cohort study

Background: Few studies have investigated the subsequent rate of hospital and outpatient clinic utilization in those who receive continuing care and have documented frequent usage over one year. Such knowledge may be helpful in identifying those who would benefit from preventive interventions. The aim of this study was to investigate and compare the subsequent rate of hospital and outpatient clinic utilization among older people with 0, 1, 2, 3 or more hospital stays in the first year following the initiation of continuing care. A further aim was to compare these groups regarding demographic data, health complaints, functional and cognitive ability, informal care and mortality. Methods: A total of 1079 people, aged 65 years or older, who received a decision regarding the initiation of continuing care during the years 2001, 2002 or 2003 were investigated. Four groups were created based on whether they had 0, 1, 2 or >= 3 hospital stays in the first year following the initiation of continuing care and were investigated regarding the rate of hospital and outpatient clinic utilization in the subsequent 3-5 years. Results: Fifty seven percent of the sample had no hospital stay during the first year following the initiation of continuing care, 20% had 1 stay, 10% had 2 stays and 13% had three or more hospital stays (range: 3-13). Those with >= 3 hospital stays in the first year continued to have the significantly highest rate of hospital and outpatient care utilization in the subsequent years. This group accounted for 57% of hospital stays in the first year, 27% in the second year and 18% in the third year. In this group the risk of having >= 3 hospital stays in the second year was 27% and 12% in the third year. Conclusions: There is a clear need for interventions targeted on prevention of frequent hospital and outpatient clinic utilization among those who are high users of hospital care in the first year after the initiation of continuing care. Perhaps an increased availability of medically skilled staff in the day to day care of these people in the municipalities could prevent frequent hospital and outpatient clinic utilization, especially hospital readmissions

A Simplified Iohexol-Based Method to Measure Renal Function in Sheep Models of Renal Disease

12 Pág.Sheep are highly adequate models for human renal diseases because of their many similarities in the histology and physiology of kidney and pathogenesis of kidney diseases. However, the lack of a simple method to measure glomerular filtration rate (GFR) limits its use as a model of renal diseases. Hence, we aimed to develop a simple method to measure GFR based on the plasma clearance of iohexol by assessing different pharmacokinetic models: (a) CL2: two-compartment (samples from 15 to 420 min; reference method); (b) CL1: one-compartment (samples from 60 to 420 min); (c) CLlf: CL1 adjusted by a correction formula and (d) SM: simplified CL2 (15 to 300 min). Specific statistics of agreement were used to test the models against CL2. The agreement between CL1 and CL2 was low, but both CL1f and SM showed excellent agreement with CL2, as indicated by a total deviation index of ~5-6%, a concordance correlation of 0.98-0.99% and a coverage probability of 99-100%, respectively. Hence, the SM approach is preferable due to a reduced number of samples and shorter duration of the procedure; two points that improve animal management and welfare.This research received no external funding.Peer reviewe