Serum aminoacylase-1 is a novel biomarker with potential prognostic utility for long-term outcome in patients with delayed graft function following renal transplantation.

Early identification and prognostic stratification of delayed graft function following renal transplantation has significant potential to improve outcome. Mass spectrometry analysis of serum samples, before and on day 2 post transplant from five patients with delayed graft function and five with an uncomplicated transplant, identified aminoacylase-1 (ACY-1) as a potential outcome biomarker. Following assay development, analysis of longitudinal samples from an initial validation cohort of 55 patients confirmed that the ACY-1 level on day 1 or 2 was a moderate predictor of delayed graft function, similar to serum creatinine, complementing the strongest predictor cystatin C. A further validation cohort of 194 patients confirmed this association with area under ROC curves (95% CI) for day 1 serum (138 patients) of 0.74 (0.67–0.85) for ACY-1, 0.9 (0.84–0.95) for cystatin C, and 0.93 (0.88–0.97) for both combined. Significant differences in serum ACY-1 levels were apparent between delayed, slow, and immediate graft function. Analysis of long-term follow-up for 54 patients with delayed graft function showed a highly significant association between day 1 or 3 serum ACY-1 and dialysis-free survival, mainly associated with the donor–brain–dead transplant type. Thus, proteomic analysis provides novel insights into the potential clinical utility of serum ACY-1 levels immediately post transplantation, enabling subdivision of patients with delayed graft function in terms of long-term outcome. Our study requires independent confirmation

Networks in coronary heart disease genetics as a step towards systems epidemiology

We present the use of innovative machine learning techniques in the understanding of Coronary Heart Disease (CHD) through intermediate traits, as an example of the use of this class of methods as a first step towards a systems epidemiology approach of complex diseases genetics. Using a sample of 252 middle-aged men, of which 102 had a CHD event in 10 years follow-up, we applied machine learning algorithms for the selection of CHD intermediate phenotypes, established markers, risk factors, and their previously associated genetic polymorphisms, and constructed a map of relationships between the selected variables. Of the 52 variables considered, 42 were retained after selection of the most informative variables for CHD. The constructed map suggests that most selected variables were related to CHD in a context dependent manner while only a small number of variables were related to a specific outcome. We also observed that loss of complexity in the network was linked to a future CHD event. We propose that novel, non-linear, and integrative epidemiological approaches are required to combine all available information, in order to truly translate the new advances in medical sciences to gains in preventive measures and patients care.British Heart Foundation; European Commission; British Medical Research Council; the US National Institutes of Health and Du Pont Pharma, Wilmington

Acute kidney injury: prevention, detection, and management. Summary of updated NICE guidance for adults receiving iodine-based contrast media.

The National Institute for Health and Care Excellence (NICE) has recently updated the guideline for Acute kidney injury: prevention, detection and management (NG148), providing new recommendations on preventing acute kidney injury (AKI) in adults receiving intravenous iodine-based contrast media. The association between intravenous iodinated contrast media and AKI is controversial, particularly with widespread use of iso-osmolar agents. Associations between contrast media administration and AKI are largely based on observational studies, with inherent heterogeneity in patient populations, definitions applied, and timing of laboratory investigations. In an attempt to mitigate risk, kidney protection has typically been employed using intravenous volume expansion and/or oral acetylcysteine. Such interventions are in widespread use, despite lacking high-quality evidence of benefit. In the non-emergency setting, glomerular filtration rate (GFR) measurements should be obtained within the preceding 3 months before offering intravenous iodine-based contrast media. In the acute setting, adults should also have their risk of AKI assessed before offering intravenous iodine-based contrast media; however, this should not delay emergency imaging. Based on the evidence available from randomised controlled trials, the NICE committee recommends that oral hydration should be encouraged in adults at increased risk of AKI and that volume expansion with intravenous V fluids should only be considered for inpatients at particularly high risk