Predicting acute kidney injury: current status and future challenges.

Acute kidney injury (AKI) is characterized by an acute decline in renal function and is associated to increased mortality rate, hospitalization time, and total health-related costs. The severity of this 'fearsome' clinical complication might depend on, or even be worsened by, the late detection of AKI, when the diagnosis is based on the elevation of serum creatinine (SCr). For these reasons, in recent years a great number of new tools, biomarkers and predictive models have been proposed to clinicians in order to improve diagnosis and prevent the development of AKI. The purpose of this narrative paper is to review the current state of the art in prediction and early detection of AKI and outline future challenges.

Endogenous Ouabain: An Old Cardiotonic Steroid as a New Biomarker of Heart Failure and a Predictor of Mortality after Cardiac Surgery.

Cardiovascular diseases remain the main cause of mortality and morbidity worldwide; primary prevention is a priority for physicians. Biomarkers are useful tools able to identify high-risk individuals, guide treatments, and determine prognosis. Our aim is to investigate Endogenous Ouabain (EO), an adrenal stress hormone with hemodynamic effects, as a valuable biomarker of heart failure. In a population of 845 patients undergoing elective cardiac surgery, we have investigated the relationships between EO and echocardiography parameters/plasmatic biomarker of cardiac function. EO was found to be correlated negatively with left ventricular EF (p = 0.001), positively with Cardiac End-Diastolic Diameter (p = 0.047), and positively with plasmatic NT-proBNP level (p = 0.02). Moreover, a different plasmatic EO level (both preoperative and postoperative) was found according to NYHA class (p = 0.013). All these results have been replicated on an independent cohort of patients (147 subjects from US). Finally, a higher EO level in the immediate postoperative time was indicative of a more severe cardiological condition and it was associated with increased perioperative mortality risk (p = 0.023 for 30-day morality). Our data suggest that preoperative and postoperative plasmatic EO level identifies patients with a more severe cardiovascular presentation at baseline. These patients have a higher risk of morbidity and mortality after cardiac surgery.

TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives.

BACKGROUND: Thiazide diuretics have been recommended as a first-line antihypertensive treatment, although the choice of 'the right drug in the individual essential hypertensive patient' remains still empirical. Essential hypertension is a complex, polygenic disease derived from the interaction of patient's genetic background with the environment. Pharmacogenomics could be a useful tool to pinpoint gene variants involved in antihypertensive drug response, thus optimizing therapeutic advantages and minimizing side effects. METHODS AND RESULTS: We looked for variants associated with blood pressure response to hydrochlorothiazide over an 8-week follow-up by means of a genome-wide association analysis in two Italian cohorts of never-treated essential hypertensive patients: 343 samples from Sardinia and 142 from Milan. TET2 and CSMD1 as plausible candidate genes to affect SBP response to hydrochlorothiazide were identified. The specificity of our findings for hydrochlorothiazide was confirmed in an independent cohort of essential hypertensive patients treated with losartan. Our best findings were also tested for replication in four independent hypertensive samples of European Ancestry, such as GENetics of drug RESponsiveness in essential hypertension, Genetic Epidemiology of Responses to Antihypertensives, NORdic DILtiazem intervention, Pharmacogenomics Evaluation of Antihypertensive Responses, and Campania Salute Network-StayOnDiur. We validated a polymorphism in CSMD1 and UGGT2. CONCLUSION: This exploratory study reports two plausible loci associated with SBP response to hydrochlorothiazide: TET2, an aldosterone-responsive mediator of αENaC gene transcription; and CSMD1, previously described as associated with hypertension in a case-control study.