Detection of Drug-Induced Acute Kidney Injury in Humans Using Urinary KIM-1, miR-21,-200c, and-423

Drug-induced acute kidney injury (AKI) is often encountered in hospitalized patients. Although serum creatinine (SCr) is still routinely used for assessing AKI, it is known to be insensitive and nonspecific. Therefore, our objective was to evaluate kidney injury molecule 1 (KIM-1) in conjunction with microRNA (miR)-21, -200c, and -423 as urinary biomarkers for drug-induced AKI in humans. In a cross-sectional cohort of patients (n = 135) with acetaminophen (APAP) overdose, all 4 biomarkers were significantly (P < .004) higher not only in APAP-overdosed (OD) patients with AKI (based on SCr increase) but also in APAP-OD patients without clinical diagnosis of AKI compared with healthy volunteers. In a longitudinal cohort of patients with malignant mesothelioma receiving intraoperative cisplatin (Cp) therapy (n = 108) the 4 biomarkers increased significantly (P < .0014) over time after Cp administration, but could not be used to distinguish patients with or without AKI. Evidence for human proximal tubular epithelial cells (HPTECs) being the source of miRNAs in urine was obtained first, by in situ hybridization based confirmation of increase in miR-21 expression in the kidney sections of AKI patients and second, by increased levels of miR-21, -200c, and -423 in the medium of cultured HPTECs treated with Cp and 4-aminophenol (APAP degradation product). Target prediction analysis revealed 1102 mRNA targets of miR-21, -200c, and -423 that are associated with pathways perturbed in diverse pathological kidney conditions. In summary, we report noninvasive detection of AKI in humans by combining the sensitivity of KIM-1 along with mechanistic potentials of miR-21, -200c, and -423

Research and Science Today No. 1(5)/2013

Research and Science Today Journal is a publication founded in 2011 and it is dedicated to the students of all levels (license, master and doctoral) of faculties in the country and abroad. We want to offer the participants the opportunity to present their scientific works in the following areas: Social Sciences, Economic Sciences, Legal Sciences, Humanities, Education Sciences, Engineering, Medicine and Sport. This journal provides students the opportunity to create and/or to improve their abilities to write scientific papers. So each appearance (two appearances per year at which we can add supplements) contains a number of papers written by students, masters and doctoral from the faculties from the country or/and abroad. The journal promotes original studies contributing to the progress of knowledge and it is motivated by the need to address issues of theory and practice in the areas mentioned above

Effects of Early Placement of Transjugular Portosystemic Shunts in Patients With High-Risk Acute Variceal Bleeding: a Meta-analysis of Individual Patient Data

BACKGROUND & AIMS: Compared with drugs plus endoscopy, placement of transjugular portosystemic shunt within 72 hours of admission to the hospital (early or preventive transjugular intrahepatic portosystemic shunt [TIPS], also called preemptive TIPS) increases the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survive for 1 year. However, the benefit of preemptive TIPS is less clear for patients with a Child-Pugh score of B and active bleeding (CP-B+AB). We performed an individual data meta-analysis to assess the efficacy of preemptive TIPS in these patients and identify factors associated with reduced survival of patients receiving preemptive TIPS. METHODS: We searched publication databases for randomized controlled trials and observational studies comparing the effects of preemptive TIPS versus endoscopy plus nonselective beta-blockers in the specific population of high-risk patients with cirrhosis and acute variceal bleeding (CP-B+AB or Child-Pugh C, below 14 points), through December 31, 2019. We performed a meta-analysis of data from 7 studies (3 randomized controlled trials and 4 observational studies), comprising 1327 patients (310 received preemptive TIPS and 1017 received drugs plus endoscopy). We built adjusted models to evaluate risk using propensity score for baseline covariates. Multivariate Cox regression models were used to assess the factors associated with survival time. The primary endpoint was effects of preemptive TIPS versus drugs plus endoscopy on 1-year survival in the overall population as well as CP-B+AB and Child-Pugh C patients. RESULTS: Overall, preemptive TIPS significantly increased the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survived for 1 year, compared with drugs plus endoscopy (hazard ratio [HR] 0.443; 95% CI 0.323-0.607; P < .001). This effect was observed in CP-B+AB patients (HR 0.524; 95% CI 0.307-0.896; P = .018) and in patients with Child-Pugh C scores below 14 points (HR 0.374; 95% CI 0.253-0.553; P < .001). Preemptive TIPS significantly improved control of bleeding and ascites without increasing risk of hepatic encephalopathy in Child-Pugh C and CP-B+AB patients, compared with drugs plus endoscopy. Cox analysis of patients who received preemptive TIPS showed that patients could be classified into 3 categories for risk of death, based on age, serum level of creatinine, and Child-Pugh score. In each of these risk categories, preemptive TIPS increased the proportion of patients who survived for 1 year, compared with drugs plus endoscopy. CONCLUSIONS: In a meta-analysis of data from 1327 patients with cirrhosis, acute variceal bleeding, and Child-Pugh score between 10 and 13 points or CP-B+AB, preemptive TIPS increased the proportion who survived for 1 year, in both subgroups separately, compared with drugs plus endoscopy.status: publishe

Incidence and factors predictive of recurrent thrombosis in patients with non-cirrhotic portal vein thrombosis.

BACKGROUND AND AIMS Clinical guidelines do not recommend long-term anticoagulation in non-cirrhotic splanchnic vein thrombosis (NC-SVT) without underlying thrombophilia because it is assumed that there is a very low risk of recurrent thrombosis (RT). Our first aim was to describe the incidence of RT in patients with NC-SVT without indication for long-term anticoagulation. The second aim was to identify RT risk factors and afterwards verify them in a validation cohort. METHODS Multicenter retrospective observational study evaluating risk factors for RT in 64 patients with NC-SVT of idiopathic/local etiology. In a subgroup of 48 patients the potential value of additional thrombophilic parameters to predict RT was analyzed. Findings were validated in 70 independent patients with idiopathic/local NC-SVT. RESULTS Of the 64 patients, 17 (26%) presented splanchnic and/or extra-splanchnic RT (overall-RT) during follow-up (cumulative incidence: 2%, 10%, 19% and 34% at 1, 2, 5 and 10 years). 53% of splanchnic RT were asymptomatic. No clinical or biochemical parameters predicted overall-RT. However, in the 48 patients with additional comprehensive thrombophilic study, factor VIII ≥ 150% was the only independent factor predicting overall-RT (HR 7.10 (CI 2.17 - 23.17) p 150% (HR 3.71 (1.31 - 10.5), p < 0.01). The predictive value of factor VIII was confirmed both in patients with idiopathic and with local etiology. CONCLUSIONS Patients with idiopathic/local NC-SVT are at risk of overall-RT. Splanchnic RT can be asymptomatic and requires screening for its detection. Values of factor VIII ≥ 150% may help identify patients at high risk of overall-RT who could benefit from long-term anticoagulation. LAY SUMMARY Patients with idiopathic/isolated local factor non cirrhotic splanchnic vein thrombosis (NC-SVT) were previously thought to be at minimal risk of rethrombosis. Our results show a 25% incidence of rethrombosis and support the indication of close follow-up to identify new thrombotic events, specially in patients with factor VIII >150%