Kinetics of urinary cell cycle arrest markers for acute kidney injury following exposure to potential renal insults

Objectives:Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 predict the development of acute kidney injury following renal insults of varied aetiology. To aid clinical interpretation, we describe the kinetics of biomarker elevations around an exposure. Design:In an ancillary analysis of the multicenter SAPPHIRE study, we examined the kinetics of the urinary [tissue inhibitor of metalloproteinase-2]•[insulin-like growth factor binding protein 7] in association with exposure to common renal insults (major surgery, IV radiocontrast, vancomycin, nonsteroidal anti-inflammatory drugs, and piperacillin/tazobactam). Setting:Thirty-five sites in North America and Europe between September 2010 and June 2012. Patients:Seven hundred twenty-three critically ill adult patients admitted to the ICU. Interventions: None. Measurements and Main Results:We compared the urinary [tissue metalloproteinase-2]•[insulin growth factor binding protein 7] kinetics from the day prior to exposure up to 5 days after exposure in patients developing acute kidney injury stage 2–3, stage 1, or no acute kidney injury by Kidney Disease Improving Global Outcome criteria. Among the 723 patients, 679 (94%) had at least one, 70% had more than one, and 35% had three or more exposures to a known renal insult. There was a significant association between cumulative number of exposures up to study day 3 and risk of acute kidney injury (p = 0.02) but no association between the specific type of exposure and acute kidney injury (p = 0.22). With the exception of radiocontrast, patients who developed acute kidney injury stage 2–3 after one of the five exposures, had a clear rise and fall of urinary [tissue inhibitor of metalloproteinase-2]•[insulin-like growth factor binding protein 7] from the day of exposure to 24–48 hours later. In patients without acute kidney injury, there was no significant elevation in urinary [tissue inhibitor of metalloproteinase-2]•[insulinlike growth factor binding protein 7]. Conclusions:Exposure to potential renal insults is common. In patients developing acute kidney injury stage 2–3, the kinetics of urinary [tissue inhibitor of metalloproteinase-2]•[insulin-like growth factor binding protein 7] matched the exposure except in the case of radiocontrast.</p

Whole blood thiamine (WBT) and delirium occurrencein the Intensive Care Unit (ICU)

Introduction: thiamine di-phosphate (TDP) is an essential cofactor inglucose metabolism, glutamate transformation and in cholinesterase activity, all reported in delirium occurrence [1]. We proposed that adeficiency in Whole Blood Thiamine (WBT) could increase risk of delirium occurrence in patients admitted to the Intensive Care Unit (ICU).Objectives: to establish whether there is a relationship between deficiency in WBT and ICU delirium occurrence in a cohort of ICU admissions from Gelre Hospital, Netherlands.Methods. an anonymised patient dataset was approved and obtained from Gelre ICU. This was a secondary analysis of a previous study on WBT in ICU patients (2). Delirium was assessed twice a day, using confusion assessment method-intensive care unit (CAM-ICU). A day indelirium was defined as 1 or more positive CAM-ICU scores in 24 h.The pathology range for WBT deficiency was ≤ 100 nmol/litre. An initial analysis was carried out to explore whether normal levels of WBT at t-0 h, t24 hrs or t48 hrs resulted in a lower incidence of delirium during ICU admission. The analysis is reported as odds ratio (OR) and 95%confidence interval (CI).Results: the original ICU patient cohort was admitted between 2009to 2010. There were 57 patients and WBT was reported at t-0, t-24and t-48. Analysis reported a comarable rate of delirium in those with normal WBT (&gt; 100 nmol/litre) compared to those that were WBT deficient(≤ 100 nmol/litre) at t-0, t-24 and t-48, (OR: 0.68 [95% confidence interval (CI): 0.23–1.97]), (OR: 0.63 [95% CI: 0.20–2.00]) and (OR: 0.70[95% CI: 0.21–2.31]) respectively. Regression analysis was performed with age and sepsis as confounding variables, no significant differences were observed.[Table 1. Relationship between WBT on ICU admission, t-24 h, t-48 h and delirium occurrence in ICU not included].Conclusion: in this small dateset, no relationship could be detectedbetween WBT and delirium occurrence on ICU admission, and 24 and48 h post admission. The lack of significance with regards to confoundingvariable of sepsis and age could be attributed to small patientnumbers. Further analysis with a larger dataset is needed to investigatethe research question.<br/