Fluid balance and conventional and novel biomarkers of acute kidney injury in cardiovascular surgery.

AIM: Fluid balance (FB) is an emerging predictor of acute kidney injury (AKI). We investigated the comparative utility of FB with conventional and novel biomarkers to predict AKI in cardiovascular surgery patients. METHODS: Data collected in a prospective, observational study designed to investigate the relationship between FB and AKI in an academic medical center were utilized for analyses. FB, routine clinical parameters, conventional and novel biomarkers in 100 consecutive cardiovascular surgery patients was analyzed. RESULTS: Each variable studied was divided into quartiles and the lowest quartile served as the referent quartile. The adjusted OR for AKI for the highest vs. lowest quartile of FB was 4.98 (CI95%1.38-24.10, P=0.046), serum creatinine (SCr) 11.54 (CI95% 1.37-97.18, P=0.024), urine NGAL 2.76 (CI95% 0.48-15.93, P=0.255) and IL-18 2.31 (CI95% 0.41-13.16, P=0.346, and serum MCP-1 4.93 (CI95% 0.81-30.09, P=0.084) and TNF-alpha 15.59 (CI95% 1.19-204.19, P=0.036). Comparison of ROC curves demonstrated that the diagnostic performance of FB and SCr to predict AKI were comparable, as were FB with urine NGAL and IL-18 and serum MCP-1 and TNF-alpha.. While there was a graded relationship with the risk for AKI according to quartiles for FB, SCr and serum TNF-alpha, the remaining biomarkers including urine NGAL were not independent predictors of AKI. CONCLUSION: At 24 hours postoperatively, the performance of FB to predict AKI was comparable to that of preoperative conventional and postoperative 24-hour novel biomarkers.

Functional mapping and DNA sequence of an equine herpesvirus 1 origin of replication.

The genome of equine herpesvirus 1 (EHV-1) defective interfering (DI) particle DNA originates from discrete regions within the standard (STD) EHV-1 genome: the left terminus (0.0 to 0.04 map units) and the inverted repeats (0.78 to 0.79 and 0.83 to 0.87 map units of the internal inverted repeat; 0.91 to 0.95 and 0.99 to 1.00 map units of the terminal inverted repeat). Since DI DNA must contain cis-acting DNA sequences, such as replication origins, which cannot be supplied in trans by the STD EHV-1 virus, regions of the EHV-1 genome shown to be in DI DNA were assayed for the presence of a viral origin of DNA replication. Specifically, STD EHV-1 DNA fragments encompassing the genomic regions present in DI particle DNA were inserted into the vector pAT153, and individual clones were tested by transfection assays for the ability to support the amplification and replication of plasmid DNA in EHV-1-infected cells. The Sma-1 subfragment of the internal inverted repeat sequence (0.83 to 0.85 map units) was shown to contain origin of replication activity. Subcloning and BAL 31 deletion analysis of the 2.35-kilobase-pair (kbp) Sma-1 fragment delineated a 200-bp fragment that contained origin activity. The origin activities of all EHV-1 clones which were positive by the transfection assay were confirmed by methylation analysis by using the methylation-sensitive restriction enzymes DpnI and MboI. DNA sequencing of the 200-bp fragment which contained an EHV-1 origin of replication indicated that this region has significant homology to previously characterized origins of replication of human herpesviruses. Furthermore, comparison of known origin sequences demonstrated that a 9-bp sequence, CGTTCGCAC, which is conserved among all origins of replication of human lytic herpesviruses and which is contained within the 18-bp region in herpes simplex virus type 1 origins shown by others to be protected by an origin-binding protein (P. Elias, M. E. O'Donnell, E. S. Mocarski, and I. R. Lehman, Proc. Natl. Acad. Sci. USA 83:6322-6326) is also conserved across species in the EHV-1 origin of replication.