Dataset Information

Plasma sRAGE enables prediction of acute lung injury after cardiac surgery in children.

ABSTRACT:

Introduction

Acute lung injury (ALI) after cardiac surgery is associated with a high postoperative morbidity and mortality, but few predictors are known for the occurrence of the complication. This study evaluated whether elevated plasma levels of soluble receptor for advanced glycation end products (sRAGE) and S100A12 reflected impaired lung function in infants and young children after cardiac surgery necessitating cardiopulmonary bypass (CPB).

Methods

Consecutive children younger than 3 years after cardiac surgery were prospectively enrolled and assigned to ALI and non-ALI groups, according to the American-European Consensus Criteria. Plasma concentrations of sRAGE and S100A12 were measured at baseline, before, and immediately after CPB, as well as 1 hour, 12 hours, and 24 hours after operation.

Results

Fifty-eight patients were enrolled and 16 (27.6%) developed postoperative ALI. Plasma sRAGE and S100A12 levels increased immediately after CPB and remained significantly higher in the ALI group even 24 hour after operation (P < 0.01). In addition, a one-way MANOVA revealed that the overall sRAGE and S100A12 levels were higher in the ALI group than in the non-ALI group immediately after CPB (P < 0.001). The multivariate logistic regression analysis showed that the plasma sRAGE level immediately after CPB was an independent predictor for postoperative ALI (OR, 1.088; 95% CI, 1.011 to 1.171; P = 0.025). Increased sRAGE and S100A12 levels immediately after CPB were significantly correlated with a lower PaO2/FiO2 ratio (P < 0.01) and higher radiographic lung-injury score (P < 0.01), as well as longer mechanical ventilation time (sRAGEN: r = 0.405; P = 0.002; S100A12N: r = 0.322; P = 0.014), longer surgical intensive care unit stay (sRAGEN: r = 0.421; P = 0.001; S100A12N: r = 0.365; P = 0.005) and hospital stay (sRAGEN: r = 0.329; P = 0.012; S100A12N: r = 0.471; P = 0.001).

Conclusions

Elevated sRAGE and S100A12 levels correlate with impaired lung function, and sRAGE is a useful early biomarker of ALI in infants and young children undergoing cardiac surgery.

SUBMITTER: Liu X

PROVIDER: S-EPMC3580637 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Plasma sRAGE enables prediction of acute lung injury after cardiac surgery in children.

Liu XiWang X Chen QiXing Q Shi ShanShan S Shi Zhuo Z Lin Ru R Tan LinHua L Yu JianGen J Shu Qiang Q Fang XiangMing X

Critical care (London, England) 20120522 3

<h4>Introduction</h4>Acute lung injury (ALI) after cardiac surgery is associated with a high postoperative morbidity and mortality, but few predictors are known for the occurrence of the complication. This study evaluated whether elevated plasma levels of soluble receptor for advanced glycation end products (sRAGE) and S100A12 reflected impaired lung function in infants and young children after cardiac surgery necessitating cardiopulmonary bypass (CPB).<h4>Methods</h4>Consecutive children younge ...[more]

PMID: 22616947

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Project description:Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) may be related to the increase of chronic kidney disease and mortality in critically ill patients, so developing potential biomarkers is particularly important for disease prediction and early diagnosis. The purpose of this study was to investigate the alteration profiles of plasma metabolome and the possible links with urinary metabolome in patients with CSA-AKI. Methods: Non-targeted metabolomics was performed on plasma samples collected from groups of patients with CSA-AKI at different time points, including Before_AKI (uninjured kidney), AKI_Day1 (injured kidney) and AKI_Day14 (recovered kidney). The differential plasma metabolites associated with CSA-AKI were screened out using multivariate and univariate statistical methods, and altered metabolic pathways were identified by examining the Kyoto Encyclopedia of Genes and Genomes database. After receiver operating characteristic analysis to obtain potential biomarkers, the differential plasma metabolites with Level 1 were used for correlation analysis and metabolomic interplay with urinary metabolome. Results: Nearly 1750 plasma metabolites were identified through bioinformatics methods at Annotation Levels 1-3. The plasma metabolome of injured kidney can be well separated from the plasma metabolomes of uninjured or recovered groups, but the plasma samples from the AKI_Day14 and Before_AKI groups cannot be distinguished using statistical analysis. Compared with the uninjured kidney group, the patients with CSA-AKI displayed dramatic changes in plasma metabolism, particularly for amino acid metabolism. As for the potential biomarkers with Level 1 identification in the plasma metabolome, carnitines and amino acid metabolites exhibited a significant positive correlation, while carnitines and organic acids in plasma also involved in the metabolomic interplay with urinary metabolome. Conclusions: Plasma metabolite disorder was observed in patients with CSA-AKI due to ischaemia and medical treatment, and the recovered patients’ systemic status were able to return to normal. This work provides data on plasma metabolite markers on CSA-AKI and possible link to urinary metabolome.

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Project description:Background: The recent integration of genomic data with electronic health records has enabled large scale genomic studies on a variety of perioperative complications, yet genome-wide association studies on acute kidney injury have been limited in size or confounded by composite outcomes. Genome-wide association studies can be leveraged to create a polygenic risk score which can then be integrated with traditional clinical risk factors to better predict postoperative complications, like acute kidney injury. Methods: Using integrated genetic data from two academic biorepositories, we conduct a genome-wide association study on cardiac surgery-associated acute kidney injury. Next, we develop a polygenic risk score and test the predictive utility within regressions controlling for age, gender, principal components, preoperative serum creatinine, and a range of patient, clinical, and procedural risk factors. Finally, we estimate additive variant heritability using genetic mixed models. Results: Among 1,014 qualifying procedures at Vanderbilt University Medical Center and 478 at Michigan Medicine, 348 (34.3%) and 121 (25.3%) developed AKI, respectively. No variants exceeded genome-wide significance (p < 5 × 10-8) threshold, however, six previously unreported variants exceeded the suggestive threshold (p < 1 × 10-6). Notable variants detected include: 1) rs74637005, located in the exonic region of NFU1 and 2) rs17438465, located between EVX1 and HIBADH. We failed to replicate variants from prior unbiased studies of post-surgical acute kidney injury. Polygenic risk was not significantly associated with post-surgical acute kidney injury in any of the models, however, case duration (aOR = 1.002, 95% CI 1.000-1.003, p = 0.013), diabetes mellitus (aOR = 2.025, 95% CI 1.320-3.103, p = 0.001), and valvular disease (aOR = 0.558, 95% CI 0.372-0.835, p = 0.005) were significant in the full model. Conclusion: Polygenic risk score was not significantly associated with cardiac surgery-associated acute kidney injury and acute kidney injury may have a low heritability in this population. These results suggest that susceptibility is only minimally influenced by baseline genetic predisposition and that clinical risk factors, some of which are modifiable, may play a more influential role in predicting this complication. The overall impact of genetics in overall risk for cardiac surgery-associated acute kidney injury may be small compared to clinical risk factors.

Dataset Information

Plasma sRAGE enables prediction of acute lung injury after cardiac surgery in children.

Introduction

Methods

Results

Conclusions

Publications

Plasma sRAGE enables prediction of acute lung injury after cardiac surgery in children.

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