Article

Plasma Receptor for Advanced Glycation End-products Predicts Duration of ICU Stay and Mechanical Ventilation in Patients After Lung Transplantation

Keio University, Edo, Tokyo, Japan
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation (Impact Factor: 6.65). 08/2007; 26(7):675-80. DOI: 10.1016/j.healun.2007.04.002
Source: PubMed

ABSTRACT

Primary graft dysfunction, formerly termed reperfusion pulmonary edema, is the leading cause of short-term complications after lung transplantation. New evidence shows that alveolar type I epithelial cells play an active role in alveolar fluid transport and are therefore presumed to be critical in the absorption of pulmonary edema. We tested the potential relevance of a novel marker of alveolar type I cell injury, the receptor for advanced glycation end-products (RAGE), to short-term outcomes of lung transplantation.
The study was a prospective, observational cohort study of 20 patients undergoing single lung, bilateral lung or combined heart-lung transplantation. Plasma biomarkers were measured 4 hours after allograft reperfusion.
Higher plasma RAGE levels were associated with a longer duration of mechanical ventilation and longer intensive care unit length of stay, in contrast to markers of alveolar type II cell injury, endothelial injury and acute inflammation. Specifically, for every doubling in plasma RAGE levels, the duration of mechanical ventilation increased on average by 26 hours, adjusting for ischemia time (95% confidence interval [CI] 7.4 to 44.7 hours, p = 0.01). Likewise, for every doubling of plasma RAGE levels, intensive care unit length of stay increased on average by 1.8 days, again adjusting for ischemia time (95% CI 0.13 to 3.45 days p = 0.04). In contrast, the clinical diagnosis of primary graft dysfunction was not as predictive of these short-term outcomes.
Higher levels of plasma RAGE measured shortly after reperfusion predicted poor short-term outcomes from lung transplantation. Elevated plasma RAGE levels may have both pathogenetic and prognostic value in patients after lung transplantation.

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    • "Glial fibrillary acidic protein (GFAP) Yes/Yes Highly selective for CNS injury [11] [19] [132] Brain Spectrin breakdown products Yes/Yes Can indicate mechanism of cell death [25] [26] [132] Intercellular adhesion molecule-1 (ICAM1) Yes/Yes Not a specific indicator of lung injury [133] [134] von Willebrand factor No/Yes Can predict lung injury after sepsis [134] Surfactant protein D Yes/Yes Correlated with poor outcome and death [134] [135] Soluble receptor for advanced glycation end-products (sRAGE) Yes/Yes Admittance levels correlate with outcome [136] [137] Lung High mobility group box protein -1 (HMGB-1) Yes/Yes Correlates with trauma severity and poor outcome [38] Alanine and aspartate aminotransferases Yes/Yes Indicators of liver function [41] [138] [139] Alkaline phosphatase Yes/Yes Indicator of liver function [41] [138] Gamma glutamyl transferase No/Yes Indicator of liver function [41] Bilirubin Yes/Yes Presence in urine indicates liver damage [42] [43] [140] Cytokeratin-18 No/No Caspase-mediated breakdown indicates liver damage [141] [142] Liver Arginosuccinate synthetase, Sulfotransferase 2A1, "
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    • "Sharma et al. showed that TNF-α production by alveolar macrophages mediates alveolar type II epithelial cell activation and KC production in an in vitro hypoxiareoxygenation model (Sharma, et al., 2007). Recent studies also implicate alveolar type I cellreleased mediators such as soluble receptor for advanced glycation end products (sRAGE) as a potential biomarker and indicator of lung injury after lung transplantation (Calfee, et al., 2007). This new marker may be useful given the recent discovery of the role of alveolar type I cells in alveolar fluid clearance (Johnson, et al., 2006). "

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