Plasma levels of receptor for advanced glycation end products, blood transfusion, and risk of primary graft dysfunction

Jason D. Christie, Chirag V. Shah, Steven M. Kawut, Nilam Mangalmurti, David J. Lederer, Joshua R. Sonett, Vivek N. Ahya, Scott M. Palmer, Keith Wille, Vibha Lama, Pali D. Shah, Ashish Shah, Ann Weinacker, Clifford S. Deutschman, Benjamin A. Kohl, Ejigayehu Demissie, Scarlett Bellamy, Lorraine B. Ware

Research output: Contribution to journalArticle

Abstract

Rationale: The receptor for advanced glycation end products (RAGE) is an important marker of lung epithelial injury and may be associated with impaired alveolar fluid clearance. We hypothesized that patients with primary graft dysfunction (PGD) after lung transplantation would have higher RAGE levels in plasma than patients without PGD. Objectives:Totest the association of solubleRAGE(sRAGE)levels with PGD in a prospective, multicenter cohort study. Methods: We measured plasma levels of sRAGE at 6 and 24 hours after allograft reperfusion in 317 lung transplant recipients at seven centers. The primary outcome was grade 3 PGD (PaO2/FIO2 < 200 with alveolar infiltrates) within the first 72 hours after transplantation. Measurements and Main Results: Patients who developed PGD had higher levels of sRAGE than patients without PGD at both 6 hours (median 9.3 ng/ml vs. 7.5 ng/ml, respectively; P = 0.028) and at 24 hours post-transplantation (median 4.3 ng/ml vs. 1.9 ng/ml, respectively; P < 0.001). Multivariable logistic regression analyses indicated that the relationship between levels of sRAGE and PGD was attenuated by elevated right heart pressures and by the use of cardiopulmonary bypass. Median sRAGE levels were higher in subjects with cardiopulmonary bypass at both 6 hours (P = 0.003) and 24 hours (P < 0.001). sRAGE levels at 6 hours were significantly associated with intraoperative red cell transfusion (Spearman's ρ= 0.39, P = 0.002 in those with PGD), and in multivariable linear regression analyses this association was independent of confounding variables (P = 0.02). Conclusions: Elevated plasma levels of sRAGE are associated with PGD after lung transplantation. Furthermore, plasma sRAGE levels are associated with blood product transfusion and use of cardiopulmonary bypass.

Original languageEnglish (US)
Pages (from-to)1010-1015
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Volume180
Issue number10
DOIs
StatePublished - Nov 15 2009

Keywords

  • Acute lung injury
  • Lung transplantation
  • Primary graft dysfunction
  • Receptor for advanced glycation end products
  • Reperfusion injury

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Christie, J. D., Shah, C. V., Kawut, S. M., Mangalmurti, N., Lederer, D. J., Sonett, J. R., Ahya, V. N., Palmer, S. M., Wille, K., Lama, V., Shah, P. D., Shah, A., Weinacker, A., Deutschman, C. S., Kohl, B. A., Demissie, E., Bellamy, S., & Ware, L. B. (2009). Plasma levels of receptor for advanced glycation end products, blood transfusion, and risk of primary graft dysfunction. American journal of respiratory and critical care medicine, 180(10), 1010-1015. https://doi.org/10.1164/rccm.200901-0118OC