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

https://doi.org/10.1016/j.healun.2007.04.002Get rights and content

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Section snippets

Subjects

Between May and August 2004, 20 consecutive patients undergoing single or bilateral lung transplantation or heart–lung transplantation at the Cleveland Clinic were enrolled in this prospective, observational study. All organs were preserved in Euro-Collins solution during the period of study. The study was approved by the Institutional Review Board for Research of the Cleveland Clinic Foundation.

ISHLT Primary Graft Dysfunction Severity Score Calculation

ISHLT PGD severity scores were calculated for all subjects using data collected within 6 hours of

Results

Demographic characteristics of the 20 study subjects are summarized in Table 2. The mean age of the subjects was 48 years, and the majority of subjects were female. Chronic obstructive pulmonary disease was the most common reason for lung transplantation (n = 10, 50%), and 11 of 20 patients (55%) underwent single lung transplantation. The subjects’ post-operative clinical characteristics and short- and long-term outcomes are described in Table 3. Of note, 11 subjects (55%) had some degree of

Discussion

The most important result of this study is that plasma RAGE levels 4 hours after lung allograft reperfusion predicted the duration of mechanical ventilation and ICU length of stay, even after adjusting for allograft ischemia time. In contrast, markers of alveolar type II cell injury, endothelial injury and acute inflammation were not predictive of these outcomes. Furthermore, in this small sample, plasma RAGE had better prognostic value for these short-term outcomes than the clinical diagnosis

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    Supported by NIH/NHLBI HL51856.

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