Elevated plasma clara cell secretory protein concentration is associated with high-grade primary graft dysfunction

Abstract

Primary graft dysfunction (PGD) is the leading cause of early posttransplant morbidity and mortality after lung transplantation. Clara cell secretory protein (CC16) is produced by the nonciliated lung epithelium and may serve as a plasma marker of epithelial cell injury. We hypothesized that elevated levels of CC16 would be associated with increased odds of PGD. We performed a prospective cohort study of 104 lung transplant recipients. Median plasma CC16 levels were determined at three time points: pretransplant and 6 and 24 h posttransplant. The primary outcome was the development of grade 3 PGD within the first 72 h after transplantation. Multivariable logistic regression was performed to evaluate for confounding by donor and recipient demographics and surgical characteristics. Twenty-nine patients (28%) developed grade 3 PGD within the first 72 h. The median CC16 level 6 h after transplant was significantly higher in patients with PGD [13.8 ng/mL (IQR 7.9, 30.4 ng/mL)] than in patients without PGD [8.2 ng/mL (IQR 4.5, 19.1 ng/mL)], p = 0.02. Elevated CC16 levels were associated with increased odds of PGD after lung transplantation. Damage to airway epithelium or altered alveolar permeability as a result of lung ischemia and reperfusion may explain this association.

Figure 1

Plasma CC16 concentration 6 hours after transplant in all patients stratified by the development of Grade 3 PGD any time in the first 72 hours. Horizontal line indicates median concentration. The upper and lower limits of the box indicate the interquartile range. Solid circles represent outliers. P-value reported is from Wilcoxon rank sum test and is corrected for multiple comparisons.

Figure 2

Plasma CC16 concentration pre-transplant, 6 hours post-transplant, and post-operative day 1 stratified by the three most common diagnoses leading to transplant in all patients. P-values reported are for Kruskal-Wallis equality-of-populations rank test. Horizontal line indicates median concentration. The upper and lower limits of the box indicate the interquartile range.

Figure 3

Plasma CC16 concentration 6 hours after transplant in IPF or Non-IPF patients stratified by the development of Grade 3 PGD any time in the first 72 hours. Horizontal line indicates median concentration. The upper and lower limits of the box indicate the interquartile range. Solid circles represent outliers. P-value reported is from Wilcoxon rank sum test.