What is the best biomarker for diagnosis of rejection in heart transplantation?

ABSTRACT

INTRODUCTION: Acute cellular rejection is a major cause of graft loss in heart transplantation (HT). Endomyocardial biopsy remains the gold standard for its diagnosis, but it is an invasive procedure not without risk. A proinflammatory state exists in rejection that could be assessed by determining plasma levels of inflammatory biomarkers. OBJECTIVE: To analyze the utility of various inflammatory markers, which is most important and what values best classify patients to diagnose rejection. MATERIALS AND METHODS: A prospective study in 123 consecutive cardiac transplant recipients was conducted from January 2002 to December 2006. Fibrinogen protein (Fgp) and function (Fgf), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and sialic acid (SA) determinations were performed at one, two, four, six, nine, and 12 months post-HT at the same time as biopsies. Coronary arteriography and intravascular ultrasound were performed on the first and last follow-up visits. Heart-lung transplants, retransplants, pediatric transplants, patients who died in the first month, and patients who refused consent were excluded. Also excluded were determinations that coincided with renal dysfunction, active infection, hemodynamic instability, or a non-evaluable biopsy. The final analysis included 79 patients and 294 determinations. The correlation between the levels of these biomarkers and the presence of rejection in the biopsy (> or = ISHLT grade 3) was studied. RESULTS: We did not find significant differences in the values of any of the markers analyzed on the six follow-up visits. Only CRP showed significant and sustained differences between the two groups (with and without rejection) from the second follow-up visit (month 2). The area under the curve showed significant differences in Fgp (0.614, p = 0.013), Fgf (0.585, p = 0.05), TNF-alpha (0.605, p = 0.02), SA (0.637, p = 0.002) and mainly CRP (0.765, p = 0.0001). CRP levels below 0.87 mg/dL ruled out rejection with a specificity of 90%. CONCLUSIONS: Among the inflammatory markers analyzed, CRP was the most useful parameter for non-invasive screening of acute cellular rejection in the first year post-HT.