Study 1: unexpected high incidence of coronary artery disease and abnormal platelet reactivity in long-term pediatric kidney transplant recipients

Abstract

L ong-term outcomes of children who undergo renal transplantation are unknown. However, as they enter adulthood, many will have risk factors for developing coronary artery disease (CAD). Certain noninvasive tests may detect early CAD. Electron-beam computed tomography (EBCT) can measure the amount of coronary artery calcification (CAC), which correlates with the presence of atherosclerotic CAD. In addition, abnormal platelet function has been linked to increased risk for atherogenesis and CAD. The purpose of this study was to determine the incidence of CAD by using EBCT in adults who underwent renal transplantation as children and determine whether presence of accelerated atherogenesis is associated with enhanced platelet reactivity. Eight pediatric kidney transplant recipients with good long-term allograft function ( 10 years) underwent evaluation by EBCT. The CAC score was determined by standardized technique. Platelet reactivity was assessed by measures of dense granule secretory rate, metabolic content, and spontaneous microaggregate formation. Results were compared with those in age-matched controls. The mean age at transplantation was 14 years (range, 10-16). Mean age at evaluation was 45 years (range, 23-48). Mean follow-up in this group was 17 years (range, 10-23). All received cyclosporine-based immunosuppression. Seven had 2 or more clinical risk factors for CAD. All were asymptomatic at the time of evaluation. Seven out of 8 patients had significant CAC detected on EBCT. When compared with ageand gender-matched controls, study patients had CAC scores 99% (n 4), 95% to 99% (n 2), and 75% to 95% (n 1). Platelets from those with CAC were significantly more likely to form microaggregates after mild stimulation compared with those without CAC (P .02). Also, they were more likely to form microaggregates (P .03), had slower dense granule secretion (P .04), and had lower metabolic stores (P .03) compared with controls. Conclusion: The incidence of CAC by EBCT in long-term pediatric kidney transplant recipients is much higher than expected compared with the general population. Besides clinical risk factors, it appears that platelets from these patients are more reactive, which may place them at further increased risk for thrombotic complications of atherosclerosis. Our data suggest that measures to decrease risk factors for CAD should be undertaken as children approach young adulthood. From the William J. von Liebig Transplant Center, Mayo Clinic; and the Department of Radiology; and Division of Cardiovascular Medicine, Mayo Clinic, Rochester, MN. © 2004 Elsevier Inc. All rights reserved. 0955-470X/04/1704-0000$30.00/0 doi:10.1016/j.trre.2003.10.006