Progression of Endothelial Dysfunction, Atherosclerosis, and Arterial Stiffness in Stable Kidney Transplant Patients: A Pilot Study

Abstract

Background Kidney transplant patients suffer from vascular abnormalities and high cardiovascular event rates, despite initial improvements post-transplantation. The nature of the progression of vascular abnormalities in the longer term is unknown. This pilot study investigated changes in vascular abnormalities over time in stable kidney transplant patients long after transplantation. Methods Brachial artery flow-mediated dilation (FMD), nitroglycerin-mediated dilation, carotid-femoral pulse wave velocity (cf-PWV), ankle-brachial pressure index, and common carotid artery intima-media thickness (CCA-IMT) were assessed in 18 kidney transplant patients and 17 controls at baseline and 3-6 months after. Results There was no difference in age (51±13 vs. 46±11; P=0.19), body mass index (26±5 vs. 25±3; P=0.49), serum cholesterol (4.54±0.96 vs. 5.14±1.13; P=0.10), systolic blood pressure (BP) (132±12 vs. 126±12; P=0.13), diastolic BP (82±9 vs. 77±8; P=0.10), or diabetes status (3 vs. 0; P=0.08) between transplant patients and controls. No difference existed in vascular markers between patients and controls at baseline. In transplant patients, FMD decreased (-1.52±2.74; P=0.03), cf-PWV increased (0.62±1.06; P=0.03), and CCA-IMT increased (0.35±0.53; P=0.02). No changes were observed in controls. Conclusions Markers of vascular structure and function worsen in the post-transplant period on long-term follow-up, which may explain the continued high cardiovascular event rates in this population.

Decreased Cathepsin-K Mirrors the Severity of Subclinical Atherosclerosis in Kidney Transplant Recipients

“…Increased carotid intima-media thickness (IMT) is largely considered as a footprint of incipient atherosclerosis, as well as a robust risk stratifier for CV mortality also in the Ktx setting [3]. Although Ktx often elicits a significant improvement in IMT as compared to patients remaining on maintenance dialysis [4], abnormally increased IMT persists in a large part of asymptomatic Ktx recipients and may worsen over time to frank atherosclerosis, driven by various factors such as immunosuppressive therapy, dyslipidaemia and di-abetes [5,6]. Cathepsin-K (CatK) is a cysteine protease endowed with collagenase and elastase activities, which has recently been implicated in the pathogenesis of progressive atherosclerosis [7].…”