Endothelial dysfunction in renal transplant patients is closely related to serum cyclosporine levels

Abstract

Background: Cyclosporine (CsA), one of the standard agents used in renal transplant recipients, has been considered to cause endothelial dysfunction and to contribute to arterial complications posttransplant. Since concentration-dependent effects of CsA on endothelial functions in humans have not been examined, this study was performed to investigate this relationship.

Methods: Fifteen renal transplant patient and 20 healthy subjects (controls) were evaluated for brachial artery endothelial function using high-resolution vascular ultrasound just before the CsA dosage (baseline) and at the second hour after the administration. Endothelium-dependent and -independent vasodilatations (EDD and EID, respectively) were assessed by establishing of the responses to reactive hyperemia and by using sublingual nitroglycerine, respectively. CsA levels were assessed at baseline and at second hour, times when performing brachial artery measurements.

Results: There were no significant differences between recipients and controls with respect to atherosclerosis risk factors. Mean EDD of recipients at baseline times were significantly less than those in controls (9.1% +/- 5.5% vs 15.2% +/- 7.2%, respectively; P < .001). CsA levels at trough and at second hour were 153.9 +/- 74.8 ng/mL and 646.8 +/- 163.2 ng/mL, respectively (P < .0001). Recipient, EDD at second hour was significantly reduced compared to baseline values (5.3% +/- 3.6% vs 9.1% +/- 5.5% respectively; P = .014) while changes in EID and in the diameter of the brachial artery between baseline and second hour were insignificant.

Conclusion: Endothelial dysfunction evaluated by brachial ultrasound in renal transplant recipients is closely related to CsA levels. It is more pronounced at 2 hours after CsA dosage, at the time of peak drug levels.