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  • Impact of late calcineurin inhibitor withdrawal on ambulatory blood pressure and carotid intima media thickness in renal transplant recipients.

Impact of late calcineurin inhibitor withdrawal on ambulatory blood pressure and carotid intima media thickness in renal transplant recipients.

Transplantation (2013-05-30)
Jacqueline S Mourer, Eelco J P de Koning, Erik W van Zwet, Marko J K Mallat, Ton J Rabelink, Johan W de Fijter
ABSTRACT

Calcineurin inhibitors (CNIs) have an unfavorable cardiovascular risk profile in renal transplant recipients. The aim of this substudy was to assess the effects of late CNI or mycophenolate mofetil (MMF) withdrawal on ambulatory blood pressure monitoring and carotid intima media thickness. A total of 119 stable renal transplant recipients on triple regimen with steroids, a CNI and MMF were randomized into either the concentration-controlled CNI or MMF withdrawal groups. Patients were treated for traditional cardiovascular risk factors according to predefined targets. Ambulatory blood pressure monitoring and measurements of intima media thickness were performed at baseline and after 1, 2, and 3 years after randomization. CNI withdrawal resulted in a significant decline in both ambulatory day- and nighttime blood pressures (daytime: systolic blood pressure, -1.6 mm Hg/y, P=0.018; diastolic blood pressure, -1.3 mm Hg/y, P=0.002; nighttime systolic blood pressure: -1.9 mm Hg/y, P=0.008; diastolic blood pressure: -1.3 mm Hg/y, P=0.014), which was not observed after MMF withdrawal. There was no difference in the proportion of nocturnal nondippers (both groups, 69%, P=0.95). Despite the reduction in ambulatory blood pressure, no effect of CNI withdrawal on carotid intima media thickness was found. In stable renal transplant recipients, late CNI withdrawal from a triple drug regimen decreased blood pressure in comparison with MMF withdrawal but had no specific impact on carotid intima media thickness. Considering the high prevalence of hypertension in patients on CNI therapy, most stable renal transplant recipients may benefit from late CNI withdrawal by improved blood pressure control.

MATERIALS
Product Number
Brand
Product Description

Supelco
Cyclosporin A, VETRANAL®, analytical standard
Sigma-Aldrich
Cyclosporin A, 97.0-101.5% (on dried basis)
Sigma-Aldrich
Cyclosporin A, from Tolypocladium inflatum, ≥95% (HPLC), solid
Supelco
Tacrolimus solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Mycophenolic acid solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Cyclosporin A, BioReagent, from Tolypocladium inflatum, for molecular biology, ≥95%
Supelco
Cyclosporine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Mycophenolic acid, ≥98%
Sigma-Aldrich
Mycophenolic acid, powder, BioReagent, suitable for cell culture
Supelco
Cyclosporin A solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®