The effect of calcineurin inhibitors on endothelial function in renal transplant recipients

Abstract

Endothelial dysfunction is of vital importance, as it may cause ischemia and dysfunction in various organs. Despite, this problem has been well documented in patients with end-stage renal disease (ESRD), there is not enough data considering this issue following renal transplantation. One of the potential causes of endothelial dysfunction in renal transplant recipients may be administration of calcineurin inhibitors. The aim of this study is to evaluate the effects of two different calcineurin inhibitors [cyclosporin A (CsA) and tacrolimus (FK506)] on endothelial function in renal transplant patients. Forty-four renal transplant recipients [22 on FK506 (group I) and 22 on CsA (group II)] were studied. Endothelial functions of the brachial artery were evaluated by using high resolution vascular ultrasound. Endothelium-dependent and -independent vasodilations were assessed by establishing reactive hyperemia and using sublingual nitroglycerine (NTG), respectively. Results are presented as percentage change from baseline values. Significant endothelial dysfunction was noted in renal transplant patients treated with CsA. While endothelium-dependent vasodilation was 12.1 +/- 5.1% in group I and it was 6.5 +/- 3.7% in group II (p < 0.001). The increase in brachial artery diameter after sublingual NTG was 20.1 +/- 6.3 and 12.7 +/- 5.6% in groups I and II, respectively. This indicates that the endothelium-dependent and -independent vasodilation of the patients on FK506 is better preserved than the patients on CsA therapy. Besides, blood flow volume (BFV) increase was 51.2 +/- 39.4 and 43.9 +/- 24.3%, in groups I and II, respectively, in reactive hyperemia period (p > 0.05). Post-transplant course of renal transplant recipients is complicated by endothelial dysfunction. This problem is more prominent in patients on CsA therapy, which can predispose these patients to more frequent cardiac complications.

Early Exercise Training After Renal Transplantation and Asymmetric Dimethylarginine: The Effect of Obesity

“…The study design did not allow to compare the effects of cyclosporine A- and tacrolimus-based regimes. Earlier data suggest that calcineurin inhibitors induce endothelial dysfunction in renal transplant patients, probably by suppressing NO synthesis [32,33]. However, according to our results, ADMA levels were significantly higher in obese patients after renal transplantation, although the immunosuppression regimens were similar in both groups.…”

Immunomodulator FTY720 Induces eNOS-Dependent Arterial Vasodilatation via the Lysophospholipid Receptor S1P 3

“…These findings suggest that, unlike conventional immunosuppressive drugs, FTY720 may preserve vascular structure and function and help prevent cardiovascular morbidity and mortality that often occurs in transplant recipients. 18,19 …”

Effects of Immunosuppressive agents on neutrophils inflammatory response in humans: An inflammatory perspective on coronary allograft vasculopathy

“…In this study, CsA caused some detrimental effects on capillary morphology and resulted in a significant increase in capillary ET-1 release, while TAC did not [66] . Furthermore, CsA yielded a greater impairment in brachial endothelial function using high resolution vascular ultrasound in renal transplant patients, compared with TAC treated patients [67] . Additionally, in another clinical study comparing the effects of both CNIs on endothelial function, ET-1 levels and vascular remodeling in CTx patients, the investigators reported that microvascular endothelial function was worst, concomitantly with higher ET-1 plasma levels, and a larger increase in coronary intimal area in CsA-treated patients [63] .…”