Propionyl-<i>L</i>-Carnitine Therapy: Effects on Endothelin-1 and Homocysteine Levels in Patients with Peripheral Arterial Disease and End-Stage Renal Disease

Abstract

Background/Aims: Recent data have addressed the issue of higher levels of homocysteine (Hcy) and endothelin-1 (ET-1) in end-stage renal disease (ESRD) that may be considered an independent predictor for cardiovascular disease. The prevalence of peripheral arterial disease (PAD) in patients with ESRD has been reported to be relevant, highlighting its clinical importance. We aimed to explore the therapeutic role of propionyl-L-carnitine (PLC) in hemodialysis patients with PAD by measuring ankle/brachial index (ABI), ET-1 and Hcy. Design: Randomized, double-blind, placebo-controlled trial. Methods: Sixty-four patients on hemodialysis with chronic renal insufficiency and PAD were assigned to receive either intravenous PLC (600 mg) or placebo 3 times weekly for 12 months. The ABI and plasma levels of ET-1 and Hcy were measured at baseline, 6 and 12 months. Results: In the PLC-treated group, progressive increases in ABI were observed, while in the placebo group the reverse trend was seen. Highly significant and progressive reductions in plasma levels of ET-1 and Hcy, compared to baseline, were also seen in the PLC-treated group. Conclusions: Hemodynamic flow, endothelial profile and Hcy levels were ameliorated by the administration of PLC in hemodialysis patients with ESRD and PAD.

Electronegative low-density lipoprotein increases the risk of ischemic lower-extremity peripheral artery disease in uremia patients on maintenance hemodialysis

“…Previous studies have shown that oxidative stress is associated with PAD in hemodialysis patients. Reducing oxidative stress in these patients with propionyl L-carnitine can significantly increase nitric oxide formation, decrease vasoconstrictive endothelin-1 production, and improve vascular hemodynamic flow 46, 47 . Together, these findings suggest that the association between L5% and lower-extremity PAD in uremia patients may in part be attributed to the promotion of oxidative stress by L5 LDL.…”

Pharmacological effects and clinical applications of propionyl-L-carnitine

“…78,89,90 These contradictory findings might be explained by differences in study design, since trials that showed enhanced blood flow included higher doses of PLC. More recent trials also identified a reduction in oxidative stress markers 78,91,92 and an enhanced bioavailability of NO 78,92 in PAD patients treated with PLC. In particular, a recent outstanding study by Stasi et al 93 showed that PLC injection accelerates rabbit hind-limb post-ischemic blood flow recovery and the restoration of vascular function by sustaining positive dilative arteriogenetic remodeling and by reducing oxidative-stress-induced impaired endothelial function.…”

“…These contradictory findings might be explained by differences in study design, since trials that showed enhanced blood flow included higher doses of PLC. More recent trials also identified a reduction in oxidative stress markers 78,91,92 and an enhanced bioavailability of NO 78,92 in PAD patients treated with PLC. In particular, a recent outstanding study by Stasi et al 93 .…”

Carnitine derivatives

“…In recent years, PLC has shown therapeutic benefits in the management of disease such as peripheral vascular disease, myocardial ischemia, congestive heart failure, and erectile dysfunction ( Table 2) [68][69][70][71][72][73][74][75][76][77][78][79].…”