Supplementation with high-dose trans-resveratrol improves ultrafiltration in peritoneal dialysis patients: a prospective, randomized, double-blind study

Abstract

Background Ultrafiltration (UF) failure mostly contributes to technical failure in peritoneal dialysis (PD) patients, and one of its responsible factors is peritoneal angiogenesis. Resveratrol has been proposed to have an angiogenesis-ameliorating effect on tumor patients. We hypothesize transresveratrol has beneficial effects on angiogenesis-related markers in PD patients. Methods In this prospective, randomized, and double-blind trial, 72 patients were randomly assigned to 12-week treatment of low-dose or high-dose (150 or 450 mg/d) trans-resveratrol or a placebo. Visits were scheduled at 0, 4, 8, and 12 weeks after treatment. Clinical indices including 24-hour UF volume, UF rate, 24-hour urine volume, residual renal function, and dialysis adequacy (kt/v) were measured. Angiogenesis markers including vascular endothelial growth factor (VEGF), fetal liver kinase-1 (Flk-1), angiopoietin-2 (Ang-2), tyrosine kinase 2 (Tie-2), and thrombospondin-1 (Tsp-1) in peritoneal effluent were also assessed by enzyme-linked immunosorbent assay. Results Finally, 64 out of 72 patients were analyzed, 18 in the high-dose group, 22 in the low-dose group, and 24 in the placebo group. Over the 12-week period, patients in the high-dose group [mean change from baseline (95% CI): 171.4 (141.3-201.5) (mL), p ¼ 0.003 (Net UF); 11.3(10.5-12.1) (mL/h), p ¼ 0.02 (UF rate)] or the low-dose group [mean change from baseline (95% CI: 98.1 (49.5-146.7) (mL), p ¼ 0.007 (Net UF); 6.5 (4.4-8.6) (mL/h), p ¼ 0.04 (UF rate)] versus the placebo group had a significantly greater improvement in mean net UF volume and UF rate. The appearance rates of VEGF, Flk-1, and Ang-2 were more significantly reduced (appearance rates of Tie-2 and Tsp-1 increased) in the high-dose group versus the placebo group, but not in the low-dose group. Conclusion Supplementation with trans-resveratrol is beneficial to improve ultrafiltration in PD patients, and high-dose supplementation may improve ultrafiltration by ameliorating angiogenesis induced by conventional lactate-buffered PD solutions.

Health benefits of resveratrol: Evidence from clinical studies

“…Long term peritoneal dialysis induces angiogenesis and facilitates increased transport of small solutes which eventually lead to a loss of ultrafiltration capacity or ultrafiltration failure . In patients under peritoneal dialysis, resveratrol was tested at two doses (150 and 450 mg/d) to observe any effects on ultrafiltration efficacy . Various clinical indices of renal and ultrafiltration capacity such as 24 hour UF volume, UF rate, and 24 hour urine volume dialysis adequacy were found to be significantly improved in a dose‐dependent manner .…”

“…In patients under peritoneal dialysis, resveratrol was tested at two doses (150 and 450 mg/d) to observe any effects on ultrafiltration efficacy . Various clinical indices of renal and ultrafiltration capacity such as 24 hour UF volume, UF rate, and 24 hour urine volume dialysis adequacy were found to be significantly improved in a dose‐dependent manner . Moreover, analysis of the peritoneal angiogenesis markers, VEGF, fetal liver kinase 1, angiopoietin 2, TEK receptor tyrosine kinase, and thrombospondin 1, were found to be significantly modulated by resveratrol, but only at higher doses …”

“…170 Moreover, analysis of the peritoneal angiogenesis markers, VEGF, fetal liver kinase 1, angiopoietin 2, TEK receptor tyrosine kinase, and thrombospondin 1, were found to be significantly modulated by resveratrol, but only at higher doses. 170 Oxidative stress and inflammation are important contributing factors in patients with CKD and secondary nephropathies. 171 Inflammation, and small solutes such as glucose and glucose degradation products contribute to angiogenesis.…”

Effects of RNA interference-mediated gene silencing of VEGF on the ultrafiltration failure in a rat model of peritoneal dialysis

“…In addition, approximately 30% patients may suffer UFF following PD treatment for approximately 5 years [ 7 ]. UFF largely contributes to the technical failure seen in PD patients [ 8 ].…”

Polyphenols Attenuate Highly-Glycosylated Haemoglobin-Induced Damage in Human Peritoneal Mesothelial Cells

“…In the presence of quercetin, which induced cytoprotection, potentially based on its antioxidant effects in this model [ 88 ]. Chong-Ting et al (2016) demonstrated that supplementation with trans-resveratrol improved ultrafiltration in PD patients, and high-dose supplementation may improve ultrafiltration by ameliorating angiogenesis induced by conventional lactate-buffered PD solutions [ 89 ]. In another study, Firuzi et al (2016) concluded that silymarin could be considered a complementary therapy to reduce PD-related complications in patients with ESRD undergoing PD.…”