Z YAO1, B GUI1, X MA1, S MA1
1Nephrology Department, The Second Affiliated Hospital Of Xi’an Jiaotong University, Xi’an, China
Background and Aim: Diethyl citrate (Et2Cit) is a new anticoagulant drug synthesized by our team. We verified its inhibitory effects on vascular smooth muscle cells (VSMCs) calcification induced by high phosphorus in our previous study. This research aimed to investigate the inhibitory effects of Et2Cit on vascular calcification (VC) in adenine-induced chronic renal failure (CRF) rats and to determine an anticoagulant drug that also inhibits VC in vivo.
Methods: Rats were divided into 4 groups: the control group (normal diet); the model group (0.75% adenine and 0.9% high phosphorus diet from day 1 to 28); the low-dose Et2Cit group (model rats with 750 mg/kg Et2Cit from day 1 to 42); and the high-dose Et2Cit group (model rats with 1500 mg/kg Et2Cit from day 1 to 42). The rats were euthanized at day 43 with blood and aortas collections. Then biochemical indices in serum, von-Kossa staining, calcium and phosphorus contents, alkaline phosphatase (ALP) activity, alpha smooth muscle actin (α-SMA) protein and runt-related transcription factor 2 (RUNX2) protein expressions in aortas were assessed.
Results: CRF model group had extensive VC compared with control group. Compared to CRF model group, treatment with Et2Cit dose-dependently reduced the area of VC, reduced phosphorus and calcium contents in serum and aortas (P < 0.05) without reducing blood urea nitrogen (BUN) and creatinine (Cr) levels (P > 0.05). Also, Et2Cit treatment group had lower ALP activity, lower RUNX2 protein expressions and higher α-SMA protein expressions than model group.
Conclusions: Et2Cit prevented VC in adenine-induced CRF rats, thus may be a potential drug for both anticoagulation and VC prevention in CRF patients.
Professor Gui is the director of Nephrology Department from the Second Hospital of Xi’an Jiaotong University (Xi’an, China). He has been doing research in anticoagulation therapy in hemodialysis patients for more than 10 years. Considering the inevitable side effects of sodium citrate during the anticoagulation process, he designed and synthesized diethyl citrate and verified its anticoagulation effects. He published 20 English papers as the first or the correspondence author in nephrology field.