Abstract
Vascular calcification is highly prevalent in patients with chronic hemodialysis. Increased acetatemia during hemodialysis sessions using acetate-acidified bicarbonate has also been associated with several abnormalities, By contrast, these abnormalities were not induced by citrate-acidified bicarbonate dialysis. Moreover, citrate is biocompatible alternative to acetate in dialysis fluid. However, the effects of citrate on vascular calcification during hemodialysis had not been studied in detail. This study analyzed herein the effects of acetate- or citrate-acidified bicarbonate dialysis on vascular calcification. Citrate has been shown to inhibit calcification in urine in hemodialysis patients. Therefore, our hypothesis is that citrate-acidified bicarbonate dialysis could reduce vascular calcification. Blood samples before and after hemodialysis from patients on acetate- or citrate-acidified bicarbonate dialysis were collected in heparin-containing tubes (n = 35 and n = 25 respectively). To explore the effect of pre- and post-dialysis plasmatic bicarbonate and citrate on vascular calcification, rats aortic rings cultured ex vivo in Minimum Essential Medium containing 0.1% FBS and 45-calcium as radiotracer were used (n = 24). After 7 days of incubation aortic rings were dried, weighed and radioactivity was measured via liquid scintillation counting. Bicarbonate levels increase calcium accumulation in rat aortic wall in a dose-response manner (pH = 7.4). Moreover, citrate prevents calcium accumulation, with a mean inhibitor concentration (IC50) value of 733 µmol/L. During acetate-acidified bicarbonate dialysis, bicarbonate and citrate levels in plasma increase (22.29 ± 3.59 versus 28.63 ± 3.56 mmol/L; p < 0.001) and decrease (133.3 ± 53.6 versus 87.49 ± 32.3 µmol/L, p < 0.001), respectively. These changes in pos-hemodialysis plasma significantly (p < 0.001) alter calcium accumulation in the aortic wall (38.9% higher). Moreover, citrate-acidified bicarbonate dialysis increases post-hemodialysis citrate levels 5-fold (145 ± 79.8 versus 771.6 ± 184.3 µmol/L), reducing calcium accumulation in the aortic wall. Citrate-acidified bicarbonate dialysis reduces plasmatic calcium and pH variations during dialysis session (Δ[Ca2+] = −0.019 ± 0.089; ΔpH = 0.098 ± 0.043) respect to acetate-acidified bicarbonate dialysis (Δ[Ca2+] = 0.115 ± 0.118; ΔpH = 0.171 ± 0.078). To our knowledge, our study is the first to show that citrate protects against calcium accumulation in rat aortic walls ex vivo. Therefore, citrate-acidified bicarbonate dialysis may be an alternative approach to reduce calcification in hemodialysis patients without additional cost.
Highlights
Vascular calcification, a predictor of cardiovascular disease and all-cause mortality[1], is frequently observed in chronic hemodialysis patients, mainly because serum phosphorus and calcium levels are frequently higher in these patients[2]
Rat aortic rings incubated for 7 days in MEM containing different concentrations of bicarbonate showed dose-dependent increases in calcium accumulation (Fig. 1)
Increased acetatemia during hemodialysis sessions using acetate-acidified bicarbonate has been associated with several abnormalities, including increases in oxidative stress, pro-inflammatory cytokines and nitric oxide synthesis
Summary
A predictor of cardiovascular disease and all-cause mortality[1], is frequently observed in chronic hemodialysis patients, mainly because serum phosphorus and calcium levels are frequently higher in these patients[2]. Hydro-electrolyte disturbances that occur during hemodialysis increase the risk of vascular calcification due to incremental increases in calcium concentration[3], alkaline phosphatase activity, and alkalosis[4]. To prevent magnesium carbonate and calcium carbonate precipitation in dialysis fluid containing bicarbonate, an acid, such as acetate, is usually added, but causes side effects. Www.nature.com/scientificreports that occur during hemodialysis increase the risk of vascular calcification due to incremental increases in calcium concentration and alkalosis. The effects of using citrate in the dialysate on the development of vascular calcification are unclear and have been poorly studied. This study compared the effects of acetate- and citrate-acidified bicarbonate dialysis on vascular calcification. Because citrate inhibits calcification in hemodialysis patient urine, we determined whether citrate-acidified bicarbonate dialysis reduces vascular calcification in these patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
