Impact of post-dialysis calcium level on ex vivo rat aortic wall calcification

Abstract

ObjectivesVascular calcification is a frequent complication in chronic haemodialysis patients and is associated with adverse outcomes. Serum calcium and phosphate levels and imbalances in calcification regulators are thought to contribute to the process. In this regard, the dialysate calcium concentration is a modifiable tool for modulating the risk of vascular calcification. We explored pre-and post-dialysis phosphate and calcium concentrations in stable chronic haemodialysis patients treated by dialysis with the KDIGO-suggested 1.5 mmol/L calcium dialysate to investigate the effects on ex vivo calcification of rat aortic rings. Approach and resultsAt the end of haemodialysis, mean serum calcium levels were increased in 88% of paired pre-/post-dialysis samples, while mean serum phosphate and parathyroid hormone levels were decreased. Rat aortic ring cultures grown at the same calcium and phosphate concentrations revealed that pre-and post-dialysis resulted in a similar degree of calcification. By contrast, haemodialysis with unchanged serum calcium resulted in a 5-fold reduction in calcium deposition. ConclusionDialysis with the widely prescribed 1.5 mmol/L calcium dose results in persistent high serum calcification potential in a sizable proportion of patients, driven by increased post-dialysis calcium concentration. This could potentially be mitigated by individualising dialysate calcium dosage based on pre-dialysis serum calcium levels.

Impact of acetate- or citrate-acidified bicarbonate dialysate on ex vivo aorta wall calcification

“…Each patient underwent a conventional, purely diffusive 4 hour (mid-week) hemodialysis session without hemodiafiltration, using a high flux helixone dialyzer (Fresenius, CUF, 59 mL/h/mmHg; surface, 1,8 m 2 ) and Dialysis Machine Fresenius 5008 in acetate-acidified bicarbonate dialysis, according to previous studies 3,4,7 . In case of citrate-acidified bicarbonate dialysis, high flux helixone dialyzer (Polyflux 21H, Gambro, CUF 78 ml/min/ mmHg, surface 2.1 m 2 ) and Dialysis Machine Artis Baxter were used.…”

“…Blood samples before and after hemodialysis were collected in heparin-containing tubes and centrifuged at 5000 rpm for 5 min at 4 °C, according to previous studies 3,4,7 . Plasma samples were frozen in liquid nitrogen and stored at −80 °C until further use, as previously studies 3,4 . This study was conducted according to the Declaration of Helsinki and was approved by the Ethics Committees of Research of University Hospital Fundación Jiménez Díaz (Madrid, Spain) and University Hospital 12 de Octubre (Madrid, Spain).…”

“…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 . 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.…”

Uremic Toxins Affecting Cardiovascular Calcification: A Systematic Review

“…Apo −/− mice with 5/6 nephrectomy displayed aortic valve calcification 12 weeks after surgery both when fed a high phosphate diet as well as a control diet, though with increased calcium deposits detected upon high phosphate diet [36]. Additionally, elevated calcium levels triggered calcification in human VSMC in vitro as well as ex vivo studies with rat aortic rings [38,40].…”

“…The calcium-phosphate metabolism is one of the key factors for initiation and progression of vascular calcification in CKD [60] and in vitro as well as ex vivo studies showed increased calcification upon increased levels of calcium [38,40] or inorganic phosphate [29,32,33,35]. In late stage CKD (CKD 4-5), most of CKD patients present with hyperphosphatemia [61,62].…”