Citric-acid dialysate improves the calcification propensity of hemodialysis patients: A multicenter prospective randomized cross-over trial

Abstract

IntroductionThe concentration of dialysate calcium (dCa) has been suggested to affect vascular calcification, but evidence is scarce. Calcification propensity reflects the intrinsic capacity of serum to prevent calcium and phosphate to precipitate.The use of citric-acid dialysate may have a beneficial effect on the calcification propensity due to the chelating effect on calcium and magnesium. The aim of this study was to compare the intradialytic and short-term effects of haemodialysis with either standard acetic-acid dialysate with dCa1.50 (A1.5) or dCa1.25 (A1.25), as well as citric-acid dialysate with dCa1.50 (C1.5) in bicarbonate dialysis on the calcification propensity of serum.MethodsChronic stable hemodialysis patients were included. This multicenter randomized cross-over study consisted out of a baseline week (A1.5), followed by the randomized sequence of A1.25 or C1.5 for one week after which the alternate treatment was provided after a washout week with A1.5. Calcification propensity of serum was assessed by time-resolved nephelometry where the T50 reflects the transition time between formation of primary and secondary calciprotein particles.ResultsEighteen patients (median age 70 years) completed the study. Intradialytic change in T50 was increased with C1.5 (121 [90–152]min) compared to A1.25 (83 [43–108]min, p<0.001) and A1.5 (66 [18–102]min, p<0.001). During the treatment week, predialysis T50 increased significantly from the first to the third session with C1.5 (271 [234–291] to 280 [262–339]min, p = 0.002) and with A1.25 (274 [213–308] to 307 [256–337]min, p<0.001), but not with A1.5 (284 [235–346] to 300 [247–335]min, p = 0.33).ConclusionCalcification propensity, as measured by the change in T50, improved significantly during treatment in C1.5 compared to A1.25 and A1.5. Long-term studies are needed to investigate the effects of different dialysate compositions concentrations on vascular calcification and bone mineral disorders.

Effect of citric-acid dialysate on the QTC-interval

“…Although the effects on QTc appeared in general to be relatively minor in our study population, we suggest that this study can contribute to the clinical decision to individualize the optimal dialysate for each patient, which can be based on the calcification propensity 1 , haemodynamic stability, calcium balance, the pre-existing QTc-interval or the use of QTc-prolongating medications. Extrapolating the results of our study, the effects of dCit with dCa 1.5 on the QTc-interval and calcium mass balances are comparable to those of dAcet with a 0.25 mmol/l lower dCa which is used worldwide.…”

“…This could be due to the lower Ca concentration in dialysate, as observed in a study by Severi et al 22 . An important factor to incorporate in choosing the right dialysate concentration is whether a neutral calcium balance can be reached 1 , 26 . For example, calcium-profiled haemodialysis suggested by Severi et al might have a similar QTc interval as high dCa, but with a more negative balance 17 .…”

“…We have conducted a multicenter, randomized cross-over trial in two Dutch hospitals with the primary focus on the effect of the different dialysate concentrations on calcification propensity and calcium mass balance. These have been published elsewhere 1 . The study design has been published before 1 .…”

“…These have been published elsewhere 1 . The study design has been published before 1 . Patients with an a priori QTc prolongation of ≥ 470 ms were excluded from participation.…”

“…Although lower dialysate calcium concentrations (dCa) may positively affect the calcification tendency in serum of haemodialysis (HD) patients 1 , it may also potentially have a prolonging effect on cardiac action potential 2 – 4 . In addition, the PACE study suggested that predialysis low serum potassium (K) and ionized calcium (iCa) are associated with higher risk prolongation of heart rate-corrected QT-intervals (QTc) 5 .…”