Wald Ron, Rabbat Christian G, Girard Louis, Garg Amit X, Tennankore Karthik, Tyrwhitt Jessica, Smyth Andrew, Rathe-Skafel Andrea, Gao Peggy, Mazzetti Andrea, Bosch Jackie, Yan Andrew T, Parfrey Patrick, Manns Braden J, Walsh Michael
Divisions of Nephrology and.
Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
Clin J Am Soc Nephrol. 2017 Jun 7;12(6):965-973. doi: 10.2215/CJN.10941016. Epub 2017 May 26.
Hyperphosphatemia is common among recipients of maintenance dialysis and is associated with a higher risk of mortality and cardiovascular events. A large randomized trial is needed to determine whether lowering phosphate concentrations with binders improves patient-important outcomes. To inform such an effort we conducted a pilot randomized controlled trial.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a randomized controlled trial of prevalent hemodialysis recipients already receiving calcium carbonate as a phosphate binder at five Canadian centers between March 31, 2014 and October 2, 2014. Participants were randomly allocated to 26 weeks of an intensive phosphate goal of 2.33-4.66 mg/dl (0.75-1.50 mmol/L) or a liberalized target of 6.20-7.75 mg/dl (2.00-2.50 mmol/L) by titrating calcium carbonate using a dosing nomogram. The primary outcome was the difference in the change in serum phosphate from randomization to 26 weeks.
Fifty-three participants were randomized to the intensive group and 51 to the liberalized group. The median (interquartile range) daily dose of elemental calcium at 26 weeks was 1800 (1275-3000) mg in the intensive group, and 0 (0-500) mg in the liberalized group. The mean (SD) serum phosphate at 26 weeks was 4.53 (1.12) mg/dl (1.46 [0.36] mmol/L) in the intensive group and 6.05 (1.40) mg/dl (1.95 [0.45] mmol/L) in the liberalized group. Phosphate concentration in the intensive group declined by 1.24 (95% confidence interval, 0.75 to 1.74) mg/dl (0.40 [95% confidence interval, 0.24 to 0.56] mmol/L) compared with the liberalized group. There were no statistically significant differences between the two groups in the risk of hypercalcemia, hypocalcemia, parathyroidectomy, or major vascular events.
It is feasible to achieve and maintain a difference in serum phosphate concentrations in hemodialysis recipients by titrating calcium carbonate. A large trial is needed to determine if targeting a lower serum phosphate concentration improves patient-important outcomes.
高磷血症在维持性透析患者中很常见，且与更高的死亡风险和心血管事件相关。需要进行一项大型随机试验来确定使用磷结合剂降低磷酸盐浓度是否能改善对患者至关重要的结局。为了给这样的研究提供信息，我们开展了一项先导性随机对照试验。
设计、地点、参与者及测量方法：我们于2014年3月31日至2014年10月2日在加拿大的五个中心，对已接受碳酸钙作为磷结合剂的血液透析患者进行了一项随机对照试验。通过使用给药剂量表滴定碳酸钙，将参与者随机分配至26周强化磷酸盐目标为2.33 - 4.66mg/dl（0.75 - 1.50mmol/L）或宽松目标为6.20 - 7.75mg/dl（2.00 - 2.50mmol/L）的组。主要结局是从随机分组至26周时血清磷酸盐变化的差异。
53名参与者被随机分配至强化组，51名被分配至宽松组。强化组在26周时元素钙的每日剂量中位数（四分位间距）为1800（1275 - 3000）mg，宽松组为0（0 - 500）mg。强化组在26周时的平均（标准差）血清磷酸盐为4.53（1.12）mg/dl（1.46 [0.36] mmol/L），宽松组为6.05（1.40）mg/dl（1.95 [0.45] mmol/L）。与宽松组相比，强化组的磷酸盐浓度下降了1.24（95%置信区间，0.75至1.74）mg/dl（0.40 [95%置信区间，0.24至0.56] mmol/L）。两组在高钙血症、低钙血症、甲状旁腺切除术或主要血管事件的风险方面无统计学显著差异。
通过滴定碳酸钙来实现并维持血液透析患者血清磷酸盐浓度的差异是可行的。需要进行一项大型试验来确定将血清磷酸盐浓度目标设定得更低是否能改善对患者至关重要的结局。
