Supplementary Material for: Association of Phosphate Containing Solutions with Incident Hypophosphatemia in Critically Ill Patients Requiring Continuous Renal Replacement Therapy

<b><i>Background:</i></b> Hypophosphatemia in critically ill patients is a common electrolyte disturbance associated with a myriad of adverse effects. Critically ill patients requiring continuous renal replacement therapy (CRRT) are at high risk of hypophosphatemia and often require phosphate supplementation during therapy. The aim of this study was to evaluate the association of phosphate versus non-phosphate containing CRRT solutions with incident hypophosphatemia in critically ill patients requiring CRRT. <b><i>Materials and Methods:</i></b> This is a single-center, retrospective, cohort study at a tertiary academic medical center of 1,396 adult patients requiring CRRT during their intensive care unit stay comprising 7,529 (phosphate containing) and 4,821 (non-phosphate containing) cumulative days of CRRT. Multivariable logistic regression was used to model the primary outcome of hypophosphatemia during CRRT according to exposure to phosphate versus non-phosphate containing CRRT solutions. <b><i>Results:</i></b> Incident hypophosphatemia during CRRT, serum phosphate &lt;2.5 mg/dL or 0.81 mmol/L, was significantly higher in the non-phosphate versus phosphate containing solution group: 304/489 (62%) versus 175/853 (21%) (<i>p</i> &lt; 0.001). Cumulative phosphate supplementation was also significantly higher in the non-phosphate versus phosphate containing solution group: 79 (IQR: 0–320) versus 0 (0–16) mmol (<i>p</i> &lt; 0.001). Non-phosphate solutions were associated with an 8-fold increase in the incidence of hypophosphatemia (adjusted OR 8.05; 95% CI 5.77, 11.26; <i>p</i> &lt; 0.001). <b><i>Discussion/Conclusions:</i></b> The use of phosphate containing CRRT solutions was independently associated with reduced risk of incident hypophosphatemia and decreased phosphate supplementation during CRRT. Interventional studies to confirm these findings are needed.

**背景**：重症患者合并低磷血症是一类常见的电解质紊乱，可引发多种不良结局。需接受连续肾脏替代治疗（continuous renal replacement therapy, CRRT）的重症患者属于低磷血症高危人群，治疗期间常需补充磷酸盐。本研究旨在评估需行CRRT的重症患者中，使用含磷酸盐与不含磷酸盐的CRRT置换液与新发低磷血症的相关性。

**材料与方法**：本研究为单中心回顾性队列研究，纳入某三级学术医疗中心的1396名在重症监护病房住院期间需接受CRRT的成年患者，其CRRT治疗累计时长分为含磷酸盐组7529天、不含磷酸盐组4821天。采用多变量logistic回归模型，根据患者暴露于含/不含磷酸盐的CRRT置换液的情况，分析CRRT期间低磷血症这一主要结局。

**结果**：CRRT期间新发低磷血症（血清磷酸盐浓度＜2.5 mg/dL或0.81 mmol/L）在不含磷酸盐置换液组的发生率显著高于含磷酸盐组：不含磷酸盐组为304/489（62%），含磷酸盐组为175/853（21%）（*p* < 0.001）。不含磷酸盐组的累计磷酸盐补充量亦显著更高：79（四分位距（interquartile range, IQR）：0–320）mmol vs 0（0–16）mmol（*p* < 0.001）。使用不含磷酸盐置换液可使低磷血症发生率升高8倍（校正后比值比（odds ratio, OR）=8.05；95%置信区间（confidence interval, CI）：5.77, 11.26；*p* < 0.001）。

**讨论与结论**：使用含磷酸盐的CRRT置换液可独立降低新发低磷血症的风险，并减少CRRT期间的磷酸盐补充量。未来需开展干预性研究以验证本研究结论。