Kovesdy Csaba P, Lu Jun Ling, Wall Barry M, Gyamlani Geeta, Naseer Adnan, Wallick Angela, Han Zhongji, Thomas Fridtjof, Quarles L Darryl, Jarmukli Nabil
Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, Tennessee, USA.
Division of Nephrology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Kidney Int Rep. 2018 Mar 23;3(4):897-904. doi: 10.1016/j.ekir.2018.03.011. eCollection 2018 Jul.
Abnormal phosphorus homeostasis develops early in chronic kidney disease (CKD). It is unclear if its correction results in improved clinical outcomes in non-dialysis dependent CKD.
We conducted a randomized controlled, parallel design clinical trial in 120 patients with estimated glomerular filtration rate 15 to 59 ml/min per 1.73 m and abnormal phosphorus homeostasis (serum phosphorus >4.6 mg/dl, parathyroid hormone [PTH] >70 pg/ml or tubular reabsorption of phosphorus [TRP] <80%). Patients were randomized to open-label lanthanum carbonate versus calcium acetate versus dietary intervention over 1 year. The co-primary outcomes were month 12 (vs. baseline) biochemical (serum phosphorus, TRP, PTH, calcium, bone-specific alkaline phosphatase [bALP], and fibroblast growth factor 23 [FGF23]) and vascular parameters (coronary artery calcium score, pulse wave velocity, and endothelial dysfunction) in all patients. Secondary outcomes were between-treatment differences in change for each parameter between month 12 and baseline. All analyses were intention to treat.
Baseline characteristics were similar in the 3 groups. A total of 107 patients (89%) completed 12 months of follow-up. Differences were not significant at month 12 (vs. baseline) for any of the outcomes except bALP (median [25th, 75th] percentile at month 12 versus baseline: 13.8 [10.6, 17.6] vs. 15.8 [12.1, 21.1], < .001) and FGF23 (132 [99, 216] vs. 133 [86, 189], = .002). Changes for all outcomes were similar in the 3 arms except for PTH, which was suppressed more effectively by calcium acetate ( < .001).
A 1-year intervention to limit phosphorus absorption using dietary restriction or 2 different phosphorus binders resulted in decreased bALP suggesting improved bone turnover, but no other significant changes in biochemical or vascular parameters in patients with CKD stage 3/4. (ClinicalTrials.gov: NCT01357317).
慢性肾脏病（CKD）早期就会出现磷稳态异常。目前尚不清楚纠正这种异常是否能改善非透析依赖型CKD患者的临床结局。
我们对120例估计肾小球滤过率为每分钟15至59 ml/1.73 m²且磷稳态异常（血清磷>4.6 mg/dl、甲状旁腺激素[PTH]>70 pg/ml或磷肾小管重吸收[TRP]<80%）的患者进行了一项随机对照、平行设计的临床试验。患者被随机分为开放标签的碳酸镧组、醋酸钙组或饮食干预组，为期1年。共同主要结局是所有患者在第12个月（与基线相比）的生化指标（血清磷、TRP、PTH、钙、骨特异性碱性磷酸酶[bALP]和成纤维细胞生长因子23 [FGF23]）和血管参数（冠状动脉钙化评分、脉搏波速度和内皮功能障碍）。次要结局是第12个月与基线相比各参数变化的组间差异。所有分析均采用意向性治疗。
3组的基线特征相似。共有107例患者（89%）完成了12个月的随访。除bALP（第12个月与基线相比的中位数[第25、75百分位数]：13.8 [10.6, 17.6] 对 15.8 [12.1, 21.1]，P <.001）和FGF23（132 [99, 216] 对 133 [86, 189]，P =.002）外，第12个月（与基线相比）的任何结局差异均无统计学意义。除PTH外，3组所有结局的变化相似，醋酸钙对PTH的抑制作用更有效（P <.001）。
采用饮食限制或两种不同的磷结合剂进行为期1年的干预以限制磷吸收，可使bALP降低，提示骨转换改善，但对3/4期CKD患者的生化或血管参数无其他显著变化。（ClinicalTrials.gov：NCT01357317）
