Pluquet Maxime, Laville Solène M, Brazier François, Ureña-Torres Pablo, El Esper Najeh, Kamel Said, Choukroun Gabriel, Liabeuf Sophie
MP3CV Laboratory, Jules Verne University of Picardie, Amiens, France.
Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, Amiens, France.
Clin Kidney J. 2024 Nov 13;18(1):sfae343. doi: 10.1093/ckj/sfae343. eCollection 2025 Jan.
The serum calcification propensity test (or T50 test) might become a standard tool for the assessment of vascular calcification risk and T50 might be a valuable biomarker in clinical trials of treatments intended to slow the progression of vascular calcification. Literature data suggest that non-calcium-containing phosphate binders can influence T50 in chronic dialysed patients. However, it is not clear whether similar interventions are effective in patients at earlier stages of chronic kidney disease (CKD).
The FGF23 Reduction: Efficacy of a New phosphate binder in CHronic kidney disease (FRENCH) trial was a multicentre, double-blind, placebo-controlled, randomized trial of sevelamer carbonate in participants with stage 3b/4 CKD. In this subanalysis of the FRENCH data, T50 and other laboratory variables (including fetuin-A and ionized and total magnesium) were measured centrally at baseline and after 12 weeks of treatment.
A total of 96 patients were screened and 78 (55 men and 23 women) met the inclusion criteria and were randomized to receive placebo ( = 39) or sevelamer carbonate ( = 39). The median patient age was 66 years [interquartile range (IQR) 56-72], the median eGFR was 25 ml/min/1.73 m (IQR 21-30) and the mean T50 was 335 minutes (standard deviation 82). In a linear regression model, T50 was independently associated with serum ionized magnesium, fetuin-A and bicarbonate levels and inversely associated with phosphate concentration. The within-group changes in the mean T50 between week 0 and week 12 were not significant in the sevelamer group or the placebo group {4.6 minutes [95% confidence interval (CI) -13.6-22.8; = .61] and 7.8 minutes [95% CI -16.4-32.1; = .51], respectively}. Furthermore, we did not observe significant changes in fetuin-A and magnesium levels.
A 12-week course of the non-calcium-containing phosphate binder sevelamer carbonate was not associated with a significant change in T50 in patients with stage 3b/4 CKD. Phosphate binders might not be an effective strategy for modifying serum calcification propensity in non-dialysis-dependent patients with CKD.
血清钙化倾向试验（或T50试验）可能会成为评估血管钙化风险的标准工具，且T50可能是旨在减缓血管钙化进展的治疗临床试验中的一个有价值的生物标志物。文献数据表明，不含钙的磷结合剂可影响慢性透析患者的T50。然而，尚不清楚类似干预措施对慢性肾脏病（CKD）早期患者是否有效。
成纤维细胞生长因子23降低：新型磷结合剂在慢性肾脏病中的疗效（FRENCH）试验是一项多中心、双盲、安慰剂对照、随机试验，研究对象为3b/4期CKD患者，给予碳酸司维拉姆治疗。在对FRENCH数据的这项亚组分析中，在基线和治疗12周后集中测量T50和其他实验室变量（包括胎球蛋白-A、离子化镁和总镁）。
共筛查了96例患者，78例（55例男性和23例女性）符合纳入标准并被随机分为接受安慰剂（n = 39）或碳酸司维拉姆（n = 39）治疗。患者年龄中位数为66岁[四分位间距（IQR）56 - 72]，估算肾小球滤过率（eGFR）中位数为25 ml/min/1.73m²（IQR 21 - 30），平均T50为335分钟（标准差82）。在一个线性回归模型中，T50与血清离子化镁、胎球蛋白-A和碳酸氢盐水平独立相关，与磷酸盐浓度呈负相关。司维拉姆组和安慰剂组在第0周和第12周之间平均T50的组内变化均无显著性差异{分别为4.6分钟[95%置信区间（CI）-13.6 - 22.8；P = .61]和7.8分钟[95% CI -16.4 - 32.1；P = .51]}。此外，我们未观察到胎球蛋白-A和镁水平有显著变化。
对于3b/4期CKD患者，为期12周的不含钙磷结合剂碳酸司维拉姆疗程与T50的显著变化无关。对于非透析依赖的CKD患者，磷结合剂可能不是改变血清钙化倾向的有效策略。
