Riccio Eleonora, Sabbatini Massimo, Bruzzese Dario, Grumetto Lucia, Marchetiello Cristina, Amicone Maria, Andreucci Michele, Guida Bruna, Passaretti Davide, Russo Giacomo, Pisani Antonio
Department of Nephrology, Second University of Naples, Naples, Italy.
Chair of Nephrology, Department of Public Health, Federico II University of Naples, Naples, Italy.
Clin Exp Nephrol. 2018 Jun;22(3):529-538. doi: 10.1007/s10157-017-1504-8. Epub 2017 Nov 20.
The accumulation of p-cresol, a metabolic product of aromatic amino acids generated by intestinal microbiome, increases the cardiovascular risk in chronic kidney disease (CKD) patients. Therefore, therapeutic strategies to reduce plasma p-cresol levels are highly demanded. It has been reported that the phosphate binder sevelamer (SEV) sequesters p-cresol in vitro, while in vivo studies on dialysis patients showed controversial results. Aim of our study was to evaluate the effect of SEV on p-cresol levels in non-dialysis CKD patients.
This was a single-blind, randomized placebo-controlled trial (Registration number NCT02199444) carried on 69 CKD patients (stage 3-5, not on dialysis), randomly assigned (1:1) to receive either SEV or placebo for 3 months. Total p-cresol serum levels were evaluated at baseline (T0), and 1 (T1) and 3 months (T3) after treatment start. The primary end-point was to evaluate the effect of SEV on p-cresol levels.
Compared to baseline (T0, 7.4 ± 2.7 mg/mL), p-cresol mean concentration was significantly reduced in SEV patients after one (- 2.06 mg/mL, 95% CI - 2.62 to - 1.50 mg/mL; p < 0.001) and 3 months of treatment (- 3.97 mg/mL, 95% CI - 4.53 to - 3.41 mg/mL; p < 0.001); no change of plasma p-cresol concentration was recorded in placebo-treated patients. Moreover, P and LDL values were reduced after 3 months of treatment by SEV but not placebo.
In conclusion, our study represents the first evidence that SEV is effective in reducing p-cresol levels in CKD patients in conservative treatment, and confirms its beneficial effects on inflammation and lipid pattern.
对甲酚是肠道微生物群产生的芳香族氨基酸的代谢产物，其在慢性肾脏病（CKD）患者体内的蓄积会增加心血管疾病风险。因此，迫切需要降低血浆对甲酚水平的治疗策略。据报道，磷结合剂司维拉姆（SEV）在体外可螯合对甲酚，而针对透析患者的体内研究结果存在争议。我们研究的目的是评估SEV对非透析CKD患者对甲酚水平的影响。
这是一项单盲、随机、安慰剂对照试验（注册号NCT02199444），纳入69例CKD患者（3-5期，未接受透析），随机（1:1）分配接受SEV或安慰剂治疗3个月。在基线期（T0）以及治疗开始后1个月（T1）和3个月（T3）评估血清总对甲酚水平。主要终点是评估SEV对对甲酚水平的影响。
与基线期（T0，7.4±2.7mg/mL）相比，接受SEV治疗的患者在治疗1个月后（-2.06mg/mL，95%CI -2.62至-1.50mg/mL；p<0.001）和3个月后（-3.97mg/mL，95%CI -4.53至-3.41mg/mL；p<0.001）对甲酚平均浓度显著降低；接受安慰剂治疗的患者血浆对甲酚浓度无变化。此外，SEV治疗3个月后P和低密度脂蛋白值降低，而安慰剂组未降低。
总之，我们的研究首次证明SEV对保守治疗的CKD患者降低对甲酚水平有效，并证实了其对炎症和脂质谱的有益作用。
