Department of Nephrology, Nippon Medical School Chiba Hokusoh Hospital.
Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School.
J Nippon Med Sch. 2024;91(4):352-356. doi: 10.1272/jnms.JNMS.2024_91-403.
Febuxostat is recommended for treatment of severe hyperuricemia in chronic kidney disease (CKD). We previously reported a significant positive correlation between fractional excretion of uric acid (FEUA) and estimated excretion of uric acid (eEUA) in patients receiving febuxostat and proposed that the addition of uricosuric agents could further decrease serum uric acid (sUA) levels by enhancing FEUA and eEUA in patients treated with febuxostat.
This retrospective study included 34 patients with CKD who were categorized into three groups (G3-G5) according to their estimated glomerular filtration rate (eGFR). The effects on sUA, FEUA, and eEUA of adding dotinurad (0.5 mg/day) to febuxostat (10 mg/day) were evaluated in these patients. Specifically, we examined changes in sUA, FEUA, and eEUA in each group after the addition of dotinurad.
Dotinurad significantly increased FEUA in all groups and notably decreased sUA in groups G3 and G4 but not in group G5. There was no significant change in eEUA in any group. Dotinurad maintained the significant positive correlation between FEUA and eEUA in patients receiving febuxostat.
This study is the first to show the effect of combining dotinurad with febuxostat in lowering sUA levels in G3 and G4 patients. Additional research is required in order to clarify the pharmacological mechanisms of dotinurad in patients with CKD.
别嘌醇用于治疗慢性肾脏病(CKD)患者的严重高尿酸血症。我们之前报道过,接受别嘌醇治疗的患者的尿酸排泄分数(FEUA)与估算的尿酸排泄量(eEUA)之间存在显著正相关,并且我们提出在接受别嘌醇治疗的患者中添加尿酸排泄剂可以通过增强 FEUA 和 eEUA 进一步降低血清尿酸(sUA)水平。
本回顾性研究纳入了 34 名 CKD 患者,根据估算肾小球滤过率(eGFR)将他们分为三组(G3-G5 组)。在这些患者中评估了添加多尼尿酸(0.5mg/天)对别嘌醇(10mg/天)的 sUA、FEUA 和 eEUA 的影响。具体而言,我们检查了在添加多尼尿酸后各组 sUA、FEUA 和 eEUA 的变化。
多尼尿酸显著增加了所有组的 FEUA,并显著降低了 G3 和 G4 组的 sUA,但 G5 组无明显变化。任何一组的 eEUA 均无明显变化。多尼尿酸维持了接受别嘌醇治疗的患者中 FEUA 和 eEUA 之间的显著正相关。
本研究首次表明,在 G3 和 G4 患者中,联合使用多尼尿酸和别嘌醇降低 sUA 水平的效果。为了阐明 CKD 患者中多尼尿酸的药理学机制,需要进一步研究。