Sugihara Shinobu, Yamamoto Yasutaka, Teramoto Kei, Hamada Toshiro, Miyazaki Satoshi, Ogino Kazuhide, Kuwabara Masanari, Ohtahara Akira, Mizuta Einosuke, Ichida Kimiyoshi, Endo Yusuke, Minato Hiroyuki, Ninomiya Haruaki, Kato Masahiko, Yamamoto Kazuhiro, Hisatome Ichiro
Matsue Health Service Center, Shimane University, Matsue, Japan.
Yasutaka Yamamoto Cardiology/Internal Medicine Clinic, Fuji, Japan.
Clin Exp Nephrol. 2025 Feb;29(2):173-181. doi: 10.1007/s10157-024-02558-8. Epub 2024 Oct 3.
Extremely low uric acid (UA) levels or increased urinary UA (Uua) excretion might be risk factors for kidney disease in renal hypouricemia (RHU) patients, but their relationship with kidney dysfunction is unclear. This study investigated time-dependent changes in eGFR in RHU patients.
This multicenter retrospective study assessed UA metabolism and changes in eGFR (median 5.5 years) in 13 RHU patients. We then compared eGFR change in 7 of 13 RHU patients whose eGFR could be measured for 4 years with those in normouricemic group (n = 31). In addition, 7 RHU patients were divided into two groups based on URAT1 gene mutations: homozygote and compound heterozygote mutations (Homo/Com group, n = 3), and wild-type and heterogeneous mutations (WT/Hetero group, n = 4).
In 13 RHU patients, the median and mean serum UA (SUA) were 0.8 (0.4-2.5) and 1.1 ± 0.7 mg/dL. The median and mean Uua were 44.3 (12.7-141.1) and 49.7 ± 36.2 mg/dL. The median and mean urinary urate clearance (Cua/Ccr) were 46.8 (11.3-73.6) and 43.3 ± 19.7%. Over 4 years, eGFR did not change in the RHU group but declined in the normouricemic group. Annual mean eGFR decline and change rate in the RHU group were the same as those in the normouricemic group (- 1.09 ± 1.11 vs. - 1.09 ± 1.92 mL/min/1.73 m/year, p = 0.996) (- 1.74 ± 1.96 vs. - 1.36 ± 2.10%, p = 0.664). And no significant difference was found in eGFR decline or change rate between Homo/Com and WT/Hetero groups (- 0.33 ± 1.03 vs. - 1.67 ± 0.85 mL/min/1.73 m/year, p = 0.116) (- 0.61 ± 1.62 vs. - 2.59 ± 1.91%, p = 0.210).
RHU from URAT1 genetic mutation may not show eGFR decline over 4 consecutive years.
极低尿酸（UA）水平或尿UA（Uua）排泄增加可能是肾性低尿酸血症（RHU）患者肾病的危险因素，但其与肾功能不全的关系尚不清楚。本研究调查了RHU患者估算肾小球滤过率（eGFR）的时间依赖性变化。
这项多中心回顾性研究评估了13例RHU患者的UA代谢及eGFR变化（中位时间5.5年）。然后，我们将13例RHU患者中7例可测量4年eGFR的患者的eGFR变化与正常尿酸血症组（n = 31）的患者进行比较。此外，7例RHU患者根据尿酸转运蛋白1（URAT1）基因突变分为两组：纯合子和复合杂合子突变（纯合子/复合杂合子组，n = 3），以及野生型和异质突变（野生型/异质组，n = 4）。
13例RHU患者的血清UA（SUA）中位数和平均值分别为0.8（0.4 - 2.5）和1.1±0.7mg/dL。Uua中位数和平均值分别为44.3（12.7 - 141.1）和49.7±36.2mg/dL。尿尿酸清除率（Cua/Ccr）中位数和平均值分别为46.8（11.3 - 73.6）和43.3±19.7%。4年期间，RHU组的eGFR未发生变化，但正常尿酸血症组有所下降。RHU组的年平均eGFR下降率和变化率与正常尿酸血症组相同（-1.09±1.11 vs. -1.09±1.92 mL/min/1.73m/年，p = 0.996）（-1.74±1.96 vs. -1.36±2.10%，p = 0.664）。纯合子/复合杂合子组和野生型/异质组之间的eGFR下降率或变化率无显著差异（-0.33±1.03 vs. -1.67±0.85 mL/min/1.73m/年，p = 0.116）（-0.61±1.62 vs. -2.59±1.91%，p = 0.210）。
由URAT1基因突变引起的RHU患者可能在连续4年中未出现eGFR下降。
