Pediatrics, Division of Nephrology, Children's Hospital of Richmond at Virginia Commonwealth University, 1000 E. Broad St Box 980498, Richmond, VA, 23298, USA.
University of Vermont Larner College of Medicine, 89 Beaumont Ave, Burlington, VT, 05405, USA.
Pediatr Nephrol. 2020 May;35(5):883-889. doi: 10.1007/s00467-019-04432-2. Epub 2020 Jan 20.
Sickle cell nephropathy (SCN) is a progressive disease that contributes significant morbidity and mortality in sickle cell disease (SCD), yet it remains poorly understood. Hyperuricemia negatively impacts renal function in the non-sickle cell population but is understudied in SCD.
We performed a cross-sectional analysis of the first 78 pediatric SCD patients enrolled in a cohort study. The mechanism of development of hyperuricemia (defined, serum uric acid (UA) ≥ 5.5 mg/dL) was characterized as a result of either UA overproduction or inefficient renal excretion by the Simkin index and fractional clearance of urate (FCU) equations. Associations between hyperuricemia and albuminuria or estimated glomerular filtration rate (eGFR) were determined by linear regression.
The prevalence of hyperuricemia in this young population (mean age 11.6 ± 3.77 years) was 34.2%. Only 1 hyperuricemic participant overproduced UA by Simkin index, while 62.5% were inefficient renal excretors of UA (FCU < 4%). Hyperuricemia was associated with a significant decrease in average eGFR, -27 ml/min/1.73m below normouricemia (mean eGFR 151.6 ± 40.32), p = 0.0122. Notably, the previously accepted association between decline of eGFR with age is significantly modified by hyperuricemia stratification, where hyperuricemia explains 44% of the variance in eGFR by age (R = 0.44, p = 0.0004) and is nonsignificant in normouricemia (R = 0.07, p = 0.0775).
These findings indicate that hyperuricemia may be associated with early eGFR decline in SCN. This association must be further characterized in prospective cohort studies in SCN, and hyperuricemia must be investigated as a potential therapeutic target for SCN.
镰状细胞肾病（SCN）是一种进行性疾病，在镰状细胞病（SCD）中导致显著的发病率和死亡率，但仍未被充分理解。高尿酸血症对非镰状细胞人群的肾功能有负面影响，但在 SCD 中研究不足。
我们对纳入队列研究的前 78 名儿科 SCD 患者进行了横断面分析。通过 Simkin 指数和尿酸分数清除率（FCU）方程，将高尿酸血症（定义为血清尿酸（UA）≥5.5mg/dL）的发生机制特征化为尿酸产生过多或肾脏排泄效率低下。通过线性回归确定高尿酸血症与蛋白尿或估计肾小球滤过率（eGFR）之间的关系。
在这个年轻人群（平均年龄 11.6±3.77 岁）中，高尿酸血症的患病率为 34.2%。只有 1 名高尿酸血症患者通过 Simkin 指数产生过多的 UA，而 62.5%的患者 UA 肾脏排泄效率低下（FCU＜4%）。高尿酸血症与平均 eGFR 显著降低相关，与正常尿酸血症相比，eGFR 降低了-27ml/min/1.73m（平均 eGFR 为 151.6±40.32，p=0.0122）。值得注意的是，高尿酸血症分层显著改变了 eGFR 随年龄下降的先前关联，高尿酸血症解释了 eGFR 随年龄变化的 44%的方差（R=0.44，p=0.0004），而在正常尿酸血症中则不显著（R=0.07，p=0.0775）。
这些发现表明，高尿酸血症可能与 SCN 中的早期 eGFR 下降有关。这种关联必须在 SCN 的前瞻性队列研究中进一步表征，并且必须将高尿酸血症作为 SCN 的潜在治疗靶点进行研究。
