BACKGROUND 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. METHODS 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. RESULTS 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/1.73m2 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 (R2 = 0.44, p = 0.0004) and is nonsignificant in normouricemia (R2 = 0.07, p = 0.0775). CONCLUSION 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.

中文翻译：

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高尿酸血症与小儿镰状细胞病患者肾小球滤过率降低有关。

背景技术镰状细胞性肾病（SCN）是一种进展性疾病，其在镰状细胞性疾病（SCD）中引起显着的发病率和死亡率，但仍知之甚少。高尿酸血症会对非镰状细胞群的肾功能产生负面影响，但在SCD中并未得到充分研究。方法我们对参加队列研究的前78名儿科SCD患者进行了横断面分析。高尿酸血症（定义为血清尿酸（UA）≥5.5 mg / dL）的发展机制是由于Simkin指数和尿酸盐分数清除率（FCU）方程导致UA过度生产或肾排泄效率低下的结果。高尿酸血症与蛋白尿或估计的肾小球滤过率（eGFR）之间的关联通过线性回归确定。结果在这个年轻人口（平均年龄11.6±3.77岁）中，高尿酸血症的患病率为34.2％。根据Simkin指数，只有1名高尿酸血症参与者过量生产UA，而62.5％是UA的无效肾排泄物（FCU <4％）。高尿酸血症与平均eGFR显着降低有关，低于正常尿酸血症-27 ml / min / 1.73m2（平均eGFR 151.6±40.32），p = 0.0122。值得注意的是，高尿酸血症分层显着改善了先前公认的eGFR下降与年龄之间的关联，其中高尿酸血症解释了eGFR随年龄变化的44％（R2 = 0.44，p = 0.0004），而在正常尿酸血症中无统计学意义（R2 = 0.07， p = 0.0775）。结论这些发现表明高尿酸血症可能与SCN中早期eGFR下降有关。