Natural history and variability in albuminuria in pediatric and murine sickle cell anemia.
Natural history and variability in albuminuria in pediatric and murine sickle cell anemia.
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DOI：
10.1182/bloodadvances.2023010101
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发表时间：
2023-11-28
期刊：
影响因子：
7.5
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中科院分区：
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考虑10年前进行ACR筛查。ACR水平为100 mg/g应被视为蛋白尿的危险因素。肾保护SCA试验应考虑到蛋白尿测量的高变异性。描述镰状细胞性贫血（SCA）患者蛋白尿的自然病史至关重要；然而，目前缺乏这些数据并影响循证指南。我们对儿童蛋白尿的发展进行了自然历史研究。我们确定了血红蛋白SS/ s0地中海贫血≥5年的参与者，在稳定状态的临床访问中进行白蛋白与肌酐比值（ACR）测量。参与者的特征为持续性、间歇性或从不蛋白尿。我们确定了持续性蛋白尿的患病率，使用ACR≥100mg /g作为预测因子，以及ACR测量值的变化。我们对这项研究进行了镜像，以确定SCA小鼠模型中蛋白尿测量的变化。在355名HbSS/SB0型地中海贫血患者中，我们确定了1728个ACR测量值，其中17%为持续性蛋白尿，13%为间歇性蛋白尿。持续性蛋白尿患者中有13%在10岁前出现异常ACR。单次ACR测量≥100 mg/g与持续性蛋白尿的几率增加55.5倍（95%可信区间，12.3-527）相关。在ACR≥100mg /g的参与者中，我们发现重复测量结果存在显著的变异性。初始和后续测量的中位ACR分别为175.8 mg/g（四分位数范围[IQR]， 135-242）和117.3 mg/g （IQR, 64-292）。人类ACR的变异性反映在小鼠模型中蛋白尿的20%变异性上。该证据建议采用重复ACR测量的标准，考虑在10岁前筛查ACR，并使用ACR bb0 100 mg/g作为进展的危险因素。儿童和小鼠肾保护临床试验需要考虑重复ACR测量的高变异性。
Consider ACR screening prior to 10 years. ACR levels >100 mg/g should be considered a risk factor for albuminuria. Renoprotective SCA trials should account for high variability in albuminuria measurements. It is critical to characterize the natural history of albuminuria in patients with sickle cell anemia (SCA); however, these data are currently lacking and affecting evidence-based guidelines. We performed a natural history study of the development of pediatric albuminuria. We identified participants with hemoglobin SS/SB0 thalassemia ≥5 years with albumin to creatinine ratio (ACR) measurements performed at a steady-state clinic visit. Participants were characterized as either persistent, intermittent, or never albuminuria. We determined the prevalence of persistent albuminuria, use of ACR ≥100 mg/g as a predictor, and variation in ACR measurements. We mirrored this study to determine the variation in albuminuria measurements in the SCA murine model. Among 355 participants with HbSS/SB0 thalassemia with 1728 ACR measurements, we identified 17% with persistent and 13% with intermittent albuminuria. Thirteen percent of participants with persistent albuminuria developed an abnormal ACR before 10 years of age. A single ACR measurement ≥100 mg/g was associated with 55.5 times (95% confidence interval, 12.3-527) higher odds of having persistent albuminuria. Among participants with ACR ≥100 mg/g, we identified significant variability in the results of repeated measurements. The median ACR at the initial and next measurements were 175.8 mg/g (interquartile range [IQR], 135-242) and 117.3 mg/g (IQR, 64-292). The human variability in ACR was mirrored by ∼20% variability in albuminuria in murine model. This evidence suggests adopting standards for repeating ACR measurements, consider screening for ACR before 10 years of age, and using an ACR >100 mg/g as a risk factor for progression. Pediatric and murine renoprotective clinical trials need to consider the high variability in repeated ACR measurements.