Department of Clinical Pathology, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait City, Kuwait.
Department of Pediatrics, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait City, Kuwait.
Ann Hematol. 2021 Jun;100(6):1401-1409. doi: 10.1007/s00277-021-04500-4. Epub 2021 Apr 2.
Sickle cell nephropathy (SCN) develops via altered hemodynamics and acute kidney injury, but conventional screening tests remain normal until advanced stages. Early diagnostic biomarkers are needed so that preventive measures can be taken. This study evaluates the role of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of SCN in steady state and vaso-occlusive crisis (VOC). In this case-control study, 74 sickle cell disease (SCD) patients (37 in steady state and 37 in VOC) and 53 control subjects had hematological and biochemical measurements including plasma and urine NGAL. Univariate and logistic regression analyses were used to find the associations between variables. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance characteristics of plasma and urine NGAL for detection of VOC. Plasma and urine NGAL, urine microalbumin:creatinine ratio, and urine protein:creatinine ratio were significantly higher in VOC. Microalbuminuria was present in 17.1% steady state and 32.0% VOC patients. Microalbuminuria showed significant correlations with age, plasma NGAL, WBC, and hemolytic parameters. Area under the ROC curve for plasma NGAL was 0.69 (95%CI = 0.567-0.813; p = 0.006) and 0.86 (95%CI = 0.756-0.954; p < 0.001) for urine NGAL. Urine NGAL cut-off value of 12.0 ng/mL had 95% sensitivity and 65% specificity. These results confirm the presence of nephropathy during VOC and suggest that plasma and urine NGAL would be useful in the identification of SCN. Urine NGAL should be used as the screening biomarker, and patients with VOC and urine NGAL > 12.0 ng/mL should be selected for aggressive management to prevent progression of renal damage.
镰状细胞肾病 (SCN) 通过改变血液动力学和急性肾损伤发展，但常规筛查测试在晚期仍保持正常。需要早期诊断生物标志物，以便采取预防措施。本研究评估中性粒细胞明胶酶相关脂质运载蛋白 (NGAL) 作为 SCN 在稳定状态和血管阻塞性危象 (VOC) 中的生物标志物的作用。在这项病例对照研究中，74 名镰状细胞病 (SCD) 患者（37 名在稳定状态，37 名在 VOC）和 53 名对照者进行了血液学和生化测量，包括血浆和尿液 NGAL。使用单变量和逻辑回归分析来发现变量之间的关联。接收者操作特征 (ROC) 曲线用于确定血浆和尿液 NGAL 检测 VOC 的诊断性能特征。VOC 患者的血浆和尿液 NGAL、尿微量白蛋白：肌酐比和尿蛋白：肌酐比均显着升高。17.1%的稳定状态和 32.0%的 VOC 患者存在微量白蛋白尿。微量白蛋白尿与年龄、血浆 NGAL、白细胞和溶血性参数显着相关。血浆 NGAL 的 ROC 曲线下面积为 0.69（95%CI = 0.567-0.813；p = 0.006），尿液 NGAL 为 0.86（95%CI = 0.756-0.954；p < 0.001）。尿液 NGAL 的截断值为 12.0 ng/mL 时，具有 95%的敏感性和 65%的特异性。这些结果证实了 VOC 期间存在肾病，并表明血浆和尿液 NGAL 将有助于识别 SCN。尿液 NGAL 应作为筛选生物标志物，选择尿液 NGAL > 12.0 ng/mL 的 VOC 患者进行积极管理，以防止肾损伤进展。
