Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu) among Agricultural Communities in Sri Lanka.
Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu) among Agricultural Communities in Sri Lanka.
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DOI：
10.1371/journal.pntd.0004979
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发表时间：
2016-09
影响因子：
3.8
通讯作者：
Siribaddana SH
中科院分区：
文献类型：
--
作者：
De Silva PM;Mohammed Abdul KS;Eakanayake EM;Jayasinghe SS;Jayasumana C;Asanthi HB;Perera HS;Chaminda GG;Chandana EP;Siribaddana SH
病因不明的慢性肾脏病（CKDu）是斯里兰卡农村地区农业社区中的一种新兴流行病。受害者没有表现出共同的致病因素，然而，组织病理学研究表明，CKDu是一种小管间质性疾病。尿白蛋白或白蛋白-肌酐比值仍被用作识别CKDu的传统诊断工具，但产生的准确性和患病率数据值得怀疑。尿液生物标志物已用于类似的肾病，并因其在确定CKDu和早期肾损伤方面的灵敏度、特异性和准确性而得到广泛认可。然而，这些生物标志物从未在斯里兰卡用于诊断CKDu。从斯里兰卡的4个地区，即马塔拉和努沃勒埃利耶（没有CKDu流行的农业地区）以及斯里兰卡南部汉班托塔区的两个CKDu新兴地区，即Angunakolapelessa（EL 1）和Bandagiriya（EL 2）招募了男性农民（n = 1 734）。测定白蛋白尿（ACR ≥ 30 mg/g）、基于血清肌酐的肾小球滤过率（eGFR）估计值、肌酐标准化尿肾损伤分子（KIM-1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）。EL 1和EL 2地区首次发现14例（18%）新的CKDu病例和9例（9%）新的CKDu病例，这些病例以前被认为是非地方性疾病，并与持续性白蛋白尿（ACR ≥ 30 mg/g Cr）有关。在Matara（CM）和Nuwara Eliya（CN）的非地方病研究地点未发现CKDu病例。尿液生物标志物分析显示，在EL 1和EL 2中，尿KIM-1和NGAL在新发CKDu病例中显著升高。然而，我们也报告了显着较高的KIM-1和NGAL在EL 1和EL 2明显健康的农民相比，两个对照组。这些观察结果可能表明，在没有持续性白蛋白尿和尿KIM-1和NGAL的潜在能力，在斯里兰卡南部的农业社区早期检测肾损伤可能早期肾损伤。慢性肾脏病（CKD）是世界各地具有挑战性的全球健康问题。随着时间的推移，肾功能损害是显著的，但CKD的迹象可能不会被看到，直到相当大的损害肾功能。CKD的两个主要原因是糖尿病和高血压。然而，除了已知的因素外，最近在热带地区的农业工作中报告了新形式的CKD。这种神秘的CKD的原因是未知的，被称为病因不明的慢性肾脏病（CKDu）。临床诊断依赖于尿标志物，传统的基于肌酐的标志物可能会低估疾病的患病率。因此，开发用于早期检测的新的敏感标记物肯定会改善全世界的治疗和患者管理。
Chronic Kidney Disease of uncertain etiology (CKDu) is an emerging epidemic among farming communities in rural Sri Lanka. Victims do not exhibit common causative factors, however, histopathological studies revealed that CKDu is a tubulointerstitial disease. Urine albumin or albumin-creatinine ratio is still being used as a traditional diagnostic tool to identify CKDu, but accuracy and prevalence data generated are questionable. Urinary biomarkers have been used in similar nephropathy and are widely recognised for their sensitivity, specificity and accuracy in determining CKDu and early renal injury. However, these biomarkers have never been used in diagnosing CKDu in Sri Lanka. Male farmers (n = 1734) were recruited from 4 regions in Sri Lanka i.e. Matara and Nuwara Eliya (farming locations with no CKDu prevalence) and two CKDu emerging locations from Hambantota District in Southern Sri Lanka; Angunakolapelessa (EL1) and Bandagiriya (EL2). Albuminuria (ACR ≥ 30mg/g); serum creatinine based estimation of glomerular filtration rate (eGFR); creatinine normalized urinary kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were measured. Fourteen new CKDu cases (18%) from EL1 and nine CKDu cases (9%) from EL2 were recognized for the first time from EL1, EL2 locations, which were previously considered as non-endemic of the disease and associated with persistent albuminuria (ACR ≥ 30mg/g Cr). No CKDu cases were identified in non-endemic study locations in Matara (CM) and Nuwara Eliya (CN). Analysis of urinary biomarkers showed urinary KIM-1 and NGAL were significantly higher in new CKDu cases in EL1 and EL2. However, we also reported significantly higher KIM-1 and NGAL in apparently healthy farmers in EL 1 and EL 2 with comparison to both control groups. These observations may indicate possible early renal damage in absence of persistent albuminuria and potential capabilities of urinary KIM-1 and NGAL in early detection of renal injury among farming communities in Southern Sri Lanka. Chronic Kidney Disease (CKD) is a challenging global health issue around the world. Impairment of kidney function with time is eminent, but indications of CKD may not be seen until considerable damage to kidney functions. Two main causes of CKD are diabetes and high blood pressure. However recently new form of CKD has been reported among agricultural works in the tropics other than known factors. The causes for this mysterious CKD are unknown and termed as Chronic Kidney Disease of uncertain etiology (CKDu). Clinical diagnosis depends on urinary markers and conventional creatinine based markers may underestimate the prevalence of the disease. Therefore, development of new sensitive markers for the early detection may certainly improve the treatment and patient management around the world.
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影响因子：
3.7
作者：
Chung HJ;Pellegrini KL;Chung J;Wanigasuriya K;Jayawardene I;Lee K;Lee H;Vaidya VS;Weissleder R
通讯作者：
Weissleder R
影响因子：
3
作者：
Mishra, Jaya;Ma, Qing;Devarajan, Prasad
通讯作者：
Devarajan, Prasad
影响因子：
2.3
作者：
Jayatilake N;Mendis S;Maheepala P;Mehta FR;CKDu National Research Project Team
通讯作者：
CKDu National Research Project Team
影响因子：
5
作者：
LARSEN, K
通讯作者：
LARSEN, K
影响因子：
19.6
作者：
Athuraliya, Nimmi T. C.;Abeysekera, Tilak D. J.;Jones, Alison L.
通讯作者：
Jones, Alison L.