De Silva Pallagae Mangala C S, Mohammed Abdul Khaja Shameem, Eakanayake Eakanayake M D V, Jayasinghe Sudheera Sammanthi, Jayasumana Channa, Asanthi Hewa Bandulage, Perera Hettiarachigae S D, Chaminda Gamage G Tushara, Chandana Ediriweera P S, Siribaddana Sisira H
Department of Zoology, Faculty of Science, University of Ruhuna, Matara, Sri Lanka.
Department of Pharmacology, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka.
PLoS Negl Trop Dis. 2016 Sep 19;10(9):e0004979. doi: 10.1371/journal.pntd.0004979. eCollection 2016 Sep.
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.
病因不明的慢性肾脏病(CKDu)在斯里兰卡农村的农业社区中呈流行趋势。患者未表现出常见的致病因素,然而,组织病理学研究表明CKDu是一种肾小管间质性疾病。尿白蛋白或白蛋白-肌酐比值仍被用作诊断CKDu的传统工具,但所产生的准确性和患病率数据存在疑问。尿生物标志物已用于类似的肾病,并且因其在确定CKDu和早期肾损伤方面的敏感性、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个地区招募了男性农民(n = 1734),即马特勒和努沃勒埃利耶(无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流行地区;安古纳科拉佩莱萨(EL1)和班达吉里亚(EL2)。测量了蛋白尿(ACR≥30mg/g);基于血清肌酐估算的肾小球滤过率(eGFR);肌酐标准化的尿肾损伤分子(KIM-1)和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)。首次从EL1和EL2地区确认了14例新的CKDu病例(18%)来自EL1,9例CKDu病例(9%)来自EL2,这些地区以前被认为该疾病非流行区且与持续性蛋白尿(ACR≥30mg/g Cr)相关。在马特勒(CM)和努沃勒埃利耶(CN)的非流行研究地区未发现CKDu病例。尿生物标志物分析显示,EL1和EL2新确诊的CKDu病例中尿KIM-1和NGAL显著升高。然而,我们还报告称,与两个对照组相比,EL1和EL2中看似健康农民的KIM-1和NGAL也显著更高。这些观察结果可能表明在无持续性蛋白尿的情况下可能存在早期肾损伤,以及尿KIM-1和NGAL在斯里兰卡南部农业社区早期检测肾损伤方面的潜在能力。