Getting to the cause of Chronic Kidney Disease of unknown cause (CKDu)

了解不明原因慢性肾脏病 (CKDu) 的病因

• 批准号: MR/V033743/1
• 负责人: Neil Pearce
• 金额: $ 237.44万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV033743%2F1
• 关键词: Getting; cause; Chronic; Kidney; Disease

There is an epidemic of primarily tubular-interstitial chronic kidney disease (CKD) clustering in agricultural communities in low-and-middle income countries (LMICs). Although it is currently unclear whether there is a common underlying cause, these conditions have been collectively termed CKD of unknown cause (CKDu). CKDu is estimated to have led to the premature deaths of tens to hundreds of thousands of young adults in LMICs over the last two decades. Thus, there is an urgent need to understand the aetiology and pathophysiology of these condition(s) and to develop preventive interventions.We have now established that CKDu exists in Central America (Nicaragua) and South Asia (India, Sri Lanka), but not in some other tropical countries (Malawi, Peru). It is not clear yet whether the epidemics in Central America and South Asia have common causes or different causes, which is why is it important to conduct research using the same protocols and methods in these different regions. Together with colleagues we have established prospective studies in affected communities in Nicaragua, South India, Sri Lanka to investigate the causes of the epidemics of CKDu, and factors which affect prognosis. We already have published striking findings from Nicaragua, where 10% of the community, who were apparently healthy when we started following them, have lost one-third of their kidney function in two years of follow-up - so something very alarming and striking is occurring. The underlying hypothesis is that CKDu is caused by unknown factors to which the populations have become exposed due to the changes in agricultural practice, or other environmental changes (e.g. water supply), over recent decades. The objectives of the proposed Programme Grant research are to investigate the environmental causes of renal decline in these high-risk populations, using both standardised instruments capturing occupational and environmental exposures. We will address four proposed causes of CKDu: (i) metals and metaloids; (ii) agrochemicals; (iii) infections by organisms that affect the kidney; and (iv) heat/dehydration. To achieve these objectives we aim to: (i) extend the follow-up to at least four years in each of the three studies (Nicaragua, India, Sri Lanka); (ii) expand each prospective study to a total of 1000 participants to increase the power of the primary analyses; (iii) use standardized questionnaires to capture self-reported exposures; (iv) directly measure exposures to metals, agrochemicals, infections and heat/dehydration; (v) identify potential biomarkers of early disease; and (vi) identify genetic factors which affect decline in kidney function.

在低和中间收入国家（LMIC）的农业社区（LMIC）中，有主要是肾小管间隙慢性肾脏疾病（CKD）的流行病。尽管目前尚不清楚是否存在共同的根本原因，但这些条件已被统称为未知原因的CKD（CKDU）。据估计，在过去的二十年中，CKDU导致了数十万年轻人的LMIC年龄至数十万年轻人的过早死亡。因此，迫切需要了解这些疾病的病因和病理生理学，并制定预防性干预措施。我们现在已经确定，中美洲（尼加拉瓜）和南亚（印度，斯里兰卡）的CKDU存在，但在其他一些热带国家（马拉维，秘鲁）中不存在。尚不清楚中美洲和南亚的流行病是否具有共同的原因或不同原因，这就是为什么在这些不同地区使用相同的方案和方法进行研究很重要的原因。与同事一起，我们在尼加拉瓜，南印度，斯里兰卡建立了前瞻性研究，以调查CKDU流行病的原因，以及影响预后的因素。我们已经发表了来自尼加拉瓜的引人注目的发现，那里有10％的社区（显然我们开始关注他们时都很健康，他们在两年的随访中都失去了肾脏功能的三分之一 - 因此，发生了一些非常令人震惊和惊人的事情。基本的假设是，CKDU是由于近几十年来由于农业实践的变化或其他环境变化（例如供水）而导致的未知因素引起的。 拟议计划赠款研究的目标是使用捕获职业和环境暴露的标准化工具来调查这些高风险人群肾脏下降的环境原因。我们将解决CKDU的四个拟议原因：（i）金属和金属素； （ii）农化学； （iii）影响肾脏的生物感染； （iv）热/脱水。为了实现这些目标，我们旨在：（i）将后续行动扩展到至少四年的三个研究中（尼加拉瓜，印度，斯里兰卡）； （ii）将每项前瞻性研究扩展到总共1000名参与者，以增加主要分析的能力； （iii）使用标准化问卷来捕获自我报告的暴露； （iv）直接测量暴露于金属，农业化学物质，感染和热/脱水； （v）确定早期疾病的潜在生物标志物； （vi）确定影响肾脏功能下降的遗传因素。

项目成果

Environmental risk factors for reduced kidney function due to undetermined cause in India: an environmental epidemiologic analysis.

• DOI: 10.1097/ee9.0000000000000170
• 发表时间: 2021-10
• 期刊: Environmental epidemiology (Philadelphia, Pa.)
• 作者: Hamilton SA;Jarhyan P;Fecht D;Venkateshmurthy NS;Pearce N;Narayan KMV;Ali MK;Mohan V;Tandon N;Prabhakaran D;Mohan S
• 通讯作者: Mohan S

Population-level detection of early loss of kidney function: 7-year follow-up of a young adult cohort at risk of Mesoamerican nephropathy

早期肾功能丧失的人群水平检测：对具有中美洲肾病风险的年轻成人队列进行 7 年随访

• DOI: 10.1093/ije/dyad151
• 发表时间: 2023
• 期刊: International Journal of Epidemiology
• 影响因子: 7.7
• 作者: Gonzalez-Quiroz M

The Authors Respond

作者回应

• DOI: 10.1097/ede.0000000000001668
• 发表时间: 2023
• 期刊: Epidemiology
• 影响因子: 5.4
• 作者: Pearce N