Linking groundwater chemistry to bovine kidney damage: A one health perspective on fluoride-DOM-hard water interactions in CKDu-hotspots.

Chronic Kidney Disease of Uncertain etiology (CKDu), has been reported in Central America, India, Sri Lanka, and certain other places around the world (Chandrajith et al., 2011; Dharmawardana et al., 2015). CKDu has threaten the health of people in Sri Lanka, with incidence rates as high as 15-23% in the North Central Province (NCP) (Hettithanthri et al., 2021). However, there has been a limited number of studies conducted within the context of CKDu in ‘One Health’ approach, which need to recognize that the health of people is closely connected to the health of animals and our shared environment. This ‘One Heath’ approach is vital to understand the concerns between ‘Systems’ and ‘Stresses’ to explore the collective ‘Solutions’. CKDu is recognized as a multifactorial disease influenced by environmental, occupational and lifestyle factors etc. Yet, numerous studies have demonstrated that CKDu is linked with the quality of groundwater to the people (Dharmawardana et al., 2015; Chandrajith et al., 2024; Wasana et al., 2016; Wimalawansa and Dissanayake, 2022). However, no research work has reported yet, the effects of such drinking water exposures to the CKD/CKDu prevalence for animals in their natural environment. Specifically, it is worthwhile to explore whether animals residing in high CKDu prevalence areas exhibit similar detrimental effects on their renal functions as humans experience or possess any inherent resilience mechanisms. Since the majority of people affected by CKDu reside in agricultural communities, it is vital to concern about the impact of ground water to renal function of their cattle use for milk production. Also, data for the clinical biochemistry parameters by considering their kidney functions of cattle in those areas is not available. As such, it is an urgent need to address these concerns to understand the effects of environmental exposures on both humans and animals in CKDu endemic areas under one health approach. Also, it is a pressing necessity under the United Nation’s Sustainable Development Goals (SDG). As such, this research focuses on addressing the SDGs aiming for; good health and wellbeing, clean water, poverty and hunger reduction.

Groundwater is a crucial resource for 1.5 billion people worldwide, with 33% of South-Asia’s population using self-supplied water (UNESCO and U.N.E.S. and C.O, 2022; Haddad et al., 2018). In Sri Lanka, over 90% of rural areas rely on groundwater, including high CKDu prevalence areas (Balasubramanya et al., 2020; Dazhou et al., 2023; Foster et al., 2021; Indika et al., 2022). Inorganic ions, such as fluoride ions, hardness, and ionicity/electrolytes, have been linked to CKDu (Chandrajith et al., 2024; Wasana et al., 2012, 2016, 2017; Dharmawardana, 2018; Imbulana and Oguma, 2021). Certain studies have shown positive correlations between higher levels of dissolved organic matter (DOM) and sulfate, calcium, and total iron in high CKDu prevalence areas (Cooray et al., 2019; Makehelwala et al., 2019; Zeng et al., 2023). Further, divalent cations in groundwater interacting with DOM under alkaline conditions may form toxic substances and facilitate F-release (Regan et al., 2017; Zeng et al., 2024). Thus, potentially offering a possible etiological factor for CKDu, yet poorly recognized concern so far (Chandrajith et al., 2024; Zeng et al., 2023). Therefore, this study aimed to; (1) examine associations between fluoride, metal ions, and dissolved organic matter (DOM) in high-hardness drinking water with bovine serum biochemical parameters in regions with a high CKDu prevalence; (2) explore context-specific threshold values for selected drinking water parameters and serum biochemistry markers [blood urea nitrogen (BUN), serum creatinine (SCR), serum albumin (SAL), and total protein (TP)] as preliminary screening indicators for identifying cattle potentially at higher risk of kidney dysfunction (3) propose hypothesis-generating mechanistic pathways, describing how interactions among fluoride, water hardness, and DOM components may contribute to renal stress through the formation of potentially harmful complexes.

As such, the derived threshold values need to be interpreted as exploratory and region-specific screening tools, developed from a regional dataset, and require independent validation before broader application. Nonetheless, integrating groundwater chemistry with bovine serum biochemistry in this manner offers a conceptual framework that may inform cost-effective, preventive research strategies for CKD/CKDu within a One Health approach.