Multi-pronged research on endemic chronic kidney disease of unknown etiology in Sri Lanka: a systematic review

Arambegedara, Dinushi; Jayasinghe, Saroj; Udagama, Preethi

doi:10.1007/s11356-021-17316-6

Cited by 7 publications

(9 citation statements)

References 125 publications

(239 reference statements)

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“…These correlations may be related to genetic predisposition or to a common exposome. In Sri Lanka, three variants in LAMB2 and one in KCNA10 were observed in CKDu cases only, and genes related to oxidative stress were upregulated three-fold [18]. Although yet to be studied, epigenetic alterations likely have an important role in this disease.…”

Section: Genetic Predispositionmentioning

confidence: 98%

“…Diabetes, significant hypertension, and high-grade proteinuria are considered exclusionary, although may occur in later stages of CKDu [17]. Patients typically present with CKD stage 3 or 4, although an acute presentation has been reported with fever, vomiting, and headaches [15,18,19]. In Central America, transiently increased blood pressure with an elevated serum creatinine level during active farm work has been associated with subsequent kidney functional decline and CKDu [20].…”

Section: Key Pointsmentioning

confidence: 99%

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Chronic kidney disease with unknown cause across the global spectrum

Nast

2023

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewIn the 1990s, a type of chronic kidney disease with unknown cause (CKDu) was identified in Central America and Sri Lanka. Patients lacked hypertension, diabetes, glomerulonephritis, or other usual causes of kidney failure. Affected patients are predominantly male agricultural workers aged 20--60 years, living in economically disadvantaged areas with poor access to medical care. Patients typically present late and progress to end-stage kidney disease within 5 years, resulting in social and economic hardship for families, regions, and countries. This review covers the current state of knowledge for this disease. Recent findingsThe prevalence of CKDu is increasing in known endemic regions and across the globe, reaching epidemic proportions. There is primary tubulointerstitial injury with secondary glomerular and vascular sclerosis. No definitive etiologic factors have been identified, and these may vary or overlap in different geographic locations. The leading hypotheses include exposure to agrochemicals, heavy metals and trace elements, and kidney injury from dehydration/heat stress. Infections and lifestyle factors may play a role, but are likely not key. Genetic and epigenetic factors are beginning to be explored. SummaryCKDu is a leading cause of premature death in young-to-middle-aged adults in endemic regions and has become a public health crisis. Studies are underway to investigate clinical, exposome, and omics factors, and hopefully will provide insights into pathogenetic mechanisms resulting in biomarker discovery, preventive measures, and therapeutics.

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Section: Genetic Predispositionmentioning

confidence: 98%

Section: Key Pointsmentioning

confidence: 99%

Chronic kidney disease with unknown cause across the global spectrum

Nast

2023

Current Opinion in Nephrology &Amp; Hypertension

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“…The northcentral dry zone is considered to be the CKDu hotspot in Sri Lanka, but the disease prevalence has propagated to other parts of the dry zone, particularly to the Uva Province (Fig. 1; Arambegedara et al, 2022). The present study selected the districts of Anuradhapura and Polonnaruwa in northcentral Sri Lanka which encompass an area of approximately10,500 km 2 (boxed area in Fig.…”

Section: Study Areamentioning

confidence: 99%

Chemical Distinctions of Groundwater Consumed by Communities Affected by Chronic Kidney Disease of Unknown Etiology in Northcentral Sri Lanka: Implications for Multiple Contributory and Inhibitory Ions

Prame,

Siriwardana,

Hettiarachchi

et al. 2024

Preprint

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Long-term exposure to contaminated drinking water from shallow dug wells is widely suspected to be the cause of chronic kidney disease of unknown etiology (CKDu) which prevails in northcentral Sri Lanka. Although several hydrogeochemical studies have been conducted in this area, studies that have attempted robust statistical comparisons between waters consumed by CKDu-affected and CKDu-free communities within the endemic area are rare, and the causative agents of the disease remain elusive. We attempted to determine the hydrochemical differences between the groundwater consumed by CKDu-affected communities and that consumed by CKDu-unaffected communities living in the CKDu-endemic area based on a substantial new dataset that ensures the robustness of the statistical and graphical comparisons. The study revealed that SO42−, PO43−, NO3−, Sr, Mg, Ba, Pb, and Cu were significantly greater in CKDu-linked water and were positively correlated with the incidence of CKDu, indicating their causative role. Manganese and Zn levels were significantly lower in CKDu-linked water and were negatively correlated with CKDu-incidence, indicating an impeding effect. Our results agree with the elevated hardness and F− values reported in previous work. However, statistical and graphical comparisons do not support the widely speculated role of F− in the incidence of CKDu. Toxic metals and metalloids except for V occur at concentrations accepted as safe for human consumption. Subtle but significant contributions from several chemical constituents occurring in concentrations accepted to be safe and permissible could be interpreted as supporting evidence for the participatory role of multiple ions, probably imposing a deleterious synergistic effect.

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“…However, the exact prevalence of CKDu and the associated socioeconomic burden may be underreported in the communities due to the lack of adequate epidemiological studies. 6 Early diagnosis of CKDu is the key to timely interventions. As the disease is asymptomatic and relatively nonproteinuric in the initial stages, this is often difficult.…”

Section: Introductionmentioning

confidence: 99%

“…However, the exact prevalence of CKDu and the associated socioeconomic burden may be underreported in the communities due to the lack of adequate epidemiological studies. 6 …”

Section: Introductionmentioning

confidence: 99%

Prevalence of Chronic Kidney Disease of Uncertain Etiology Within Selected Farming Communities in Rural Sri Lanka

Ekanayake,

De Silva,

Gunasekara

et al. 2023

Can J Kidney Health Dis

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Background: Chronic kidney disease of uncertain etiology (CKDu) is an emergent health concern, particularly in tropical farming communities in several global hotspots, including Sri Lanka. This particular nephropathy is characterized by a progressive decline in kidney function in the absence of conventional chronic kidney disease (CKD) risk factors such as diabetes mellitus, hypertension, and other identifiable kidney disorders. As it is almost asymptomatic at early stages, CKDu is mostly diagnosed at late stages with significant kidney damage. Hence, the identification of disease susceptibility and vulnerable communities at the earliest possible instances is highly important for the management of the disease. Objective: We aimed to compare kidney health across three different farming communities in Sri Lanka to identify CKDu susceptibilities. Methods: A cross-sectional study was performed with three selected farming communities: paddy farmers (PF; N = 581), sugarcane farmers (SF; N = 550), and vegetable farmers (VF; N = 244) in comparison with an age-matched control group of nonfarming (NF; N = 225) individuals. A medical examination was performed to investigate health status and medical history, whereas a urinalysis was performed to determine creatinine and albumin contents. Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR) were used for assessment of kidney function. CKDu susceptibility was determined based on eGFR, and urinary ACR adhering to the clinical practice guidelines in Sri Lanka. Results: The median (interquartile range [IQR]) eGFR levels of PF (85 mL/min/1.73 m2 [72-97]) and SF (93 mL/min/1.73 m2 [73-112]) were significantly lower than that of the NF group (103 mL/min/1.73 m2 [87-125]) ( P < .0001), whereas eGFR of VF (100 mL/min/1.73 m2 [80-111]) was not significantly different compared with NF. The median (IQR) urinary ACR levels of the study groups, PF, SF, VF, and NF, were 0.59 (0.26-1.45), 0.46 (0.28-0.88), 0.45 (0.34-0.90), and 0.44 (0.34-1.02) mg/mmol, respectively. However, urinary ACR did not differ significantly across the study groups ( P > .05). The prevalence of CKDu within PF (13.60%), SF (12.54%), and VF (6.67%) communities was significantly higher ( P < .05) compared with the NF (2.67%). Of the total CKD cases, CKDu susceptible cases represented 73%, 69%, 50%, and 25% in PF, SF, VF, and NF, respectively, indicating a high risk of CKDu susceptibility among farming communities. Moreover, a noteworthy association of CKDu was observed with agrochemical exposure (odds ratio [OR] = 3.11, 95% confidence interval [CI] = 1.36-7.09). Concerning the farming practices, sugarcane farming showed the highest association with CKDu prevalence (OR = 3.40, 95% CI = 1.49-7.78). Conclusions: Compared with the nonfarming group, a significant risk of CKDu was observed in the three farming communities, particularly among paddy and sugarcane farmers. Longitudinal epidemiological studies to identify vulnerable farming communities and associated risk factors are critically needed to develop effective management strategies against CKDu within farming communities.

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Multi-pronged research on endemic chronic kidney disease of unknown etiology in Sri Lanka: a systematic review

Cited by 7 publications

References 125 publications

Chronic kidney disease with unknown cause across the global spectrum

Chronic kidney disease with unknown cause across the global spectrum

Chemical Distinctions of Groundwater Consumed by Communities Affected by Chronic Kidney Disease of Unknown Etiology in Northcentral Sri Lanka: Implications for Multiple Contributory and Inhibitory Ions

Prevalence of Chronic Kidney Disease of Uncertain Etiology Within Selected Farming Communities in Rural Sri Lanka

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