Ruwanpathirana et al. BMC Public Health (2019) 19:763 https://doi.org/10.1186/s12889-019-7117-2 RESEARCH ARTICLE Open Access Prevalence and risk factors for impaired kidney function in the district of Anuradhapura, Sri Lanka: a cross-sectional population-representative survey in those at risk of chronic kidney disease of unknown aetiology Thilanga Ruwanpathirana1, Sameera Senanayake1* , Nalika Gunawardana2, Asoka Munasinghe3, Samitha Ginige1, Deepa Gamage1, Jagath Amarasekara1, Buddi Lokuketagoda4, Pubudu Chulasiri4, Sarath Amunugama4, Paba Palihawadana1, Ben Caplin5 and Neil Pearce6 Abstract Background: Over the last 20 years there have been reports of a form of chronic kidney disease of unknown cause (CKDu) affecting rural communities in the North Central Province of Sri Lanka. Valid prevalence estimates, using a standardised methodology, are needed to assess the burden of disease, assess secular trends, and perform international comparisons. Methods: We conducted a cross-sectional representative population survey in five study areas with different expected prevalences of CKDu. We used a proxy definition of CKDu involving a single measure of impaired kidney function (eGFR< 60 mL/min/1.7m2, using the CKD-Epi formula) in the absence of hypertension, diabetes or heavy proteinuria. Results: A total of 4803 participants (88.7%) took part in the study and 202 (6.0%; 95% CI 5.2–6.8) had a low eGFR in the absence of hypertension, diabetes and heavy proteinuria and hence met the criteria for proxy CKDu. The proportion of males (11.2%; 95% CI 9.2–13.1) were triple than the females (3.7%; 95% CI 2.9–4.5). Advancing age and history of CKD among parents or siblings were risk factors for low GFR among both males and females while smoking was found to be a risk factor among males. Conclusions: These data, collected using a standardised methodology demonstrate a high prevalence of impaired kidney function, not due to known causes of kidney disease, in the selected study areas of the Anuradhapura district of Sri Lanka. The aetiology of CKDu in Sri Lanka remains unclear and there is a need for longitudinal studies to describe the natural history and to better characterise risk factors for the decline in kidney function. Keywords: Sri Lankan agricultural nephropathy, Chronic interstitial nephritis in agricultural communities, Chronic kidney disease of unknown cause * Correspondence: [email protected]; http://www.epid.gov.lk 1Epidemiology Unit, Ministry of Health, 231, De Saram Place, Colombo 10, Sri Lanka Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Ruwanpathirana et al. BMC Public Health (2019) 19:763 Page 2 of 11 Background burden of CKDu [14]. The present survey was under- Chronic kidney disease of unknown aetiology (CKDu) is taken using the DEGREE protocol, to estimate the of major public health importance in Sri Lanka, affecting prevalence and geographical distribution of low eGFR in predominantly farming communities. The problem was the district of Anuradhapura which is the district which first identified in the early 1990s among rice farmers of records the highest numbers of patients with CKDu in the North Central province [1–3], specifically in the dis- Sri Lanka. The study also aimed to identify risk factors trict of Anuradhapura. The emergence of CKDu in Sri associated with low eGFR, with a view to investigating Lanka coincided with the recognition of similar kidney these further using a prospective cohort design. disease of unknown cause in agricultural communities in Central America [4]. This was seen mainly among agri- cultural workers (particularly sugar cane plantation Methods workers) in the west coast of the Mesoamerican isthmus. The study followed the core protocol of the Disadvan- Nicaragua and El-Salvador are the two countries which taged Populations eGFR Epidemiology Study (DEGREE) are most affected. More recently, similar reports of [14], but added additional questions on risk factors rele- CKDu have emerged from the Uddanam District of vant to the Sri Lankan situation. Andhra Pradesh in South India [5]. Local and international researchers have proposed sev- Study design and study setting eral hypotheses as to the causes of CKDu. Environmen- This was a community-based cross-sectional household tal pollution due to heavy metals such as cadmium [6] survey. The study was conducted in five geographically and arsenic [7] and agrochemicals such as glyphosate demarcated communities in the district of Anuradhapura [8], excess fluorides coupled with hardness in water [9], from March to May 2017. The government routinely con- infections such as leptospirosis and hantavirus [10] and ducts community-based screening in Anuradhapura, and genetic factors [3], exposure to fungal and bacterial classifies the Grama Niladhari areas (the smallest adminis- toxins [11] and heat stress [12] are among the hypoth- trative units of a district) into three levels of endemicity eses. Support for these hypotheses has been mostly de- for CKD/CKDu. The five areas were selected based on the rived from cross-sectional studies, which have often existing classification of Grama Niladhari areas as high/ focused on single factors, and which have not taken into moderate/low levels of endemicity of CKDu with one account the confounding effects of other potential risk community from the group classified as ‘low and two factors, or interactions between risk factors. areas each from the groups of moderate and high (Fig. 1 In Sri Lanka, CKDu has been reported to be common and Fig. 2). and increasing in prevalence [13], although robust stan- dardized data to support these claims are lacking. Routine data sources are inadequate for accurate estimation of the Study participants prevalence and trends of CKD or CKDu. For example, All adults above the age of 18 years, whose main place of routine morbidity and mortality surveillance through hos- residence (defined as living in the setting for at least for pital statistics and vital registration systems do not include 5 days of the week for the past 6 months) was in the a specific category for CKDu, and estimates of deaths due study area, were invited to take part. Exclusion criteria to CKD are likely to be subjected to substantial ascertain- were: (i) pregnancy; and (ii) patients undergoing treat- ment bias. Furthermore, community-based screening pro- ment for cancer. About 1000 eligible study participants grammes in areas designated as ‘high risk’ have suffered were selected from each of the study areas to allow ac- from low or differential response rates and/or have not curate estimates of the prevalence of CKDu each study collected kidney function data on the entire study popula- area. These numbers also provide sufficient statistical tion (e.g. in some studies, eGFR has only been measured power for comparisons between study areas or between in those with elevated urine protein tests). population subgroups [14]. The updated voter’s lists of Given the public health importance of the issue of the selected five study areas was used in the stage of CKDu for global health, and to promote generation of planning of the study to define the extent of the geo- comparable evidence across studies in various countries graphical area that would be needed to recruit 1000 eli- with uniform measures that ensure quality of data, an gible study units. All of the households in the defined international group has been formed to address these is- study area were visited and all eligible adults were in- sues, the Disadvantaged Populations eGFR Epidemiology vited to take part. Study information was provided, and (DEGREE) collaboration. This group has developed a those giving informed written consent were recruited to protocol for cross-sectional surveys of eGFR distribution the study. A team of 10 graduates from a University lo- in low- and middle- income communities to provide a cated in the district were trained to recruit the study basis for internationally comparable estimates of the participants. Ruwanpathirana et al. BMC Public Health (2019) 19:763 Page 3 of 11 Fig. 1 Study settings and their characteristics Data collection and were verified later by a medical doctor. Upon comple- Upon recruitment, all participants were issued a unique tion of the questionnaire, study participants were provided identifying number. Information on socio-demographic with a container and an instruction sheet on collecting the characteristics, medical history, specifically past medical early morning urine sample and were requested to visit history of diabetes mellitus and hypertension and other the ‘clinic’ on the following day before work for the an- potential risk factors were collected in the home using an thropometry measurements and biological sample collec- interviewer-administered questionnaire developed for this tion. Revisits to the houses were done to recruit any study, by the trained interviewers (Additional file 1). The eligible study participants who were not available in the medical and treatment records were also photographed, house at the time of the first visit. The ‘clinics’ were set up Ruwanpathirana et al. BMC Public Health (2019) 19:763 Page 4 of 11 Fig. 2 Flow diagram to select the study setting Ruwanpathirana et al. BMC Public Health (2019) 19:763 Page 5 of 11 within the study areas in locations that were acceptable through the questionnaires to assess and to ensure the and accessible to all the villagers and about 100 were in- quality of data entry.