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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 8
| Issue : 1 | Page : 13-19 |
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A critical evaluation of anthropological, biochemical, and geo-climatic factors related to chronic kidney disease with unknown etiology in Sri Lanka
Santhushya Hewapathirange1, Ayesha Madagedara2, Rohana Chandrajith3, Nishantha Nannayakkara1
1 Center for Research, National Hospital, Kandy, Sri Lanka
2 Center for Research, National Hospital, Kandy; Department of Fundamentals of Nursing, Faculty of Nursing, University of Colombo, Colombo, Sri Lanka
3 Department of Geology, Faculty of Science, University of Peradeniya, Peradeniya, Sri Lanka
| Date of Submission | 07-Dec-2022 |
| Date of Decision | 20-Feb-2023 |
| Date of Acceptance | 23-Feb-2023 |
| Date of Web Publication | 30-Mar-2023 |
Correspondence Address:
Nishantha Nannayakkara
Center for Research, National Hospital, Kandy
Sri Lanka
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ed.ed_27_22
Background: Chronic kidney disease of unknown etiology (CKDu) is a critical health issue among farming communities of the dry zone in Sri Lanka.
Aims and Objectives: This study was conducted to identify the possible anthropological, biochemical, and geo-environmental characteristics of CKDu, comparing an affected and nonaffected community.
Materials and Methods: Serum creatinine (SC) levels were measured and estimated glomerular filtration rate values were calculated in both communities based on a stratified sampling method. Anthropological data, such as population structure, farming behavior, and poverty statistics, were obtained from the respective government officials. Geo-climatic data including elevation, monthly average temperature, rainfall, humidity, ultraviolet intensity, and sunshine hours were obtained for study areas.
Results: The most striking difference between the two communities is significantly high SC in male individuals between the age categories of 40–60 in the CKDu endemic area in comparison to nonendemic participants in the same age category from the nonendemic area.
Conclusion: Significant differences were observed in migration, drinking water sources, and hot humid environment between the two studied regions.
Keywords: Chronic kidney disease of unknown etiology, dry zone of Sri Lanka, geo-climatic factors, heat stress
How to cite this article:
Hewapathirange S, Madagedara A, Chandrajith R, Nannayakkara N. A critical evaluation of anthropological, biochemical, and geo-climatic factors related to chronic kidney disease with unknown etiology in Sri Lanka. Environ Dis 2023;8:13-9 |
How to cite this URL:
Hewapathirange S, Madagedara A, Chandrajith R, Nannayakkara N. A critical evaluation of anthropological, biochemical, and geo-climatic factors related to chronic kidney disease with unknown etiology in Sri Lanka. Environ Dis [serial online] 2023 [cited 2023 May 31];8:13-9. Available from: http://www.environmentmed.org/text.asp?2023/8/1/13/372862 |
| Introduction | |  |
Chronic kidney disease (CKD) is one of the most widespread noncommunicable diseases, posing substantial worldwide health and economic burden.[1] CKD of unknown etiology (CKDu), an emerging disease for the past two decades, is not associated with any known etiologies such as hypertension, diabetes mellitus, polycystic kidneys, or glomerulonephritis.[2],[3] A multifactorial etiology for CKDu is suggested by the existence of toxicological, occupational, and environmental risk factors in these areas. Agrochemical exposure, environmental contaminants, recurrent periods of dehydration brought on by heat stress, and an underlying genetic predisposition are some major susceptible causes.[4] CKDu is prevalent among agricultural communities in tropical and subtropical regions with low-socioeconomic capacity.[5],[6],[7] The disease is confined to discrete pockets of dry agricultural areas in an affected country, with varying prevalence from one community to another.[7],[8],[9],[10]
In Sri Lanka, CKDu exhibits a clustered distribution in certain geographical locations in the dry zone including North Central, Uva, Central - Uva province boundary, Eastern and North-Western provinces.[11-14] CKDu endemic localities are confined to the dry zone-low country (DL1 and DL2) and intermediate-low country (IL1, IL2, and IL3) according to the agroecological regions of Sri Lanka [Figure 1]. This distinctiveness highlights the importance of studying geo-climatic and anthropological characteristics of CKDu endemic areas in contrast to the nonendemic regions. | Figure 1: Clustered distribution of CKDu in Sri Lanka with respect to agroecological zones[29] and CKDu: Chronic kidney disease of unknown etiology[14]
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By and large, infectious diseases, more specifically vector-borne diseases, are governed by geo-climatic factors. However, the influence of geo-climatic factors on noncommunicable diseases is rarely studied. Nevertheless, in the Chinese population, endemic diseases such as goiter, Keshan disease, dental and skeletal fluorosis, and diabetes are directly influenced by geological factors of the terrain, climate, soil, and biome organic combination.[15] Numerous studies have been carried out in Sri Lanka investigating trace elements and mineral composition of groundwater and soil environment concerning the CKDu endemicity.[14],[16],[17] However, the influence of geo-climatic factors on CKDu has not been adequately addressed. Therefore, this study aimed to investigate the underlying causes for spatial endemicity of CKDu in Sri Lankan, concerning geo-climatological and anthropological factors.
| Materials and Methods | | |
For this study, ethical approval for the study was obtained from the Ethics Review Committee of the Faculty of Medicine, University of Peradeniya, Sri Lanka. Informed and written consent was obtained from the participants before the data collection after explaining the purpose of the study. Wilgamuwa, an emerging CKDu hotspot situated in the intermediate low-country region of Sri Lanka, was selected as the endemic area. Male participants were randomly selected from the registered voters' lists. Males aged <30 and more than 60 were excluded from the cohort. 20–24 participants were selected from 20 villages in Wilgamuwa, using the stratified random sampling technique. Following the same procedure, a similar cohort of age 30–60 was selected as the control group from Maturata, a CKDu nonendemic locality situated in the intermediate zone mid-country, where farming communities are also inhabited.
Biometric data
Participants were tested for blood pressure and random blood sugar using standard protocols. A venous blood sample (2 ml) was withdrawn for biochemical tests. All blood samples were kept on ice and were transferred to the laboratory within 6 h. Samples were then separated by centrifugation at 3,000 rpm for 10 min and serum was kept frozen at −80°C until analysis was completed.
Information on population structure was obtained from the resource profile data of 2019, provided by the administrative offices of Wilgamuwa and Hanguranketha (Maturata). Poverty statistics was obtained from the Department of Statistics and Census, Sri Lanka. Informative data related to farming behavior and community dynamics were obtained from agriculture services offices and administrative offices of both regions.
Geo-climactic data
Monthly average meteorological data for the year 2019, including temperature (°C), rainfall (mm), humidity (%), ultraviolet (UV) intensity, and sunshine hours (h), were gathered from worldweatheronline.com, which have been primarily retrieved through the European Centre for Medium-Range Weather Forecasts atmospheric model output, World Meteorological Organization, National Centers for Environmental Prediction, Global Forecast System atmospheric model output, Global Telecommunication System, land, ship, and data buoy observations, global weather satellite imagery from both polar-orbiting and geostationary satellites, and Japan Meteorological Agency atmospheric model for northern Asia. Local weather stations were unavailable for both localities at a precise distance. Geo-climatic data of agroecological zones of Sri Lanka were obtained from the National Spatial Data Infrastructure of Sri Lanka.
Statistical analysis
Statistical analysis of data was performed using (IBM® SPSS® Statistics software version 22), and Grapher 13 was used in the radar plot design. Two-tailed t-tests were performed to determine the significance between the biochemical data and meteorological data of two representative groups.
| Results | | |
Randomly selected 214 and 102 male individuals in the age category of 30–60 from Wilgamuwa and Maturata participated in the study as representative groups. Their physiological and biochemical results were categorized and compared [Table 1]. The most striking difference between the two communities was the significantly high serum creatinine (SC) (t = 3.5175, P = 0. 0005) levels in participants from CKDu endemic area (M = 109.00, standard deviation [SD] = 66.41) in comparison to nonendemic participants in the age category between 40 and 60 (M = 85.41, SD = 18.78). According to their kidney function, they were divided into estimated glomerular filtration rate categories under the guidelines of the National Kidney Foundation, USA [Table 2]. | Table 1: Physiological and biochemical results and comparison (t-tests) of the participants from Wilgamuwa and Maturata
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 | Table 2: Comparison of two study groups according to their estimated glomerular filtration rate categories under the guidelines of the National Kidney Foundation, USA
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The first written evidence of community establishment in Wilgamuwa dates back to 1871 A.D. However, proper colonization of Wilgamuwa was established in several stages under the accelerated Mahaweli development program and other irrigation projects in 1962, 1968, and 1984. By now, 10,498 families are inhabited in Wilgamuwa and the total population is 35,283. Among them, 2,265 (6.4%) individuals occupy suburb territory, while the rest of the 93.6% reside in rural village areas. When considering the ethnicity of the population, 99.9% are Sinhalese (resource profile data, 2019). Maturata has written historical evidence of its colonization, which dates back to 1600 A.D. The community has expanded itself over the centuries. By now, 1,805 families are inhabited the region, and the total population is around 5,880. All the families occupy rural territories and represent diverse ethnicity including Sinhalese 5,424 (92.0%), Sri Lankan Tamils 348 (5.91%), Muslims 92 (1.56%), and Indian Tamils 13 (0.2%) (resource profile data, 2019).
Sociodemographic characteristics between the two areas were almost identical, other than the ethnic composition. Indeed, Wilgamuwa is solely occupied by Sinhalese, but in Maturata, there were other ethnic groups in smaller proportions, even though the vast majority was Sinhalese (92.2%). In particular, there was no difference between people below the poverty line in Maturata (10.38%) and Wilgamuwa (11.90%) [Table 3]. The majority of the individuals were farmers by default in both areas. Nevertheless, there was a striking difference in the proportion of people who involve in full-time farming. In Wilgamuwa it is 73%, whereas 44% in Maturata [Figure 2]. Full-time farming indicates a higher risk of exposure to occupational risk factors attributed to CKDu such as heat stress, poor access to safe water, and exposure to agrochemicals. However, almost all in both Wilgamuwa and Maturata were exclusively using agrochemicals in their farming practices. | Figure 2: Employment structure of (a) Wilgamuwa, (b) Maturata (constructed using the data obtained from the resource profile data of 2019, provided by the administrative offices of Wilgamuwa and Hanguranketha)
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 | Table 3: Comparison of the latest available (2012/2013) poverty statistics for two study areas
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Main dietary patterns are similar in both regions, which include homemade rice and curry. In Wilgamuwa, the major drinking water resource has shifted to reverse osmosis water since 2017, while a considerable amount of people are still depending on groundwater and public water supplies. The community in Maturata depends mainly on natural springs and shallow well water. In both communities, around 50% of men are engaged in regular alcohol drinking and smoking practices and the case of betel chewing is around 70%. Both areas have sustained agricultural communities over the years. However, some of the youths of both communities have been involved in other employment options, while farming serves them as a secondary source of income [Figure 2]. Anyhow, seasonal framing pattern plays a crucial role in their lifestyle [Table 4]. | Table 4: Detailed comparison of farming patterns and behaviors of two study areas
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Along with the significant difference in SC values, certain geo-climatic characteristics such as monthly average temperature (°C), rainfall (mm), humidity (%), UV intensity, and sunshine hours were significantly higher in Wilgamuwa than in Maturata [Figure 3] and [Table 5]. Furthermore, the two study areas had a notable altitudinal difference, with Wilgamuwa being 528 MASL and Maturata being 976 masl. | Figure 3: Radar plot of the meteorological variables of Wilgamuwa vs. Maturata for the year of 2019
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 | Table 5: Meteorological data comparison (t.tests) for Wilgamuwa and Maturata for the year 2019
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| Discussion | | |
CKDu is an environmentally based disease in pockets of rural and dry zones farming communities of Sri Lanka. We compared anthropological, socioeconomic, environmental, characteristics, and SC levels in an affected community and a nonaffected community from CKDu. Most strikingly, the CKDu-affected community has abruptly migrated to virgin hot semiarid areas with substandard water quality. On contrary, inhabitation in the nonendemic area resulted from slow and natural population migration over centuries. Noteworthy, the proportion of people with kidney dysfunction was significantly high in CKDu affected community, confirming the endemicity of the disease. We selected only males of the most affected age group of CKDu for the study.[11],[16] However, there were no distinguishable differences regarding agrochemical usage, dominant livelihood, and socioeconomic status between these two communities.
The nonendemic area for CKDu, Maturata, was colonized due to natural population migrations in the 16th century, and the population was grown on its own for ages while adapting to the environment. In contrast, colonization of Wilgamuwa was implemented more drastically by the families dispatched mostly from the wet zone of the country, in parallel to water diversion projects under the green revolution after the 1960s. Other than this, most of the anthropological traits in both CKDu endemic and nonendemic communities were generally comparable in terms of their community structure, which is dominated by rural agricultural communities. At the time of resettlement, water scarcity was the most serious concern in these areas, but later people had to experience a series of health conditions related due to contaminants in groundwater (fluorosis and renal stone disease). This implies that Wilgamuwa was populated with people who had just a little time to develop any genetic and behavioral adaptations to the environmental conditions without even receiving basic life needs.
Naturally, terrace farming is selected in Maturata because of the hilly terrain layout. In contrast, flat land farming is dominating in Wilgamuwa, due to the undulating terrain. Undoubtedly, terrace farming encourages the simple drainage and drain of irrigation waters through sediments which avoid stagnation, interactions with natural constituents as well as accumulated toxin residues. Conversely, flat land farming causes irrigation water to retain for much longer periods, promoting the penetration of excessively added nutrients/agrochemical compounds into groundwater columns. Indeed, the theoretical risk of interactions between natural water constituents and artificial contaminants could be high in CKDu endemic areas with a higher risk of precipitating toxicity in CKDu endemic areas.[17],[18],[19],[20] Noteworthy, the human behavior which depends on farming activities has not been regular or even within a year.
In Wilgamuwa, paddy farming solely depends on irrigation water, whereas in Maturata, they use both irrigation and rainwater for their agricultural activities. It is noted that several investigators have reported on contamination of irrigation water with toxic substances, derived from agrochemicals, during their journey from wet zone mountains to lowland dry areas. In the same way, people in Maturata rely on freely available natural water sources of springs and shallow wells for drinking purposes. Instead, dug well water has been the primary water source of drinking in Wilgamuwa. However, the majority of Wilgamuwa residents have switched to RO water since 2017, owing to the CKDu outbreak. This observation indicates that if the etiology of CKDu is drinking water related, the incidence will continue to drop in the years to come. However, risk factors like weather conditions are likely to be more and more unhealthy in the future, especially with the effects of global warming.
When comparing the contrasting difference of the meteorological factors which drives the heat stress and dehydration including monthly average temperature (°C), UV intensity, and sunshine hours between two localities, it suggests that the farmers in CKDu endemic areas are at higher risk of developing heat-related adverse health effects than the nonendemic farmers. Nevertheless, in the evaluations of the potential etiological factors for CKDu in Sri Lanka, there was no sufficient evidence to support the role of direct heat stress in the occurrence of CKDu.[21] However, chronic heat stress-induced dehydration followed by rehydration is one of the attributed factors that contribute to CKDu.[22],[23],[24]
Some studies suggest that this disease could be an example of a problem that is worsened by global warming.[25],[26],[27] Heat stress is well known to precipitate kidney disease by different mechanisms. Among them, acute tubular injury from heat or exercise-induced rhabdomyolysis, crystalluria due to hyperuricemia, prerenal kidney injury due to hypovolemia, tubular damage due to the activation of the polyol-fructokinase pathway, and tubular or glomerular injury due to the persistent activation of vasopressin were attributed in CKDu. [26,27] For instance, a cross-sectional study conducted in Nicaragua reported that people living close to the coast has a higher CKDu prevalence than those living at high altitudes, indicating a role of heat stress and chronic dehydration.[9] In general, CKDu endemic areas in tropical countries are characterized by extreme heat and high-humid low-altitude regions with a higher risk of heat exhaustion.[28]
| Conclusion | | |
We report comparably adverse weather conditions and higher exposure to natural and artificial toxins in genetically and behaviorally vulnerable groups of people in CKDu endemic areas in comparison to the nonendemic area for CKDu.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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