Comparison of biochemical characteristics between an endemic and a nonendemic area for CKDu Sri Lanka

A Medagedara; Pasan Hewavitharane; Rohana Chandrajith; Hemalika T K. Abeysundara; RO Thatil; S Thennakoon; Buddhisha Mahanama; N Weerasuriya; A Thilakarathne; Nishantha Nanayakkara

doi:10.4103/ed.ed_3_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 7 | Issue : 2 | Page : 47-51

Comparison of biochemical characteristics between an endemic and a nonendemic area for CKDu Sri Lanka

A Medagedara¹, Pasan Hewavitharane², Rohana Chandrajith³, Hemalika T K. Abeysundara⁴, RO Thatil⁵, S Thennakoon⁶, Buddhisha Mahanama², N Weerasuriya⁷, A Thilakarathne⁷, Nishantha Nanayakkara²
¹ Center for Research, National Hospital, Kandy; Department of Fundamentals of Nursing, Faculty of Nursing, University of Colombo, Sri Lanka
² Center for Research, National Hospital, Kandy, Sri Lanka
³ Department of Geology, Faculty of Science, University of Peradeniya, Sri Lanka
⁴ Department of Statistics and Computer Sciences, Faculty of Science, University of Peradeniya, Sri Lanka
⁵ Department of Crop Sciences, Faculty of Agriculture, University of Peradeniya, Sri Lanka
⁶ Department of Community Medicine, Faculty of Medicine, University of Peradeniya, Sri Lanka
⁷ Provincial Director of Health Services, Central Province, Sri Lanka

Date of Submission	22-Jan-2022
Date of Decision	02-Mar-2022
Date of Acceptance	11-Mar-2022
Date of Web Publication	30-Jun-2022

Correspondence Address:
Nishantha Nanayakkara
Center for Research, National Hospital, Kandy
Sri Lanka

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ed.ed_3_22

Abstract

Introduction: Chronic kidney disease with uncertain etiology (CKDu) was first recognized in the 1990s in Sri Lanka. Considering the distribution of CKDu in the country, clusters of endemic and nonendemic areas can be identified. This study was carried out to compare the biochemical characteristics between CKDu endemic and nonendemic areas in Sri Lanka.
Materials and Methods: A cross-sectional study was carried out among randomly selected males between the age category of 30 and 60 years in selected villages of Wilgamuwa (endemic) and Hanguranketha (nonendemic), located in the dry and wet zone, respectively.
Results: The total participation percentage from the endemic area was 74.7% (224 out of 300 invitees). Out of 150 participants invited from the nonendemic area, only 100 participated in the study cohort. There was a striking difference between the two areas in serum creatinine levels (P = 0.001). When considering the behavioral patterns of the two study areas, the main occupation was farming and there was no significant difference between the behaviors of the people in the selected areas. A significant number of participants (n = 31, 13.8%) from the endemic area had high serum creatinine levels with a mean of 109 μmol/L (standard deviation [SD] = 66.41) (normal: 90–116 μmol/L). Whereas, in the nonendemic area, only 3 (3%) participants had elevated creatinine levels with a mean value of 85.41 μmol/L (SD = 18.78). A significant difference was observed in the two groups in the mean values of serum creatinine levels (P = 0.001). The mean value of random blood sugar (RBS) was 113.56 mg/dL (SD = 44.38) and 119.10 mg/dL (SD = 50.48) in endemic and nonendemic areas, respectively. There was no significant difference between the mean values of RBS (P = 0.2). The mean serum cholesterol was slightly higher in Wilgamuwa (119.26 mg/dl, SD = 45.31) compared to Hanguranketha (189.02 mg/dl, SD = 45.09). However, that was not statistically significant (P = 0.6).
Conclusions: Serum creatinine is remarkably increased in CKDu endemic areas. RBS and serum cholesterol are less significant according to the endemicity of CKDu.

Keywords: Chronic kidney disease of unknown etiology, endemicity, Hanguranketha, serum creatinine, Wilgamuwa

How to cite this article:
Medagedara A, Hewavitharane P, Chandrajith R, K. Abeysundara HT, Thatil R O, Thennakoon S, Mahanama B, Weerasuriya N, Thilakarathne A, Nanayakkara N. Comparison of biochemical characteristics between an endemic and a nonendemic area for CKDu Sri Lanka. Environ Dis 2022;7:47-51

How to cite this URL:
Medagedara A, Hewavitharane P, Chandrajith R, K. Abeysundara HT, Thatil R O, Thennakoon S, Mahanama B, Weerasuriya N, Thilakarathne A, Nanayakkara N. Comparison of biochemical characteristics between an endemic and a nonendemic area for CKDu Sri Lanka. Environ Dis [serial online] 2022 [cited 2023 Mar 28];7:47-51. Available from: http://www.environmentmed.org/text.asp?2022/7/2/47/349540

Introduction

Chronic kidney disease (CKD) is among the major non-communicable disease burdens worldwide, which are defined as abnormalities of kidney structure or function, present for >3 months, with implications the health.^[1] Diabetes, hypertension, and various forms of glomerulonephritis are the well-recognized etiologies of CKD.^[2] The prevalence of CKD in an area is decided by the abundance of risk factors of CKD among that population. Hence, CKD is more prevalent in communities with a higher prevalence of diabetes, hypertension, ischemic heart disease, multiple comorbidities, and specifically in the elderly population with a mean age between 50 and 70 years.^[3] In contrast, a new form of CKD which is not attributed to known risk factors has been described mainly in Central America, Sri Lanka, and India.^[4]

The disease affected young people who live in geographically confined areas in dry zone farming communities in Sri Lanka.^[5] Considering the distribution pattern of the disease, CKD with uncertain etiology (CKDu) is more likely an environmentally induced disease in agricultural areas of tropical countries rather than an occupational disease among farmers.^[6] The exact geographical distribution or dispersion of disease is important in identifying specific risk factors. Identifying the dispersion of a disease is a challenge as it needs specific, sensitive diagnostic tools followed by total population screening to identify all true positives.

The prevalence of CKDu is different from one country to another, which depends on several factors on top of true prevalence such as diagnostic criteria or case definition, consistency of source data, and distribution pattern of the disease. Moreover, the disease could be either evenly distributed throughout the affected area or clustered together within an endemic area. However, several researchers have claimed that the prevalence of CKDu ranges from 8% to 21% in reported countries.^[7] In Nicaragua and El Salvador, the estimated prevalence of CKDu is about 10%–20% of the total population.^[8] In some areas of Nicaragua and El Salvador, up to 19%–40% of the male and 5%–14% of the female inhabitants have CKD/CKDu with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m².^[9]

A study conducted in Uddanam, a fertile subtropical low-altitude territory in the southern Indian state of Andhra Pradesh, has revealed the prevalence of subjects having low eGFR and proteinuria (CKD/CKDu) is 18.23%. Alarmingly, 73% of the affected population were absent of major risk factors, such as diabetes and long-standing hypertension, implying that a significant proportion of the population is afflicted with the entity CKDu. In Sri Lanka, CKDu is mainly observed in three provinces, namely, northcentral, the northern parts of the Uva (Mahiyanganaya and Girandurukotte), and some parts of the northwestern province (Nikawewa) [Figure 1].^[10]

Figure 1: Distribution of CKDu in Sri Lanka and study regions. CKDu: Chronic kidney disease with uncertain etiology

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These areas together are treated as a hypothetical geographical terrain called the North Central Region. A population-based cross-sectional study has estimated the point prevalence of CKDu between 15.1% and 22.9% in some districts of Anuradhapura, Polonnaruwa, and Badulla.^[2] The most recent studies reported that the prevalence of CKDu in endemic regions in Sri Lanka ranges from 15% to 20% among residents aged 30 to 60 years.^[11] All endemic areas are located within the dry zone of the country despite farming being dominant in most areas of Sri Lanka.

A door-to-door screening of the total population is the gold standard to describe the dispersion of a disease, but it is costly, time-consuming, and likely to exhaust the health system of a resource-poor country like Sri Lanka. Instead, a carefully selected representative sample is a cost-effective alternative to predict the disease burden in the suspected area. Understanding the national demand, this study was carried out in two areas, endemic versus nonendemic, with similar socioeconomic characteristics. Wilgamuwa is a dry zone endemic area with an average annual temperature of 26.5°C and Hanguranketha is a wet zone nonendemic area with an annual average temperature of 20.5°C (https://www. worldweatheronline. com/).

The main focus of this study is to define the endemicity of CKDu, based on the best cutoff serum creatinine level in the affected proportion in the most vulnerable group: high, intermediate, and low prevalence for the smallest administrative area of the country.

Materials and Methods

A cross-sectional study was carried out during the period from August 2019 to January 2020, selecting 10 villages in Wilgamuwa (endemic, dry zone area) and Hanguranketha (nonendemic, wet zone area). Ethical approval for the study was obtained from the Ethics Review Committee of the Faculty of Medicine, University of Peradeniya, Sri Lanka. Written informed consent was obtained from the participants before the data collection of the study. Since the disease is dominant among male farmers and the highest prevalence was reported in the age group of 30–60 years,^[5],[12] only that group was selected using a stratified random sampling technique. Three hundred participants from the Wilgamuwa region and 150 participants from the Hanguranketha region were included in the study. All the participants were provided a participation identification number and the demographic data were collected during the recruiting of subjects using a pretested interviewer-administered questionnaire. Blood pressure, dipstick urine test and anthropometric measures including height and weight were recorded using standard methods. A venous blood sample (3 ml) was obtained under aseptic conditions in plain acid-washed centrifuge tubes by trained, registered nursing officers. All samples were kept on ice and transferred to the laboratory within 6 h. Serum was separated immediately by centrifugation at 3,000 rpm for 10 min and kept frozen at–20°C until analysis was completed. Serum creatinine and serum cholesterol were measured using standard Jaffe's method at the Nephrology Laboratory of the National Hospital, Kandy. The proportion of people in each serum creatine cutoff interval was calculated initially for the total population and later for each village. The best proportion which discriminates endemic areas from nonendemic areas was selected to define the endemicity.

Results

Population characteristics

In the endemic CKDu region, only 224 (75%) of the invited 300 individuals have attended the clinic [Table 1]. Participants from the nonendemic area (control area) were recruited from a screening program carried out in the selected area where out of 150 participants were invited from which only 100 participated.

Table 1: Participation percentages from study regions of Wilgamuwa and Haguranketha

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[Table 2] shows the village-based serum creatinine levels in Wilgamuwa and Hanguranketha. The striking difference between the two areas was serum creatinine levels and it was statistically significant (P = 0.001). Considering the behavioral patterns of the two areas, the main occupation was farming and there was no significant difference between the behaviors of the people in the two areas.

Table 2: Serum creatinine levels in the subjects from the Wilgamuwa and Haguranketha regions

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Interestingly, for each creatinine cutoff level, there was a significant difference in the proportion of participants between the endemic area and the control area. According to the two-sample proportion test, the percentages of subjects included in each serum creatinine interval between the endemic and nonendemic groups were significantly different at a 5% significance level. The proportion of patients with “Nil,” “Trace,” and “1+” for urine protein was significantly different between the endemic and the nonendemic groups. However, the proportion of patients with “2+” and “3+” was not significantly different.

Discussion

CKDu is an emerging environmental disease that is dominated among male populations in rural dry zone farming communities of tropical countries. Geographically high prevalent areas of CKDu are found in many parts of Mesoamerican countries such as El Salvador, Guatemala, Nicaragua, Costa Rica, and Mexico, in addition to Asian regions of India, and Sri Lanka.^[13],[14] In Sri Lanka, CKDu prevalence has been calculated using either hospital records or screening data. In practice, screening clinics have been regularly predominated by females and the elderly when missing the most affected young or middle-aged males. There was another 20%–30% drop in detected patients at the level of referral from a field clinic to a local renal clinic.^[15] Moreover, the case definition of CKDu is comprehensive and complicated and hence practically difficult to apply in resource-poor, overcrowded, regional clinics, making a room for frequent errors in differentiating CKDu from other forms of CKD. Further, CKDu prevalence has been reported to the total population in a particular area assuming the spatial distribution is even. On the contrary, limited available geographic information system mapping of patients suggested a clustered dispersion of patients even within an endemic region. Identifying these drawbacks, we compared the serum creatinine levels of the most vulnerable group of CKDu using subjects of males between the ages of 30–60 years, from an endemic area located in the dry zone and nonendemic wet zone region aiming to develop a model to define the endemicity of disease to the smallest administrative area in the country.

The mean age of the participants in the Wilgamuwa area was 42.18 ± 6.80 and the mean age of the participants from the Hanguranketha region was 48.30 ± 8.01. These results are similar to those recorded in previous studies in Sri Lanka as well as other countries where CKDu is recorded.^{[5],[16],[17]} Usually, CKDu is a disease that is diagnosed during the 4^th and 5^th decades of life, but kidney damage may initiate long before the clinical elevation of serum creatinine levels as it requires at least 40%–50% of kidney damage to have an abnormal creatinine value (>116 mg/dl).

We report a significant difference in the proportion of serum creatinine levels between CKDu endemic and nonendemic areas. Interestingly, the proportion of people with serum creatinine levels higher than 90 mg/dl was high in the endemic area, whereas in the nonendemic area, majority of subjects fall in the <90 mg/dl category. The mean serum creatinine level of the endemic area was 109 mg/dl (±66.41), whereas it was 85.41 mg/dl (±18.78) in the nonendemic region. There was a significant difference between the mean serum creatinine levels in Wilgamuwa and Hanguranketha regions (P = 0.001, α = 0.05) according to the independent sample t-test [Table 3]. Further, there is an obvious difference in serum creatinine among the two studied populations with a skewed distribution in an endemic area. Meanwhile, the proportion of people with serum creatinine between 90 and 116 mg/dl was significantly higher in the endemic area. Our findings strongly support the existence of subclinical cases with “normal creatinine” in the endemic area. These participants, as well as the majority of undetected cases after a creatinine-based total population screening program, might present as CKDu in the future. Unfortunately, these individuals were not only identified as cases but also missing an important period for interventions to change the outcome of the disease.

Table 3: Demographic and clinical characteristics of the endemic and nonendemic regions

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Serum creatinine level ≥100 mg/dl was taken as the cutoff value in identifying positive cases in study villages. The prevalence of the number with creatinine >100 mg/dl is further analyzed with quartile values of Q1 = 35%, Q2 = 36.6%, and Q3 = 39%. Hence, villages with a positive case prevalence of more than 35% have been categorized as high prevalent (hot spot) and a positive case prevalence of less than 10% as low prevalent (cold spots) areas. If the prevalence of positive cases was between 10% and 34%, those areas were categorized as intermediate areas favoring the uneven distribution of the disease. Nevertheless, serum creatinine levels in Sonuththa (a GN division in endemic areas) are similar to the trend in the nonendemic area, suggesting the possibility of unaffected areas even within an endemic area. Our results can be used as a model to define the endemicity of CKDu, high, intermediate, or low, in a sample of people between 20 and 30 to the smallest administrative area with a population between 200 and 1000, using a widely available cheap test, serum creatinine tests.

Conclusions

Although many studies were carried out all over the CKDu-affected areas, the exact CKDu prevalence up-to-date remains unclear. Our study demonstrated a significant difference between serum creatinine values (prevalence of CKDu) in two different geographical areas with the same sociodemographic features. A comparably higher disease prevalence was observed in CKDu endemic areas and the proposed model could be an effective way to identify CKDu endemic areas using a small number of participants in a suspected area. Further, CKDu is not distributed evenly in endemic regions and study findings demonstrated 3 phases of disease dispersion as high prevalent areas (>30%), moderate prevalent areas (20%–30%), and low prevalent areas (<10%). Health authorities in Sri Lanka could adapt these levels when determining the endemicity of CKDu.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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