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Early Renal Damage Among Children Living in the Region of Highest Burden of Chronic Kidney Disease of Unknown Etiology (Ckdu) in Sri Lanka S

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Early Renal Damage Among Children Living in the Region of Highest Burden of Chronic Kidney Disease of Unknown Etiology (Ckdu) in Sri Lanka S Agampodi et al. BMC Nephrology (2018) 19:115 https://doi.org/10.1186/s12882-018-0911-8 RESEARCH ARTICLE Open Access Early renal damage among children living in the region of highest burden of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka S. B. Agampodi1, G. S. Amarasinghe1*, P. G. C. R. Naotunna1, C. S. Jayasumana2 and S. H. Siribaddana3 Abstract Background: Chronic kidney disease of unknown origin (CKDu) in Sri Lanka is grouped with several other epidemics of similar nature across the world as Chronic Interstitial Nephritis in Agricultural Communities (CINAC). In CKDu endemic countries, the focus has mainly been on adults. We hypothesized that studying distribution and factors associated with elevated urine albumin to creatinine ratio (UACR), an early marker of kidney injury, among children living in a CKDu endemic area may provide important clues about the onset and progression of the disease. Methods: This cross sectional study was performed in rural primary schools in North Central Province of Sri Lnaka, a CKDu high endemic region. Total of 2880 students aging 5 to 11 years from 67 schools were enrolled for urinalysis in a random spot urine sample. Bedside Schwartz formula was used to measure estimated glomerular filtration rate (eGFR) on all children with UACR > 30 mg/g in Polonnaruwa district and a group of age matched controls. A standard multiple linear regression using log transformed UACR as the dependent variable was performed. Mean eGFR were compared between UACR elevated group and controls using independent sample t test. Results: Median UACR was 10.3 mg/g. Sex, ethnicity, history of having a chronic disease and age uniquely contributed to the multiple regression model which only explained 2.8% of the variance in the log of the UACR (p < 0.001). Only 15 (0.5%) had UACR> 300 mg/g while 8.2% (n = 236) had UACR between 30 to 300 mg/g and 89.8% (n =203)of them did not have a chronic disease (Chi square 2.21, p = 0.091). Mean eGFR was significantly lower in the group with elevated UACR (88.9 mg/dl/1.73 m2, 95% CI for mean 86.4- 91.3) compared to group with normal UACR (93.7 mg/dl/1.73 m2,95% CI 91.1- 96.3) (t 2.7, p 0.007). Three out of the four students with eGFR less than 60 mg/dl/1.73 m2 had moderately elevated UACR. Conclusion: This study provides evidence to suggest that children in CKDu endemic regions are having an early renal damage. This observation needs to be investigated further in order to understand the worldwide epidemic of CKDu. Background clinicopathological similarities and are also referred to as Epidemics of chronic kidney disease of unknown origin Chronic Interstitial Nephritis in Agricultural Communi- (CKDu) resulting in progressive deterioration of renal ties (CINAC) [4]. Though exact etiology has not been function causing end stage renal failure that cannot be confirmed yet, multiple factors such as exposure to linked to a known causative factor are reported from environmental toxins, heavy metals, heat stress, and gen- different regions of the world including areas of Sri etic susceptibility are assumed to be responsible for ori- Lanka, India and Central America [1–3]. CKDu in Sri gin of the disease [5]. Lanka and Mesoamerican nephropathy demonstrate Renal insult leading to CKDu may start on a very early age, specially due to exposure to environmental toxins * Correspondence: [email protected] [6]. However, in countries where CKDu is a major public 1Department of Community Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka health issue, the focus is mainly on adult age groups. In Full list of author information is available at the end of the article Sri Lanka, a country with a heavy burden of CKDu, © The Author(s). 2018 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. Agampodi et al. BMC Nephrology (2018) 19:115 Page 2 of 7 neither the screening programmes nor the studies pay been reported annually from Anuradhapura and attention on children and possibility of early renal dam- Polonnaruwa districts between 2011 to 2015 [20]. age. Nevertheless, young patients have been reported in Data collection was carried out in October to some studies from Sri Lanka. For an example, 2 (7.7%) December 2014. out of 26 less than 20 years old individuals participating in a screening programme in Madawachiya (Anuradha- Study population pura district, Sri Lanka) were reported to have stage 3-5 School children studying in grade 1 to 5 (aging 5 to CKD (GFR less than 60 ml/min/1.73 m2)[7]. According 11 years) attending very difficult and difficult schools to a hospital based study, 11.2% CKDu patients treated (classified according to number of students, accessibility at the tertiary care center of Anuradhapura district were and facilities available at the school) in NCP were the between 15 to 30 years of age [8]. CKDu has been study population for the present study. reported in 10-15 years old children in North Central Province (NCP) as well [9]. Significance of these findings Study sample on describing epidemiology of CKDu in young popula- The sampling frame for the original study included 701 tion is limited by small number of younger participants rural primary schools in the province and 100 schools and need for different Glomerular filtration rate (GFR) were selected using a multi stage cluster sampling. From estimation methods for children. each school, 50 students in 5 to 11 years age group were Screening children for renal problems is predomin- enrolled randomly. antly done using urinalysis due to none-invasive nature From the original sample, 2880 children from 67 of the test. It has been used in several countries across schools from five educational zones representing both the world with varying success in identifying and pre- Anuradhapura and Polonnaruwa districts were selected venting permanent renal diseases [10]. School based for the present study. From this, children attending 42 urinalysis programmes, specially in Asian countries such schools from Polonnaruwa district were selected for as Japan and Korea have shown success in reducing the eGFR analysis. It included all the children with elevated progress to end stage renal disease through early identi- UACR (> 30 mg/g) in Polonnaruwa and an age matched fication of asymptomatic renal diseases [11, 12]. sample of children with UACR less than 30 mg/g. Urine albumin to creatinine ratio (UACR) in a spot sample is an early marker of kidney injury [13, 14]. Fur- Variables ther, the presence of proteinuria has also been described We used district, sex, age, ethnicity, family history of as a risk factor for rapid progression and poorer progno- kidney disease, history of having a chronic disease, sis of CKD [15, 16]. We hypothesized that studying dis- drinking water source, BMI for age (z value) and tribution and factors associated with elevated UACR hemoglobin concentration as predictor variables. among children living in a CKDu endemic area may Several methods are available to estimate urine albu- provide important clues about the onset and progression min excretion. Urine albumin excretion in a 24-h urine of the disease. We report here the first Sri Lankan study collection is considered the best bust is difficult to be on renal functions of children in the province with the assessed specially in children. Albumin and albumin to highest burden of CKDu. creatinine ratio in a random spot urine sample are more convenient methods that are used [21]. Methods National Kidney Foundation (NKF) reference ranges Study design for UACR was used to classify urine albumin excretion This is a part of a large school based cross sectional (UACR< 30 mg/g – normal, 30-300 mg/g –moderately study conducted among rural primary school children increased, > 300 mg/g – severely increased [21]. in North Central Province (NCP). Detailed method- Serum creatinine (SCr) was assessed using IDMS ology of the larger study has been described else- traceable modified Jaffe method. GFR was calculated where [17]. using the beside Schwartz formula (eGFR = kL/SCr, k = 0.413). Though early stages of CKD may have GFR levels Study setting below 90 mg/dl/1.73m2, GFR < 60 mg/dl/1.73 m2 was The study was carried out in Anuradhapura and used as the cutoff for low GFR [16]. Polonnaruwa districts of the NCP, in the dry zone of Sri The WHO cutoff upper limit of the reference range Lanka. Estimated population of Anuradhapura and (11.5 g/dl) was used to define anemia [22]. Polonnaruwa districts were 893,000 and 419,000 respect- ively in 2015 [18]. Majority of the population engage in Data sources/measurement paddy cultivation [19]. According to ministry of health, A self-administered questionnaire was sent to parents approximately 1000 and 500 CKD/CKDu patients has prior to the day of data collection. Trained medical Agampodi et al. BMC Nephrology (2018) 19:115 Page 3 of 7 graduates measured weight and height. A random spot Table 1 Characteristics of the 2880 rural primary school urine sample was collected on the day of data collection. children from North Central Province, Sri Lanka Trained nurses drew blood samples.
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