BIOMARKER-BASED SCREENING FOR EARLY DETECTION OF ADOLESCENT RENAL INJURY IN DRY CLIMATIC ZONE COMMUNITIES IN SRI LANKA IN RELATION TO ENVIRONMENTAL HEAT, FLUORIDE, AND BODY WEIGHT STATUS

Kidney diseases resemble a wide spectrum of pathophysiological conditions that compromise the performance of kidneys via undesirable structural and functional alterations driven by many environmental, physiological, and genetic factors. The early stages of these diseases are mostly asymptomatic, and remain undetectable within the limits of sensitivity of conventional biomarkers. Characterization of susceptibilities and potential risks as early as possible contributes effective management of kidney diseases through appropriate therapeutic and preventive interventions. In this regard, the development of screening approaches with more robust biomarkers is highly important. Hence this study aimed to investigate the applicability of urinary kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) as biomarkers for early detection of pediatric renal injury with insights on renal health outcomes associated with environmental fluoride, ambient heat, and bodyweight status prioritizing the pediatric communities in the dry climatic zone in Sri Lanka, where the chronic kidney disease of uncertain etiology (CKDu) has become an emergent public health threat. Education zones within the dry climatic zone were stratified according to the burden of CKDu as endemic, emerging, and non-endemic for the selection of boys and girls of secondary grades from government schools. Midstream morning urine samples of the participants were analyzed for creatinine and albumin using a clinical chemistry analyzer while quantification of KIM-1 and NGAL was based on an enzyme-linked immunosorbent assay (ELISA). Urinary KIM-1, NGAL, and albumin-creatinine ratio (ACR) were used for the interpretation of renal function. A comparative assessment of environmental thermal comfort was performed with regional biometeorological indices, and the determination of urinary fluoride was performed using an ion selective electrode (ISE). According to the guidelines of the World Health Organization, LMS-based body mass index (BMI) z-scores  and percentiles, participants were identified in different BMI strata: severely thin, thin, normal weight, overweight, and obese for assessment of associated kidney health outcomes. The median reference interval ranges for creatinine adjusted KIM-1 and NGAL (ng/mgCr)  were 0.018 - 0.561 and 2.507 - 9.318 for boys and 0.015 - 0.366 and 2.038 - 3.998 for girls  respectively.  In the comparative assessment, Urinary KIM-1 levels in both boys and girls in  CKDu endemic zones were significantly high compared to the boys and girls in CKDu  emerging and non-endemic zones. Urinary NGAL and ACR levels showed no significant differences among the three study groups. Urinary biomarker levels of the participants with  high heat exposure showed no significant difference compared to those with low heat exposure in both CKDu endemic and non endemic regions.  Significantly high urinary ACR and NGAL levels were observed in participants with high fluoride exposure compared to those with low fluoride exposure in CKDu endemic and non-endemic regions respectively. A significant increase of urinary KIM-1 was observed only in boys from CKDu non-endemic regions. There was no significant variability of the three renal biomarkers across the five BMI strata. Significantly elevated urinary KIM-1 levels in the participants from CKDu-affected regions, especially in the absence of albuminuria, may indicate potential subclinical early renal damage. No plausible evidence was found to ascertain casual associations of heat exposure and body weight status with the renal health of participants in the dry zone while high  fluoride exposure appeared to be a potential risk factor. There is an eminent risk of renal injury for children and adolescents in CKDu endemic regions, and KIM-1 can be adopted as a sensitive biomarker to characterize early renal injury. Implementation of effective healthcare policies is highly recommended to ensure the renal health of pediatric communities in Sri Lanka prioritizing the CKDu-affected regions.  

Keywords: Body mass index, fluoride exposure, heat exposure, kidney injury, pediatrics, 
renal biomarkers.