Prevalence of Chronic Kidney Disease of Uncertain Etiology Within Selected Farming Communities in Rural Sri Lanka.

Background: Chronic kidney disease of uncertain etiology (CKDu) is an emergent health concern, particularly in tropical farming communities in several global hotspots, including Sri Lanka. This particular nephropathy is characterized by a progressive decline in kidney function in the absence of conventional chronic kidney disease (CKD) risk factors such as diabetes mellitus, hypertension, and other identifiable kidney disorders. As it is almost asymptomatic at early stages, CKDu is mostly diagnosed at late stages with significant kidney damage. Hence, the identification of disease susceptibility and vulnerable communities at the earliest possible instances is highly important for the management of the disease. Objective: We aimed to compare kidney health across three different farming communities in Sri Lanka to identify CKDu susceptibilities. Methods: A cross-sectional study was performed with three selected farming communities: paddy farmers (PF; N = 581), sugarcane farmers (SF; N = 550), and vegetable farmers (VF; N = 244) in comparison with an age-matched control group of nonfarming (NF; N = 225) individuals. A medical examination was performed to investigate health status and medical history, whereas a urinalysis was performed to determine creatinine and albumin contents. Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR) were used for assessment of kidney function. CKDu susceptibility was determined based on eGFR, and urinary ACR adhering to the clinical practice guidelines in Sri Lanka. Results: The median (interquartile range [IQR]) eGFR levels of PF (85 mL/min/1.73 m2 [72-97]) and SF (93 mL/min/1.73 m2 [73-112]) were significantly lower than that of the NF group (103 mL/min/1.73 m2 [87-125]) (P < .0001), whereas eGFR of VF (100 mL/min/1.73 m2 [80-111]) was not significantly different compared with NF. The median (IQR) urinary ACR levels of the study groups, PF, SF, VF, and NF, were 0.59 (0.26-1.45), 0.46 (0.28-0.88), 0.45 (0.34-0.90), and 0.44 (0.34-1.02) mg/mmol, respectively. However, urinary ACR did not differ significantly across the study groups (P > .05). The prevalence of CKDu within PF (13.60%), SF (12.54%), and VF (6.67%) communities was significantly higher (P < .05) compared with the NF (2.67%). Of the total CKD cases, CKDu susceptible cases represented 73%, 69%, 50%, and 25% in PF, SF, VF, and NF, respectively, indicating a high risk of CKDu susceptibility among farming communities. Moreover, a noteworthy association of CKDu was observed with agrochemical exposure (odds ratio [OR] = 3.11, 95% confidence interval [CI] = 1.36-7.09). Concerning the farming practices, sugarcane farming showed the highest association with CKDu prevalence (OR = 3.40, 95% CI = 1.49-7.78). Conclusions: Compared with the nonfarming group, a significant risk of CKDu was observed in the three farming communities, particularly among paddy and sugarcane farmers. Longitudinal epidemiological studies to identify vulnerable farming communities and associated risk factors are critically needed to develop effective management strategies against CKDu within farming communities.

Contexte: L'insuffisance rénale chronique d'étiologie incertaine (IRCi) est un problème de santé émergent, en particulier dans les collectivités agricoles de plusieurs régions tropicales dans le monde, dont le Sri Lanka. Cette néphropathie particulière se caractérise par un déclin progressif de la fonction rénale en absence de facteurs de risque classiques de l'IRC comme le diabète, l'hypertension et d'autres troubles rénaux identifiables. L'IRCi étant quasi asymptomatique dans les stades précoces, elle est souvent diagnostiquée à des stades avancés et en présence de lésions rénales importantes. Il serait donc très pertinent d'identifier les populations vulnérables et d'évaluer le plus tôt possible leur prédisposition à l'IRCi, afin de faciliter la prise en charge de la maladie. Objectif: Notre objectif était de comparer la santé rénale de trois différentes populations agricoles du Sri Lanka afin d'évaluer leur prédisposition à l'IRCi. Méthodologie: Une étude transversale a été réalisée auprès de trois populations agricoles, soit les cultivateurs de riz (CR; n=581), de canne à sucre (CCS; n=550) et de légumes (CL; n=244). Les groupes étudiés ont été comparés à un groupe témoin d'individus non-agriculteurs (NA; n=225) d'âge similaire. Les sujets se sont soumis à un examen de leur état de santé et leurs antécédents médicaux, ainsi qu'à une analyse d'urine pour déterminer leurs taux urinaires de créatinine et d'albumine. Le débit de filtration glomérulaire estimé (DFGe) et le rapport albumine-créatinine urinaire (RAC) ont servi à évaluer la fonction rénale. La prédisposition à l'IRCi a été établie sur la base du DFGe et du RAC urinaire, conformément aux recommandations de pratique clinique au Sri Lanka. Résultats: Le DFGe médian (ÉIQ) des CR (85 ml/min/1,73 m2 [72-97]) et des CCS (93 ml/min/1,73 m2 [73-112]) était significativement inférieur à celui du groupe témoin (103 ml/min/1,73 m2 [87-125]) (p < 0.0001); aucune différence significative n'a été observée pour le groupe des CL (100 ml/min/1,73 m2 [80-111]). Le RAC urinaire médian (ÉIQ) s'établissait à 0,59 mg/mmol (0,26-1,45) pour les CR, à 0,46 mg/mmol (0,28-0,88) pour les CCS, à 0,45 mg/mmol (0,34-0,90) pour les CL et à 0,44 mg/mmol (0,34-1,02) pour le groupe témoin; soit aucune différence significative pour le RAC urinaire entre les groupes à l'étude (p > 0.05). La prévalence de l'IRCi dans les populations de CR (13,60 %), de CCS (12,54 %) et de CL (6,67 %) était significativement plus élevée (p < 0.05) que dans le groupe témoin (2,67 %). Sur le total des cas d'IRC, ceux qui montraient une prédisposition à l'IRCi représentaient 73 % (CR), 69 % (CCS), 50 % (CL) et 25 % (NA) des cas d'IRC de chaque groupe, ce qui indique un risque élevé de prédisposition à l'IRCi dans les communautés agricoles. On a en outre observé une association notable entre l'IRCi et l'exposition aux agents agrochimiques (RC : 3,11 [IC 95 % : 1,36-7,09]). En ce qui concerne les différentes pratiques agricoles, la culture de la canne à sucre a montré la plus forte association avec la prévalence d'IRCi (RC : 3,40 [IC 95 % : 1,49-7,78]). Conclusion: Un risque significativement plus élevé d'IRCi a été observé dans les trois communautés agricoles par rapport au groupe des non-agriculteurs, en particulier chez les cultivateurs de riz et de canne à sucre. Il est essentiel de procéder à des études épidémiologiques longitudinales visant à identifier les communautés agricoles vulnérables et les facteurs de risque associés, afin d'élaborer des stratégies efficaces pour prévenir l'IRCi au sein de ces communautés.

Urinary biomarkers indicate pediatric renal injury among rural farming communities in Sri Lanka.

Pediatric renal injury is an emerging health concern in communities affected by chronic kidney disease of uncertain etiology (CKDu). Early detection of susceptibilities through highly sensitive and specific biomarkers can lead to effective therapeutic and preventive interventions against renal diseases. Here, we aimed to investigate the utility of kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in early detection of renal abnormalities in selected pediatric communities in Sri Lanka. The study areas were stratified as CKDu endemic, emerging, and non-endemic based on the prevalence of CKDu, and a total of 804 school students (10-18 years of age) participated in the study. The median (IQR) urinary KIM-1 levels of the participants were 0.193 (0.026-0.338), 0.082 (0.001-0.220) and 0.040 (0.003-0.242) ng/mgCr for CKDu endemic, emerging and non-endemic regions respectively. Participants from CKDu endemic regions reported elevated (p < 0.0001) urinary KIM-1 expression compared to those from the other regions. The median (IQR) NGAL levels in participants from CKDu endemic (2.969; 1.833-5.641), emerging (3.374; 1.766-6.103), and non-endemic (3.345; 1.742-5.128 ng/mgCr) regions showed no significant difference. Also, urinary albumin-creatinine ratio (UACR) showed no significant differences across gender or residency. The prevalence of albuminuria was 1-2% in the locations irrespective of CKDu burden. Albuminuric participants reported higher (p < 0.05) urinary KIM-1 levels in comparison to normoalbuminuric participants. Significantly elevated urinary KIM-1 expression in a pediatric population from CKDu affected regions, especially in the presence of albuminuria, may indicate low-grade early renal damage supporting the utility of KIM-1 as a quantifiable biomarker.

Urinary Biomarkers of Renal Injury KIM-1 and NGAL: Reference Intervals for Healthy Pediatric Population in Sri Lanka.

Emerging renal biomarkers (e.g., kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)) are thought to be highly sensitive in diagnosing renal injury. However, global data on reference intervals for emerging biomarkers in younger populations are lacking. Here, we aimed to determine reference intervals for KIM-1 and NGAL across a pediatric population in Sri Lanka; a country significantly impacted by the emergence of chronic kidney disease of unexplained etiology (CKDu). Urine samples were collected from children (10-18 years) with no prior record of renal diseases from the dry climatic zone of Sri Lanka (N = 909). Urinary KIM-1 and NGAL concentrations were determined using the enzyme-linked immunosorbent assay (ELISA) and adjusted to urinary creatinine. Biomarker levels were stratified by age and gender, and reference intervals derived with quantile regression (2.5th, 50th, and 97.5th quantiles) were expressed at 95% CI. The range of median reference intervals for urinary KIM-1 and NGAL in children were 0.081-0.426 ng/mg Cr, 2.966-4.850 ng/mg Cr for males, and 0.0780-0.5076 ng/mg Cr, 2.0850-3.4960 ng/mg Cr for females, respectively. Renal biomarkers showed weak correlations with age, gender, ACR, and BMI. Our findings provide reference intervals to facilitate screening to detect early renal damage, especially in rural communities that are impacted by CKDu.