Kidney Disease Of Uncertain Etiology Research Articles

Systematic Review of Kidney Injury Biomarkers for the Evaluation of CKD of Uncertain Etiology

IntroductionChronic kidney disease of uncertain etiology (CKDu) is an incompletely defined phenotype of CKD affecting young individuals mostly in agricultural communities in Central America and South Asia. CKDu is a diagnosis of exclusion made in individuals from endemic regions. MethodsWe conducted a systematic review of the primary literature on urinary and plasma kidney injury biomarkers measured in the setting of CKDu (through February 2023). Literature was identified via a Web of Science search and hand search of the references of previously identified literature. Search terms included “CKDu,” “Mesoamerican Nephropathy,” “CKD of unknown etiology,” “Chronic Interstitial Nephritis in Agricultural Communities,” “biomarker,” “urin*,” and/or “plasma.” ResultsA total of 25 papers were included. The two most frequently measured biomarkers were urinary kidney injury molecule-1 and urinary neutrophil gelatinase-associated lipocalin. There was substantial variability in study design, laboratory assay methods, and statistical methodology which prohibited meta-analysis. ConclusionBiomarkers that identify tubulointerstitial disease early and accurately may substantially accelerate progress in the study of CKDu and facilitate public health approaches that eventually lead to its prevention and elimination. To date, the literature is limited by relatively small sample sizes and methodological limitations which should be addressed in future studies.

Metabolome evidence of CKDu risks after chronic exposure to simulated Sri Lanka drinking water in zebrafish

It is still a serious public health issue that chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka poses challenges in identification, prevention, and treatment. What environmental factors in drinking water cause kidney damage remains unclear. This study aimed to investigate the risks of various environmental factors that may induce CKDu, including water hardness, fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM). The research focused on comprehensive metabolome analysis, and correlation with transcriptomic and gut microbiota changes. Results revealed that chronic exposure led to kidney damage and pancreatic toxicity in adult zebrafish. Metabolomics profiling showed significant alterations in biochemical processes, with enriched metabolic pathways of oxidative phosphorylation, folate biosynthesis, arachidonic acid metabolism, FoxO signaling pathway, lysosome, pyruvate metabolism, and purine metabolism. The network analysis revealed significant changes in metabolites associated with renal function and diseases, including 20-Hydroxy-LTE4, PS(18:0/22:2(13Z,16Z)), Neuromedin N, 20-Oxo-Leukotriene E4, and phenol sulfate, which are involved in the fatty acyls and glycerophospholipids class. These metabolites were closely associated with the disrupted gut bacteria of g_ZOR0006, g_Pseudomonas, g_Tsukamurella, g_Cetobacterium, g_Flavobacterium, which belonged to dominant phyla of Firmicutes and Proteobacteria, etc., and differentially expressed genes (DEGs) such as egln3, ca2, jun, slc2a1b, and gls2b in zebrafish. Exploratory omics analyses revealed the shared significantly changed pathways in transcriptome and metabolome like calcium signaling and necroptosis, suggesting potential biomarkers for assessing kidney disease.

Successful diagnosis and treatment of recurrent atypical hemolytic uremic syndrome posttransplantation caused by the heterozygous deletion of CFH in a patient with end-stage kidney disease of uncertain etiology.

Successful diagnosis and treatment of recurrent atypical hemolytic uremic syndrome posttransplantation caused by the heterozygous deletion of CFH in a patient with end-stage kidney disease of uncertain etiology.

The Role of Water Quality in the Pathogenesis of CKDu with Respect to Fluoride

Introduction: Despite much research on chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka the etiology and pathogenesis remains obscure. The fluoride level in the ground water in CKDu prevalent area was considered as one of the suspected etiological factor for the disease. Methodology: A review was conducted through MEDLINE and Google Scholar databases for peer reviewed publications on ground water analysis related to CKDu areas globally. Results: Groundwater plays as the primary source of drinking water in these disease prevalent areas. The occurrence of the disease and the fluoride metabolism in the CKDu patients would give much evidence for the correlation. The factors which decide the water intake of a person, and the fluoride level in the ground water are the critical factors for fluoride intake. There are recommended levels of fluoride for each country. The pathogenesis of Fluoride for the renal damage was well described at cellular level changes. It is associated with oxidative stress leading to organelle damage. Conclusion: Therefore, urinary fluoride can be used as an early indicator of CKDu. Further, Fluoride toxicity occurs in combination of heavy metals such as Mg, Mn and As, Pb etc. Although no clear etiological factor was recognized, Fluoride could be considered as a possible etiological factor for CKDu. As preventive measures, provision of fluoride-free drinking water in the affected areas, early detection of fluoride toxicity can be recommended.

Environmental fluoride exposure and implications on potential pediatric kidney health risks: an approach with urinary biomarkers.

Environmental fluoride exposure at elevated levels is potentially linked to kidney injury, and may contribute to chronic kidney disease of uncertain etiology (CKDu) as a risk factor. However, this link remains unclear, and examining the risk of kidney damage from early life fluoride exposure may provide important insights. Hence, this study aimed to investigate associations of fluoride exposure with pediatric kidney health in CKDu impacted and unimpacted communities in Sri Lanka. Considering the geographical variations in environmental fluoride, climate, and prevalence of CKDu, four study groups were established within selected education zones in CKDu-endemic dry zone regions (D-En), and CKDu-nonendemic regions within the dry (D-NE), wet (W-NE), and intermediate (I-NE) climatic zones. The study population included 922 school students (11-18 years of age). Participants in each group were divided into four subgroups based on quartiles of respective urinary fluoride (UF) distribution for comparison of urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and albumin-creatinine ratio (ACR). UF levels in participants particularly in CKDu endemic dry zone regions were significantly high compared to the other regions. Significantly high median urinary NGAL (in D-NE) and ACR (in D-EN, and W-NE) levels were observed in subgroups of higher UF quartiles. Albuminuria was not particularly identified in subjects with high UF excretion. Urinary KIM-1 showed no significant variation across the UF quartile subgroups. Linear regression identified weak associations of UF with kidney injury biomarkers. Fluoride exposure is particularly high in CKDu-endemic dry zone communities. As implied by kidney injury biomarkers, a strong link between fluoride exposure and pediatric kidney health was not evident at the observed exposure levels in the study regions.

Serum Aldosterone in patients with Chronic Kidney Disease of uncertain etiology in Girandurukotte and Wilgamuwa, Sri Lanka

The Renin Angiotensin Aldosterone System (RAAS) is the main regulator of body fluid and electrolyte balance in the human body. Features of RAAS activation, such as hypertension and fluid retention, are not apparent in some categories of CKD-like tubular interstitial diseases. The beneficial effects of RAAS blockers are controversial if not activated. This study was conducted to identify the features of RAAS activation in CKDu and to evaluate the representativeness of Aldosterone as a marker of activation. A cross-sectional study was conducted on 119 definite CKDu patients at the renal clinics in Girandurukotte and Wilgamuwa, Sri Lanka. The basic biochemical parameters, serum electrolytes, and osmolality were measured by using serum and urine samples of the participants. Statistical analysis was performed in IBM SPSS statistics version 23. Only 4.4% and 6.7% of study subjects had increased serum Aldosterone and serum Angiotensin II. There was a significant positive correlation between serum Aldosterone with serum creatinine (r=0.477, p<0.01) and Angiotensin II (r=0.379, p<0.01). Inversely, it was negatively correlated with eGFR (r=-0.353, p<0.01). Moreover, serum aldosterone had a significant elevation in the late stages (p=0.024) than early stages and was significantly associated with proteinuria (p=0.032). Results showed no indications of activated RAAS in patients with the diagnosis of definite CKDu. A significant number of the population had hypernatremia which is positively correlated with hyperosmolality, indicating dehydration. The possibility of subclinical dehydration that may have an effect with faster progression.

Probiotics mitigate kidney damage after exposure to Sri Lanka's local groundwater from chronic kidney disease with uncertain etiology (CKDu) prevalent area in zebrafish

Groundwater in Sri Lanka, contaminated with environmental toxins, is suspected to potentially induce chronic kidney disease of uncertain etiology (CKDu) in humans. This study aims to elucidate the potential mitigating effects of probiotics on kidney damage induced by exposure to this local groundwater (LW) in zebrafish. We used zebrafish as a model organism and exposed them to local groundwater to evaluate the risk of CKDu. Probiotics were then added at a concentration of 108 colony-forming units per milliliter (CFU/mL). Our findings revealed that exposure to local groundwater resulted in abnormalities, such as tail deletion and spinal curvature in zebrafish larvae. However, the addition of probiotics mitigated these effects, improving the hatching rate, heart rate, length, weight, deformity rate, survival rate, and abnormal behavior of zebrafish. It also positively influenced the differential expression levels of kidney development and immunity-related genes (dync2h1, foxj1, pkd2, gata3, slc20a1, il1β, and lyso). Furthermore, exposure to LW decreased both the diversity and abundance of microbiota in zebrafish larvae. However, treatment with probiotics, such as L. plantarum and L. rhamnosus partially restored the disrupted gut microbiota and significantly impacted the cellular process pathways of the microbial community, as determined by KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis. In conclusion, this study highlights the risks associated with Sri Lanka's local groundwater from a CKDu prevalent area and confirms the beneficial effects of different probiotics. These findings may provide new insights into bacterial function in host kidney health.

Body mass index and implications for pediatric kidney health: a cross-sectional study with urinary biomarkers.

Extremes of unhealthy body weight, particularly obesity, are known to increase the risk of chronic kidney diseases. However, the current knowledge of kidney health outcomes associated with unhealthy body weight remains incomprehensive, especially in pediatrics. Therefore, the present study aimed to evaluate body mass index (BMI) and its potential associations with kidney health in a selected subset of school students in Sri Lanka. This cross-sectional study was conducted among students of both sexes in the range of 11-18years of age (N = 1078) in education zones with no reported cases of chronic kidney disease of uncertain etiology. Based on sex- and age-specific BMI percentiles (LMS method), the participants were classified into five BMI groups (severely thin, thin, healthy, overweight, and obese) for measurement of urinary biomarkers of kidney injury: kidney injury molecule (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and albumin creatinine ratio (ACR). The median urinary levels ofNGAL, ACR, and particularly KIM-1, which is a more sensitive indicator of kidney injury, showed no significant differences across the BMI strata. Importantly, moderate correlations of BMI with KIM-1 and NGAL were identified in severely thin girls. According to the present study, these findings do not produce plausibly strong evidence to establish a potential association of BMI with altered kidney function in the studied pediatric communities. Particularly, a likelihood of abnormal kidney health outcomes associated with undernutrition is apparent in severely thin girls. However, in-depth studies are warranted to develop a comprehensive understanding of the associations of nutritional status with pediatric kidney health in Sri Lanka. A higher resolution version of the Graphical abstract is available as Supplementary information.

Describing Natural History and Exploring Risk Factors for Kidney Function Decline in Persons With CKD of Uncertain Etiology in Sri Lanka

Chronic kidney disease of uncertain etiology (CKDu) is a leading cause of death of adults in Sri Lanka's dry region. We initiated the Kidney Progression Project (KiPP) to prospectively follow 292 persons with Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) 20 to 60 ml/min per 1.73 m2 living in a CKDu endemic area. Using data from 3-year follow-up, we assessed kidney function decline (>30% from baseline eGFR), and the composite outcome of >30% eGFR decline, eGFR<15 ml/min or death, and explored the association of the 2 outcomes with baseline demographic, residential, and clinical parameters accounting for baseline eGFR. Median eGFR at enrollment was 28 ml/min among 71 women; 30 ml/min among 221 men; 91% to 99% had trace or no proteinuria during follow-up. At enrollment, median serum sodium, uric acid, and potassium were 143 mmol/l, 6.3 mg/dl, 4.5 meq/l, respectively among women; and 143 mmol/l, 6.9 mg/dl, 4.3 meq/l among men. Mean slope of eGFR decline was-0.5 (SD 4.9) ml/min/yr. In exploratory analyses, men with greater years of education and those living in northern region of the study area experienced lower likelihood of disease progression (hazard ratios [HR] 0.87 [0.77-0.98] per additional year and 0.33 [0.12-0.89] for northern versus other subregions, respectively). There was a suggestion that men drinking well water had higher likelihood and men living further away from reservoirs had lower likelihood of >30% decline in eGFR (HR 2.07 [0.95-4.49] for drinking well water versus not, and HR 0.58 [0.32-1.05] per kilometer distance, respectively). The overall rate of kidney function decline was slow in this CKDu cohort, similar to other nonalbuminuric CKD, and event rates were similar among men and women. Further etiologic investigations could focus on specific residence locale and water use.

Prepubertal to adulthood exposure to low doses of glyphosate-based herbicide increases the expression of the Havcr1 (Kim1) biomarker and causes mild kidney alterations

Glyphosate is a nonselective and postemergent herbicide used to combat weeds in several crops, which raises concerns about risks to human health since residues are detected in urine, human milk, surface water and several types of food. Feces and urine are the major routes of elimination of glyphosate, making the kidney a sensitive target for the development of toxicity. In fact, farmers are at high risk of developing chronic kidney disease. In this sense, this study aims to investigate kidney function by measuring the serum levels of urea and creatinine, examining the histological morphology, and analyzing the mRNA expression of genes related to tubular transport of ions, urea and urates and the biomarker of kidney disease Kim1, and the levels of lead in the kidney in male Wistar rats orally exposed to low levels of glyphosate-based herbicide (GBH: 0, 0.5 or 5 mg/kg) from weaning to adult life by gavage. GBH0.5 showed reduced serum urea concentration, presence of tubulointerstitial swelling and mononuclear cell infiltration into the interstitium, increased gene expression of Kim1 and reduced gene expression of Slc14a1. GBH5 showed reduced serum urea and increased serum creatinine concentrations, tubulointerstitial swelling, interstitial fibrosis, and reduced expression of Trpm6 and Trpv5. Exposure to GBH did not affect the levels of Pb in the kidneys of animals. In conclusion, glyphosate at low doses may cause mild kidney damage. It is necessary to evaluate whether the long-term effects of this constant injury may contribute to the development of chronic kidney disease of uncertain etiology.

Leptospirosis: A Potential Culprit for Chronic Kidney Disease of Uncertain Etiology

Purpose: Chronic kidney disease of uncertain etiology (CKDu) is an environmental nephropathy in which the etiological factors are yet uncertain. Leptospirosis, a spirochetal infection that is common among agricultural communities, has been identified as a potential etiology for CKDu beyond environmental nephropathy. Although CKDu is a chronic kidney disease, in endemic regions, an increasing number of cases are reported with features suggestive of acute interstitial nephritis without any known reason (AINu), with or without background CKD. The study hypothesizes that exposure to pathogenic leptospires is one of the causative factors for the occurrence of AINu. Method: This study was carried out using 59 clinically diagnosed AINu patients, 72 healthy controls from CKDu endemic region (endemic controls [ECs]), and 71 healthy controls from CKDu non-endemic region (non-endemic controls [NECs]). Results: The seroprevalence of 18.6, 6.9, and 7.0% was observed in the AIN (or AINu), EC, and NEC groups, respectively, from the rapid IgM test. Among 19 serovars tested, the highest seroprevalence was observed at 72.9, 38.9, and 21.1% in the AIN (AINu), EC, and NEC groups, respectively, by microscopic agglutination test (MAT), particularly for serovar Leptospira santarosai serovar Shermani. This emphasizes the presence of infection in AINu patients, and this also suggests that Leptospira exposure might play an important role in AINu. Conclusion: These data suggest that exposure to Leptospira infection could be one of the possible causative factors for the occurrence of AINu, which may lead to CKDu in Sri Lanka.

Environmental heat exposure and implications on renal health of pediatric communities in the dry climatic zone of Sri Lanka: An approach with urinary biomarkers.

Prolonged heat exposure during outdoor physical exertion can result in adverse renal health outcomes, and it is also supposed to be a driver of chronic kidney disease of uncertain etiology (CKDu) in tropical regions. School students are more likely to experience high heat exposure during outdoor sports practices, and the current knowledge on potential renal health outcomes associated with heat exposure carries many knowledge gaps. Hence, the present study aimed to perform biomarker-based assessment of the likelihood of pediatric renal injury focusing the communities in the dry climatic zone in Sri Lanka, where it prevails relatively harsh climate and high prevalence of CKDu. School students who engaged in regular outdoor sports practices (high-heat exposure), and an age-matched control of students who did not engage in sports practices (low-heat exposure) from four educational zones: Padavi Sripura (N = 159) and Medirigiriya (N = 171), Uhana (N = 165) and Thanamalwila (N = 169) participated in this cross-sectional study representing CKDu endemic and non-endemic regions. Effective temperature (ET), wet-bulb globe temperature (WBGT), heat index (HI) and humidex were used for comparison of thermal comfort in the environment. The intensity of environmental heat measured by thermal comfort indices showed no significant difference (p > 0.05) among the study regions. Urinary kidney injury molecule (KIM-1) and albumin-creatinine ratio (ACR) in participants with high heat exposure did not differ significantly from those in the control groups in the four study zones, where urinary neutrophil gelatinase-associated lipocalin showed substantial differences in some groups. Irrespective of heat exposure, increased KIM-1 excretion was observed (p < 0.01) in participants of CKDu endemic regions compared to those in non-endemic areas. Within the context of our findings, there is no plausibly strong evidence to establish potential association of heat exposure with the likelihood of developing renal injury or abnormal renal outcomes in dry zone school students in Sri Lanka.

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

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. We aimed to compare kidney health across three different farming communities in Sri Lanka to identify CKDu susceptibilities. 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. 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). 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.

Early Ultrastructural Changes in Biopsies From Patients With Symptomatic CKD of Uncertain Etiology

Although the investigation of chronic kidney disease of uncertain etiology (CKDu) has identified many possible influencing factors in recent years, the exact pathomechanism of this disease remains unclear. In this study, we collected 13 renal biopsies from patients with symptomatic CKDu (Sym-CKDu) from Sri Lanka with well-documented clinical and socioeconomic factors. We performed light microscopy and electron microscopic evaluation for ultrastructural analysis, which was compared with 100 biopsies from German patients with 20 different kidney diseases. Of the 13 Sri Lankan patients, 12 were men (92.3%), frequently employed in agriculture (50%), and experienced symptoms such as feeling feverish (83.3%), dysuria (83.3%), and arthralgia (66.6%). Light microscopic evaluation using activity and chronicity score revealed that cases represented early stages of CKDu except for 2 biopsies, which showed additional signs of diabetes. Most glomeruli showed only mild changes, such as podocyte foot process effacement on electron microscopy. We found a spectrum of early tubulointerstitial changes including partial loss of brush border in proximal tubules, detachment of tubular cells, enlarged vacuoles, and mitochondrial swelling associated with loss of cristae and dysmorphic lysosomes with electron-dense aggregates. None of these changes occurred exclusively in Sym-CKDu; however, they were significantly more frequent in these cases than in the control cohort. In conclusion, our findings confirm the predominant and early alterations of tubular structure in CKDu that can occur without significant glomerular changes. The ultrastructural changes do not provide concrete evidence of the cause of CKDu but were significantly more frequent in Sym-CKDu than in the controls.

Evaluating Serum RBP4 as an Auxiliary Biomarker for CKDu Diagnosis

Background: A chronic interstitial disease, chronic kidney disease of uncertain etiology (CKDu), has emerged as a notable contributor to the CKD burden in rural Sri Lanka. Most therapeutic and diagnostic approaches to CKD focus on glomerular diseases, and thus are not fully applicable to CKDu. Serum proteins, specifically those with the profile of markers representing different facets of a disease, are beneficial for a comprehensive evaluation of diseases, and hence in CKD. Our aim was to identify the role of serum-retinol-binding protein 4 (RBP4), a marker of the proximal tubule, in the diagnosis of CKDu. Methods: Definite CKDu cases were recruited from the renal clinic in Girandurukotte and Wilgamuwa (endemic regions). Healthy controls were recruited from Mandaramnuwara (nonendemic area). The levels of RBP4 and creatinine in serum were measured. An immunoassay (ELISA) was performed on the serum samples. The stages of CKD/ CKDu were classified according to eGFR. Results: Serum RBP4 was significantly increased in CKDu patients compared to CKD patients and healthy controls. The results show that the ratio of normalized serum RBP4 to serum creatine (S.cr) acts as a better competitive marker for CKDu (AUC 0.762, sensitivity 0.733) than CKD (AUC 0.584, sensitivity 0.733) when compared against healthy controls. Furthermore, the RBP4:S.cr ratio showed higher discriminating power (AUC 0.743) between CKDu and CKD, suggesting that the RBP4: S.cr ratio has potential as a serum marker to differentiate CKDu from CKDu. Conclusion: The RBP4: S.cr ratio was identified as a plausible indicator for differentiating CKDu from CKD with &gt;70% sensitivity and specificity. Therefore, it could be used in the evaluation of the tubular interstitial involvement of CKD.

Occupational heat exposure alone does not explain chronic kidney disease of uncertain aetiology (CKDu) in Sri Lanka

• The association of occupational heat exposure with CKDu remains debated. • kidney function of individuals in three occupational groups, farmers, fisherfolk and plantation workers in Sri Lanka was assessed. • CKDu risk was lowest in occupational group with highest heat exposure. • CKDu risk was higher among farmers and workers with low to moderate heat exposure. • Heat stress does not appear to be the main driver of CKDu. Chronic kidney disease of uncertain aetiology (CKDu) is an emerging health concern in tropical farming communities. The role ofoccupational heat exposure as a potential driver of CKDu remains debated. Our study examines occupational heat exposure kidney health in three occupational groups in Sri Lanka. We recruited participants from three occupational groups from three climatic zones; fisherfolk from the dry and intermediate zones (N=225), paddy farmers from the intermediate zone (N=180) and tea plantation workers from the wet zone (N=70). Serum creatinine, cystatin-C, urea and uric acid, estimated glomerular filtration rate and urinary albumin-creatinine ratio were used as diagnostic criteria of renal impairment. CKDu susceptibility was at the highest among farmers (13.33%), with a significant differentce compared to the fisherfolk (5.36%; p=0.0003). Among the plantation workers, CKDu susceptibility was 5.71%, and it was not significantly different compared to the farmers (p=0.087) and the fisherfolk (p=0.427). Despite higher exposure to heat stress and dehydration, as indicated by the highest simplified wet bulb globe temperature (sWBGT) in the work environments, fisherfolk reported the lowest CKDu susceptibility, while farmers and workers with low to moderate heat exposure showed an increased incidence of abnormal renal function. Further, a multivariable regression analysis identified a significant effect of occupation (p=0.005), agrochemical exposure (p=0.001) and age (p=0.001) on the likelihood of CKDu susceptibility while the sWBGT in the working environments showed no significant effect (p=0.227). With the evidence from our findings, heat exposure alone does not appear to be the leading driver of CKDu in Sri Lanka, suggesting that the nephropathy is more likely to be associated with occupational risks such as agrochemical exposures.

Preliminary assessment of heavy metals intake via food in CKDu affected Uddanam region of Srikakulam, Andhra Pradesh, India

ABSTRACT The present study aimed to assess metal/heavy metal intake by the population via food environment of the Uddanam region, a hotspot for chronic kidney disease of uncertain aetiology (CKDu) in India. The food samples included rice/paddy, marine/freshwater fish, green gram/black gram (whole), and green leafy vegetables (GLVs, i.e. amaranth/spinach). These were analysed for metal/heavy metal (chromium, nickel, copper, arsenic, lead, magnesium, calcium, aluminium, manganese, iron, zinc, barium, cadmium, mercury, and uranium) content using standard procedures. The total heavy metal intake was calculated as a sum of the intake from each food source. The daily dietary intake was compared to safe intake levels (from the Institute of Medicine of the National Academies and National Institute of Nutrition). The intake was higher than safe levels for lead, chromium, and manganese. It is advisable to reduce heavy metal exposure by adopting agricultural practices and public health interventions in terms of diet.

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.

Assessing groundwater quality using the Water Quality Index (WQI) and GIS in the Uva Province, Sri Lanka

The prime objective of this study is to develop a water quality index (WQI) to identify the relationship between the drinking water quality and the prevalence of Chronic Kidney Disease of Uncertain Etiology (CKDu) in the Uva Province (UP). For this, all CKDu patients in the province were recorded. 251 groundwater samples were collected and analyzed for their major cations and anions. Following this procedure, the spatial distribution maps for CKDu patients, water quality parameters and WQI were generated. The results revealed that, 20.3% of groundwater samples are categorized under “excellent” in terms of the drinking water quality, 21.2% of the samples are categorized under “good”, 20.3% of the samples are categorized under “poor”, 9.9% of the samples are categorized under “very poor”, and 28.3% of the samples are categorized under “unsuitable” in terms of the WQI. According to the results, the most significant correlation was recorded between fluoride content in the samples and WQI (0.96). Statistical analysis showed that the WQI has a strong positive correlation (0.68) with the spatial distribution of CKDu patients in the UP inferring that groundwater quality has a significant effect on the prevalence of CKDu in the UP. Moreover, these maps can be effectively used by decision makers for groundwater quality management activities in the UP, Sri Lanka.

Chronic Kidney Disease of Uncertain Etiology in Sri Lanka: Curing between Medicine and Traditional Culture

Chronic Kidney Disease of unknown origin (CKDu) has appeared across Sri Lanka’s North Central Province (NCP) since the 1990s as an epidemic, unexplained by conventional associated risk factors. During the past few decades, a large number of studies attempted to determine the unknown etiology of CKDu. Despite these investigations, no concrete conclusions were developed, though a number of contradictory hypotheses emerged. The present ethnographic study was carried out in two endemic areas, labelled as “CKDu hotspots”, and illuminates how curing takes place between biomedicine and traditional cultural practices. Our ethnographic study thoroughly scrutinized three decades of lived experience, lay-perceptions and local discourses on CKDu. We used a qualitative study design with a transcendental phenomenological approach and employed a mixture of ethnographic methods. Data collection techniques included participant observation, in-depth interviews, focus group discussions and key informant interviews. Data was analysed by using an interpretive thematic analysis model. Findings revealed that lay people have constructed a popular discourse on CKDu, and we explored their views on the origin, etiology and prevalence of CKDu in their locality over the past few decades. Patients’ narratives revealed that there were currently a number of gaps in service delivery. These were mainly due to distant relationships between healthcare providers and CKDu patients. Lay people in affected communities were marginalized throughout the investigation process to determine the unknown etiology, their involvement marginalized to merely acting as objects for scientific instigation. The affected communities strongly believed that CKDu was a recent phenomenon resulting from the mismanagement of the natural environment due to social and lifestyle changes. These findings highlight local dynamics of healthcare seeking behaviours which demand complementary medicine system, particularly given the number of limitations in the biomedical system. Empirical evidence generated from this study suggests a conceptual shift to an ethno-medical model to address CKDu. Improving cultural competency and communication skills among healthcare providers in public health are crucial in order to apply a “bio-psychosocial perspective” in healthcare delivery system and bridging the gap between hospital and the community.