Search Results (11)

Fluoride is increasingly discussed as a geogenic risk factor for chronic kidney disease of uncertain etiology (CKDu); an epidemic of kidney disease is affecting hot tropical farming communities worldwide. Emerging evidence continues to support the association between high-fluoride exposure and kidney injury, particularly in regions with high fluoride levels. However, while fluoride’s geogenic nature leads to prolonged exposure through water and food sources, the direct impact on kidney health remains incompletely understood. This review explores the relationship between fluoride exposure and adverse kidney health outcomes, especially in the context of CKDu, synthesizing findings from epidemiological studies conducted worldwide. While a broad range of studies show widespread dental fluorosis prevalence in regions with high environmental fluoride levels in Sri Lanka, India, China, and Mexico, such correlation was not evident for CKDu and environmental fluoride levels. Notably, the spatial distribution patterns of CKDu and exposure risk through high fluoride levels in drinking water exhibit some inconsistencies, suggesting fluoride alone may not be the sole driver of CKDu. This review underscores the kidney health risks of fluoride exposure while emphasizing the need for further studies that consider multiple interacting factors beyond fluoride exposure in examination of environmental triggers of CKDu. Full article

Over the past two decades, Mesoamerican endemic nephropathy (MeN) has become a major public health problem in certain regions of Mexico and Central American countries. The etiology of this disease is multifactorial, and important environmental factors have been described, such as chronic heat stress, recurrent episodes of dehydration, infections, and exposure to toxins of chemical and biological origin. Genetic and epigenetic factors have been proposed to play significant roles in MeN. Recent studies have analyzed the role of these factors in MeN. In some cases, these factors appear to be associated with accelerated deterioration of established kidney disease due to preexisting endothelial dysfunction and tubulopathy. In other cases, they appear to be associated with early kidney damage, even before occupational exposure, suggesting that they may play a relevant role in the genesis of the disease. Other factors appear to act as risk reducers for developing MeN in areas with a high prevalence of the disease. Therefore, this disease has a rather complex multifactorial etiology, with possible polygenic contributions, possible epigenetic phenomena, and multiple environmental factors. Full article

Background: Molecular analysis in patients with nephrolithiasis (NL) and/or nephrocalcinosis (NC) enables more accurate evaluation of underlying etiologies. The existing clinical evidence regarding genetic testing in adults with NL comprises only a few cohort studies. Materials and Methods: We retrospectively analyzed 49 adult patients diagnosed with NL and/or NC from a single center, on whom we performed a genetic test using a nephrolithiasis panel. We reviewed the phenotype of the patients and compared the cases with positive and negative molecular diagnosis. Results: In total, 49 adult patients with NL and/or NC underwent genetic testing. Of the tested patients, 29 (59.2%) patients had 24 abnormal variants in 14 genes. Mendelian diseases were diagnosed in 14 (28.6%) cases: cystinuria (SLC3A1, SLC7A9; n = 4), hereditary distal renal tubular acidosis (SLC4A1; n = 3), Dent disease (CLCN5; n = 2), familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (CLDN16; n = 1), infantile hypercalcemia type 1 (CYP24A1; n = 1), primary hyperoxaluria type 1 (AGXT; n = 1), Bartter syndrome type 2 (KCNJ1; n = 1), and autosomal dominant tubulointerstitial kidney disease (UMOD; n = 1). Eight (16.3%) patients had pathogenic or likely pathogenic monoallelic variants as predisposing factors for NL and/or NC, and seven (14.3%) had biallelic or monoallelic variants of uncertain significance. Patients with positive genetic tests had a lower estimated glomerular filtration rate (p = 0.03) and more frequent NL associated with NC (p = 0.007) and were unlikely to have arterial hypertension (p = 0.03) when compared with patients with negative tests. Conclusions: Our study shows an increased effectiveness of molecular diagnosis and highlights the benefits of genetic testing. NL associated with NC and the presence of chronic kidney disease are the characteristics that should prompt the clinician to suspect an inherited form of NL and/or NC. Full article

Chronic kidney disease of uncertain etiology (CKDu) has emerged with growing evidence linking it to environmental exposures. This case–control study aimed to evaluate serum and urine trace elements (TEs) in CKDu patients, comparing them with those from control groups from endemic and non-endemic regions. TEs were analyzed in 406 participants (CKDu = 75, endemic CKD (ECKD) = 82, non-endemic CKD (NECKD) = 85, endemic control (EC) = 79, non-endemic control (NEC) = 85 using Inductively Coupled Plasma Mass Spectrometry. Means ± standard deviations were compared via the t-test and categorical variables by the chi-square test. Compared to non-endemic groups, Al, Mn, Ni, Cu, Cd, and Ba in serum and urine were significantly higher in endemic areas. CKDu patients showed elevated serum V, Cr, Zn, As, and U and urinary Cr, Mn, Fe, Co, Ni, and Rb compared to ECKD. Compared to NEC, CKDu patients had higher serum Zn, As, and Ba and urinary Al, Cr, Mn, Fe, Co, Ni, and Cu. Significant increases in serum V, Zn, As, Cd, Ba, and U and urinary V, Cr, Mn, Co, Ni, Rb, and Sr were noted in CKDu vs. NECKD. Elevated serum Al, Cr, Mn, Fe, Co, etc., and urinary Be, V, Zn, Se, etc., were observed in EC vs. CKDu. Urinary TEs positively correlated with eGFR, suggesting tubular dysfunction or prolonged exposure. Serum Se, a known reno-protective TE, was low in CKDu and ECKD. This study highlights that TE levels were high not only due to exposure but also depending on kidney health. Identified group-specific TEs may be causative in CKDu, having adverse health outcomes in some groups while potentially being protective in healthy groups. Full article

Background and Objectives: Chronic Kidney Disease of uncertain or non-traditional etiology (CKDnT) is a form of chronic kidney disease of undetermined etiology (CKDu) and is not associated with traditional risk factors. The aim of this study was to investigate the association of polymorphisms rs2070744, 4b/a and rs1799983 of the NOS3 gene with CKDnT in Mexican patients. Materials and Methods: We included 105 patients with CKDnT and 90 controls. Genotyping was performed by PCR-RFLP’s, genotypic and allelic frequencies were determined and compared between the two groups using χ² analysis, and differences were expressed as odd ratios with 95% confidence intervals (CI). Values of p < 0.05 were considered statistically significant. Results: Overall, 80% of patients were male. The rs1799983 polymorphism in NOS3 was found to be associated with CKDnT in the Mexican population (p = 0.006) (OR = 0.397; 95% CI, 0.192–0.817) under a dominant model. The genotype frequency was significantly different between the CKDnT and control groups (χ² = 8.298, p = 0.016). Conclusions: The results of this study indicate that there is an association between the rs2070744 polymorphism and CKDnT in the Mexican population. This polymorphism can play an important role in the pathophysiology of CKDnT whenever there is previous endothelial dysfunction. Full article

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 >70% sensitivity and specificity. Therefore, it could be used in the evaluation of the tubular interstitial involvement of CKD. Full article

Chronic kidney disease with uncertain etiology (CKDu) is an emerging health problem in Sri Lanka, particularly among the dry-zone farming communities that use groundwater for drinking. We investigated the quality of groundwater in an area where both high- and low-prevalence clusters of CKDu have been recorded. Eighty-four groundwater and five surface water samples, covering the selected region, were collected and analyzed for both major anions and cations. The groundwater in the region is mainly of the Ca-Mg-HCO₃ type, probably due to the long residence time in fractured hard rock aquifers in this region. Irrespective of the CKDu prevalence, over 50% of samples exceeded the recommended limits for EC/TDS, alkalinity, hardness, and Mg²⁺ content in groundwater. Water hardness in CKDu clusters was dominated by Mg²⁺. High fluoride content up to 4.0 mg/L was also found in most groundwater samples from the region. The water quality index (WQI) values indicated that 42% of the groundwater samples in regions with no or low CKDu prevalence and 49% of the samples in regions with high prevalence were poor in quality. The spatial distribution of WQI and fluoride concentration overlapped, indicating the direct influence of fluoride on the groundwater quality in the study region. In addition, regions with higher WQI values overlapped with the CKDu hotspots, indicating the direct impact of groundwater quality on the disease prevalence in the studied river basin. The WQI can be used to effectively demarcate areas with possible groundwater-related health effects in the dry-zone regions of Sri Lanka. Full article

Screening approaches with more robust biomarkers, are of the utmost importance in the characterization of renal injuries, particularly among communities with high burdens of chronic kidney disease of uncertain etiology (CKDu). The present study aimed to assess the utility of two emerging biomarkers: kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in predicting renal injury in different occupational groups in Sri Lanka. A cross-sectional study was conducted with six occupational groups (n = 188): fisherfolk (FF), paddy farmers (PF), sugarcane farmers (SF), factory workers (FW) and plantation workers (PW) to assess the predictive performance of KIM-1 and NGAL against a CKDu patient (PT) group (n = 40). The median KIM-1 levels of the study groups; FF, PF, SF, FW, PW and PT were 0.67, 0.59, 0.49, 1.62, 0.67 and 5.24 ng/mgCr, respectively, while the median NGAL levels were 1.16, 2.52, 1.42, 1.71, 1.06 and 22.41 ng/mgCr respectively. In ROC analysis to predict CKDu susceptibility, the area under the curve for KIM-1 ranged from 0.88 to 0.99 for the study groups, and in overall analysis, the sensitivity and specificity were 100% and 96%, respectively, for a cutoff value of 2.76 ng/mgCr. Similarly, for NGAL the range of AUC was 0.78–0.94, and a cutoff value of 3.12 ng/mgCr produced 88% sensitivity and 82% specificity. Compared with conventional markers, KIM-1 was the best biomarker for the characterization of renal injury in the participants of the occupational groups. With further validations, KIM-1 may be adopted as a prognostic marker to identify early renal injury and CKDu susceptibilities in community screening. Full article

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. Full article

An ongoing epidemic of chronic kidney disease of uncertain etiology (CKDu) afflicts large parts of Central America and is hypothesized to be linked to heat stress at work. Mortality rates from CKDu appear to have increased dramatically since the 1970s. To explore this relationship, we assessed trends in maximum and minimum temperatures during harvest months between 1973 and 2014 as well as in the number of days during the harvest season for which the maximum temperature surpassed 35 °C. Data were collected at a weather station at a Nicaraguan sugar company where large numbers of workers have been affected by CKDu. Monthly averages of the daily maximum temperatures between 1996 and 2014 were also compared to concurrent weather data from eight Automated Surface Observing System Network weather stations across Nicaragua. Our objectives were to assess changes in temperature across harvest seasons, estimate the number of days that workers were at risk of heat-related illness and compare daily maximum temperatures across various sites in Nicaragua. The monthly average daily maximum temperature during the harvest season increased by 0.7 °C per decade between 1973 and 1990. The number of days per harvest season with a maximum temperature over 35 °C increased by approximately five days per year between 1974 and 1990, from 32 days to 114 days. Between 1991 and 2013, the number of harvest days with a maximum temperature over 35 °C decreased by two days per year, and the monthly average daily maximum temperature decreased by 0.3 °C per decade. Comparisons with weather stations across Nicaragua demonstrate that this company is located in one of the consistently hottest regions of the country. Full article

Symptom burden and health-related quality of life (HRQOL) are important predictors of how a disease affects patients’ lives, especially for endemic health problems such as chronic kidney disease of uncertain etiology (CKDu). Our study describes symptom burden, HRQOL, and associated demographic and clinical variables in CKDu patients in the Girandurukotte area, Sri Lanka. A cross-sectional study included 120 CKDu patients attending the renal clinic in the endemic area. The instruments applied were the Kidney Disease Quality of Life—Short Form (KDQOL-SF^TM) version 1.3 and CKD Symptom Index—Sri Lanka. Socio-demographic, disease-related, and anthropometric variables were also investigated. The mean age of patients was 61.87 (SD 11.31), while 69.2% were male. The mean glomerular filtration rate was 28.17 (SD 14.03) mL/min/1.73 min², and 70.8% were anemic. Bone/joint pain was the most experienced symptom while the median number of symptoms reported by patients was 5 (IQR 3–7). The mean symptom burden, physical component summary, mental component summary, and kidney-disease-specific component scores were 12.71 (SD 10.45), 68.63 (SD 19.58), 78.53 (SD 18.78), and 81.57 (SD 5.86), respectively. Age was found to be a significant predictor of HRQOL, while hemoglobin level and being a farmer were significant predictors of symptom burden. Our data indicate that CKDu patients in all stages experience at least one symptom affecting all aspects of HRQOL. Full article