Quest to identify geochemical risk factors associated with chronic kidney disease of unknown etiology (CKDu) in an endemic region of Sri Lanka-a multimedia laboratory analysis of biological, food, and environmental samples.

The emergence of a new form of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka's North Central Province (NCP) has become a catastrophic health crisis. CKDu is characterized as slowly progressing, irreversible, and asymptomatic until late stages and, importantly, not attributed to diabetes, hypertension, or other known risk factors. It is postulated that the etiology of CKDu is multifactorial, involving genetic predisposition, nutritional and dehydration status, exposure to one or more environmental nephrotoxins, and lifestyle factors. The objective of this limited geochemical laboratory analysis was to determine the concentration of a suite of heavy metals and trace element nutrients in biological samples (human whole blood and hair) and environmental samples (drinking water, rice, soil, and freshwater fish) collected from two towns within the endemic NCP region in 2012 and 2013. This broad panel, metallomics/mineralomics approach was used to shed light on potential geochemical risk factors associated with CKDu. Based on prior literature documentation of potential nephrotoxins that may play a role in the genesis and progression of CKDu, heavy metals and fluoride were selected for analysis. The geochemical concentrations in biological and environmental media areas were quantified. Basic statistical measurements were subsequently used to compare media against applicable benchmark values, such as US soil screening levels. Cadmium, lead, and mercury were detected at concentrations exceeding US reference values in many of the biological samples, suggesting that study participants are subjected to chronic, low-level exposure to these elements. Within the limited number of environmental media samples, arsenic was determined to exceed initial risk screening and background concentration values in soil, while data collected from drinking water samples reflected the unique hydrogeochemistry of the region, including the prevalence of hard or very hard water, and fluoride, iron, manganese, sodium, and lead exceeding applicable drinking water standards in some instances. Current literature suggests that the etiology of CKDu is likely multifactorial, with no single biological or hydrogeochemical parameter directly related to disease genesis and progression. This preliminary screening identified that specific constituents may be present above levels of concern, but does not compare results against specific kidney toxicity values or cumulative risk related to a multifactorial disease process. The data collected from this limited investigation are intended to be used in the subsequent study design of a comprehensive and multifactorial etiological study of CKDu risk factors that includes sample collection, individual surveys, and laboratory analyses to more fully evaluate the potential environmental, behavioral, genetic, and lifestyle risk factors associated with CKDu.

Additional perspectives on chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka--lessons learned from the WHO CKDu population prevalence study.

The recent emergence of an apparently new form of chronic kidney disease of unknown aetiology (CKDu) has become a serious public health crisis in Sri Lanka. CKDu is slowly progressive, irreversible, and asymptomatic until late stages, and is not attributable to hypertension, diabetes, or other known aetiologies. In response to the scope and severity of the emerging CKDu health crisis, the Sri Lanka Ministry of Health and the World Health Organization initiated a collaborative research project from 2009 through 2012 to investigate CKDu prevalence and aetiology. The objective of this paper is to discuss the recently published findings of this investigation and present additional considerations and recommendations that may enhance subsequent investigations designed to identify and understand CKDu risk factors in Sri Lanka or other countries.

Chronic kidney disease of unknown aetiology in Sri Lanka: is cadmium a likely cause?

BACKGROUND: The rising prevalence of chronic kidney disease (CKD) and subsequent end stage renal failure necessitating renal replacement therapy has profound consequences for affected individuals and health care resources. This community based study was conducted to identify potential predictors of microalbuminuria in a randomly selected sample of adults from the North Central Province (NCP) of Sri Lanka, where the burden of CKD is pronounced and the underlying cause still unknown. METHODS: Exposures to possible risk factors were determined in randomly recruited subjects (425 females and 461 males) from selected areas of the NCP of Sri Lanka using an interviewer administered questionnaire. Sulphosalicylic acid and the Light Dependent Resister microalbumin gel filtration method was used for initial screening for microalbuminuria and reconfirmed by the Micral strip test. RESULTS: Microalbumnuria was detected in 6.1% of the females and 8.5% of the males. Smoking (p < 0.001), alcohol use (p = 0.003), hypertension (p < 0.001), diabetes (p < 0.001), urinary tract infection (UTI) (p = 0.034) and consumption of water from wells in the fields (p = 0.025) were associated with microalbuminuria. In the binary logistic regression analysis, hypertension, diabetes mellitus, UTI, drinking well water in the fields, smoking and pesticide spraying were found to be significant predictors of microalbuminuria. CONCLUSIONS: Hypertension, diabetes mellitus, UTI, and smoking are known risk factors for microalbuminuria. The association between microalbuminuria and consumption of well water suggests an environmental aetiology to CKD in NCP. The causative agent is yet to be identified. Investigations for cadmium as a potential causative agent needs to be initiated.

Empyema Necessitans due to Interruption of Antituberculosis Treatment.

Empyema necessitans is a rare presentation of tuberculous infection, commonly encountered in immunocompromised patients. The diagnosis can be challenging due to the paucibacillary nature of the condition and nonspecific symptoms. Identifying the organism in culture is the gold standard method of diagnosis. We describe a patient with chronic kidney disease, who developed empyema necessitans due to interruption of antituberculous therapy. Initially, he was started on antituberculous therapy based on a clinical diagnosis of smear-negative pulmonary tuberculous infection; this resulted in Stevens-Johnson syndrome needing a long course of steroid therapy. He later presented with a painful chest lump and was diagnosed as empyema necessitans. Finding the etiology for this rare presentation lead to a diagnostic dilemma, finally confirming the TB infection from the culture. This case highlights the importance of being aware of unusual complications of tuberculous infection in immunocompromised settings.

Could ochratoxin A in food commodities be the cause of chronic kidney disease in Sri Lanka?

Ochratoxin A (OA) is a naturally occurring mycotoxin with nephrotoxic properties that can contaminate plant food products. OA concentrations were assessed in commonly consumed food items in the North Central Province of Sri Lanka, where chronic kidney disease is diagnosed at epidemic proportions. Ninety-eight randomly selected food samples were analysed. Mycotoxin was detected in the extract by using a MycoMonitor Ochratoxin A ELISA assay kit (Helica Biosystems Inc., USA). The levels of OA found in these food commodities were below the recommended statutory maximum limit and are unlikely to be a potential risk factor for nephropathy in the North Central Province of Sri Lanka.

Chronic renal failure in North Central Province of Sri Lanka: an environmentally induced disease.

This study was conducted to determine the aetiology of chronic renal failure (CRF) in the North Central Province of Sri Lanka. Patients (n=183) with CRF of unknown aetiology were compared with controls (n=200) who had no evidence of chronic renal dysfunction. Exposure to possible risk factors were determined by an interviewer-administered questionnaire. Being a farmer (P<0.001), using pesticides (P<0.001), drinking well water (P<0.001), a family history of renal dysfunction (P=0.001), use of ayurvedic treatment (P<0.001) and a history of snake bite (P<0.001) were risk factors for CRF of unknown aetiology. Using logistic regression analysis, a family history of chronic renal disease, taking ayurvedic treatment and history of snake bite were found to be significant predictors for CRF of unknown aetiology. There is evidence to support an environmental aetiology to CRF in Sri Lanka.