Climate change has led to significant rise of 0.8°C-0.9°C in global mean temperature over the last century and has been linked with significant increases in the frequency and severity of heat waves (extreme heat events). Climate change has also been increasingly connected to detrimental human health. One of the consequences of climate-related extreme heat exposure is dehydration and volume loss, leading to acute mortality from exacerbations of pre-existing chronic disease, as well as from outright heat exhaustion and heat stroke. Recent studies have also shown that recurrent heat exposure with physical exertion and inadequate hydration can lead to CKD that is distinct from that caused by diabetes, hypertension, or GN. Epidemics of CKD consistent with heat stress nephropathy are now occurring across the world. Here, we describe this disease, discuss the locations where it appears to be manifesting, link it with increasing temperatures, and discuss ongoing attempts to prevent the disease. Heat stress nephropathy may represent one of the first epidemics due to global warming. Government, industry, and health policy makers in the impacted regions should place greater emphasis on occupational and community interventions.

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Climate Change and the Emergent Epidemic of CKD from Heat Stress in Rural Communities: The Case for Heat Stress Nephropathy

The current chronic kidney disease epidemic, the major health issue in the rice paddy farming areas in Sri Lanka has been the subject of many scientific and political debates over the last decade. Although there is no agreement among scientists about the etiology of the disease, a majority of them has concluded that this is a toxic nephropathy. None of the hypotheses put forward so far could explain coherently the totality of clinical, biochemical, histopathological findings, and the unique geographical distribution of the disease and its appearance in the mid-1990s. A strong association between the consumption of hard water and the occurrence of this special kidney disease has been observed, but the relationship has not been explained consistently. Here, we have hypothesized the association of using glyphosate, the most widely used herbicide in the disease endemic area and its unique metal chelating properties. The possible role played by glyphosate-metal complexes in this epidemic has not been given any serious consideration by investigators for the last two decades. Furthermore, it may explain similar kidney disease epidemics observed in Andra Pradesh (India) and Central America. Although glyphosate alone does not cause an epidemic of chronic kidney disease,

https://www.infosperber.ch/data/attachements/Glysophat_Studie_Sri%20Lanka.pdf

Glyphosate, Hard Water and Nephrotoxic Metals: Are They the Culprits Behind the Epidemic of Chronic Kidney Disease of Unknown Etiology in Sri Lanka?

Chronic kidney disease (CKD) is a common progressive disease that is typically characterized by the permanent loss of functional nephrons. As injured nephrons become sclerotic and die, the remaining healthy nephrons undergo numerous structural, molecular, and functional changes in an attempt to compensate for the loss of diseased nephrons. These compensatory changes enable the kidney to maintain fluid and solute homeostasis until approximately 75% of nephrons are lost. As CKD continues to progress, glomerular filtration rate decreases, and remaining nephrons are unable to effectively eliminate metabolic wastes and environmental toxicants from the body. This inability may enhance mortality and/or morbidity of an individual. Environmental toxicants of particular concern are arsenic, cadmium, lead, and mercury. Since these metals are present throughout the environment and exposure to one or more of these metals is unavoidable, it is important that the way in which these metals are handled by target organs in normal and disease states is understood completely.

https://www.mdpi.com/1422-0067/18/5/1039/pdf

Chronic Kidney Disease and Exposure to Nephrotoxic Metals

Dehydration, a condition that characterizes excessive loss of body water, is well known to be associated with acute renal dysfunction; however, it has largely been considered reversible and to be associated with no long-term effects on the kidney. Recently, an epidemic of chronic kidney disease has emerged in Central America in which the major risk factor seems to be recurrent heat-associated dehydration. This has led to studies investigating whether recurrent dehydration may lead to permanent kidney damage. Three major potential mechanisms have been identified, including the effects of vasopressin on the kidney, the activation of the aldose reductase-fructokinase pathway, and the effects of chronic hyperuricemia. The discovery of these pathways has also led to the recognition that mild dehydration may be a risk factor in progression of all types of chronic kidney diseases. Furthermore, there is some evidence that increasing hydration, particularly with water, may actually prevent CKD. Thus, a whole new area of investigation is developing that focuses on the role of water and osmolarity and their influence on kidney function and health.

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Mechanisms by Which Dehydration May Lead to Chronic Kidney Disease.

The identification of modifiable risk factors that are associated with declining renal function is required to stem the increasing incidence of chronic kidney disease worldwide. In this Review, Howard Trachtman and colleagues discuss the impact of environmental chemicals on cardiorenal function. They highlight the ubiquity of exposure to environmental chemicals in the general public, the main sources of contamination, and the predominant adverse effects that might affect renal function.

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The effects of environmental chemicals on renal function

Background: This study describes chronic kidney disease of uncertain aetiology (CKDu), which cannot be attributed to diabetes, hypertension or other known aetiologies, that has emerged in the North Central region of Sri Lanka. Methods: A cross-sectional study was conducted, to determine the prevalence of and risk factors for CKDu. Arsenic, cadmium, lead, selenium, pesticides and other elements were analysed in biological samples from individuals with CKDu and compared with age- and sex-matched controls in the endemic and non-endemic areas. Food, water, soil and agrochemicals from both areas were analysed for heavy metals. Results: The age-standardised prevalence of CKDu was 12.9% (95% confidence interval [CI] = 11.5% to 14.4%) in males and 16.9% (95% CI = 15.5% to 18.3%) in females. Severe stages of CKDu were more frequent in males (stage 3: males versus females = 23.2% versus 7.4%; stage 4: males versus females = 22.0% versus 7.3%; P 39 years and those who farmed (chena cultivation) (OR [odds ratio] = 1.926, 95% CI = 1.561 to 2.376 and OR = 1.195, 95% CI = 1.007 to 1.418 respectively, P < 0.05). The risk was reduced in individuals who were male or who engaged in paddy cultivation (OR = 0.745, 95% CI = 0.562 to 0.988 and OR = 0.732, 95% CI = 0.542 to 0.988 respectively, P < 0.05). The mean concentration of cadmium in urine was significantly higher in those with CKDu (1.039 μg/g) compared with controls in the endemic and non-endemic areas (0.646 μg/g, P < 0.001 and 0.345 μg/g, P < 0.05) respectively. Urine cadmium sensitivity and specificity were 70% and 68.3% respectively (area under the receiver operating characteristic curve = 0.682, 95% CI = 0.61 to 0.75, cut-off value ≥0.397 μg/g). A significant dose–effect relationship was seen between urine cadmium concentration and CKDu stage (P<0.05). Urine cadmium and arsenic concentrations in individuals with CKDu were at levels known to cause kidney damage. Food items from the endemic area contained cadmium and lead above reference levels. Serum selenium was <90 μg/l in 63% of those with CKDu and pesticides residues were above reference levels in 31.6% of those with CKDu. Conclusions: These results indicate chronic exposure of people in the endemic area to low levels of cadmium through the food chain and also to pesticides. Significantly higher urinary excretion of cadmium in individuals with CKDu, and the dose–effect relationship between urine cadmium concentration and CKDu stages suggest that cadmium exposure is a risk factor for the pathogensis of CKDu. Deficiency of selenium and genetic susceptibility seen in individuals with CKDu suggest that they may be predisposing factors for the development of CKDu.

http://dh-web.org/health/ckdu/BioMed1471-2369-14-180.pdf

Chronic kidney disease of uncertain aetiology: prevalence and causative factors in a developing country.

Introduction: A double blind placebo controlled randomized trial was conducted to investigate the effect of angiotensin-converting-enzyme (ACE) inhibitor enalapril on the progression of Chronic Kidney Disease (CKD) caused by chronic exposure to nephrotoxins. Methods: 263 people aged 18-70 years diagnosed with CKD stages I, II or III who were not taking ACE inhibitors, who had no other chronic disease or contraindication for treatment with ACE inhibitors, were randomly assigned to enalapril or placebo. The main outcomes were albumin to creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Results: The mean systolic and diastolic blood pressure levels declined significantly in both enalapril and placebo groups with no significant difference in the two groups. There was a significant improvement in the albumin to creatinine ratio in the enalapril group compared to the placebo group (p<0.005). In the enalapril group, the mean albumin to creatinine ratio declined from 162.0 mg/g (SD 321.7) at baseline, to 55.4 mg/g (SD 122.4) at one year follow up; while in the placebo group, the mean albumin to creatinine ratio increased from 197.9 mg/g (SD 461.6) at baseline to 253.2 mg/g (SD 558.7), at one year follow up. In both groups, the eGFR declined significantly, during the 12 month follow-up, lower in the enalapril group, although with no significant difference. In the enalapril group the mean (eGFR) declined from 71.7 ml/min (SD 22.2) to 57.1 ml/min (SD16.1), while in the placebo group the mean eGFR declined from 73.8 ml/min (SD 24.2) to 54.7 ml/min (SD 20.3). Conclusion: Enalapril is beneficial in reducing albuminuria in patients with chronic kidney disease of uncertain aetiology.

https://www.longdom.org/open-access/randomized-controlled-trial-of-treatment-of-chronic-kidney-disease-ofuncertain-aetiolgy-with-enalapril-2161-0495-1000281.pdf

Firdosi R Mehta

Papers

Chronic kidney disease of uncertain aetiology: prevalence and causative factors in a developing country.

Randomized Controlled Trial of Treatment of Chronic Kidney Disease ofUncertain Aetiolgy with Enalapril