Ricardo Leiva

Bio: Ricardo Leiva is an academic researcher. The author has contributed to research in topics: Kidney disease & Mesoamerican nephropathy. The author has an hindex of 2, co-authored 3 publications receiving 353 citations.

Inhaled Silica Nanoparticles Causes Chronic Kidney Disease in Rats.

Abstract: INTRODUCTION Silica nanoparticles (SiNPs) released during the burning of sugarcane have been postulated to have a role in chronic kidney disease of unknown etiology. We tested the hypothesis that pristine SiNPs of the size present in sugarcane might cause chronic kidney injury when administered through the lung in rats. METHODS We administered 200 nm or 300 nm amorphous SiNPs twice weekly (4 mg/dose) or vehicle by oropharyngeal aspiration for 13 weeks to rats followed by sacrifice after an additional 13 weeks (26 weeks total). Tissues were evaluated for presence of SiNPs and evidence of histologic injury. RESULTS Both sizes of SiNPs caused kidney damage, with early tubular injury and inflammation (at week 13) that continued to inflammation and chronic fibrosis at week 26 despite discontinuing the SiNP administration. Both sizes of SiNPs caused local inflammation in the lung and kidney and were detected in the serum and urine at week 13, and the 200 nm particles also localized to the kidney with no evidence of retention of the 300 nm particles. At week 26 there was some clearance of the 200 nm silica from the kidneys, and urinary levels of SiNPs were reduced but still significant in both the 200 and 300 nm exposed rats. CONCLUSIONS Inhaled SiNPs causes chronic kidney injury that progresses despite stopping the SiNP administration. These findings are consistent with the hypothesis that human exposure to amorphous silica nanoparticles found in burned sugarcane fields could have a participatory role in chronic kidney disease of unknown etiology.

Mesoamerican Nephropathy and Kidney Disease Progression: A Case Series of Individuals With Kidney Biopsies From Nicaragua and El Salvador.

Abstract: Mesoamerican Nephropathy and Kidney Disease Progression: A Case Series of Individuals With Kidney Biopsies From Nicaragua and El Salvador To the Editor: Mesoamerican nephropathy (MeN) is a chronic kidney disease affecting rural populations in Central America, especially sugarcane workers. Prospective studies and data regarding the natural history of the disease are scarce. We have previously described kidney morphology and biochemical characteristics of MeN in 2 case series, including a 1-to-2-year-long follow-up where mean estimated glomerular filtration rate (eGFR) decline was 4.4 mL/min/1.73 m per year. Another 2-year-long prospective study of young rural men with chronic kidney disease in Nicaragua without kidney biopsies reported an average eGFR decline of 3.8 mL/min/1.73 m. We now report eGFR trends in individuals with MeN with kidney biopsies over a period of 5-7 years. Participants from our previous kidney biopsy studies in El Salvador and Nicaragua were invited to participate in this long-term follow-up. Blood and urine samples were collected and the subset of participants from Nicaragua also completed a questionnaire regarding work history. eGFR was calculated using the CKD-EPI equation. Samples were analyzed at the same local laboratory as in the baseline study. Kidney biopsy findings at baseline are described in previous publications. In hypothesis-generating analyses, associations between baseline biopsy findings and progression rate were calculated using linear regression for continuous variables and 1-way analysis of variance for categorical variables (GraphPad). Ethics committees at Hospital Nacional Rosales, El Salvador (ACTA EXP. No 11/ 2016), the National Autonomous University of Nicaragua, Nicaragua (ACTA No 31 and 83), and Stockholm, Sweden (Dnr 2015/849-32) approved the study. New written informed consent was collected from Nicaragua participants. No new informed consent was required from the

Association between Water Intake, Chronic Kidney Disease, and Cardiovascular Disease: A Cross-Sectional Analysis of NHANES Data

Abstract: Background: Evidence from animal and human studies suggests a protective effect of higher water intake on kidney function and cardiovascular disease (CVD). Here t

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

Abstract: 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.

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

Abstract: 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.

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

Abstract: 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,