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Background: Mesoamerican nephropathy is a leading contributor to premature mortality in Central America. Efforts to identify the cause are hampered by difficulties in distinguishing associations with potential initiating factors from common exposures thought to exacerbate the progression of all forms of established chronic kidney disease (CKD). We explored evidence of disease onset or departure from the healthy estimated glomerular filtration rate distribution [departure from ∼eGFR(healthy)] in an at-risk population., Methods: Two community-based cohorts (adults aged 18-30 years, n = 351 and 420) from 11 rural communities in Northwest Nicaragua were followed up over 7 and 3 years respectively. We examined associations with both (i) incident CKD and (ii) the time point of departure from ∼eGFR(healthy), using a hidden Markov model., Results: CKD occurred in men only (male incidence rate: 0.7%/year). Fifty-three (out of 1878 visits, 2.7%) and 8 (out of 1067 visits, 0.8%) episodes of probable departure from ∼eGFR(healthy) occurred in men and women, respectively. Cumulative time in sugarcane work and symptoms of excess occupational sun exposure were associated with incident CKD. The same exposures were associated with probability of departure from ∼eGFR(healthy) in time-updated analyses along with measured and self-reported weight loss, nausea, vomiting and cramps, as well as non-steroidal anti-inflammatory drug use., Conclusions: CKD burden in this population is high and risk factors for established disease are occupational. Additionally, a syndrome suggesting an alternative exposure is associated with evidence of disease onset supporting a possible separate unknown initiating factor for which further investigation is needed. Interventions to reduce the impact of occupational risks should be pursued meanwhile., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Chronic kidney disease of uncertain aetiology (CKDu) is an advanced version of chronic kidney disease (CKD) which bears a high burden on the world health economy. More than 200 articles were analysed to understand the disease responsible for more than 30,000 deaths per year. CKDu is a non-communicable occupational disease that has a progressive deterioration of the kidney in the absence of CKD risk factors such as hypertension, diabetes and glomerulonephritis, while the diagnosis is only possible at the later stages when kidney function is no longer effective. Published evidence for the existence of CKDu was found for around 35 countries. This is a growing health issue in Asia, Central America, Africa and Middle East with identified hot spots. Despite many research studies over decades, the exact root causes are still uncertain. Six main suspected causative factors are identified. Those are heat stress, strenuous labour, dehydration, use of agrochemicals, exposure to heavy metals and the use of polluted water and agricultural lands. This review summarizes four key areas which are CKDu and its general medical background, worldwide prevalence, suspected causative factors and potential circumventing steps to mitigate against CKDu. The importance of further studies addressing early detection and surveillance methods, contribution of nephrotoxins in environmental health, soil chemistry on transporting nephrotoxins, geological parameters which influence the prevalence of the disease and other related sectors to overcome the mysterious nature is highlighted. Mitigation steps to lessen the burden of CKDu are also identified., (© 2022. The Author(s).)

Chronic kidney disease of unknown cause (CKDu), also known as Mesoamerican nephropathy, typically presents as an ischemic nephropathy with chronic tubulointerstitial fibrosis in normotensive patients, rapidly progressing to kidney failure. In this first-in-human, open-label, safety study, we followed 18 patients with CKDu (stages 3-5) for 36 months after receiving a single infusion of angiogenic/anti-fibrotic autologous adipose-derived stromal vascular fraction (SVF) cells into their kidneys bilaterally via renal artery catheterization. SVF therapy was safe and well tolerated. There were no SVF-related serious adverse events and no procedural complications. Color Doppler evaluation at 2 months demonstrated increased perfusion to the interlobar and/or arcuate artery levels in each kidney evaluated (36/36) with a reduction in resistance index at the hilar artery (35/36) kidneys. Beyond 12 months, patients with initial eGFR <30 mL/minute/1.73 m2 deteriorated, whereas those ≥30 mL/minute/1.73 m2 further sustained their renal function, suggesting a possible renal protective effect in that group., (© The Author(s) 2022. Published by Oxford University Press.)

Objective: Estimate agricultural work's effect on hemoglobin (Hgb) level in men. A negative effect may indicate presence of chronic kidney disease of uncertain etiology., Methods: We use Demographic and Health Surveys data from seven African and Asian countries and use matching to control for seven confounders., Results: On average, Hgb levels were 0.09 g/dL lower among agricultural workers compared with matched controls. Significant effects were observed in Ethiopia, India, Lesotho, and Senegal, with effects from 0.07 to 0.30 g/dL lower Hgb level among agricultural workers. The findings were robust to multiple control groups and a modest amount of unmeasured confounding., Conclusions: Men engaged in agricultural work in four of the seven countries studied have modestly lower Hgb levels. Our data support integrating kidney function assessments within Demographic and Health Surveys and other population-based surveys., Competing Interests: Conflict of Interest: None declared., (Copyright © 2022 American College of Occupational and Environmental Medicine.)

Abstract In the past decades, an epidemic of chronic kidney disease (CKD) has been associated with environmental and occupational factors (heat stress from high workloads in hot temperatures and exposure to chemicals, such as pesticides and metals), which has been termed CKD of non-traditional origin (CKDnt). This descriptive review aims to present recent evidence about heat stress, pesticides, and metals as possible causes of CKDnt and provide an overview of the related Brazilian regulation, enforcement, and health surveillance strategies. Brazilian workers are commonly exposed to extreme heat conditions and other CKDnt risk factors, including increasing exposure to pesticides and metals. Furthermore, there is a lack of adequate regulation (and enforcement), public policies, and strategies to protect the kidney health of workers, considering the main risk factors. CKDnt is likely to be a significant cause of CKD in Brazil, since CKD’s etiology is unknown in many patients and several conditions for its development are present in the country. Further epidemiological studies may be conducted to explore causal associations and estimate the impact of heat, pesticides, and metals on CKDnt in Brazil. Moreover, public policies should prioritize reducing workers´ exposure and promoting their health and safety.