Occupational heat exposure and chronic kidney disease risk under climate warming: a retrospective cohort study of petrochemical workers with mechanistic insights.

Mechanisms linking occupational heat exposure with chronic diseases have been proposed. However, evidence on occupational heat exposure and cancer risk is limited. We evaluated occupational heat exposure and female breast cancer risk in a large Spanish case-control study. We enrolled 1,738 breast cancer cases and 1,910 frequency-matched population controls. A Spanish job-exposure matrix, MatEmEsp, was used to assign estimates of the proportion of workers exposed (P ≥ 25% for at least 1 year) and work time with heat stress (wet bulb globe temperature ISO 7243) for each occupation. We used three exposure indices: ever versus never exposed, lifetime cumulative exposure, and duration of exposure (years). We estimated ORs and 95% confidence intervals (CI), applying a lag period of 5 years and adjusting for potential confounders. Ever occupational heat exposure was associated with a moderate but statistically significant higher risk of breast cancer (OR 1.22; 95% CI, 1.01-1.46), with significant trends across categories of lifetime cumulative exposure and duration (P trend = 0.01 and 0.03, respectively). Stronger associations were found for hormone receptor-positive disease (OR ever exposure = 1.38; 95% CI, 1.12-1.67). We found no confounding effects from multiple other common occupational exposures; however, results attenuated with adjustment for occupational detergent exposure. This study provides some evidence of an association between occupational heat exposure and female breast cancer risk. Our results contribute substantially to the scientific literature. Further investigations are needed considering multiple occupational exposures.

BackgroundIndividuals in the workplace are exposed to various environments, tasks, and schedules. Previous studies have indicated a link between occupational exposures and an increased risk of chronic kidney disease (CKD). However, the social conditions of the work environment may also be a crucial contributing factor to CKD. Furthermore, individuals may encounter multiple occupational-related risk factors simultaneously, underscoring the importance of investigating the joint risk of different working conditions on CKD.MethodsA prospective analysis of 65,069 UK Biobank participants aged 40 to 69 years without CKD at baseline (2006–2010) was performed. A self-administered questionnaire assessed working conditions and a working conditions risk score were developed. Participants who answered “sometimes” or “often” exposure to occupational heat or occupational secondhand cigarette smoke; involved in shift work or heavy workloads (“usually” or “always”), were grouped as high-risk working conditions. Each working condition was scored as 1 if grouped as high-risk, and 0 if not. The working conditions risk score was equal to the sum of these four working conditions. Cox proportional hazard regression models were used to estimate the associations between working conditions and CKD incidence.ResultsThe mean follow-up time was 6.7 years. After adjusting for demographic, lifestyle, and working time factors, the hazard ratios for the development of CKD for heavy workloads, shift work, occupational secondhand cigarette smoke exposure, and occupational heat exposure were 1.24 (95%CI = 1.03, 1.51), 1.33 (95%CI = 1.10, 1.62), 1.13 (95%CI = 1.01, 1.26), 1.11 (95%CI = 0.99, 1.24), respectively. The risk of CKD was found to be significantly associated with an increasing working conditions risk score. Individuals with a working conditions risk score of 4 had an 88.0% (95% CI = 1.05, 3.35) higher risk of developing CKD when compared to those with a working conditions risk score of 0.ConclusionsAdverse working conditions, particularly when considered in combination, can significantly elevate the risk of chronic kidney disease (CKD). These results provide a reference for implementing measures to prevent CKD.

Published literature suggests that sleep duration and quality may be affected in adults with chronic kidney disease. However, the relationship between these two entities remains a matter of debate. The objective of this systematic review and meta-analysis is to assess the effect of sleep duration and quality on chronic kidney disease. A systematic review of the Medline/PubMed, Embase, Cochrane Library, and CINAHL databases was conducted for articles pertaining to the association between sleep duration and quality on chronic kidney disease. The main outcome was the hazard/risk ratio of chronic kidney disease in patients of varying sleep durations and quality. In total, 42 studies (2613971 patients) with a mean age of 43.55±14.01 years were included in the meta-analysis. Compared with a reference range of 7 to 8 hours of sleep, short sleep durations of ≤4 hours (RR 1.41, 95% CI: 1.16 to 1.71, P<0.01), ≤5 hours (RR 1.46, 95% CI: 1.22 to 1.76, P<0.01), ≤6 hours (RR 1.18, 95% CI: 1.09 to 1.29, P<0.01), and ≤7 hours (RR 1.19, 95% CI: 1.12 to 1.28, P<0.01) were significantly associated with an increased risk of incident chronic kidney disease. Long sleep durations of ≥8 hours (RR 1.15, 95% CI: 1.03 to 1.28, P<0.01) and ≥9 hours (RR 1.46, 95% CI: 1.28 to 1.68, P<0.01) were also significantly associated with an increased risk of incident chronic kidney disease. Meta-regression did not find any significant effect of age, gender, geographical region, and BMI and an association with sleep duration and risk of incident chronic kidney disease. Both short and long sleep durations were significantly associated with a higher risk of chronic kidney disease. Interventions targeted toward achieving an optimal duration of sleep may reduce the risk of incident chronic kidney disease.

Occupational heat exposure and stomach cancer risk in a pooled analysis of two Spanish case-control studies in the stomach cancer pooling project - StoP consortium.

Occupational heat exposure is linked to the development of kidney injury and disease in individuals who frequently perform physically demanding work in the heat. For instance, in Central America, an epidemic of chronic kidney disease of nontraditional origin (CKDnt) is occurring among manual laborers, whereas potentially related epidemics have emerged in India and Sri Lanka. There is growing concern that workers in the United States suffer with CKDnt, but reports are limited. One of the leading hypotheses is that repetitive kidney injury caused by physical work in the heat can progress to CKDnt. Whether heat stress is the primary causal agent or accelerates existing underlying pathology remains contested. However, the current evidence supports that heat stress induces tubular kidney injury, which is worsened by higher core temperatures, dehydration, longer work durations, muscle damaging exercise, and consumption of beverages containing high levels of fructose. The purpose of this narrative review is to identify occupations that may place US workers at greater risk of kidney injury and CKDnt. Specifically, we reviewed the scientific literature to characterize the demographics, environmental conditions, physiological strain (i.e., core temperature increase, dehydration, heart rate), and work durations in sectors typically experiencing occupational heat exposure, including farming, wildland firefighting, landscaping, and utilities. Overall, the surprisingly limited available evidence characterizing occupational heat exposure in US workers supports the need for future investigations to understand this risk of CKDnt.

Background and aim: Heat exposures occur frequently in many indoor and outdoor occupations. In our previous work, we observed some evidence for a positive association of occupational heat exposure and breast cancer risk. Here we seek to examine potential associations with prostate cancer risk in a large multi-country study. Methods: We performed a pooled analysis of data from 3,175 histologically confirmed prostate cancer cases and 3,529 frequency-matched controls from studies in three different countries, Spain, France, and Canada. The Finnish job exposure matrix, FINJEM, was used to apply estimates of occupational heat exposure to the lifetime occupational history of participants. Three main exposure indices were used: ever vs. never exposed, lifetime cumulative exposure (heat stress years) and duration of exposure (years) with a lag period of 5 years. We estimated odds ratios (ORs) and 95% confidence intervals (CIs), using conditional logistic regression models stratified by 5-year age groups and study and adjusted for potential confounders. Results: A total of 32% of cases and 33% of controls were classified as being ever occupationally exposed to heat. Highest heat exposed occupations included ore and metal furnace operators, firefighters, and bakers. We found no evidence for an association of ever occupational heat exposure and prostate cancer risk (OR 0.92; 95% CI 0.83, 1.03). There were also no associations observed in the highest categories of lifetime cumulative exposure or duration, and there was no evidence for a trend. Results did not change when stratifying by Gleason scores. When analysing the Spanish case-control study separately using a Spanish job exposure matrix developed for local working conditions, some odds ratios were elevated, though results were imprecise. Conclusions: Findings from this pooled study have provided no strong evidence for an association between occupational heat exposure and prostate cancer risk. Keywords: prostate cancer, occupational exposures, heat, pooled analysis

BackgroundStillbirth is a devastating adverse pregnancy outcome that may occur without any obvious reason or may occur in the context of fetal growth restriction, preeclampsia, or other obstetric complications. There is increasing evidence that women who experience stillbirths are at greater risk of long-term cardiovascular disease, but little is known about their risk of chronic kidney disease and end-stage renal disease. We conducted the largest study to date to investigate the subsequent risk of maternal chronic kidney disease and end-stage renal disease following stillbirth.ObjectiveTo identify whether pregnancy complicated by stillbirth is associated with subsequent risk of maternal chronic kidney disease and end-stage renal disease, independent of underlying medical or obstetric comorbidities.Study Design/MethodsWe conducted a population-based cohort study using nationwide data from the Swedish Medical Birth Register, National Patient Register, and Swedish Renal Register. We included all women who had live births and stillbirths from 1973 to 2012, with follow-up to 2013. Women with preexisting renal disease were excluded. Cox proportional hazard regression models were used to estimate adjusted hazard ratios and 95% confidence intervals for associations between stillbirth and maternal chronic kidney disease and end-stage renal disease respectively. We controlled for maternal age, year of delivery, country of origin, parity, body mass index, smoking, gestational diabetes, preeclampsia, and small for gestational age deliveries. Women who had a history of medical comorbidities, which may predispose to renal disease (prepregnancy cardiovascular disease, hypertension, diabetes, lupus, systemic sclerosis, hemoglobinopathy, or coagulopathy), were excluded from the main analysis and examined separately.ResultsThere were 1,941,057 unique women who had 3,755,444 singleton pregnancies, followed up over 42,313,758 person-years. The median follow-up time was 20.7 years (interquartile range, 9.9–30.0 years). 13,032 women (0.7%) had at least 1 stillbirth. Women who had experienced at least 1 stillbirth had a greater risk of developing chronic kidney disease (adjusted hazard ratio, 1.26; 95% confidence interval, 1.09–1.45) and end-stage renal disease (adjusted hazard ratio, 2.25; 95% confidence interval, 1.55–3.25) compared with women who only had live births. These associations persisted after removing all stillbirths that occurred in the context of preeclampsia, and small for gestational age or congenital malformations (for chronic kidney disease, adjusted hazard ratio, 1.33; 95% confidence interval, 1.13–1.57; for end-stage renal disease, adjusted hazard ratio, 2.95; 95% confidence interval, CI 1.86–4.68). There was no significant association observed between stillbirth and either chronic kidney disease or end-stage renal disease in women who had preexisting medical comorbidities (chronic kidney disease, adjusted hazard ratio, 1.13; 95% confidence interval, 0.73–1.75 or end-stage renal disease, adjusted hazard ratio, 1.49; 95% confidence interval, 0.78–2.85).ConclusionWomen who have a history of stillbirth may be at increased risk of chronic kidney disease and end-stage renal disease compared with women who have only had live births. This association persists independently of preeclampsia, and small for gestational age, maternal smoking, obesity, and medical comorbidities. Further research is required to determine whether affected women would benefit from closer surveillance and follow-up for future renal disease.

Abstract: Objectives: This study aimed to map the distribution of nephrolithiasis’ environmental risk factors (occupational heat and heavy metal exposure and ambient seasonal temperature) and to assess the correlations of these exposures with the best estimates of the reported nephrolithiasis incidence in Canada. Methods: The regional average heat burden was defined as the mean temperature in the hottest three months of the year for 2020, 2021, and 2022. The employment rates in the top five industries with occupational heavy metal (cadmium, lead, and arsenic) and heat exposure were obtained from the Statistics Canada 2021 database. Statistical significance was calculated based on the 95% confidence interval difference from the null hypothesis. Correlation analysis was performed between our rates of nephrolithiasis risk factors and previously published estimates of the stone incidence: kidney stone interventions and acute kidney stone event rates. Results: Lower-latitude provinces had higher overall mean temperatures in 2020 to 2022, with Ontario, Manitoba, and Prince Edward Island having the highest seasonal heat burdens, in this order. Nunavut had the lowest rate of occupational heat exposure, while the remaining regions had similar rates. Yukon, the Northwest Territories, and Nunavut had significantly higher rates of occupational heavy metal exposure compared to the remaining regions. The ambient temperature and occupation heavy metal and heat exposure showed no significant correlation with the estimates of the stone incidence. Conclusions: The occupational heat exposure was relatively similar between regions. Northern Canada had higher occupational heavy metal exposure compared to other regions. Occupational exposures and temperature variations were not associated with the nephrolithiasis incidence in Canada.

Does Inflammation Fuel the Fire in CKD?

The association between abdominal visceral adipose tissue and the risk of incident chronic kidney disease according to body mass index in the Asian population, remains unclear. We evaluated the impact of abdominal adiposity stratified by body mass index on the risk of incident chronic kidney disease. A cohort study included 11,050 adult participants who underwent health check-ups and re-evaluated the follow-up medical examination at a single university-affiliated healthcare center. Cross-sectional abdominal adipose tissue areas were measured using computed tomography. The primary outcome was progression to chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73m2). The highest quartile of visceral adipose tissue was used for the cut-off of central obesity. During the mean of 5.6 follow-up years, 104 incident chronic kidney disease cases were identified. The risk for chronic kidney disease incidence was significantly increased in the 3rd and 4th quartile ranges of visceral adipose tissue [hazard ratio (95% confidence interval)]: 4.59 (1.48-14.30) and 7.50 (2.33-24.20), respectively. In the analysis stratified by body mass index, the chronic kidney disease incidence risk was increased in the highest quartile range of visceral adipose tissue in the normal weight group: 7.06 (1.35-37.04). However, there was no significant relationship between visceral adipose tissue and chronic kidney disease in the obese group. Compared to the subjects with normal weight and absent central obesity, the hazard ratio for chronic kidney disease incidence was 2.32 (1.26-4.27) among subjects with normal weight and central obesity and 1.81 (1.03-3.15) among subjects with obesity and central obesity. Visceral adipose tissue was a significant risk factor for subsequent chronic kidney disease progression, and the association was identified only in the normal weight group. Normal-weight central obesity was associated with excess risk of chronic kidney disease, similar to the risk in the group with obesity and central obesity.

Gestational exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse fetal kidney outcomes. However, details regarding timing, specific NSAIDs, and long-term childhood kidney outcomes are limited. To evaluate the association between gestational exposure to NSAIDs and the risk of chronic kidney disease (CKD) in childhood. This national cohort study assessed 1 025 255 children born alive in Taiwan from January 1, 2007, to December 31, 2017, with follow-up until December 31, 2021. Children without valid maternal-child linkage and with incomplete birth information were excluded. Data analysis was performed from November 30, 2023, to April 30, 2024. Maternal prescriptions for NSAIDs from the last menstrual period to birth. The main outcome was childhood CKD, including congenital anomalies of the kidney and urinary tract and other kidney diseases. Cox proportional hazards regression models with stabilized inverse probability of treatment weighting (weighted hazard ratio [wHR]) and a robust sandwich estimator were used to estimate the relative risk of NSAID exposure in pregnancy, adjusted for newborn characteristics. This study included 163 516 singleton-born children (24.0%) whose mothers (mean [SD] age at birth of child, 31.25 [4.92] years) used at least 1 dispensing of an NSAID during pregnancy. Gestational NSAID exposure was significantly associated with a higher risk of childhood CKD (wHR, 1.10; 95% CI, 1.05-1.15). No association was observed between NSAID use and fetal nephrotoxicity in sibling comparisons. Elevated risks were revealed for exposure during the second trimester (wHR, 1.19; 95% CI, 1.11-1.28) and the third trimester (wHR, 1.12; 95% CI, 1.03-1.22) in singleton-born children. Specific NSAID exposures associated with higher CKD risk included indomethacin (wHR, 1.69; 95% CI, 1.10-2.60) and ketorolac (wHR, 1.28; 95% CI, 1.01-1.62) in the first trimester, diclofenac (wHR, 1.27; 95% CI, 1.13-1.42) and mefenamic acid (wHR, 1.29; 95% CI, 1.15-1.46) in the second trimester, and ibuprofen (wHR, 1.34; 95% CI, 1.07-1.68) in the third trimester. In this study, gestational exposure to NSAIDs was not associated with a substantial increase in the risk of childhood CKD when comparing between siblings. However, the findings underscore the need for caution when prescribing NSAIDs during pregnancy, particularly indomethacin and ketorolac in the first trimester, mefenamic acid and diclofenac in the second trimester, and ibuprofen in the third trimester, to ensure the safety of the offspring's kidneys.

Preeclampsia (PE) has been disproportionately prevalent in developing countries and constitutes a leading cause of maternal mortality, and also has long-term impacts, including renal consequences.This study aimed to explore the risk of persistent hypertension and kidney failure in early-onset PE (EOP) and late-onset PE (LOP) in the five years after delivery. This retrospective cohort study included women with a prior history of severe PEor normotensive pregnancy admitted to tertiary hospitals in Indonesia. The blood pressure, body mass index (BMI), urea, creatinine serum, and protein urine were analyzed, and the risk of chronic kidney disease (CKD) after five years was performed using theKidney Disease Improvement Global Outcomes (KDIGO) classification. Twenty-seven EOP, 35 LOP, and 30 normotensive cases were included. Mean blood pressure after five years was recorded as 115.6 ± 14.25 mmHg in the normotensive group, 131.82 ± 19.34 mmHg in the LOP group, and 154.96 ± 23.48 mmHg in the EOP group. According to the KDIGO classification, the normotensive group had an average 10% risk of CKD, but severe PE had a risk of CKD greater than 90%. In the severe PE group, the risk of CKD was 20.94 times higher compared to normotensive women (OR 20.94; 95% CI 2.67-163.72, p = 0.004). The risk of CKD in the EOP group was 6.75 times higher than in the LOP group (OR 6.75; 95% CI 2.19-20.76, p = 0.001), whereas persistent hypertension in the EOP group was 5.78 times higher than in the LOP group (OR 5.78; 95% CI 1.91-17.395, p = 0.002). PE women have a higher risk of CKD than normotensive women. Women with a history of EOP are more likely to develop persistent hypertension and CKD than women with a prior LOP history.

Lifelong therapy with mineralocorticoid receptor antagonists (MRAs) or surgical adrenalectomy are the recommended treatments for primary aldosteronism (PA). Whether these treatments mitigate the risk for kidney disease remains unknown. We performed a retrospective cohort study of patients with PA treated with MRAs (N=400) or surgical adrenalectomy (N=120) and age- and estimated glomerular filtration rate-matched patients with essential hypertension (N=15 474) to determine risk for chronic kidney disease and longitudinal estimated glomerular filtration rate decline. Despite similar blood pressures, patients with PA treated with MRAs had a higher risk for incident chronic kidney disease compared with essential hypertension patients (adjusted hazard ratio, 1.63; 95% confidence interval, 1.33-1.99). Correspondingly, the adjusted annual decline in estimated glomerular filtration rate was greater in PA patients treated with MRAs compared with essential hypertension patients (-1.6; 95% confidence interval, -1.4 to -1.8 versus -0.9; 95% confidence interval, -0.9 to -1.0 mL/min per 1.73 m2/y; P<0.001). In contrast, patients with unilateral PA treated with surgical adrenalectomy had no significant difference in risk for incident chronic kidney disease or in an annual decline in estimated glomerular filtration rate compared with essential hypertension patients. Among PA patients with diabetes mellitus treated with MRAs, there was a higher risk for incident albuminuria compared with essential hypertension (adjusted hazard ratio, 2.52; 95% confidence interval, 1.28-4.96). MRA therapy in PA is associated with higher risk for developing chronic kidney disease when compared with essential hypertension, and surgical adrenalectomy may mitigate this risk. When possible, curative surgical adrenalectomy may be superior to lifelong MRA therapy in preventing kidney disease in PA.

The effect of dyslipidemia on kidney disease outcomes has been inconclusive, and it requires further clarification. Therefore, we aimed to investigate the effects of genetic factors on the association between dyslipidemia and the risk of chronic kidney disease (CKD) using polygenic risk score (PRS). We analyzed data from 373,523 participants from the UK Biobank aged 40-69 years with no history of CKD. Baseline data included plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride, as well as genome-wide genotype data for PRS. Our primary outcome, incident CKD, was defined as a composite of estimated glomerular filtration rate < 60 ml/min/1.73 m2 and CKD diagnosis according to International Classification of Disease-10 codes. The effects of the association between lipid levels and PRS on incident CKD were assessed using the Cox proportional hazards model. To investigate the effect of this association, we introduced multiplicative interaction terms into a multivariate analysis model and performed subgroup analysis stratified by PRS tertiles. In total, 4,424 participants developed CKD. In the multivariable analysis, PRS was significantly predictive of the risk of incident CKD as both a continuous variable and a categorized variable. In addition, lower total cholesterol, LDL-C, HDL-C, and higher triglyceride levels were significantly associated with the risk of incident CKD. There were interactions between triglycerides and intermediate and high PRS, and the interactions were inversely associated with the risk of incident CKD. This study showed that PRS presented significant predictive power for incident CKD and individuals in the low-PRS group had a higher risk of triglyceride-related incident CKD.

BackgroundSocioeconomic status (SES) and cardiorespiratory fitness (CRF) are each independently associated with chronic kidney disease. The interplay among SES, CRF, and chronic kidney disease is not well understood. We aimed to evaluate the separate and joint associations of SES and CRF with chronic kidney disease risk in a cohort of Caucasian men. MethodsIn 2099 men aged 42-61 years with normal kidney function at baseline, SES was self-reported and CRF was directly measured using a respiratory gas exchange analyzer during cardiopulmonary exercise testing. Hazard ratios (HRs) (95% confidence interval) were estimated for chronic kidney disease. ResultsA total of 197 chronic kidney disease events occurred during a median follow-up of 25.8 years. Comparing low versus high SES, the multivariable-adjusted HR (95% confidence interval) for chronic kidney disease was 1.55 (1.06-2.25), which remained consistent on further adjustment for CRF 1.53 (1.06-2.22). Comparing high versus low CRF, the multivariable-adjusted HR for chronic kidney disease was 0.66 (0.45-0.96), which persisted on further adjustment for SES 0.67 (0.46-0.97). Compared with high SES-high CRF, low SES-low CRF was associated with an increased risk of chronic kidney disease 1.88 (1.23-2.87), with no evidence of an association for low SES-high CRF and chronic kidney disease risk 1.32 (0.85-2.05). Positive additive (relative excess risk due to interaction = 0.31) and multiplicative (ratio of HRs = 1.14) interactions were found between SES and CRF in relation to chronic kidney disease risk. ConclusionsIn middle-aged and older males, SES and CRF are each independently associated with risk of incident chronic kidney disease. There exists an interplay among SES, CRF and chronic kidney disease risk, with high CRF levels appearing to offset the increased chronic kidney disease risk related to low SES.