Assessing Unconventional Oil and Gas Exposure in the Appalachian Basin: Comparison of Exposure Surrogates and Residential Drinking Water Measurements.

Health studies report associations between metrics of residential proximity to unconventional oil and gas (UOG) development and adverse health endpoints. We investigated whether exposure through household groundwater is captured by existing metrics and a newly developed metric incorporating groundwater flow paths. We compared metrics with detection frequencies/concentrations of 64 organic and inorganic UOG-related chemicals/groups in residential groundwater from 255 homes (Pennsylvania n = 94 and Ohio n = 161). Twenty-seven chemicals were detected in ≥20% of water samples at concentrations generally below U.S. Environmental Protection Agency standards. In Pennsylvania, two organic chemicals/groups had reduced odds of detection with increasing distance to the nearest well: 1,2-dichloroethene and benzene (Odds Ratio [OR]: 0.46, 95% confidence interval [CI]: 0.23-0.93) and m- and p-xylene (OR: 0.28, 95% CI: 0.10-0.80); results were consistent across metrics. In Ohio, the odds of detecting toluene increased with increasing distance to the nearest well (OR: 1.48, 95% CI: 1.12-1.95), also consistent across metrics. Correlations between inorganic chemicals and metrics were limited (all |ρ| ≤ 0.28). Limited associations between metrics and chemicals may indicate that UOG-related water contamination occurs rarely/episodically, more complex metrics may be needed to capture drinking water exposure, and/or spatial metrics in health studies may better reflect exposure to other stressors.

Impacts of long-term ambient particulate matter and gaseous pollutants on circulating biomarkers of inflammation in male and female health professionals.

BACKGROUND: Systemic inflammation may serve as a biological mechanism linking air pollution to poor health but supporting evidence from studies of long-term pollutant exposure and inflammatory cytokines is inconsistent. OBJECTIVE: We studied associations between multiple particulate matter (PM) and gaseous air pollutants and pro- and anti-inflammatory cytokines within two nationwide cohorts of men and women. METHODS: Data were obtained from 16,151 women in the Nurses' Health Study and 7,930 men in the Health Professionals' Follow-up Study with at least one measure of circulating adiponectin, C-Reactive Protein (CRP), Interleukin-6 (IL-6) or soluble tumor necrosis-factor receptor-2 (sTNFR-2). Exposure to PM with aerodynamic diameter ≤2.5, 2.5-10, and ≤10 µm (PM2.5, PM2.5-10, PM10) and nitrogen dioxide (NO2) was estimated using spatio-temporal models and were linked to participants' addresses at the time of blood draw. Averages of the 1-, 3-, and 12-months prior to blood draw were examined. Associations between each biomarker and pollutant were estimated from linear regression models adjusted for individual and contextual covariates. RESULTS: In adjusted models, we observed a 2.72% (95% CI: 0.43%, 5.95%), 3.11% (-0.12%, 6.45%), and 3.67% (0.19%, 7.26%) increase in CRP associated with a 10 µg/m3 increase in 1-, 3-, and 12- month averaged NO2 in women. Among men, there was a statistically significant 5.96% (95% CI: 0.07%, 12.20%), 6.99% (95% CI: 0.29%, 14.15%), and 8.33% (95% CI: 0.35%, 16.94%) increase in CRP associated with a 10 µg/m3 increase in 1-, 3-, and 12-month averaged PM2.5-10, respectively. Increasing PM2.5-10 was associated with increasing IL-6 and sTNFR-2 among men over shorter exposure durations. There were no associations with exposures to PM2.5 or PM10, or with adiponectin. Findings were robust to sensitivity analyses restricting to disease-free controls and non-movers. CONCLUSIONS: Across multiple long-term pollutant exposures and inflammatory markers, associations were generally weak. Focusing on specific pollutant-inflammatory mechanisms may clarify pathways.

A Multiregion Analysis of Shale Drilling Activity and Rates of Sexually Transmitted Infections in the United States.

BACKGROUND: Fossil fuel extraction from deep shale rock formations using new drilling technologies such as hydraulic fracturing has rapidly increased in the Unites States over the past decade. Increases in nonlocal, specialized workers to meet the demands of this complex industry have been suggested to influence the rates of sexually transmitted infections (STIs) in counties with shale drilling activity; these associations may vary geographically. In this multiregion analysis, we examine the associations between shale drilling activity and rates of 3 reportable STIs in Colorado, North Dakota, and Texas, states with active shale drilling. METHODS: We obtained annual reported rates of chlamydia, gonorrhea, and syphilis from the Centers for Disease Control and Prevention, number of active shale wells from Enverus (formerly known as DrillingInfo), and sociodemographic covariates from the US Census Bureau. We used multivariable mixed-effects Poisson regression modeling to estimate rate ratios (RR) with 95% confidence intervals (CIs) adjusted for potential confounders and secular trends. RESULTS: In Texas, county-years with high drilling activity had 10% increased rates of chlamydia (RR, 1.10; 95% CI, 1.04-1.17) and 15% increased rates of gonorrhea (RR, 1.15; 95% CI, 1.04-1.28), compared with county-years with no drilling. No statistically significant associations were reported for syphilis or for any STIs in Colorado or North Dakota. CONCLUSIONS: Associations between shale drilling and chlamydia and gonorrhea in Texas may reflect increased risk in areas with higher drilling activity and a greater number of major metropolitan areas. Interstate differences highlight the need for local epidemiology to prioritize community health policies.

A community-based evaluation of proximity to unconventional oil and gas wells, drinking water contaminants, and health symptoms in Ohio.

Over 4 million Americans live within 1.6 km of an unconventional oil and gas (UO&G) well, potentially placing them in the path of toxic releases. We evaluated relationships between residential proximity to UO&G wells and (1) water contamination and (2) health symptoms in an exploratory study. We analyzed drinking water samples from 66 Ohio households for 13 UO&G-related volatile organic compounds (VOCs) (e.g., benzene, disinfection byproducts [DBPs]), gasoline-range organics (GRO), and diesel-range organics. We interviewed participants about health symptoms and calculated metrics capturing proximity to UO&G wells. Based on multivariable logistic regression, odds of detection of bromoform and dibromochloromethane in surface water decreased significantly as distance to nearest UO&G well increased (odds ratios [OR]: 0.28-0.29 per km). Similarly, distance to nearest well was significantly negatively correlated with concentrations of GRO and toluene in ground water (rSpearman: -0.40 to -0.44) and with concentrations of bromoform and dibromochloromethane in surface water (rSpearman: -0.48 to -0.50). In our study population, those with higher inverse-distance-squared-weighted UO&G well counts within 5 km around the home were more likely to report experiencing general health symptoms (e.g. stress, fatigue) (OR: 1.52, 95%CI: 1.02-2.26). This exploratory study, though limited by small sample size and self-reported health symptoms, suggests that those in closer proximity to multiple UO&G wells may be more likely to experience environmental health impacts. Further, presence of brominated DBPs (linked to UO&G wastewater) raises the question of whether UO&G activities are impacting drinking water sources in the region. The findings from this study support expanded studies to advance knowledge of the potential for water quality and human health impacts; such studies could include a greater number of sampling sites, more detailed chemical analyses to examine source attribution, and objective health assessments.

Association of Residential Exposure to Hazardous Air Pollutants with Risk of Non-Hodgkin Lymphoma and Multiple Myeloma.

BACKGROUND: Certain hazardous air pollutants (HAP) are known or suspected to pose immunological or cancer risk to humans, but evidence is limited from the general population. METHODS: We assessed associations between residential exposure to HAPs at the census tract level and incident non-Hodgkin lymphoma (NHL) and multiple myeloma in the Nurses' Health Study (NHS, 1986-2012) and NHSII (1989-2019). We used the covariate-adjusted proportional hazards model to estimate hazard ratios (HR) of NHL, major NHL subtypes, and multiple myeloma per interquartile range increase in exposure to a given HAP and pooled the cohort-specific estimates using fixed-effects meta-analyses. RESULTS: There were 810 NHL and 158 multiple myeloma cases in NHS (1,700,707 person-years) and 379 NHL and 59 multiple myeloma cases in NHSII (2,820,772 person-years). Most HRs approximated unity. Meta-analyses did not show consistent evidence of associations between any HAP exposure and risk of NHL or multiple myeloma. CONCLUSIONS: Exposure to HAPs was not consistently associated with risks of NHL or multiple myeloma in these nationwide prospective cohorts of women. IMPACT: This is the first nationwide study assessing associations between residential HAP exposures and risk of lymphoid malignances in prospective cohorts and focuses on women, who have frequently been underrepresented in (primarily occupational) studies of exposure to HAPs.

Residential Green Space and Cognitive Function in a Large Cohort of Middle-Aged Women.

Importance: Green space can decelerate cognitive decline by supporting physical activity, psychological restoration, or reducing exposure to air pollution. However, existing studies on the association of green space with cognitive decline are limited. Objective: To examine whether residential green space was associated with cognitive function in middle-aged women. Design, Setting, and Participants: Starting in 1989, the Nurses' Health Study II enrolled 116 429 female nurses aged 25 to 42 years residing in the US. In 2014 to 2016, 40 082 women were invited to complete an online cognitive battery. This cohort study analyzed women who had data on both green space exposure and cognitive measures. Data analysis was conducted from June to October 2021. Exposures: Residential exposure to green space was assessed using the Normalized Difference Vegetation Index, a satellite-derived indicator of the quantity of ground vegetation. Landsat satellite data at 270-m and 1230-m buffers around each participants' residential addresses in 2013 were used. Main Outcomes and Measures: In 2014 to 2016, cognitive function was measured using a self-administered online battery, the Cogstate Brief Battery, consisting of 4 tasks measuring psychomotor speed, attention, learning, and working memory; 3 composite scores, averaging together all tasks, psychomotor speed/attention, and learning/working memory, were created. In addition, the study evaluated potential mediators, including air pollution, depression, and physical activity. Results: The analytical sample included 13 594 women, of whom 13 293 (98%) were White. Mean (SD) age was 61.2 (4.6) years. In models adjusted for age at assessment, race, childhood, adulthood, and neighborhood socioeconomic status, green space was associated with higher scores on the global Cogstate composite (mean difference per IQR in green space, 0.05; 95% CI, 0.02 to 0.07), and psychomotor speed/attention (mean difference in score, 0.05 standard units; 95% CI, 0.02 to 0.08). This difference in scores is similar to the difference observed in women 1 year apart in age in the data. By contrast, there was no association between green space and learning/working memory (mean difference, 0.0300; 95% CI, -0.0003 to 0.0500). Conclusions and Relevance: These findings suggest that increasing residential green space may be associated with modest benefits in cognition in middle-aged women.

Impact of neighborhood socioeconomic status, income segregation, and greenness on blood biomarkers of inflammation.

BACKGROUND: Neighborhood deprivation is linked with inflammation, which may explain poorer health across populations. Behavioral risk factors are assumed to largely mediate these relationships, but few studies have examined this. We examined three neighborhood contextual factors that could exert direct effects on inflammation: (1) neighborhood socioeconomic status, (2) an index of concentration at extremes (that measures segregation), and (3) surrounding vegetation (greenness). METHODS: Using blood samples and addresses collected from prospective cohorts of 7,930 male (1990-1994) and 16,183 female (1986-1990) health professionals with at least one inflammatory marker, we prospectively linked neighborhood contextual factors to inflammatory biomarkers (adiponectin, C-reactive protein, interleukin-6, soluble tumor necrosis factor receptor-2). Log-transformed, z-scaled component measures were used to calculate an inflammation score. Neighborhood socioeconomic status and index of concentration of extremes were obtained from the 1990 decennial census and linked to participant addresses. Surrounding greenness was assessed from satellite data and focal statistics were applied to generate exposures within 270 m and 1230 m of the participants' address. We fit multiple linear regression models adjusting for demographic, clinical, and behavioral risk factors. RESULTS: Higher neighborhood socioeconomic status was associated with lower inflammation score in women (ß for interquartile range increase = -27.7%, 95% CI: -34.9%, -19.8%) and men (ß = -21.2%, 95% CI: -31.0%, -10.1%). Similarly, participants in neighborhoods with higher concentrations of high-income households were associated with lower inflammation score in women (ß = -27.8%, 95% CI: -35.8%, -18.7%) and men (ß = -16.4%, 95% CI: -29.7%, -0.56%). Surrounding greenness within 270 m of each participant's address was associated with lower inflammation score in women (ß = -18.9%, 95% CI: -28.9%, -7.4%) but not men. Results were robust to sensitivity analyses to assess unmeasured confounding and selection bias. DISCUSSION: Our findings support the hypothesis that adverse neighborhood environments may contribute to inflammation through pathways independent of behavioral risk factors, including psychosocial stress and toxic environments.

Associations between Nature Exposure and Health: A Review of the Evidence.

There is extensive empirical literature on the association between exposure to nature and health. In this narrative review, we discuss the strength of evidence from recent (i.e., the last decade) experimental and observational studies on nature exposure and health, highlighting research on children and youth where possible. We found evidence for associations between nature exposure and improved cognitive function, brain activity, blood pressure, mental health, physical activity, and sleep. Results from experimental studies provide evidence of protective effects of exposure to natural environments on mental health outcomes and cognitive function. Cross-sectional observational studies provide evidence of positive associations between nature exposure and increased levels of physical activity and decreased risk of cardiovascular disease, and longitudinal observational studies are beginning to assess long-term effects of nature exposure on depression, anxiety, cognitive function, and chronic disease. Limitations of current knowledge include inconsistent measures of exposure to nature, the impacts of the type and quality of green space, and health effects of duration and frequency of exposure. Future directions include incorporation of more rigorous study designs, investigation of the underlying mechanisms of the association between green space and health, advancement of exposure assessment, and evaluation of sensitive periods in the early life-course.

Sustaining planetary health through systems thinking: Public health's critical role.

Understanding and responding to adverse human health impacts of global environmental change will be a major priority of 21st century public health professionals. The emerging field of planetary health aims to face this challenge by studying and promoting policies that protect the health of humans and of the Earth's natural systems that support them. Public health, drawing on its experience of guiding policies to improve population health, has contributed to planetary health's development. Yet, few public health practitioners are familiar with planetary health's systems-oriented approaches for understanding relationships between economic development, environmental degradation, and human health. In this narrative review, we present key planetary health concepts and show how systems thinking has guided its development. We discuss historical approaches to studying impacts of economic development on human health and the environment. We then review novel conceptual frameworks adopted by planetary health scientists to study and forecast impacts of policies that influence human health and Earth's natural systems at varying spatiotemporal scales. We conclude by presenting examples of how applying the "Doughnut" model (an economic framework where the needs of people are met without overshooting the world's ecological limits) could guide policies for promoting health co-benefits to humans and natural systems.

Interaction between Long-Term Exposure to Fine Particulate Matter and Physical Activity, and Risk of Cardiovascular Disease and Overall Mortality in U.S. Women.

BACKGROUND: Increased respiration during physical activity may increase air pollution dose, which may attenuate the benefits of physical activity on cardiovascular disease (CVD) risk and overall mortality. OBJECTIVES: We aimed to examine the multiplicative interaction between long-term ambient residential exposure to fine particulate matter <2.5 microns (PM2.5) and physical activity in the association with CVD risk and overall mortality. METHODS: We followed 104,990 female participants of the U.S.-based prospective Nurses' Health Study from 1988 to 2008. We used Cox proportional hazards models to assess the independent associations of 24-months moving average residential PM2.5 exposure and physical activity updated every 4 y and the multiplicative interaction of the two on CVD (myocardial infarction and stroke) risk and overall mortality, after adjusting for demographics and CVD risk factors. RESULTS: During 20 years of follow-up, we documented 6,074 incident CVD cases and 9,827 deaths. In fully adjusted models, PM2.5 exposure was associated with modest increased risks of CVD [hazard ratio (HR) for fifth quintile ≥16.5 µg/m3 compared to first quintile <10.7 µg/m3: 1.09, 95% confidence interval (CI): 0.99, 1.20; ptrend=0.05] and overall mortality (HR fifth compared to first quintile: 1.10, 95% CI: 1.02, 1.19; ptrend=0.07). Higher overall physical activity was associated with substantially lower risk of CVD [HR fourth quartile, which was ≥24.4 metabolic equivalent of task (MET)-h/wk, compared to first quartile (<3.7MET-h/wk): 0.61, 95% CI: 0.57, 0.66; ptrend<0.0001] and overall mortality (HR fourth compared to first quartile: 0.40, 95% CI: 0.37, 0.42; ptrend<0.0001). We observed no statistically significant interactions between PM2.5 exposure and physical activity (overall, walking, vigorous activity) in association with CVD risk and overall mortality. DISCUSSION: In this study of U.S. women, we observed no multiplicative interaction between long-term PM2.5 exposure and physical activity; higher physical activity was strongly associated with lower CVD risk and overall mortality at all levels of PM2.5 exposure. https://doi.org/10.1289/EHP7402.

Effect of delay in cord clamping 45 versus 60 s on very preterm singleton infants.

BACKGROUND: In the range of timing suggested by American College of Obstetricians and Gynecologists 30 to 60 s, preterm infants may potentially derive more short and long-term benefits with delayed cord clamping (DCC) for at least 60 s. However, there are concerns with longer resuscitation delay in this vulnerable population. OBJECTIVE: To compare the clinical consequences of 45 versus 60 s delay in umbilical cord clamping in singleton infants born between 230/7 to 316/7 weeks gestation. STUDY DESIGN: We implemented DCC process in very preterm singleton infants, initially for 45 s and later, modified the policy to increase the delay to 60 s. We compared the infants born and received DCC (n = 60) during the 45 s study period (DCC-45 cohort), from Aug.19, 2013, to Aug.18, 2014 to the infants born and received DCC (n = 63) during the 60 s study period (DCC-60 cohort), from Feb.1, 2015, to Jan.31, 2016. RESULTS: The incidence of necrotizing enterocolitis in DCC-60 cohort was 0% compared to 8% in the DCC-45 cohort (P = 0.02). Similarly, incidence of culture-positive sepsis was significantly lower in the DCC-60 cohort compared to DCC-45 cohort (8% versus 18%; P = 0.04). Incidence of mortality and other major morbidities were similar between both groups. Length of stay was significantly lower in DCC-60 cohort compared to DCC-45 cohort. CONCLUSION: DCC for 60 s in very preterm singleton infants was safe, feasible and not associated with any adverse maternal or neonatal short-term outcomes compared to DCC for 45 s.

Shale gas activity and increased rates of sexually transmitted infections in Ohio, 2000-2016.

BACKGROUND: The growing shale gas ("fracking") industry depends on a mobile workforce, whose influx could have social impacts on host communities. Sexually transmitted infections (STIs) can increase through sexual mixing patterns associated with labor migration. No prior studies have quantified the relationship between shale gas activity and rates of three reportable STIs: chlamydia, gonorrhea, and syphilis. METHODS: We conducted a longitudinal, ecologic study from 2000-2016 in Ohio, situated in a prolific shale gas region in the United States (US). Data on reported cases of chlamydia, gonorrhea, and syphilis by county and year were obtained from the Ohio Department of Health. All 88 counties were classified as none, low, and high shale gas activity in each year, using data from the Ohio Department of Natural Resources. Annual rate ratios (RR) and 95% confidence intervals (95% CIs) were calculated from mixed-effects Poisson regression models evaluating the relationship between shale gas activity and reported annual STI rates while adjusting for secular trends and potential confounders obtained from the US Census. RESULTS: Compared to counties with no shale gas activity, counties with high activity had 21% (RR = 1.21; 95%CI = 1.08-1.36) increased rates of chlamydia and 19% (RR = 1.27; 95%CI 0.98-1.44) increased rates of gonorrhea, respectively. No association was observed for syphilis. CONCLUSION: This first report of a link between shale gas activity and increased rates of both chlamydia and gonorrhea may inform local policies and community health efforts.

Unconventional oil and gas development and risk of childhood leukemia: Assessing the evidence.

The widespread distribution of unconventional oil and gas (UO&G) wells and other facilities in the United States potentially exposes millions of people to air and water pollutants, including known or suspected carcinogens. Childhood leukemia is a particular concern because of the disease severity, vulnerable population, and short disease latency. A comprehensive review of carcinogens and leukemogens associated with UO&G development is not available and could inform future exposure monitoring studies and human health assessments. The objective of this analysis was to assess the evidence of carcinogenicity of water contaminants and air pollutants related to UO&G development. We obtained a list of 1177 chemicals in hydraulic fracturing fluids and wastewater from the U.S. Environmental Protection Agency and constructed a list of 143 UO&G-related air pollutants through a review of scientific papers published through 2015 using PubMed and ProQuest databases. We assessed carcinogenicity and evidence of increased risk for leukemia/lymphoma of these chemicals using International Agency for Research on Cancer (IARC) monographs. The majority of compounds (>80%) were not evaluated by IARC and therefore could not be reviewed. Of the 111 potential water contaminants and 29 potential air pollutants evaluated by IARC (119 unique compounds), 49 water and 20 air pollutants were known, probable, or possible human carcinogens (55 unique compounds). A total of 17 water and 11 air pollutants (20 unique compounds) had evidence of increased risk for leukemia/lymphoma, including benzene, 1,3-butadiene, cadmium, diesel exhaust, and several polycyclic aromatic hydrocarbons. Though information on the carcinogenicity of compounds associated with UO&G development was limited, our assessment identified 20 known or suspected carcinogens that could be measured in future studies to advance exposure and risk assessments of cancer-causing agents. Our findings support the need for investigation into the relationship between UO&G development and risk of cancer in general and childhood leukemia in particular.

A systematic evaluation of chemicals in hydraulic-fracturing fluids and wastewater for reproductive and developmental toxicity.

Hydraulic-fracturing fluids and wastewater from unconventional oil and natural gas development contain hundreds of substances with the potential to contaminate drinking water. Challenges to conducting well-designed human exposure and health studies include limited information about likely etiologic agents. We systematically evaluated 1021 chemicals identified in hydraulic-fracturing fluids (n=925), wastewater (n=132), or both (n=36) for potential reproductive and developmental toxicity to triage those with potential for human health impact. We searched the REPROTOX database using Chemical Abstract Service registry numbers for chemicals with available data and evaluated the evidence for adverse reproductive and developmental effects. Next, we determined which chemicals linked to reproductive or developmental toxicity had water quality standards or guidelines. Toxicity information was lacking for 781 (76%) chemicals. Of the remaining 240 substances, evidence suggested reproductive toxicity for 103 (43%), developmental toxicity for 95 (40%), and both for 41 (17%). Of these 157 chemicals, 67 had or were proposed for a federal water quality standard or guideline. Our systematic screening approach identified a list of 67 hydraulic fracturing-related candidate analytes based on known or suspected toxicity. Incorporation of data on potency, physicochemical properties, and environmental concentrations could further prioritize these substances for future drinking water exposure assessments or reproductive and developmental health studies.

Response predictions for organisms water-exposed to metal mixtures: a meta-analysis.

To develop a multimetal toxicity model requires insight into the relationships between the composition of metal mixtures and their toxicological effects on organisms. As a first step in developing such a model, quantitative data from binary and higher mixture studies of Cu, Cd, and Zn were compiled and used to assess trends in toxicological effects on various organisms. The findings of this meta-analysis show relatively little occurrence of additive effects compared with antagonistic and synergistic effects. This observation held true irrespective of test species, environmental compartment, or metal concentrations in the mixture. However, the type of effect was significantly correlated with the metal combination tested and the selected toxicological endpoint. It was also found that different methods were used for assessing deviation from additivity in the various individual studies. For robust comparison, standardization on this point is required. Toxicological responses of organisms to metal mixtures were shown to be hard to predict and were often slightly less than or slightly more than additive. The interactions observed could not be explained by metal-metal interactions alone. We therefore conclude that with current scientific knowledge it is not yet possible to predict responses to metal mixtures in individual cases; at best this is possible only in terms of general patterns. Nevertheless, in the context of environmental risk policy, the assumption of additivity produces a conservative prediction of toxicity, because toxicity of a metal mixture will be either predicted correctly or overpredicted by default in approximately 75% of all cases. The use of models based on noninteraction is satisfactory from this regulatory perspective.

Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size.

BACKGROUND AND OBJECTIVES: We compared the estimations of Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to a gold standard GFR measurement using (125)I-iothalamate, within strata of GFR, gender, age, body weight, and body mass index (BMI). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: For people who previously underwent a GFR measurement, bias, precision, and accuracies between measured and estimated kidney functions were calculated within strata of the variables. The relation between the absolute bias and the variables was tested with linear regression analysis. RESULTS: Overall (n = 271, 44% male, mean measured GFR 72.6 ml/min per 1.73 m(2) [SD 30.4 ml/min per 1.73 m(2)]), mean bias was smallest for MDRD (P < 0.01). CKD-EPI had highest accuracy (P < 0.01 compared with Cockcroft-Gault), which did not differ from MDRD (P = 0.14). The absolute bias of all formulas was related to age. For MDRD and CKD-EPI, absolute bias was also related to the GFR; for Cockcroft-Gault, it was related to body weight and BMI as well. In all extreme subgroups, MDRD and CKD-EPI provided highest accuracies. CONCLUSIONS: The absolute bias of all formulas is influenced by age; CKD-EPI and MDRD are also influenced by GFR. Cockcroft-Gault is additionally influenced by body weight and BMI. In general, CKD-EPI gives the best estimation of GFR, although its accuracy is close to that of the MDRD.