Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.

There is little evidence on the short-term impact of fine particulate matter (PM2.5) on renal health, and the potential interactions and various influences of PM2.5 components on renal health have not been examined. We investigated whether short-term (≤28 days) ambient PM2.5 and 15 PM2.5 components were associated with serum uric acid (SUA), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and odds of incident chronic kidney disease (CKD) using both mixed-effect and Bayesian kernel machine regression (BKMR) models in the Normative Aging Study. This analysis included 2466 study visits from 808 older males enrolled during 1998–2016 with available data. BKMR showed positive relationships of PM2.5 mixture with SUA and odds of CKD, and an inverse relationship with eGFR. In the 28-day exposure window, an interquartile range (IQR) increase in vanadium was associated with a 0.244-mg/dL higher SUA. IQR increases in sulfur and lead were associated with a 1.281- and 1.008-mL/min/1.73m2 decrease in eGFR, respectively. The same change in sulfur was also associated with a 39% higher odds of CKD. Our findings provide solid evidence supporting short-term adverse effects of PM2.5 on renal health and further highlight that components from oil combustion and regional pollution may be major contributors.

The potential effect of short-term exposure to air pollution on mitochondrial DNA (mtDNA) methylation remains to be explored. This study adopted an experimental exposure protocol nested with an intervention study on L-arginine (L-Arg) supplementation. Participants walked along a traffic road for 2h in the last day of a 14-day intervention to investigate the effects of short-term personal exposure to air pollution on platelet mtDNA methylation and the possible modifying effects of L-Arg supplementation. Results showed that short-term personal exposure to air pollutants was associated with hypomethylation in platelet mtDNA. Specifically, 2-h fine particulate matter (PM2.5) exposure during the outdoor walk was significantly associated with hypomethylation in mt12sRNA and ATP6; 24-h black carbon (BC) exposure from the start of the walk till next morning and 2-h NO2 exposure was significantly associated with hypomethylation in ATP8; and 24-h PM2.5 exposure, 2-h and 24-h BC exposure were significantly associated with hypomethylation in D-loop. Supplementation with L-Arg could mitigate the air pollution effects on methylation in ATP8 and D-loop. These findings suggest that platelet mtDNA methylation may be sensitive effect biomarker for short-term exposure to air pollution and may help deepen the understanding of the epigenetic mechanisms of adverse cardiovascular effects of air pollution.

{BACKGROUND: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. RESULTS: We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E-03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang's 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (beta = - 0.12, 95% CI = [- 0.16, - 0.08] change in log-transformed eGFR per unit increase in MRS

Air pollution, especially fine particulate matter (PM2.5), may impair cognitive performance1–3, but its short-term impact is poorly understood. We investigated the short-term association of PM2.5 with the cognitive performances of 954 white males measured as global cognitive function and Mini-Mental State Examination (MMSE) scores and further explored whether taking nonsteroidal anti-inflammatory drugs (NSAIDs) could modify their relationships. Higher short-term exposure to PM2.5 demonstrated nonlinear negative associations with cognitive function. Compared with the lowest quartile of the 28-d average PM2.5 concentration, the 2nd, 3rd and 4th quartiles were associated with 0.378, 0.376 and 0.499 unit decreases in global cognitive function score, 0.484, 0.315 and 0.414 unit decreases in MMSE score and 69, 45 and 63% greater odds of low MMSE scores (≤25), respectively. Such adverse effects were attenuated in users of NSAIDs compared to nonusers. This study elucidates the short-term impacts of air pollution on cognition and warrants further investigations on the modifying effects of NSAIDs.