Abstract
Premature renal ageing is a risk factor for cardio-vascular adverse events, the development of chronic kidney disease (CKD) and progression towards end stage renal disease (ESRD). ESRD is associated with low quality of life, high morbidity and mortality, and tremendous health care expenses. The incidence of ESRD varies greatly among countries with 6% in The Netherlands compared to 11% in Sao Paulo. One of the neglected factors possibly underlying heterogeneity in renal ageing is the exposure to environmental factors. Recently epidemiological studies have linked exposure to Particulate Matter in aerodynamic air (PM2.5) to an increased risk of CKD. Epigenetic changes, oxidative stress and chronic inflammation are among the mechanisms mediating the adverse health effects of PM2.5. Research into the interplay between individual exposure to PM2.5, epigenetic responses and premature renal ageing is limited. Our project will fill the gap of this knowledge. We hypothesize that exposure to PM2.5 forms an accelerator of renal ageing, enhancing the risk of CKD. To unravel the molecular and biological changes induced by PM2.5 exposure in the kidney, we will use a unique experimental model: the Harvard Ambient Particle Concentrator, in which mice will be exposed to PM2.5 during the ageing process and after the induction of renal injury. Using this setup, we will identify a unique signature of PM2.5, encompassing epigenetic, transcriptomic and metabolic changes, which will be evaluated as a risk factor for renal health span in observational cohorts in the Netherlands and in Sao Paulo. We envision that this signature will predict individual differences in renal function decline and will be important to adopt preventive measures to promote renal healthy ageing. Additionally, using state-of-the-art techniques, we aim at the chemical, elemental characterization and traceability of PM2.5 components in blood, kidney and urine, to unravel which elements of PM2.5 are toxic for the kidneys. (AU)
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