PM-KIDNEY: Pollution is the Motor of premature ageing of the KIDNEY
Description: Men kan stellen dat een mens zo oud is als zijn nieren. Versnelde veroudering van nierweefsel veroorzaakt nierfalen en vroegtijdig overlijden. Er zijn grote geografische verschillen in het optreden van nierfalen. Opvallend is dat nierfalen in Sao Paolo (Brazilië) twee keer zo vaak voorkomt als in Nederland. Een mogelijke oorzaak voor dit verschil is blootstelling aan omgevingsfactoren zoals fijnstof. De mate van luchtvervuiling is in Sao Paolo veel groter dan in Nederland. In dit project zal worden onderzocht of, en op welke manier, fijnstof in de omgevingslucht het verouderingsproces van de nieren versnelt. Muizen zullen worden blootgesteld aan fijnstof, waarna de moleculaire veranderingen in de nieren in kaart gebracht worden. De specifieke moleculaire veranderingen die hierbij aan het licht komen zullen worden vergeleken met gegevens uit grote bevolkingsonderzoeken in Brazilië en NL. In de toekomst kan dit onderzoek leiden tot behandelingen om versnelde nierveroudering te voorkomen.\n\nApplication summary: 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 healthspan 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.
Funder: ZonMw
Funding type: research
Funder scheme: ["Vitaliteit & Levensloop"]
Start date: 2020-07-01
End date: 2026-03-01
Investigator: prof. dr. J.J.T.H. Roelofs
Institution: Amsterdam UMC Locatie AMC
Funded outputs count: 0
Funder award ID: zonmw-457002002-25782
OpenAlex ID: G8471413286