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Pollution is the motor of premature ageing of the kidney

Grant number: 19/19433-0
Support Opportunities:Research Projects - Thematic Grants
Duration: July 01, 2020 - June 30, 2025
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Convênio/Acordo: Netherlands Organisation for Scientific Research (NWO)
Principal Investigator:Lucia da Conceição Andrade
Grantee:Lucia da Conceição Andrade
Principal researcher abroad: Alessandra Tammaro
Institution abroad: University of Amsterdam (UvA), Netherlands
Principal researcher abroad: Sandrine Florquin
Institution abroad: University of Amsterdam (UvA), Netherlands
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Pesquisadores principais:
Paulo Hilário Nascimento Saldiva
Associated researchers:Andréa Teixeira Ustra ; Camila Eleuterio Rodrigues ; Itamar de Souza Santos ; laura janka zires ; Maria de Fátima Andrade ; Mariana Matera Veras ; Talita Rojas Cunha Sanches
Associated grant(s):23/00552-5 - The effect of filter lifespan in continuous renal replacement therapy on the rate of new infections in critically ill patients: a prospective multicenter observational trial, AP.R SPRINT
22/14274-4 - Making green work for health, AP.R SPRINT
Associated scholarship(s):24/03904-2 - Histology and immunohistochemistry analyzes on mouse tissue exposed to PM 2.5., BP.TT
22/11110-0 - Pollution is the motor of premature ageing of the kidney, BP.PD
22/11975-1 - Pollution is the motor of premature ageing of the kidney, BP.DD
21/06514-2 - Influence of air pollution on the progression of acute kidney injury to chronic kidney disease, BP.IC
19/26385-2 - Influence of atmospheric pollution in acute kidney injury (AKI), BP.IC

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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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CASTRO, LETICIA URBANO CARDOSO; OTSUKI, DENISE AYA; SANCHES, TALITA ROJAS; SOUZA, FELIPE LIMA; SANTINHO, MIRELA APARECIDA RODRIGUES; DA SILVA, CLEONICE; NORONHA, IRENE DE LOURDES; DUARTE-NETO, AMARO NUNES; GOMES, SAMIRAH ABREU; MALBOUISSON, LUIZ-MARCELO SA; et al. Terlipressin combined with conservative fluid management attenuates hemorrhagic shock-induced acute kidney injury in rats. SCIENTIFIC REPORTS, v. 12, n. 1, p. 13-pg., . (19/19433-0)

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