Kidney Week

Abstract: FR-PO1225

Air Pollution Accelerates Aging of the Kidneys, Lungs, and Heart

Session Information

• CKD: Mechanisms, AKI, and Beyond - 2
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• De Castro, Leticia U., Universidade de Sao Paulo, São Paulo, SP, Brazil

Leticia U. De Castro, PhD

• Sanches, Talita R. C., Universidade de Sao Paulo, São Paulo, SP, Brazil

Talita R. C. Sanches, PhD

• Oliveira, Iuri Jesus, Universidade de Sao Paulo, São Paulo, SP, Brazil

Iuri Jesus Oliveira, PharmD

• Souza, Felipe Lima, Universidade de Sao Paulo, São Paulo, SP, Brazil

Felipe Lima Souza, MSc

• Parra, Antonio Carlos, Universidade de Sao Paulo, São Paulo, SP, Brazil

Antonio Carlos Parra

• Kers, Jesper, University of Amsterdam, Amsterdam, Netherlands

Jesper Kers, MD, PhD

• Roelofs, Joris, University of Amsterdam, Amsterdam, Netherlands

Joris Roelofs, MD, PhD

• Saldiva, Paulo, Universidade de Sao Paulo, São Paulo, SP, Brazil

Paulo Saldiva, MD, PhD

• Tammaro, Alessandra, University of Amsterdam, Amsterdam, Netherlands

Alessandra Tammaro, PhD

• Andrade, Lucia, Universidade de Sao Paulo, São Paulo, SP, Brazil

Lucia Andrade, MD, PhD

Background

Air pollution affects multiple organs, causing approximately 4.2 million premature deaths worldwide each year. The respiratory system is especially affected by exposure to fine particulate matter (PM_2.5), which has also been correlated with cardiovascular disease. We have previously shown that PM_2.5 aggravates ischemia/reperfusion injury-induced AKI in mice, as well as being associated with greater albuminuria and a higher risk of incident CKD.

Methods

Eight-week-old mice were housed for 18 months in exposome chambers in São Paulo, Brazil. The chambers allowed the entry of unfiltered or HEPA-filtered air (UFA and HFA, respectively). Kidneys, hearts and lungs were biopsied, and kidney specimens were assessed with a pathomics-based deep learning model to evaluate changes in morphology. To investigate molecular changes, we performed bulk RNA sequencing, as well as lipidomic/metabolomic profiling to examine gene expression, cellular lipid composition and small-molecule metabolites. At age 12 months, mice underwent echocardiography.

Results

Serum cystatin C was higher (i.e., renal function was lower) in the UFA group (0.76±0.09 vs. 0.90±0.04 ng/mL, P<0.05). UFA group mice developed glomerular hypertrophy, glomerulosclerosis, tubular dilation and arterial wall thickening, indicating structural remodeling, as well as dysregulation of genes associated with fatty acid metabolism, including Slc27a2, Cd36, Pparα, Cpt1a, Fatp4 and Cpt1c—key hallmarks of kidney disease. In the UFA group, there were elevated triglyceride species; higher levels of glycolipids, such as Hex2Cer; accumulation of acetyl-CoA, a key product of lipid metabolism; higher leukocyte counts in the blood (P<0.05); and higher CD43+ cell counts in the lungs (P<0.05). UFA group mice had greater systolic left ventricular internal diameters and E/A ratios (P<0.05 for both), which can indicate diastolic dysfunction. At age 18 months, heart weights were greater in UFA group mice (P<0.05), as were the right ventricle, right septum and extent of fibrosis.

Conclusion

Lifelong PM_2.5 exposure induces structural kidney damage and reprograms renal lipid and energy metabolisms, as well as inducing inflammation, thus accelerating renal, pulmonary and cardiac aging. (Support by FAPESP)

Funding

• Government Support – Non-U.S.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.202553wztr4e