Abstract: PO0420
Air Pollution Aggravates Ischemia-Reperfusion-Induced AKI in Mice
Session Information
- AKI: Repair and Progression
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Parra, Antonio Carlos, Nephrology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
- Tammaro, Alessandra, Department of Pathology, Amsterdam UMC, Amesterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, Netherlands
- Graner, Mariana, Nephrology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
- Umesaki Itto, Lucas Yuji, Nephrology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
- Kers, Jesper, Department of Pathology, Amsterdam UMC, Amesterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, Netherlands
- Roelofs, Joris, Department of Pathology, Amsterdam UMC, Amesterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, Netherlands
- Veras, Mariana, Nephrology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
- Rodrigues, Camila Eleuterio, Nephrology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
- Florquin, Sandrine, Department of Pathology, Amsterdam UMC, Amesterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, Netherlands
- Sanches, Talita R., Nephrology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
- Andrade, Lucia, Nephrology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
Background
The biggest city in Latin America is São Paulo (SP), where disorganized urbanization has had a negative impact on air quality and vehicle emissions are the main source of fine particulate matter (PM2.5). Epidemiological studies have linked PM2.5 exposure to an increased risk of CKD. The mechanisms mediating the adverse health effects of PM2.5 include epigenetic changes, oxidative stress and inflammation. The role of PM2.5 in AKI has yet to be described. We hypothesized that PM2.5 exposure would aggravate renal ischemia/reperfusion (I/R) injury in mice.
Methods
In temperature-/humidity-controlled chambers within an ambient particle concentrator, animals were exposed to a concentrated PM2.5 stream (PM2.5) or to high-efficiency particulate air-filtered clean air (CA). Mass concentrations of PM were measured with an airborne particulate monitor, and the target dose was 600 µg m−3/day (equivalent of the daily exposure in SP). After 12 weeks, some PM2.5 and CA mice underwent bilateral 30-min clamping of the kidney hila and subsequent reperfusion. All studies were performed 48 h after I/R. Groups: CA, PM2.5, CA+I/R and PM2.5+I/R. Data are mean±SEM.
Results
Renal TLR4 protein expression was higher in CA+I/R and PM2.5+I/R than in CA and PM2.5 (128±2.1 and 146±2.0 vs. 97.5±2.1 and 98.0±0.9%; P<0.05), also being much higher in PM2.5+I/R than in CA+I/R (P<0.05). Manganese superoxide dismutase levels were higher in PM2.5+I/R than in CA+I/R, AF and PM2.5 (146±12 vs. 99±3.6, 102±3.9 and 96±2.8; P<0.05).
Conclusion
PM2.5 aggravates I/R-induced AKI by decreasing renal Klotho protein, leading to increased renal TLR4 expression and inflammatory cell infiltration. (FAPESP, NWO)
Biochemistry and histology
CA (n=4) | PM2.5 (n=7) | CA+I/R (n=11) | PM2.5+I/R (n=14) | |
Creatinine Clearance (mL/min) | 0.67±0.20 | 0.83±0.33 | 0.76±0.34 | 0.28±0.26a |
FENa (%) | 0.13±0.03 | 0.10±0.03 | 0.12±0.02 | 0.30±0.07a |
Urinary Osmolalty (mOsm/kg) | 2045±244 | 1949±175 | 1764±300 | 1106±184a |
Tubular Injury Score | 0.00 | 0.00 | 1.0±0.56 | 3.6±0.64a |
Klotho* (%+area/high power field) | 4.7±0.8 | 4.8±0.4 | 2.2±0.15b | 1.1±0.24a |
F480*(%+area/high power field) | 0.71±0.15 | 0.44±0.04 | 0.83±0.11 | 1.35±0.16b |
Ki67* (+cells/high power field) | 1.55±0.41 | 1.32±0.38 | 15.4±7.7 | 30.6±5.44b |
ly6G* (+cells/high power field) | 0.67±0.10 | 1.10±0.20 | 12.19±6.55b | 61.84±11.29a |
*Immunohistochemical analysis; aP<0.05 vs. CA, PM2.5 and CA+I/R; bP<0.05 vs. CA and PM2.5.
Funding
- Government Support – Non-U.S.