Abstract: FR-PO371
Hypoxia Attenuates Tubulointerstitial Injury, Inflammation, and Oxidative Stress in the Adenine Overload Model
Session Information
- CKD: Mechanisms - II
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Zambom, Fernanda FF, Univ of Sao Paulo, Sao Paulo, Brazil
- Tessaro, Helena Mendonca, Univ of Sao Paulo, Sao Paulo, Brazil
- Albino, Amanda H., Univ of Sao Paulo, Sao Paulo, Brazil
- Foresto-Neto, Orestes, Univ of Sao Paulo, Sao Paulo, Brazil
- Pião, Janice, Univ of Sao Paulo, Sao Paulo, Brazil
- Malheiros, Denise M., Univ of Sao Paulo, Sao Paulo, Brazil
- Camara, Niels Olsen Saraiva, Univ of Sao Paulo, Sao Paulo, Brazil
- Fujihara, Clarice K., Univ of Sao Paulo, Sao Paulo, Brazil
- Zatz, Roberto, Univ of Sao Paulo, Sao Paulo, Brazil
Background
Adenine excess (ADE) leads to renal deposition of crystals (Crys) and tubulointerstitial nephritis via NFκB. Tissue hypoxia (HYP) has been considered a pathogenic factor in Chronic Kidney Disease (CKD). We showed recently that chronic HYP was renoprotective in rats with 5/6 renal ablation (Nx). Here we investigated a possible beneficial effect of HYP in ADE.
Methods
Male Munich-Wistar rats received standard (C) or 0.5% ADE chow. Six C and 8 ADE rats breathed 21% O2 (NOR), while 8 C and 8 ADE rats were kept under 12% O2 (HYP). After 2 wk, we assessed hemoglobin (Hb, g/dL), tail-cuff pressure (TCP, mmHg), urine albumin/creatinine (Ualb/Ucr), left kidney/body weight (x100), crystal density (Crys/mm2), urine KIM1 (ng/mL), cortical macrophages (MΦ) and angiotensin II+ (AII+) cells/mm2 and collagen-1 (%Coll-1), as well as the renal content of nuclear p65, IL6, CASP1, HO1, SOD1 (WB) and IL1β (pg/mg). Renal HYP was confirmed by pimonidazole staining. .
Results
HYP reduced renal hypertrophy, tubular injury, interstitial inflammation/fibrosis and the content of p65 and IL6, but not CASP1 or IL1β, suggesting specific NFκB inhibition, while lowering HO1 and increasing SOD1.
Conclusion
As in Nx, breathing 12% O2 limited renal injury in the ADE model and attenuated NFκB and oxidative stress, suggesting the existence of a common pathogenic mechanism and the need to review the role of tissue hypoxia in CKD. FAPESP/CNPq.
| CNOR | ADENOR | CHYP | ADEHYP | |
| Hb | 13±1 | 14±1 | 16±1* | 16±1# |
| TCP | 148±3 | 162±3* | 146±2 | 161±3* |
| UALB/UCR | 0.1±0.1 | 0.4±0.1* | 0.2±0.1* | 0.2±0.1# |
| LKW/BW | 0.5±0.1 | 0.9±0.1* | 0.4±0.1 | 0.7±0.1*# |
| Crys | - | 44±4 | - | 40±4 |
| KIM-1 | 0.2±0.1 | 10.2±1.6* | 0.2±0.1 | 4.6±1.8# |
| MΦ | 27±5 | 366±20* | 24±2 | 201±14*# |
| AII | 3±1 | 7±1* | 2±1 | 3±1# |
| %Coll-1 | 2.5±0.1 | 8.8±0.3* | 2.5±0.2 | 5.2±0.3*# |
| p65 | 1.0±0.1 | 2.5±0.4* | 1.3±0.1 | 1.2±0.2# |
| IL6 | 1.0±0.1 | 3.1±0.3* | 1.1±0.2 | 2.4±0.2*# |
| CASP1 | 1.0±0.1 | 2.8±0.3* | 1.7±0.4 | 2.3±0.3 |
| IL1β | 2.1±0.3 | 18.4±1.7 | 1.8±0.2 | 17.5±2.3 |
| HO1 | 1.0±0.1 | 2.6±0.3* | 0.8±0.1 | 1.9±0.2*# |
| SOD1 | 1.0±0.1 | 0.2±0.1* | 0.9±0.2 | 0.4±0.1*# |
Mean±SE;*p<0.05 vs C, #p<0.05 vs ADENOR
Funding
- Government Support - Non-U.S.