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Kidney Week

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.

 CNORADENORCHYPADEHYP
Hb13±114±116±1*16±1#
TCP148±3162±3*146±2161±3*
UALB/UCR0.1±0.10.4±0.1*0.2±0.1*0.2±0.1#
LKW/BW0.5±0.10.9±0.1*0.4±0.10.7±0.1*#
Crys-44±4-40±4
KIM-10.2±0.110.2±1.6*0.2±0.14.6±1.8#
27±5366±20*24±2201±14*#
AII3±17±1*2±13±1#
%Coll-12.5±0.18.8±0.3*2.5±0.25.2±0.3*#
p651.0±0.12.5±0.4*1.3±0.11.2±0.2#
IL61.0±0.13.1±0.3*1.1±0.22.4±0.2*#
CASP11.0±0.12.8±0.3*1.7±0.42.3±0.3
IL1β2.1±0.318.4±1.71.8±0.217.5±2.3
HO11.0±0.12.6±0.3*0.8±0.11.9±0.2*#
SOD11.0±0.10.2±0.1*0.9±0.20.4±0.1*#

Mean±SE;*p<0.05 vs C, #p<0.05 vs ADENOR

Funding

  • Government Support - Non-U.S.