Kidney Week

Abstract: TH-PO312

Limiting Reperfusion Pressure Protects against Renal Ischemia Reperfusion Injury

Session Information

• AKI Basic: Oxidative Injury and Nephrotoxins
  November 02, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Acute Kidney Injury

• 001 AKI: Basic

Authors

• Wei, Jin, USF, Tampa, Florida, United States

Jin Wei,

• Zhang, Jie, USF, Tampa, Florida, United States

Jie Zhang,

• Wang, Lei, USF, Tampa, Florida, United States

Lei Wang,

• Jiang, Shan, USF, Tampa, Florida, United States

Shan Jiang,

• Buggs, Jacentha Lynn, Tampa General Hospital , Tampa, Florida, United States

Jacentha Lynn Buggs,

• Liu, Ruisheng, University of South Florida College of Medicine, Tampa, Florida, United States

Ruisheng Liu,

Background

The role of hemodynamics in renal ischemia reperfusion injury (IRI) is not defined. We hypothesized that lowering renal perfusion pressure during the initial phase of reperfusion protects against renal IRI.

Results

First, we evaluated renal autoregulation by measuring changes of renal blood flow (RBF) while elevating 20 mmHg in renal artery pressure (RAP). RBF increased by 94.4±8.1% (n=5, p<0.01) in mice with 15 min renal ischemia while kept constant without significant change in sham. Then, in isolated perfused afferent arteriole, we measured myogenic response by increasing perfusion pressure from 60 to 120 mmHg, which was 1.6±0.08 µm at basal but decreased to 0.9±0.06 µm following 20 min hypoxia (n=6, p<0.01). In isolated perfused juxtaglomerular apparatus, we measured tubuloglomerular feedback (TGF) in vitro, which was 3.7±0.6 µm at basal and blunted to 1.2±0.3 µm (p<0.01) following hypoxia. TGF in vivo measured using micropuncture was 4.7±0.5 mmHg in sham and inhibited to 0.8±0.6 mmHg right after 15 min renal ischemia (n=5, p<0.01). We next measured tubular free flow pressure (P_f) using micropuncture. P_f was 11.8±1.6 mmHg at basal and decreased to 2.4±0.5 mmHg during ischemia phase, then significantly elevated to 38.2±4.1 mmHg at the beginning of reperfusion and gradually decrease to 19.8±3.7 mmHg after 45 min of reperfusion (n=5, p<0.01). We adjusted the RAP at the initial 45 min of reperfusion to 66±3 mmHg by partially clamping aorta above renal arteries (LP group) and to 102±6 mmHg by clamping superior mesentery artery (HP group), compared with normal RAP 83±4 mmHg (NP group). Accordingly, P_t was significantly lower in LP group (9.4±1.1 mmHg) (n=4, p<0.05) and higher in HP group (30.8±2.5 mmHg) (n=4, p<0.05) at 45 min compared with NP group (22.6±3.5 mmHg) (n=6). Plasma creatinine was significantly decreased in LP group (0.21±0.04 mg/dl, n=5, p<0.05) and increased in HP group (1.95±0.2 mg/dl, n=5; p<0.01) compared with NP group (0.48±0.01 mg/dl, n=6) at 24h after IRI. The percentage of necrotic tubules in histology with PAS staining was decreased in LP (9.1±3.7%) and increased in HP (32.7±2.4%) compared with NP (20.3±2.9%) (n=5, p<0.05).

Conclusion

In conclusion, intratubular pressure is elevated during the initial phase of reperfusion. Attenuation of the increase in intra-tubular pressure by limiting RAP protects against renal IRI.

Funding

• NIDDK Support