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Abstract: PO2618

Male, but Not Female, Spontaneously Hypertensive Rats (SHR) Have Sustained Renal Injury Following a Single Ischemic Insult Progressing to CKD

Session Information

Category: Acute Kidney Injury

  • 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

  • Mohamed, Riyaz, Augusta University, Augusta, Georgia, United States
  • Sullivan, Jennifer C., Augusta University, Augusta, Georgia, United States
Background

Renal ischemia-reperfusion (IR) injury is a major cause of acute kidney injury (AKI), which is an independent risk factor for the development of CKD and all-cause mortality. The goal of the current study was to test the hypothesis that hypertensive males will have greater IR injury than hypertensive females resulting in the development of CKD.

Methods

13-week old male and female SHR were subjected to sham or 30-minute warm bilateral ischemia followed by reperfusion (n=5-6). Systolic blood pressure (BP) measured weekly by tail-cuff.

Results

Plasma creatinine (Pcr) and urine protein creatinine ratio (UPCR) remained elevated at 1-week post IR in male SHR compared to sham (PIR*sex=0.005); Pcr and UPCR returned to baseline in SHR females. Histological examination of SHR kidneys 7 days post-IR showed greater increases in vascular congestion (Psex*IR=0.002) and tubular damage (Psex*IR=0.001) in males. However, glomerular filtration rate (GFR) and systolic BP were not altered in both male and female SHR at 1-week post IR. To determine if this was sustained dysfunction or simply delayed recovery, additional 13-week old male and female SHR were subjected to sham or 30-minute warm bilateral ischemia followed by 20 weeks of reperfusion (n=4-5). Male SHR showed progressive increases in UPCR (PIR<0.05) and systolic BP up to 20 weeks post-IR compared to respective shams (PIR=0.001). Whereas in female SHR, UPCR remained at baseline up to 16-week post IR compared to respective sham. However, at 20 weeks of post IR, both male and female SHR exhibit an increase in UPCR compared to respective sham control; although the increase in UPCR was greater in males (Psex=0.01; PIR*sex=0.09). Male SHR also exhibited greater decreases in glomerular filtration rate (GFR: Psex=0.025; Psex=0.12) and increases in systolic BP (Psex=0.0001; PIR*sex=0.27) compared to females.

Conclusion

Our data demonstrated that impaired renal recovery following IR in SHR males results in exaggerated progression towards CKD.

Funding

  • Other NIH Support