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Kidney Week

Abstract: SA-PO591

Ischemia Time Effects Long-Term Kidney Function in a Murine Model of Unilateral Ischemic AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Soranno, Danielle, University of Colorado Denver, Denver, Colorado, United States
  • Kirkbride-Romeo, Lara A., University of Colorado, School of Medicine, Aurora, Colorado, United States
  • Faubel, Sarah, University of Colorado Denver, Denver, Colorado, United States
Background

The duration of ischemia that allows for complete recovery remains undetermined. Parekh performed a prospective study in patients undergoing unilateral ischemia-reperfusion acute kidney injury (UiAKI) for partial nephrectomy, and evaluated histological, serum and urine biomarker changes. Their findings suggested that while there was evidence of acute biomarker and histological injury, the injury was short-lived and did not correlate with ischemia times. This study has been utilized clinically to reassure against long-term renal damage following prolonged ischemia, but did not include outcomes beyond the immediate post-operative period.

Methods

Adult male C57BL/6 mice underwent UiAKI or sham procedure on the left kidney for 32 or 60 minutes. Serum and urine biomarkers were evaluated at 2, 6, and 24 hours, and 14 and 28 days. Transcutaneous glomerular filtration rate (tGFR) was measured serially. Additional 14 and 28 day groups underwent healthy unilateral nephrectomy 3 days prior to sacrifice in order to unmask any compensatory hyperfiltration.

Results

tGFR and histological outcomes demonstrated significant functional impairment and fibrosis despite reassuring serum biomarkers at the 14 and 28 day time-points.

Conclusion

Ischemia time correlates with functional impairment and fibrosis despite reassuring urine and serum biomarkers. Efforts to limit ischemia time in renal-sparing surgery remain warranted.

(A) Serum creatinine and (B) Urine KIM-1 were reassuring at the day 14 and 28 time-points (without nephrectomy), while functional assessment of glomerular filtration rate and histological outcomes demonstrated higher degrees of injury proportional to the ischedmia time. Specifically, 32 minutes of ischemia did not impair GFR 28 days later (C) and (E) while 60 minutes of ischemia resulted in nil function of the injured kidney (D) and (E). Picrosirius Red staining demonstrated increased fibrosis in the left injured kidney for both the 32 and 60 minute ischemia times (F). n = 5-7, p < 0.05.