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Kidney Week

Abstract: TH-PO090

Long-Term Sequelae of AKI: A Year-Long Male and Female Murine Model

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Soranno, Danielle, University of Colorado, Aurora, Colorado, United States
  • Faubel, Sarah, University of Colorado Denver, Denver, Colorado, United States
Background

There is growing appreciation that acute kidney injury (AKI) leads to systemic sequelae as well as chronic kidney disease (CKD), however most murine models of disease evaluate AKI and CKD as distinct entities, thus limiting their translational value. Herein, we performed a 1 year study of male and female BLK6 mice to determine the long-term renal and systemic sequelae of AKI.

Methods

Male and female adult BLK6 mice underwent bilateral ischemia reperfusion injury or sham procedure. Female mice underwent longer clamp times (34 min compared to 24 min) to overcome the protective effects of estrogen. Renal and systemic outcomes were tracked longitudinally in the males (1, 3, 7, 14 days, 1, 3, 6, 9, and 12 months) and at 12 months in the females.

Results

Measurements of glomerular filtration rate (tGFR), systemic inflammation, and diastolic dysfunction remained abnormal for the duration of the study.

Conclusion

Despite early normalization of serum and urine biomarkers of renal function, long-term renal and systemic sequelae were evident in both the male and female cohorts following AKI.

Representative data from the male cohort of AKI vs sham. (A) serum creatinine normalizes within several days following bilateral ischemia-reperfusion injury. (B) Measured transcutaneous glomerular filtration rate (tGFR) remains persistently low in the AKI group compared to sham. (C) Echocardiography demonstrates diastolic dysfunction with inversion of A’ E’ following AKI. (D) 1 year after AKI, mice weigh less than mice that underwent sham procedure.

Funding

  • Private Foundation Support