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Kidney Week

Abstract: SA-PO172

AKI Results in Sustained, Long-Term Alterations of Kidney Lymphatics

Session Information

  • AKI: Mechanisms - III
    November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Ghajar-Rahimi, Gelare, The University of Alabama at Birmingham Division of Nephrology, Birmingham, Alabama, United States
  • Barwinska, Daria, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Whipple, Grace, The University of Alabama at Birmingham Division of Nephrology, Birmingham, Alabama, United States
  • Kamocka, Malgorzata, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Khan, Shehnaz, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Winfree, Seth, University of Nebraska Medical Center, Omaha, Nebraska, United States
  • George, James F., The University of Alabama at Birmingham Department of Surgery, Birmingham, Alabama, United States
  • El-Achkar, Tarek M., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Agarwal, Anupam, The University of Alabama at Birmingham Division of Nephrology, Birmingham, Alabama, United States
Background

Acute kidney injury (AKI) is a serious clinical problem associated with significant morbidity and mortality that are inadequately addressed by current treatment options. The kidney endothelial system, comprised of blood and lymphatic vascular systems, responds dynamically to injury. In several models of AKI, kidney lymphatics undergo a process of expansion or lymphangiogenesis (LA). While this process is thought to be acutely protective, long-term alterations in kidney lymphatics following initial injury have never been assessed.

Methods

C57BL/6J mice subjected to bilateral ischemia-reperfusion injury (BIRI) or sham operation were followed for 1, 3, 6, and 9 months. Kidney function was monitored with serial measurements of serum creatinine (SCr) and transcutaneous glomerular filtration rate (GFR). Lymphangiogenic response was assessed by western blot and quantitative real-time PCR at end points. Large-volume confocal imaging followed by a three-dimensional tissue cytometry (3DTC) analytical approach was used to assess lymphatic architecture in relation to serial changes in kidney function.

Results

AKI was confirmed by reduced GFR and increased SCr 24 hours following BIRI. Kidney function improved over time, but BIRI mice had consistently reduced GFR relative to sham mice out to 9 months post-surgery. Histologic evaluation of glomerular and tubular damage showed a similar pattern. Expression of lymphangiogenic factors VEGF-C and VEGF-D, and lymphatic marker VEGFR-3 differed between sham and BIRI mice over time. 3DTC and volumetric tissue exploration and analysis of lymphatic architecture revealed BIRI mice consistently exhibited greater Lyve-1 than sham controls.

Conclusion

In the first long-term (9 month) study to evaluate kidney lymphatics following AKI, we show sustained alterations in the spatiotemporal dynamics of kidney lymphatic vasculature. Future studies will aim to elucidate the functional significance of injury-associated LA that persists beyond initial injury.

Funding

  • Veterans Affairs Support