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Kidney Week

Abstract: PO0632

Angiotensin II Type 1a Receptor Loss Ameliorates Chronic Tubulointerstitial Damage After Renal Ischemia Reperfusion

Session Information

  • CKD Mechanisms - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Fujita, Yoko, Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Sugaya, Takeshi, Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Ichikawa, Daisuke, Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Tanabe, Jun, Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Kimura, Kenjiro, JCHO Tokyo Takanawa Hospital, Tokyo, Japan
  • Shibagaki, Yugo, Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Ikemori, Atsuko, Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
Background

Although angiotensin II (Ang II) type 1 receptor blocker was reported to attenuate chronic tubulointerstitial damage (TID) after renal ischemia reperfusion (IR), its effect is limited. The aim of this study is to reveal whether suppressed activation of angiotensin II type 1a receptor (AT1a) ameliorates severe chronic tubulointerstitial damage (TID) after renal ischemia reperfusion (IR) .

Methods


To induce severe chronic TID after renal IR, unilateral renal ischemia for 45 min was performed via clamping of right renal pedicle using cerebral aneurysm clip in AT1a knockout homo (AT1a-/-) male mice and wild type (AT1a+/+) male mice. Right and left kidneys were removed at 3, 28 and 70 days postischemia. Left kidneys were used as control. Furthermore, another AT1a+/+ mice were administered hydralazine to maintain the same levels of systolic blood pressure (SBP) as the AT1a-/- mice because the SBP levels of the AT1a-/- mice were significantly lower compared to the AT1a+/+ mice.

Results

Acute tubular necrosis in IR-kidneys of both AT1a-/- mice and AT1a+/+ mice was observed at 3 days postischemia, and the degree was significantly more severe in the IR-kidneys of AT1a-/- mice than in the IR-kidneys of AT1a+/+ mice. Conversely, the degrees of both interstitial fibrosis at 28 and 70 days postischemia and proximal tubular loss at 70 days postischemia were significantly attenuated in the IR-kidneys of AT1a-/- mice compared to the AT1a+/+ mice. While marked renal atrophy at 70 days postischemia was induced in the AT1a+/+ mice, such a development was not provoked in theAT1a-/- mice. Although the administration of hydralazine in the AT1a+/+ mice mildly attenuated the degree of TID at 70 days postischemia, the degree of the AT1a+/+ mice was significantly greater compared to the AT1a-/- mice. Because renal expression levels of angiotensin-(1-7) protein at 28 days postischemia was significantly higher in the AT1a-/- mice compared to theAT1a+/+ mice, renala ngiotensin-(1-7) may contribute to amelioration of chronic TID after IR in the AT1a-/- mice.

Conclusion

Early administration of Ang II type 1 receptor blocker in recovery phase after AKI may be useful for prevention of AKI-to-CKD transition.

Funding

  • Private Foundation Support