Role of intratubular pressure during the ischemic phase in acute kidney injury

Am J Physiol Renal Physiol. 2017 Jun 1;312(6):F1158-F1165. doi: 10.1152/ajprenal.00527.2016. Epub 2016 Nov 9.

Abstract

Acute kidney injury (AKI) induced by clamping of renal vein or pedicle is more severe than clamping of artery, but the mechanism has not been clarified. In the present study, we tested our hypothesis that increased proximal tubular pressure (Pt) during the ischemic phase exacerbates kidney injury and promotes the development of AKI. We induced AKI by bilateral clamping of renal arteries, pedicles, or veins for 18 min at 37°C, respectively. Pt during the ischemic phase was measured with micropuncture. We found that higher Pt was associated with more severe AKI. To determine the role of Pt during the ischemic phase on the development of AKI, we adjusted the Pt by altering renal artery pressure. We induced AKI by bilateral clamping of renal veins, and the Pt was changed by adjusting the renal artery pressure during the ischemic phase by constriction of aorta and mesenteric artery. When we decreased renal artery pressure from 85 ± 5 to 65 ± 8 mmHg, Pt decreased from 53.3 ± 2.7 to 44.7 ± 2.0 mmHg. Plasma creatinine decreased from 2.48 ± 0.23 to 1.91 ± 0.21 mg/dl at 24 h after renal ischemia. When we raised renal artery pressure to 103 ± 7 mmHg, Pt increased to 67.2 ± 5.1 mmHg. Plasma creatinine elevated to 3.17 ± 0.14 mg·dl·24 h after renal ischemia. Changes in KIM-1, NGAL, and histology were in the similar pattern as plasma creatinine. In summary, we found that higher Pt during the ischemic phase promoted the development of AKI, while lower Pt protected from kidney injury. Pt may be a potential target for treatment of AKI.

Keywords: acute kidney injury; micropuncture; tubular pressure.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / physiopathology*
  • Acute Kidney Injury / prevention & control
  • Animals
  • Arterial Pressure*
  • Constriction
  • Creatinine / blood
  • Disease Models, Animal
  • Hepatitis A Virus Cellular Receptor 1 / blood
  • Ischemia / metabolism
  • Ischemia / pathology
  • Ischemia / physiopathology*
  • Ischemia / prevention & control
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology*
  • Lipocalin-2 / blood
  • Male
  • Mice, Inbred C57BL
  • Renal Artery / physiopathology*
  • Renal Artery / surgery
  • Renal Circulation*
  • Renal Veins / physiopathology*
  • Renal Veins / surgery
  • Severity of Illness Index
  • Time Factors

Substances

  • Havcr1 protein, mouse
  • Hepatitis A Virus Cellular Receptor 1
  • Lipocalin-2
  • Lcn2 protein, mouse
  • Creatinine