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 (P(t)) 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. P(t) during the ischemic phase was measured with micropuncture. We found that higher P(t) was associated with more severe AKI. To determine the role of P(t) during the ischemic phase on the development of AKI, we adjusted the P(t) by altering renal artery pressure. We induced AKI by bilateral clamping of renal veins, and the P(t) 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, P(t) 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, P(t) 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 P(t) during the ischemic phase promoted the development of AKI, while lower P(t) protected from kidney injury. P(t) may be a potential target for treatment of AKI.