Acute renal venous obstruction is more detrimental to the kidney than arterial occlusion: implication for murine models of acute kidney injury

Abstract

In this study, we compared the traditional murine model with renal pedicle clamp with models that clamped the renal artery or vein alone as well as to a whole body ischemia-reperfusion injury (WBIRI) model. Male C57BL/6J mice underwent either clamping of the renal artery, vein, or both (whole pedicle) for 30 or 45 min followed by reperfusion, or 10 min of cardiac arrest followed by resuscitation up to 24 h. After 30 min of ischemia, the mice with renal vein clamping showed the mostly increased serum creatinine and the most severe renal tubule injury. After 45 min of ischemia, all mice with renal vasculature clamping had a comparable increase in serum creatinine but the renal tubule injury was most severe in renal artery-clamped mice. Renal arterial blood flow was most decreased in mice with a renal vein clamp compared with a renal artery or pedicle clamp. A 30-or 45-min renal ischemia time led to a significant increase in the protein level of interleukin-6, keratinocyte-derived chemokine (KC), and granular colony-stimulating factor in the ischemic kidney, but the KC was the highest in the renal pedicle-clamped kidney and the lowest in the renal vein-clamped kidney. Of note, 10 min of WBIRI led to kidney dysfunction and structural injury, although less than longer time clamping of isolated renal vasculature. Our data demonstrate important differences in ischemic AKI models. Understanding these differences is important in designing future experimental studies in mice as well as clinical trials in humans.

Dendritic cells tolerized with adenosine A2AR agonist attenuate acute kidney injury

“…In recent years, an AKI model was established that more closely mimics human renal artery hypoperfusion during cardiac surgery (35)(36)(37)(38). To demonstrate that our results can be recapitulated in the artery occlusion model, we successfully established a mouse renal artery IRI model.…”

Sepsis-Associated Acute Kidney Injury: Macrohemodynamic and Microhemodynamic Alterations in the Renal Circulation

“…59 Similar results were reported in 2012 in a murine ischemiareperfusion model in which selective clamping of the renal vein was shown to mediate more severe renal injury and renal dysfunction than a similar duration of arterial occlusion. 60 Significantly, increases in venous pressure have been shown to lead directly to increased renal interstitial and peritubular pressure in the rat, 61 suggesting that venous congestion may limit glomerular filtration as well as impair renal macrovascular and microvascular perfusion. In this fashion, fluid overload and venous congestion could potentiate the increased interstitial pressure seen in sustained AKI in animal models.…”

Are all fluids bad for the kidney?

“…RBF depends on the transrenal pressure gradient, that is the difference between mean arterial pressure (MAP) and renal venous pressure (RVP). Elevated central venous pressure (CVP), translated into elevated RVP, hence reduces the transrenal pressure gradient, RBF and GFR [16,17]. A linear decrease in kidney function with increasing CVP above 10-12 mmHg was observed in patients with cardiovascular disease [18].…”