Renal congestion exacerbates acute kidney injury in mice

The number of heart failure (HF) patients is increasing. HF is frequently accompanied by kidney dysfunction and such organ failure is closely related. Recent investigations revealed that increased renal venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in HF patients; however, the underlying responsible mechanisms are unknown. We demonstrated that reduced blood flow speed in peritubular capillaries (PTCs) by renal congestion and upregulation of nuclear factor-?B (NF-?B) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral renal congestion by coarctation of the inferior vena cava between renal veins. Intravital imaging highlighted the notable dilatation of PTCs and decreased renal blood flow speed in the congestive kidney. Renal damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes (PMNs) within PTCs was observed at the acute phase after injury. Pharmacological inhibition of NF-?B ameliorated renal congestion-mediated exacerbation of kidney injury. In vitro, adhesion of PMNs on the TNFa-stimulated endothelial cells was accelerated by perfusion of PMNs at a slower speed, which was cancelled by the inhibition of NF-?B signaling. Our study demonstrates the importance of slower blood flow accompanying activated NF-?B signaling in the congestive kidney in the exacerbation of renal injury. These mechanisms may explain how increased renal venous pressure in HF patients causes the deterioration of kidney dysfunction. Inhibition of NF-?B signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased renal venous pressure. Overall design: RNAseq was used to profile mouse congestive kidney