Altered renal vascular patterning reduces ischemic kidney injury and limits vascular loss associated with aging

Abstract

The kidney vasculature has a complex arrangement, which runs in both series and parallel to perfuse the renal tissue and appropriately filter plasma. Recent studies have demonstrated that the development of this vascular pattern is dependent on netrin-1 secreted by renal stromal progenitors. Mice lacking netrin-1 develop an arterial tree with stochastic branching, particularly of the large interlobar vessels. The current study investigated whether abnormalities in renal vascular pattern altered kidney function or response to injury. To examine this, we analyzed kidney function at baseline as well as in response to recovery from a model of bilateral ischemic injury and measured vascular dynamics in aged mice. We found no differences in kidney function or morphology at baseline between mice with an abnormal arterial pattern compared to control. Interestingly, male and female mutant mice with stochastic vascular patterning showed a reduction in tubular injury in response to ischemia. Similarly, mutant mice also had a preservation of perfused vasculature with aging compared to a reduction in the control group. These results suggest that guided and organized patterning of the renal vasculature may not be required for normal kidney function; thus, modulating renal vascular patterning may represent an effective therapeutic strategy. Understanding how patterning and maturation of the arterial tree affects physiology and response to injury or aging has important implications for enhancing kidney regeneration and tissue engineering strategies.