Mapping the blood vasculature in an intact human kidney using hierarchical phase-contrast tomography

Abstract

Background: The kidney vasculature is exquisitely structured to orchestrate renal function. Structural profiling of the vasculature in intact rodent kidneys, has provided insights into renal haemodynamics and oxygenation, but has never been extended to the human kidney beyond a few vascular generations. We hypothesised that synchrotron-based imaging of a human kidney would enable assessment of vasculature across the whole organ. Methods: An intact kidney from a 63-year-old male was scanned using hierarchical phase-contrast tomography (HiP-CT), followed by semi-automated vessel segmentation and quantitative analysis. These data were compared to published micro-CT data of whole rat kidney. Results: The intact human kidney vascular network was imaged with HiP-CT at 25 μm voxels, representing a 20-fold increase in resolution compared to clinical CT scanners. Our comparative quantitative analysis revealed the number of vessel generations, vascular asymmetry and a structural organisation optimised for minimal resistance to flow, are conserved between species, whereas the normalised radii are not. We further demonstrate regional heterogeneity in vessel geometry between renal cortex, medulla, and hilum, showing how the distance between vessels provides a structural basis for renal oxygenation and hypoxia. Conclusions: Through the application of HiP-CT, we have provided the first quantification of the human renal arterial network, with a resolution comparable to that of light microscopy yet at a scale several orders of magnitude larger than that of a renal punch biopsy. Our findings bridge anatomical scales, profiling blood vessels across the intact human kidney, with implications for renal physiology, biophysical modelling, and tissue engineering.