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.
SIGNIFICANCE STATEMENT High-resolution, three-dimensional, renal vasculature models are currently highly reliant on data obtained from rodent kidneys. Obtaining this information in a human kidney is difficult, given its size and scale. Here, we overcome this challenge through synchrotron-based imaging to profile the vasculature of an intact human kidney. Organ-wide vascular network metrics are shown to be largely conserved between human and rat kidneys. Regional and spatial heterogeneities between cortical, medullary, and hilar vascular architecture are revealed, highlighting a structural basis for renal oxygen gradients in humans. This is, to our knowledge, the first time the vasculature of a human kidney has been mapped in its entirety, with implications for understanding how the hierarchy of individual blood vessel segments collectively scales to renal function.
Competing Interest Statement
ACKNOWLEDGEMENTS The authors would like to express their gratitude for the financial support provided by the Chan Zuckerberg Initiative DAF (2020-225394), an advised fund of SVCF, the MRC (MR/R025673/1), and ESRF beamtimes (md1252 & md1290). P.D.L. is supported by a Royal Academy of Engineering Chair in Emerging Technologies (CiET1819/10). D.J.J. is supported by a Foulkes Foundation Postdoctoral Fellowship. D.A.L. is supported by a Wellcome Trust Investigator Award (220895/Z/20/Z) and by the National Institute for Health Research (NIHR) Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. This research was funded in part by the Wellcome Trust [209553/Z/17/Z]. M.A. is supported by the National Institutes of Health (NIH) (HL94567 and HL134229). JJ, was also supported by the NIHR UCLH Biomedical Research Centre, UK. DISCLOSURE JJ reports fees from Boehringer Ingelheim, Roche, NHSX, Takeda and GlaxoSmithKline unrelated to the submitted work. JJ was supported by Wellcome Trust Clinical Research Career Development Fellowship 209553/Z/17/Z and the NIHR Biomedical Research Centre at University College London.