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Novel vascular morphology in human glomeruli

Neal, CR, Winlove, CP, Bell, James ORCID: and Harper, SJ 2013. Novel vascular morphology in human glomeruli. Presented at: 37th Congress of the International Union of Physiological Sciences, Birmingham, 21st July 2013. Proc 37th IUPS: Vascular & Smooth Muscle Physiology. , vol.PCC349

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Human glomeruli have a larger ratio of perfused volume to afferent arteriole conductance than mice or rats. These differences are likely to influence glomerular haemodynamics and blood pressure this study uses reconstructions of the human vascular tree to build upon previous work which revealed vascular chambers at the human glomerular vascular pole (Betteridge 2011). Seven human kidneys not required for transplantation were perfused with Soltran solution (Baxter Healthcare, UK), and transported on ice. Fresh tissue wedges were removed for multiphoton microscopy (3 kidneys) and the sample site clamped off from the rest of the kidney. The remaining kidney tissue was perfused (100mmHg pressure) with mammalian HEPES Ringer containing Ficoll 400 (25mmHg colloid osmotic pressure), followed by glutaraldehyde (2.5%) fixative at the same pressures. Tissues were dehydrated, embedded in resin and Toluidine Blue stained 1µm serial sections used to reconstruct 3D images of the glomerular vasculature. In two fresh and two fixed unstained kidneys the vasculature was imaged in 0.5-1mm thick tissue slices using multiphoton microscopy as described previously (Arkill 2010). Fibrous collagen was visualised using second harmonic generation and elastin from its intrinsic two photon autofluorescence in a multiphoton microscope. Reconstructed human glomeruli (n=14) from resin sections show both afferent arterioles (22±1µm diam. mean±SEM) and efferent arterioles (16±1µm diam.) leading into ellipsoidal vascular chambers (VCs). Afferent VCs (49±3 x 48±4 x 32±2µm diam.) are larger than efferent VCs (46±9 x 43±4 x 26±1µm diam.) and lead into (on average) 7 unbranched wide vessels (Conduit vessels; 16±1µm diam.) with a paucity of podocytes that convey blood to the peripheral glomerulus. The smaller efferent VCs have (on average) 13 highly branched vessels (10±0.4µm diam.) draining into them. VCs scale with glomerular volume and could be absent from glomeruli smaller than 160µm diameter. Multiphoton microscopy confirmed this morphology in two fresh and two fixed kidneys but also demonstrated coherent emission in Second Harmonic Generation consistent with Collagen I or III in a position matching the Vascular Chamber wall. Fibrous elastin was not detected, however the entire structure exhibited background autofluorescence. VCs and Conduit vessels are not apparent in classical biopsy sections but they are revealed by perfusion fixation at in vivo matching pressures reinflating the glomerular vascular tree to in vivo diameters. Collagen III is observed in the mesangium of collagen glomerulopathies but this report is the first to find banded collagen (I or III) in normal glomeruli. VCs and Conduit vessels are likely to be important in the distribution of blood flow among the human glomerular lobes and are implicated in glomerular disease where complications originate at the vascular pole where these structures are located.

Item Type: Conference or Workshop Item (UNSPECIFIED)
Date Type: Publication
Status: Published
Schools: Optometry and Vision Sciences
Last Modified: 17 Oct 2023 14:30

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