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Saum, K. L.

Publications and source records attributed to Saum, K. L..

2 recordsLinked to original sources

Computational and Experimental Evaluation of a Flow-Conditioning Anastomotic Device for Arteriovenous Fistula Maturation

The arteriovenous fistula (AVF) is the preferred method of vascular access for hemodialysis; however, 30-50% of AVFs undergo primary failure and are unsuitable for clinical use. As disturbed hemodynamics initiate endothelial injury and intimal hyperplasia, we designed an endovascular flow-conditioning anastomotic device (FCAD) to directly improve AVF hemodynamics and protect the anastomotic region. Using computational fluid dynamics, we characterized the flow field and wall shear stress (WSS) profiles in idealized AVF models with and without the FCAD. Incorporation of the FCAD into a brachiocephalic AVF model reduced regions of oscillatory WSS and generated a symmetrical flow profile in the draining vein compared to a reference AVF. Parametric studies also identified an FCAD geometry with a tab angle, height, and aspect ratio of 30{degrees}, 0.1 diameters, and 1.0 restored time-averaged WSS along the inner venous wall, achieving a physiological level without inducing regions of oscillatory flow throughout the cardiac cycle. Similar findings were observed with an in vitro model using particle imaging velocimetry. This study demonstrates the feasibility of the FCAD to normalize venous flow and WSS while imposing minimal resistance to blood flow. Restoring physiological WSS levels on the venous wall is expected to preserve endothelial function and improve AVF maturation.

bioengineering↗

Accelerated osteocytic citrate production in chronic kidney disease is associated with protection of the kidney

Patients with chronic kidney disease (CKD) face elevated fracture incidences, but mechanisms underlying CKD-related bone loss remain unclear. Using the adenine-induced chronic kidney injury (AdKI) murine model, we identified that AdKI induces dysregulated glucose metabolism in bones and kidneys via in vivo and ex vivo metabolic tracing. Ex vivo 13C-metabolic tracing of osteocyte-enriched femora revealed accelerated citrate production from [1,2-13C]-glucose and [U-13C]-glutamine in AdKI mice. These metabolic changes were observed together with increased circulating citrate and Slc13a5 overexpression in bones from AdKI mice. Thus, to explore the role of citrate in AdKI, we utilized mice harboring a loss of function mutation in the citrate importer SLC13A5 (Slc13a5R337*/R337*). Mutant mice displayed elevated osteocytic citrate production, and elevated circulating citrate, without significantly worsened AdKI-related bone loss. Coincident with this, Slc13a5R337*/R337* mutant mice were significantly protected from loss of kidney function with attenuated AdKI-induced nephrolithiasis. We also confirmed that Slc13a5 is highly expressed in cortical bone compared to the kidney, suggesting the effect of the mutation is mediated by SLC13A5s function outside the kidney. Altogether, this study finds that accelerated osteocytic citrate production in CKD is associated with protection of kidney function, and modulation of citrate handling may be a site for therapeutic intervention in CKD.

physiology↗