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Replacement of renal function in uremic animals with a tissue-engineered kidney

Abstract

Current renal substitution therapy with hemodialysis or hemofiltration has been the only successful long-term ex vivo organ substitution therapy to date. Although this approach is life sustaining, it is still unacceptably suboptimal with poor clinical outcomes of patients with either chronic end-stage renal disease or acute renal failure. This current therapy utilizes synthetic membranes to substitute for the small solute clearance function of the renal glomerulus but does not replace the transport, metabolic, and endocrinologic functions of the tubular cells. The addition of tubule cell replacement therapy in a tissue-engineered bioartificial kidney comprising both biologic and synthetic components will likely optimize renal replacement to improve clinical outcomes. This report demonstrates that the combination of a synthetic hemofiltration device and a renal tubule cell therapy device containing porcine renal tubule cells in an extracorporeal perfusion circuit successfully replaces filtration, transport, metabolic, and endocrinologic functions of the kidney in acutely uremic dogs.

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Figure 1: Schematic of the extracorporeal hemoperfusion circuit for the bioartificial kidney.
Figure 2: The influence in a uremic dog of sham treatment versus RAD treatment for 4-6 or 20-24 hours on the total ammonia excretion in the processed ultrafiltrate exiting the RAD.
Figure 3

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Acknowledgements

This work was supported by National Institutes of Health Grants DK-39255, DK-48175, and DK-50539, the VA Research Service, and Nephros Therapeutics. The expert technical assistance of Annie Browning and Anand Gupte, along with the excellent secretarial support of Donna Hall, is appreciated

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Correspondence to H. David Humes.

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Humes, H., Buffington, D., MacKay, S. et al. Replacement of renal function in uremic animals with a tissue-engineered kidney. Nat Biotechnol 17, 451–455 (1999). https://doi.org/10.1038/8626

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