4.6 Article

Evaluation of bioartificial renal tubule device prepared with lifespan-extended human renal proximal tubular epithelial cells

Journal

NEPHROLOGY DIALYSIS TRANSPLANTATION
Volume 27, Issue 8, Pages 3091-3099

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfr755

Keywords

acute kidney injury; bioartificial renal tubule device; inflammatory cytokine; renal proximal tubular epithelial cells; renal replacement therapy

Funding

  1. Ministry of Economy, Trade and Industry of Japan [20R3003]
  2. Kihara Memorial Yokohama Foundation for the Advancement of Life Science

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Acute kidney injury (AKI), accompanied by the development of systemic inflammatory response syndrome and multiorgan dysfunction syndrome, is associated with a high risk of death. Bioartificial renal tubule device (BTD) is a cell therapy that improves the conditions common to artificial kidney recipients treated for kidney diseases. In this paper, we describe the establishment of BTD with lifespan-extended human renal proximal tubular epithelial cells. AKI goats were established by performing bilateral nephrectomy followed by lipopolysaccharide administration. The AKI goats were treated with BTD or sham-BTD, and the two groups of animals were compared by measuring the respective life spans and the levels of blood urea nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and serum electrolytes. The expression levels of inflammatory cytokines were detected by reverse transcriptionpolymerase chain reaction, and plasma interleukin (IL)-6 levels were measured by enzyme-linked immunosorbent assay. The life span of AKI goats was extended: the lifetime with the BTD treatment compared with sham-BTD. BTD and sham-BTD showed a similar degree of small solute clearance. The expression levels of inflammatory cytokines and plasma IL-6 levels were decreased by the BTD treatment. BTD treatment results in less damage from endotoxin shock and increased life span in AKI goats. These results suggest that BTD may be a useful component of bioartificial kidneys and should be considered in the next generation of renal replacement therapies.

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