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BK Polyomavirus Replication in Renal Tubular Epithelial Cells Is Inhibited by Sirolimus, but Activated by Tacrolimus Through a Pathway Involving FKBP‐12
BK polyomavirus (BKPyV) replication causes nephropathy and premature kidney transplant failure. Insufficient BKPyV‐specific T cell control is regarded as a key mechanism, but direct effects of immunosuppressive drugs on BKPyV replication might play an additional role. We compared the effects of mammalian target of rapamycin (mTOR)‐ and calcineurin‐inhibitors on BKPyV replication in primary human renal tubular epithelial cells. Sirolimus impaired BKPyV replication with a 90% inhibitory concentration of 4 ng/mL by interfering with mTOR–SP6‐kinase activation. Sirolimus inhibition was rapid and effective up to 24�...
Source: American Journal of Transplantation - December 7, 2015 Category: Transplant Surgery Authors: H. H. Hirsch, K. Yakhontova, M. Lu, J. Manzetti Tags: Original Article Source Type: research

Xenon Treatment Protects Against Cold Ischemia Associated Delayed Graft Function and Prolongs Graft Survival in Rats
Abstract Prolonged hypothermic storage causes ischemia‐reperfusion injury (IRI) in the renal graft, which is considered to contribute to the occurrence of the delayed graft function (DGF) and chronic graft failure. Strategies are required to protect the graft and to prolong renal graft survival. We demonstrated that xenon exposure to human proximal tubular cells (HK‐2) led to activation of range of protective proteins. Xenon treatment prior to or after hypothermia–hypoxia challenge stabilized the HK‐2 cellular structure, diminished cytoplasmic translocation of high‐mobility group box (HMGB) 1 and suppressed NF‐...
Source: American Journal of Transplantation - May 24, 2013 Category: Transplant Surgery Authors: H. Zhao, H. R. Watts, M. Chong, H. Huang, C. Tralau‐Stewart, P. H. Maxwell, M. Maze, A. J. T. George, D. Ma Tags: Original Article Source Type: research