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dc.contributor.author Prókai, Ágnes
dc.contributor.author Csohány, Rózsa
dc.contributor.author Sziksz, Erna
dc.contributor.author Pap, Domonkos
dc.contributor.author Balicza-Himer L
dc.contributor.author Boros S
dc.contributor.author Magda, Balázs
dc.contributor.author Vannay, Ádám
dc.contributor.author Kis-Petik, Katalin
dc.contributor.author Fekete, Andrea
dc.contributor.author Peti-Peterdi J
dc.contributor.author Szabó, Attila
dc.date.accessioned 2016-11-03T13:45:57Z
dc.date.available 2016-11-03T13:45:57Z
dc.date.issued 2016
dc.identifier 84957436950
dc.identifier.citation pagination=325-333; journalVolume=100; journalIssueNumber=2; journalTitle=TRANSPLANTATION;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/3362
dc.identifier.uri doi:10.1097/TP.0000000000000961
dc.description.abstract BACKGROUND: Tacrolimus (Tac) and Cyclosporine A (CyA) calcineurin inhibitors (CNIs) are 2 effective immunosuppressants which are essential to prevent allograft rejection. Calcineurin inhibitors are known to be nephrotoxic. However, the precise mechanism of nephrotoxicity is not fully understood. In this study, we investigated the in vivo effects of CNIs on the local renal renin-angiotensin system in the collecting duct (CD). METHODS: Three-week-old mice were treated with either vehicle, CyA (2 mg/kg per day), Tac (0.075 mg/kg per day), CyA + Aliskiren (25 mg/kg per day), or Tac + Aliskiren for 3 weeks. Serum creatinine was measured. Renin and vascular endothelial growth factor (VEGF) contents in CD were evaluated with flow cytometry and multiphoton microscopy. The diameter of vessels was assessed with multiphoton microscopy, and the amount of renal collagen was determined by real-time polymerase chain reaction and Masson staining. RESULTS: The elevated level of serum creatinine in CNI groups was abolished by Aliskiren. Flow cytometric analysis found elevated renin content in principal cells, which was prevented by Aliskiren. This result was further confirmed with multiphoton microscopy. The VEGF content in CD correlated with reduced capillary diameter and with the formation of fibrotic islands. CONCLUSIONS: Calcineurin inhibitors induce production of renin in the CD that may contribute to decreased renal blood flow. In turn, CD responds with increased VEGF production, resulting in disproportional vessel growth, further worsening the local hypoxia and striped fibrosis surrounding the CDs. Aliskiren, a direct renin inhibitor blocks these effects and improves CNI-induced nephropathy by decreasing renin production in the CDs. Our data suggest that Aliskiren may be used for the prevention of CNI nephrotoxicity.
dc.relation.ispartof urn:issn:0041-1337
dc.title Calcineurin-Inhibition Results in Upregulation of Local Renin and Subsequent Vascular Endothelial Growth Factor Production in Renal Collecting Ducts.
dc.type Journal Article
dc.date.updated 2016-04-22T08:20:55Z
dc.language.rfc3066 en
dc.identifier.mtmt 2963548
dc.identifier.pubmed 26502369
dc.contributor.department SE/AOK/K/I. Sz. Gyermekgyógyászati Klinika
dc.contributor.department SE/AOK/K/ISZGYK/MTA-SE Gyermekgyógyászati és Nephrológiai Kutatócsoport
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote Prókai Á and Csohány R equally contributed.


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