Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function

Stacey S Kelpke, Bo Chen, Kelley M Bradley, Xinjun Teng, Phillip Chumley, Angela Brandon, Brett Yancey, Brandon Moore, Hughston Head, Liliana Viera, John A Thompson, David K Crossman, Molly S Bray, Devin E Eckhoff, Anupam Agarwal, Rakesh P Patel

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.
Original languageEnglish
Pages (from-to)304-13
Number of pages10
JournalKidney international
Volume82
Issue number3
DOIs
Publication statusPublished - Aug 2012

Keywords

  • Allopurinol
  • Animals
  • Benzoates
  • Brain Death
  • Gene Expression
  • Hemodynamics
  • Imidazoles
  • Inflammation
  • Kidney
  • Kidney Transplantation
  • Lipid Peroxidation
  • Male
  • Nitrites
  • Rats
  • Rats, Inbred Lew
  • Reperfusion Injury
  • Signal Transduction
  • Sodium Nitrite

Cite this