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

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.

• Authors: 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
• Journal: Kidney international (Kidney Int) Vol. 82 Issue 3 Pg. 304-13 (Aug 2012) ISSN: 1523-1755 [Electronic] United States
• PMID: 22534964 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Benzoates
• Imidazoles
• Nitrites
• 1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole
• Allopurinol
• Sodium Nitrite

Topics

• Allopurinol (pharmacology)
• Animals
• Benzoates (pharmacology)
• Brain Death (physiopathology)
• Gene Expression (drug effects)
• Hemodynamics (drug effects)
• Imidazoles (pharmacology)
• Inflammation (prevention & control)
• Kidney (blood supply, drug effects, injuries, physiopathology)
• Kidney Transplantation (methods, physiology)
• Lipid Peroxidation (drug effects)
• Male
• Nitrites (blood)
• Rats
• Rats, Inbred Lew
• Reperfusion Injury (genetics, physiopathology, prevention & control)
• Signal Transduction (drug effects)
• Sodium Nitrite (administration & dosage)