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

Kelpke SS, Chen B, Bradley KM, Teng X, Chumley P, Brandon A, Yancey B, Moore B, Head H, Viera L, Thompson JA, Crossman DK, Bray MS, Eckhoff DE, Agarwal A, Patel RP - Kidney Int. (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

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.

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Circulating nitrite levels are decreased during brain deathPlasma (Panel A), Red blood cell (RBC) (Panel B) and kidney (Panel C) concentrations of nitrite were measured in rats after 2h of sham (control), brain death (BD) or BD + nitrite therapy. Data show means ± SEM, n= 3–5. *P < 0.05, **P<0.02 relative to control by t-test. Panel D shows time dependent changes in plasma nitrite levels in BD and BD ± nitrite therapy groups. Data show fold change relative to time 0 (pre BD induction) and are mean ± SEM (n=2–3). P < 0.01 by 2-way ANOVA and *P<0.01 by Bonferroni post test. (Plasma nitrite levels without normalization to protein ranged between 44 – 1140nM).
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Figure 1: Circulating nitrite levels are decreased during brain deathPlasma (Panel A), Red blood cell (RBC) (Panel B) and kidney (Panel C) concentrations of nitrite were measured in rats after 2h of sham (control), brain death (BD) or BD + nitrite therapy. Data show means ± SEM, n= 3–5. *P < 0.05, **P<0.02 relative to control by t-test. Panel D shows time dependent changes in plasma nitrite levels in BD and BD ± nitrite therapy groups. Data show fold change relative to time 0 (pre BD induction) and are mean ± SEM (n=2–3). P < 0.01 by 2-way ANOVA and *P<0.01 by Bonferroni post test. (Plasma nitrite levels without normalization to protein ranged between 44 – 1140nM).

Mentions: Nitrite levels decrease during ischemic stress and nitrite therapy has been shown to improve renal function after ischemia-reperfusion 13,25,28,30. Using nitrite + nitrate as an index for NO-production, previous studies have concluded that excessive NO formation does not occur during 2h BD in rats 31. Recent studies however, have suggested that nitrite is a more selective index of NO-formation in mammals 32. Figure 1 shows that circulating nitrite levels are decreased ~60–70% after 2h of BD. However, renal nitrite levels did not change after BD.


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

Kelpke SS, Chen B, Bradley KM, Teng X, Chumley P, Brandon A, Yancey B, Moore B, Head H, Viera L, Thompson JA, Crossman DK, Bray MS, Eckhoff DE, Agarwal A, Patel RP - Kidney Int. (2012)

Circulating nitrite levels are decreased during brain deathPlasma (Panel A), Red blood cell (RBC) (Panel B) and kidney (Panel C) concentrations of nitrite were measured in rats after 2h of sham (control), brain death (BD) or BD + nitrite therapy. Data show means ± SEM, n= 3–5. *P < 0.05, **P<0.02 relative to control by t-test. Panel D shows time dependent changes in plasma nitrite levels in BD and BD ± nitrite therapy groups. Data show fold change relative to time 0 (pre BD induction) and are mean ± SEM (n=2–3). P < 0.01 by 2-way ANOVA and *P<0.01 by Bonferroni post test. (Plasma nitrite levels without normalization to protein ranged between 44 – 1140nM).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3412933&req=5

Figure 1: Circulating nitrite levels are decreased during brain deathPlasma (Panel A), Red blood cell (RBC) (Panel B) and kidney (Panel C) concentrations of nitrite were measured in rats after 2h of sham (control), brain death (BD) or BD + nitrite therapy. Data show means ± SEM, n= 3–5. *P < 0.05, **P<0.02 relative to control by t-test. Panel D shows time dependent changes in plasma nitrite levels in BD and BD ± nitrite therapy groups. Data show fold change relative to time 0 (pre BD induction) and are mean ± SEM (n=2–3). P < 0.01 by 2-way ANOVA and *P<0.01 by Bonferroni post test. (Plasma nitrite levels without normalization to protein ranged between 44 – 1140nM).
Mentions: Nitrite levels decrease during ischemic stress and nitrite therapy has been shown to improve renal function after ischemia-reperfusion 13,25,28,30. Using nitrite + nitrate as an index for NO-production, previous studies have concluded that excessive NO formation does not occur during 2h BD in rats 31. Recent studies however, have suggested that nitrite is a more selective index of NO-formation in mammals 32. Figure 1 shows that circulating nitrite levels are decreased ~60–70% after 2h of BD. However, renal nitrite levels did not change after BD.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

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.

Show MeSH
Related in: MedlinePlus