Limits...
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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Effects of nitrite administration modality on mean arterial pressure (MAP) during brain deathRats were rendered brain dead (-●-) and then administered nitrite (0.1 mg/kg) as a bolus injection (-Δ-) or over 2h (-□-). No significant difference between BD alone or BD + nitrite administered over 2h by 2-way RM ANOVA was observed. Data show mean ± SEM (n=5) for BD alone or BD + continuous infusion of nitrite.
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Figure 2: Effects of nitrite administration modality on mean arterial pressure (MAP) during brain deathRats were rendered brain dead (-●-) and then administered nitrite (0.1 mg/kg) as a bolus injection (-Δ-) or over 2h (-□-). No significant difference between BD alone or BD + nitrite administered over 2h by 2-way RM ANOVA was observed. Data show mean ± SEM (n=5) for BD alone or BD + continuous infusion of nitrite.

Mentions: During induction of BD in this model, mean arterial pressure (MAP) increases and then rapidly (within 10mins) decreases and remains lower than before BD (Figure 2). Nitrite is a vasodilator and can promote hypotension. Initial studies therefore were designed to determine the optimal conditions for nitrite administration that would not exacerbate hypotension during brain death. Bolus administration of nitrite (0.1 mg/kg) led to a lower MAP compared to BD alone (not shown). We therefore tested an alternative nitrite administration protocol in which nitrite (0.1 mg) was administered over 2h of BD. Figure 2 shows that using this protocol, nitrite did not alter MAP compared to BD alone and was tested further for potential protective effects against BD induced kidney injury.


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)

Effects of nitrite administration modality on mean arterial pressure (MAP) during brain deathRats were rendered brain dead (-●-) and then administered nitrite (0.1 mg/kg) as a bolus injection (-Δ-) or over 2h (-□-). No significant difference between BD alone or BD + nitrite administered over 2h by 2-way RM ANOVA was observed. Data show mean ± SEM (n=5) for BD alone or BD + continuous infusion of nitrite.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Effects of nitrite administration modality on mean arterial pressure (MAP) during brain deathRats were rendered brain dead (-●-) and then administered nitrite (0.1 mg/kg) as a bolus injection (-Δ-) or over 2h (-□-). No significant difference between BD alone or BD + nitrite administered over 2h by 2-way RM ANOVA was observed. Data show mean ± SEM (n=5) for BD alone or BD + continuous infusion of nitrite.
Mentions: During induction of BD in this model, mean arterial pressure (MAP) increases and then rapidly (within 10mins) decreases and remains lower than before BD (Figure 2). Nitrite is a vasodilator and can promote hypotension. Initial studies therefore were designed to determine the optimal conditions for nitrite administration that would not exacerbate hypotension during brain death. Bolus administration of nitrite (0.1 mg/kg) led to a lower MAP compared to BD alone (not shown). We therefore tested an alternative nitrite administration protocol in which nitrite (0.1 mg) was administered over 2h of BD. Figure 2 shows that using this protocol, nitrite did not alter MAP compared to BD alone and was tested further for potential protective effects against BD induced kidney injury.

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