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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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Related in: MedlinePlus

Nitrite treatment improves post-transplantation renal function after brain deathKidneys were isolated from BD rats treated with saline (-●-) or nitrite (-■-) and then transplanted. Data show serum creatinine (Panel A) and BUN (Panel B) levels in the recipient as a function of time post-transplantation. Data are means ± SEM (n=6) and significantly different (P < 0.0001 for creatinine and P< 0.005 for BUN) by 2-way ANOVA and *P<0.001 or #P<0.05 by Bonferroni post test relative to BD + nitrite.
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Figure 3: Nitrite treatment improves post-transplantation renal function after brain deathKidneys were isolated from BD rats treated with saline (-●-) or nitrite (-■-) and then transplanted. Data show serum creatinine (Panel A) and BUN (Panel B) levels in the recipient as a function of time post-transplantation. Data are means ± SEM (n=6) and significantly different (P < 0.0001 for creatinine and P< 0.005 for BUN) by 2-way ANOVA and *P<0.001 or #P<0.05 by Bonferroni post test relative to BD + nitrite.

Mentions: Kidneys from rats rendered BD for 2h which were administered either saline or nitrite were transplanted and renal function assessed by measuring plasma creatinine and BUN (blood urea nitrogen) as a function of time post transplantation. Figure 3 shows that after transplantation of a kidney after BD, plasma creatinine and BUN increased for 2–3 days and then started to decrease indicating an initial worsening of renal function followed by resolution of injury. After transplantation of kidneys isolated from BD rats treated with nitrite however, creatinine and BUN levels were lower and decreased at faster rate compared to the BD alone group. Figure 1A–C shows that protective effects of nitrite occurred without significant increased nitrite levels in the plasma, RBC or kidneys 2h after BD induction. However, Figure 1D shows that while circulating nitrite levels decrease from the onset of BD alone, with nitrite therapy, plasma nitrite levels are elevated for the initial 30–60min and then gradually decrease over the next 60 min.


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)

Nitrite treatment improves post-transplantation renal function after brain deathKidneys were isolated from BD rats treated with saline (-●-) or nitrite (-■-) and then transplanted. Data show serum creatinine (Panel A) and BUN (Panel B) levels in the recipient as a function of time post-transplantation. Data are means ± SEM (n=6) and significantly different (P < 0.0001 for creatinine and P< 0.005 for BUN) by 2-way ANOVA and *P<0.001 or #P<0.05 by Bonferroni post test relative to BD + nitrite.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Nitrite treatment improves post-transplantation renal function after brain deathKidneys were isolated from BD rats treated with saline (-●-) or nitrite (-■-) and then transplanted. Data show serum creatinine (Panel A) and BUN (Panel B) levels in the recipient as a function of time post-transplantation. Data are means ± SEM (n=6) and significantly different (P < 0.0001 for creatinine and P< 0.005 for BUN) by 2-way ANOVA and *P<0.001 or #P<0.05 by Bonferroni post test relative to BD + nitrite.
Mentions: Kidneys from rats rendered BD for 2h which were administered either saline or nitrite were transplanted and renal function assessed by measuring plasma creatinine and BUN (blood urea nitrogen) as a function of time post transplantation. Figure 3 shows that after transplantation of a kidney after BD, plasma creatinine and BUN increased for 2–3 days and then started to decrease indicating an initial worsening of renal function followed by resolution of injury. After transplantation of kidneys isolated from BD rats treated with nitrite however, creatinine and BUN levels were lower and decreased at faster rate compared to the BD alone group. Figure 1A–C shows that protective effects of nitrite occurred without significant increased nitrite levels in the plasma, RBC or kidneys 2h after BD induction. However, Figure 1D shows that while circulating nitrite levels decrease from the onset of BD alone, with nitrite therapy, plasma nitrite levels are elevated for the initial 30–60min and then gradually decrease over the next 60 min.

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