Citrate shows protective effects on cardiovascular and renal function in
ischemia-induced acute kidney injury
#MMPMID28395656
Bienholz A
; Reis J
; Sanli P
; de Groot H
; Petrat F
; Guberina H
; Wilde B
; Witzke O
; Saner FH
; Kribben A
; Weinberg JM
; Feldkamp T
BMC Nephrol
2017[Apr]; 18
(1
): 130
PMID28395656
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BACKGROUND: Ischemia and reperfusion (I/R) is one of the major causes of acute
kidney injury (AKI). Citrate reduces hypoxia-induced mitochondrial energetic
deficits in isolated proximal tubules. Moreover, citrate anticoagulation is now
frequently used in renal replacement therapy. In the present study a rat model of
I/R-induced AKI was utilized to examine renal protection by citrate in vivo.
METHODS: AKI was induced by bilateral renal clamping (40 min) followed by
reperfusion (3 h). Citrate was infused at three different concentrations
(0.3 mmol/kg/h; 0.6 mmol/kg/h and 1.0 mmol/kg/h) continuously for 60 min before
and 45 min after ischemia. Plasma calcium concentrations were kept stable by
infusion of calcium gluconate. The effect of citrate was evaluated by
biomonitoring, blood and plasma parameters, histopathology and tissue ATP
content. RESULTS: In comparison to the normoxic control group bilateral renal
ischemia led to an increase of creatinine and lactate dehydrogenase activity and
a decrease in tissue ATP content and was accompanied by a drop in mean arterial
blood pressure. Infusion of 1.0 mmol/kg/h citrate led to lower creatinine and
reduced LDH activity compared to the I/R control group and a tendency for higher
tissue ATP content. Pre-ischemic infusion of 1.0 mmol/kg/h citrate stabilized
blood pressure during ischemia. CONCLUSIONS: Citrate has a protective effect
during I/R-induced AKI, possibly by limiting the mitochondrial deficit as well as
by beneficial cardiovascular effects. This strengthens the rationale of using
citrate in continuous renal replacement therapy and encourages consideration of
citrate infusion as a therapeutic treatment for AKI in humans.
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