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01.12.2017 | Research article | Ausgabe 1/2017 Open Access

BMC Nephrology 1/2017

Citrate shows protective effects on cardiovascular and renal function in ischemia-induced acute kidney injury

BMC Nephrology > Ausgabe 1/2017
Anja Bienholz, Jonas Reis, Pinar Sanli, Herbert de Groot, Frank Petrat, Hana Guberina, Benjamin Wilde, Oliver Witzke, Fuat H. Saner, Andreas Kribben, Joel M. Weinberg, Thorsten Feldkamp
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Electronic supplementary material

The online version of this article (doi:10.​1186/​s12882-017-0546-1) contains supplementary material, which is available to authorized users.
Herbert de Groot deceased.



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.


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.


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.


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.
Additional file 1: Figure S1. Ionized plasma chloride levels. Box plots with whiskers indicating minimum and maximum, six rats per group. ** p < 0.01 vs. I/R control group. (PDF 30 kb)
Additional file 2: Figure S2. Urine output. Urine output calculated from samples collected during A 45 min before ischemia B 120–180 min of reperfusion. (PDF 22 kb)
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