Abstract
BackgroundIschemia 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.MethodsAKI 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.ResultsIn 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.ConclusionsCitrate 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.
Highlights
Ischemia and reperfusion (I/R) is one of the major causes of acute kidney injury (AKI)
We recently introduced a novel rodent based animal model for studying ischemia/reperfusion (I/R) AKI in vivo that incorporates intensive biomonitoring during the ischemic and early postischemic periods
Effects of citrate on markers of organ injury and tissue Adenosine triphosphate (ATP) content In the normoxic control group the plasma creatinine (pCrea) and plasma lactate dehydrogenase (LDH) concentrations remained stable throughout the experiment
Summary
Ischemia and reperfusion (I/R) is one of the major causes of acute kidney injury (AKI). Citrate anticoagulation is frequently used in renal replacement therapy. Renal replacement therapy is one of the major options in severe cases of AKI. Kidney Disease Improving Global Outcomes (KDIGO) guidelines suggest the use of regional citrate anticoagulation instead of heparin in patients with AKI receiving continuous renal replacement therapy [5]. This suggestion is based on Bienholz et al BMC Nephrology (2017) 18:130 superior filter longevity [6, 7], and due to a reduction in bleeding risks accompanied by regional anticoagulation limited to the extracorporeal circuit [7,8,9]. Incorporating a locally adapted protocol and adequate metabolic biomonitoring especially including ionized calcium levels during treatment citrate anticoagulation can safely be used even in patients after liver transplantation [10]
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