title: Citrate shows protective effects on cardiovascular and renal function in ischemia-induced acute kidney injury.
abstract: 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.
authors.affiliation: Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. anja.bienholz@uk-essen.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Bienholz
authors.affiliation: Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Reis
authors.affiliation: Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Pinar
authors.initials: P
authors.lastname: Sanli
authors.affiliation: Institute of Physiological Chemistry, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: de Groot
authors.affiliation: Institute of Physiological Chemistry, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Petrat
authors.affiliation: Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Hana
authors.initials: H
authors.lastname: Guberina
authors.affiliation: Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wilde
authors.affiliation: Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Fuat H
authors.initials: FH
authors.lastname: Saner
authors.affiliation: Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kribben
authors.affiliation: Department of Internal Medicine, Division of Nephrology, V.A. Ann Arbor Health System and University of Michigan, 1150 W. Medical Center Drive, 1560C MSRB II, Ann Arbor, MI, 48109-5676, USA.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Weinberg
authors.affiliation: Department of Nephrology and Hypertension, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Schittenhelmstr. 12, 24105, Kiel, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Feldkamp
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002125:Calcium Gluconate / Q000494:pharmacology; D019343:Citric Acid / Q000494:pharmacology*; D003404:Creatinine / Q000378:metabolism; D007668:Kidney / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D012077:Renal Artery; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D019343:Citric Acid; D000255:Adenosine Triphosphate; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D002125:Calcium Gluconate
keywords: Blood pressure; Citrate; Ischemia and reperfusion; Renal clamping