Balanced Hydroxyethylstarch (HES 130/0.4) Impairs Kidney Function In-Vivo without Inflammation.
Volume therapy is a standard procedure in daily perioperative care, and there is an ongoing discussion about the benefits of colloid resuscitation with hydroxyethylstarch (HES). In sepsis HES should be avoided due to a higher risk for acute kidney injury (AKI). Results of the usage of HES in patients without sepsis are controversial. Therefore we conducted an animal study to evaluate the impact of 6% HES 130/0.4 on kidney integrity with sepsis or under healthy conditions Sepsis was induced by standardized Colon Ascendens Stent Peritonitis (sCASP). sCASP-group as well as control group (C) remained untreated for 24 h. After 18 h sCASP+HES group (sCASP+VOL) and control+HES (C+VOL) received 50 ml/KG balanced 6% HES (VOL) 130/0.4 over 6 h. After 24 h kidney function was measured via Inulin- and PAH-Clearance in re-anesthetized rats, and serum urea, creatinine (crea), cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL) as well as histopathology were analysed. In vitro human proximal tubule cells (PTC) were cultured +/- lipopolysaccharid (LPS) and with 0.1-4.0% VOL. Cell viability was measured with XTT-, cell toxicity with LDH-test. sCASP induced severe septic AKI demonstrated divergent results regarding renal function by clearance or creatinine measure focusing on VOL. Soleley HES (C+VOL) deteriorated renal function without sCASP. Histopathology revealed significantly derangements in all HES groups compared to control. In vitro LPS did not worsen the HES induced reduction of cell viability in PTC cells. For the first time, we demonstrated, that application of 50 ml/KG 6% HES 130/0.4 over 6 hours induced AKI without inflammation in vivo. Severity of sCASP induced septic AKI might be no longer susceptible to the way of volume expansion.
Institute of Anaesthesia and Critical Care, University Hospital Würzburg, Würzburg, Germany.
Martin Alexander
MA
Schick
Institute of Anaesthesia and Critical Care, University Hospital Würzburg, Würzburg, Germany; Department of Anesthesiology and Intensive Care Medicine, University Medical Center Freiburg, Freiburg, Germany.
Wolfgang
W
Baar
Institute of Anaesthesia and Critical Care, University Hospital Würzburg, Würzburg, Germany.
Raphael Romano
RR
Bruno
Institute of Anaesthesia and Critical Care, University Hospital Würzburg, Würzburg, Germany; Department of Anesthesiology and Intensive Care Medicine, University Medical Center Freiburg, Freiburg, Germany.
Jakob
J
Wollborn
Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.
Christopher
C
Held
Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.
Reinhard
R
Schneider
Department of general, visceral, vascular and paediatric surgery (Department of Surgery I), University of Würzburg, Würzburg, Germany.
Sven
S
Flemming
Department of general, visceral, vascular and paediatric surgery (Department of Surgery I), University of Würzburg, Würzburg, Germany.
Nicolas
N
Schlegel
Institute of Anaesthesia and Critical Care, University Hospital Würzburg, Würzburg, Germany.
Norbert
N
Roewer
Institute of Anaesthesia and Critical Care, University Hospital Würzburg, Würzburg, Germany; Department of Medicinal Chemistry, University of Vienna, Vienna, Austria; Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
Winfried
W
Neuhaus
Institute of Anaesthesia and Critical Care, University Hospital Würzburg, Würzburg, Germany.
Christian
C
Wunder
D058186:Acute Kidney Injury / Q000097:blood / Q000209:etiology* / Q000473:pathology; D000209:Acute-Phase Proteins; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003102:Colloids; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000378:metabolism; D004195:Disease Models, Animal; D005440:Fluid Therapy / Q000009:adverse effects*; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000009:adverse effects*; D007249:Inflammation; D007275:Injections, Intravenous; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011518:Proto-Oncogene Proteins / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D014508:Urea / Q000097:blood
D000209:Acute-Phase Proteins; D015415:Biomarkers; D003102:Colloids; D055316:Cystatin C; D006895:Hydroxyethyl Starch Derivatives; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D014508:Urea; D003404:Creatinine