Balanced Hydroxyethylstarch (HES 130/0.4) Impairs Kidney Function In-Vivo without Inflammation.

Martin Alexander Schick,Reinhard Schneider,Sven Flemming,Nicolas Schlegel,Raphael Romano Bruno,Jakob Wollborn,Christian Wunder,Norbert Roewer,Winfried Neuhaus,Wolfgang Baar,Christopher Held,Joerg Latus

doi:10.1371/journal.pone.0137247

Abstract

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 6h. After 24h 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.

Highlights

Infusion therapy is a cornerstone in intensive and perioperative care to increase intravascular volume and to preserve macro- and microcirculation
This study reveals no differences in acute kidney injury (AKI) using colloids (HES, gelatine, dextran or albumin) compared to crystalloids alone[5]
We conducted this study to evaluate, whether inflammation is the key trigger for HES induced AKI in vivo, or whether HES impairs kidney function even under healthy conditions in our previously published new rat model of septic AKI [7]

Summary

Introduction

Infusion therapy is a cornerstone in intensive and perioperative care to increase intravascular volume and to preserve macro- and microcirculation. In 2008, the VISEP-study results showed an increased risk of acute kidney injury (AKI) when 10% HES 200/0.4 solution was used in septic patients[1]. With 6S-, CRYSTMAS- and CHEST-study further trials demonstrated an increased incidence of AKI, when modern 6% HES 130/0.4 or 0.42 were infused[2–4]. We demonstrated that HES induces decreased cell viability in human proximal tubules cells (PTC) in vitro (Bruno et al A&A 2014)[6]. In this trial TNF-α did not worsen the harmful impact of HES on PTC, but only applied mass of HES molecules seemed to be responsible for the derogation of human PTC. All investigated HES solutions (potato or corn derived; balanced or non balanced) and molecular sizes (3–200 kDa) revealed PTC impairments. We conducted this study to evaluate, whether inflammation is the key trigger for HES induced AKI in vivo, or whether HES impairs kidney function even under healthy conditions in our previously published new rat model of septic AKI [7]

Methods

Results

Discussion

Conclusion