• Lars Hüter, Tim-Philipp Simon, Lenard Weinmann, Tobias Schuerholz, Konrad Reinhart, Gunter Wolf, Kerstin Ute Amann, and Gernot Marx.
• Department of Anaesthesiology and Intensive Care Medicine, University of Jena, Erlanger Allee, Jena, Germany. lars.hueter@med.uni-jena.de
• Crit Care. 2009 Jan 1; 13 (1): R23.

IntroductionThe aim of the study was to evaluate some of the underlying pathomechanisms of hydroxyethylstarch (HES) induced adverse effects on renal function using 24 porcine kidneys in an isolated perfusion model over six hours.MethodsInfusion of either 10% HES 200/0.5, 6% HES 130/0.42 or Ringer's lactate (RL) was performed to achieve an haematocrit of 20% in eight kidneys from four animals per group. Physiological and pathophysiological parameters were determined (including N-acetyl-beta-aminoglucosidase as a marker for lysosomal tubular damage). Histological investigations and immunohistological stainings of the kidneys were performed.ResultsInitially after haemodilution, HES 130/0.42 and HES 200/0.5 reduced urine output compared with RL (P < 0.01). After six hours, N-acetyl-beta-aminoglucosidase was significantly higher in HES 200/0.5 (81 +/- 23 U/L) compared with HES 130/0.42 (38 +/- 12 U/L) and RL (21 +/- 13 U/L; P < 0.001). Osmotic nephrosis-like lesions (OL) of the tubuli were present in all groups showing a significantly lower number of OL in RL (1.1 +/- 0.4; P = 0.002) compared with both HES groups (HES 200/0.5 = 2.1 +/- 0.6; HES 130/0.42 = 2.0 +/- 0.5). Macrophage infiltration was significantly higher in HES 200/0.5 compared with HES 130/0.42 (1.3 +/- 1.0 vs. 0.2 +/- 0.04; P = 0.044). There was a significant increase in interstitial cell proliferation in the HES 200/0.5 group vs. HES 130/0.42 (18.0 +/- 6.9 vs. 6.5 +/- 1.6; P = 0.006) with no significant difference in RL (13.5 +/- 4.0).ConclusionsWe observed impaired diuresis and sodium excretion by HES and identified renal interstitial proliferation, macrophage infiltration and tubular damage as potential pathological mechanisms of HES-induced adverse effects on renal function using an isolated porcine renal perfusion model. Furthermore, we demonstrated that 10% HES 200/0.5 had more of a pro-inflammatory effect compared with 6% HES 130/0.42 and caused more pronounced tubular damage than 6% HES 130/0.42 and RL. OL were present in all groups, but to a lesser degree after RL administration.

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