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Hydroxyethyl starch 200/0.5 induces more renal macrophage infiltration than hydroxyethyl starch 130/0.42 in an isolated renal perfusion model

Introduction

The pathological renal mechanisms of hydroxyethylstarch (HES) are not identified. We designed an isolated renal perfusion model in which we try to identify possible mechanisms of injury between different HES preparations.

Methods

After approval of the local animal protection committee, 24 porcine kidneys in an isolated renal perfusion model of 6 hours duration were studied. We compared three different infusion solutions: 10% HES 200/0.5 (HES200) versus 6% HES 130/0.42 (HES130) versus Ringer's lactate (RL). Infusion was supplied to achieve a stable hematocrit of 0.2. Tubular damage was assessed with N-acetyl-β-D-glucosaminidase (β-NAG). After immunohistological staining, proliferation (proliferating nuclear antigen (PCNA)) and macrophage activation (ED-1+macrophages (ED-1)) were analyzed as positive cells/visual field. Effects of infusion solution and time were statistically analyzed by ANOVA for repeated measurements. The histological changes were analyzed using ANOVA.

Results

β-NAG was significantly different between groups (P < 0.001) (Figure 1). For ED-1 there were significant differences between HES200 and HES130 (1.3 ± 0.4 vs 0.17 ± 0.04, P = 0.044). Proliferation was significantly greater in the HES200 versus the HES130 group (18.8 ± 3.2 vs 7.2 ± 0.8, P = 0.008). Subanalysis of PCNA showed that these differences occurred in the interstitium and not in the glomerulus (18.0 ± 0.3 vs 6.5 ± 0.1, P = 0.006).

Figure 1
figure 1

N-acetyl-β-D-glucosaminidase over time for the three infusion solutions.

Conclusion

For the first time we identified proliferation and macrophage activation as the pathomechanism causing renal injury after HES application. Furthermore, the degree of renal injury in our model was significantly lower using HES130 compared with HES200.

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Hüter, L., Simon, T., Weinmann, L. et al. Hydroxyethyl starch 200/0.5 induces more renal macrophage infiltration than hydroxyethyl starch 130/0.42 in an isolated renal perfusion model. Crit Care 12 (Suppl 2), P232 (2008). https://doi.org/10.1186/cc6453

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