10% Hydroxyethylstarch impairs renal function and induces interstitial proliferation, macrophage infiltration and tubular damage

Hüter and colleagues recently published an experimental paper about possible pathomechanisms of hydroxyethyl-starch (HES)-induced adverse effects on renal function in an isolated perfusion model of 6 hours [1]. The authors should be congratulated for their attempt to shed light on the influence of different HES preparations on renal function, combining functional results and histological data. In the recently published prospective, randomized, controlled Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP) trial, 10% HES 200/05 caused a close to significant increase in 90-day mortality in septic patients. Renal failure and renal replacement therapy significantly increased dose dependently compared with Ringer's lactate treatment. Unfortunately, 100 out of 262 patients in the HES group received more than the maximum allowed daily dose on at least 1 day, the majority occurring on the first day after study inclusion. The patients without a violation of the maximum daily dose administration had a mortality rate even lower than that in the Ringer's lactate group [2]. In their isolated renal perfusion model, Hüter and colleagues tried to answer some of the questions originating from the VISEP trial, comparing 10% HES 200/0.5, 6% HES 130/0.42 and Ringer's lactate [1]. The hyperoncotic 10% HES, used in the VISEP study, showed severe oliguria, impaired potassium excretion and signs of lysosomal tubular damage. In contrast, isovolemic 6% HES showed no difference compared with Ringer's lactate in creatinine clearance, sodium excretion and N-acetyl-β-D-glucosamidase in urine. The 6% HES even showed a decreased inflammatory reaction compared with 10% HES and Ringer's lactate. Interestingly, osmotic-nephrosis-like lesions were found in all three groups, also to a lesser extent in the Ringer's lactate group. These lesions represent a quantity-dependent accumulation of proximal tubular lysosomes due to administration of exogenous solutes [3]. Principally, the lysosomal swelling is reversible, but any process such as ischaemia or pre-existing kidney damage that impairs lysosomal digestion further delays degradation. The presence of osmotic nephrosis does not necessarily have an impact on proximal tubular function [3]. The second significant difference between 6% HES and Ringer's lactate was the amount of urine produced [1]. The authors take this together with the increased amount of osmotic nephrosis as a sign of impaired renal function due to 6% HES. An alternative explanation for the difference in urinary output would be 0.9% NaCl, the carrier fluid of the HES solution. In an elegant animal model, Wilcox showed that hyperosmolar chloride-containing solutes reduce renal …