Volume replacement with hydroxyethyl starch: is there an influence on kidney function?

Abstract

Hydroxyethyl starch (HES) solutions are synthetic colloids with the pharmacological properties that are closest to natural colloids. In Germany, numerous types of HES preparations with different combinations of concentration, weight-averaged mean molecular weight (Mw), and hydroxyethylation pattern are available. They differ with regard to their volume-supporting capacity, intravascular half-life, and side effect profile. The elimination of HES molecules varies with the Mw and degree of substitution (DS). Large HES molecules undergo hydrolytic cleavage by alpha-amylase and are excreted in the urine, or they are phagocytosed by the reticuloendothelial system. The smaller HES molecules are eliminated by glomerular filtration. The higher the DS, the slower the metabolism and elimination of the molecule. Although HES can be used safely even in large doses in patients without altered kidney function, renal dysfunction and acute renal failure after HES infusion have been reported in patients who share several risk factors, such as preexisting renal disease, advanced age in combination with dehydration, or treatment with high doses of slow degradable HES solutions. Since there is no direct chemical toxicity of HES, the most likely mechanism for HES-induced renal dysfunction may be swelling and vacuolization of tubular cells ("osmotic nephrosis-like lesions") and tubular obstruction due to the production of hyperviscous urine. Considering this pathogenesis, it can be hypothesized that all hyperoncotic colloid solutions can induce renal impairment. In the case of HES, the risk of high plasma colloid osmotic pressure and thus the risk of acute renal failure are probably increased by high concentrations of the colloid or repeated administration of slowly degradable HES with a high Mw and DS. With adequate hydration, using sufficient amounts of crystalloids, HES has little if any adverse effects on renal function. Furthermore, modern -rapidly degradable HES solutions with a low Mw and DS, such as HES 130/0.4, do not increase the risk for renal dysfunction even when used in large amounts perioperatively.