Renal hemodynamics and tubular function are preserved when hydroxyethyl starch is dosed to acutely restore blood pressure after blood loss in rats

Abstract

Hydroxyethyl starch (HES) is used clinically to replace blood loss and stabilize hemodynamics. However, the fate of HES in the kidney and the functional consequences on kidney function have not been fully investigated. The goal of this study was to determine whether a single application of hydroxyethyl starch, dosed to rapidly restore blood pressure (BP) following a blood loss, affects renal hemodynamics or transport when assessed one week later.MethodsUnder short‐term anesthesia, Sprague‐Dawley rats were subjected to a 25% blood loss over 6.25 min via the femoral vein. Immediately thereafter, Volulyte® 6% containing HES 130/0.4 (VOL) or Hextend® 6% containing HES 670/0.7 (HEX) or a balanced crystalloid solution (Isolyte®, ISO) were infused i.v. to restore BP within 4–4.5 minutes. Pilot studies established that this required doubling of the infused volume of ISO (20ml/kg) vs VOL and HEX (each 10ml/kg). Sham operated rats without blood loss/volume substitution were used as control (CON). One week later, renal function was determined in renal clearance studies (using 3H‐inulin and paramino hippurate [PAH]) under terminal anesthesia. N=10/group.ResultsBody weight, heart rate, and plasma concentrations of glucose, chloride, calcium, phosphate and hematocrit were similar among the 4 group (not shown). Mean arterial pressure (MAP), renal hemodynamics (including GFR and renal blood flow [RBF]), tubular reabsorption of fluid, chloride (Cl), glucose, calcium (Ca), and phosphate (P), and tubular secretion of PAH were likewise not different among the 4 groups (see table: MAP [mmHg]; GFR, RBF [ml/min]; FR‐Ex, fractional renal excretion [%]). MAP GFR RBF FR‐Ex FR‐Ex FR‐Ex FR‐Ex FR‐Ex FR‐Ex fluid Cl glucose Ca P PAH CON 121±5 2.5±0.1 19.3±2.0 1.0±0.1 0.3±0.1 0.1±0.1 0.9±0.2 2.3±1.1 391±39 ISO 121±5 2.4±0.1 18.4±2.0 0.9±0.1 0.4±0.1 0.1±0.1 0.9±0.1 3.8±1.5 392±43 VOL 118±3 2.5±0.2 19.2±3.1 0.9±0.1 0.3±0.1 0.1±0.1 0.9±0.1 2.5±1.0 410±72 HEX 126±3 2.3±0.2 19.3±3.5 1.1±0.2 0.5±0.2 0.1±0.1 1.0±0.2 3.3±1.4 422±54 ConclusionA single bolus infusion of VOL or HEX, dosed to acutely restore BP after a 25% blood loss in rats, does not alter renal hemodynamics or tubular transport function compared with sham operation or volume substitution with ISO, when assessed one week later.Support or Funding InformationNational Institutes of Health O'Brien Center (P30DK079337), Fresenius Kabi Deutschland GmbH