Renal function and integrity 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 functional consequences on the kidney have not been fully investigated. Here we determine whether a single application of hydroxyethyl starch, dosed to restore blood pressure (BP) within minutes following a blood loss, affects kidney outcome when assessed one day or 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, the 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). Renal function was determined in renal clearance studies (using 3H‐inulin and paramino hippurate [PAH]) under terminal anesthesia. In separate groups of animals plasma and urine were collected and kidneys harvested for gene expression analysis. N=10–11/group.ResultsAs expected, hematocrit was significantly lower at 1 day after hemorrhage versus CON. The initial hematocrit drop at day 1 and the subsequent recovery after 1 week were similar in ISO, VOL and HEX. As indicated by similar values for body weight, blood pressure, plasma electrolytes, and hormone markers (including renin, ANP and ADH) among the 4 groups, the 3 volume substitution protocols rapidly restored the volume status at 1 day after hemorrhage and this effect was sustained 1 week later. The data also indicated that ISO, VOL and HEX similarly preserved renal hemodynamics (GFR, RBF), tubular reabsorption (Na, K, Cl, fluid, glucose, calcium, phosphate) and tubular secretion (PAH) at 1 day and 1 week after hemorrhage. Measurement of albuminuria and markers of kidney injury and inflammation (incl. urine NGAL to creatinine ratios and renal mRNA expression of KIM‐1, CCL2 and IL6) indicated that the level of injury or inflammation was not consistently increased among any of the 4 groups.ConclusionA single bolus infusion of ISO, VOL or HEX, dosed to acutely restore BP after a 25% blood loss in rats, preserved or maintained integrated kidney function to a similar extent, when assessed one day or one week later.Support or Funding InformationFresenius Kabi Deutschland GmbHThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.