Renal tissue PO2 sensing during acute hemodilution is dependent on the diluent

Sensing changes in blood oxygen content (Ca-O2) is an important physiological role of the kidney; however, the mechanism(s) by which the kidneys sense and respond to changes in Ca-O2 are incompletely understood. Accurate measurements of kidney tissue oxygen tension (Pkt(O2)) may increase our understanding of renal oxygen-sensing mechanisms and could inform decisions regarding the optimal fluid for intravascular volume resuscitation to maintain renal perfusion. In some clinical settings, starch solution may be nephrotoxic, possibly due to inadequacy of tissue oxygen delivery. We hypothesized that hemodilution with starch colloid solutions would reduce Pkt(O2) to a more severe degree than other diluents. Anesthetized Sprague-Dawley rats (n = 77) were randomized to undergo hemodilution with either colloid (6% hydroxyethyl starch or 5% albumin), crystalloid (0.9% saline), or a sham procedure (control) (n = 13-18 rats/group). Data were analyzed by ANOVA with significance assigned at P < 0.05. After hemodilution, mean arterial pressure (MAP) decreased marginally in all groups, while hemoglobin (Hb) and Ca-O2 decreased in proportion to the degree of hemodilution. Cardiac output was maintained in all groups after hemodilution. Pkt(O2) decreased in proportion to the reduction in Hb in all treatment groups. At comparably reduced Hb, and maintained arterial oxygen values, hemodilution with starch resulted in larger decreases in Pkt(O2) relative to animals hemodiluted with albumin or saline (P < 0.008). Renal medullary erythropoietin (EPO) mRNA levels increased more prominently, relative to other hypoxia-regulated molecules (GLUT-1, GAPDH, and VEGF). Our data demonstrate that the kidney acts as a biosensor of reduced Ca-O2 following hemodilution and that Pkt(O2) may provide a quantitative signal for renal cellular responsiveness to acute anemia. Evidence of a more severe reduction in Pkt(O2) following hemodilution with starch colloid solution suggests that tissue hypoxia may contribute to starch induced renal toxicity.