Effects of balanced crystalloid vs. 0.9% saline-based vs. balanced 6% tetrastarch infusion on renal function and tubular integrity in ovine endotoxemic shock

Objective: Conflicting data exist on the renal effects of hydroxyethyl starch preparations. The aim of the present study was to evaluate the impact of balanced crystalloids, as well as 0.9% saline-based and balanced 6% tetrastarch solutions, on renal function and ultrastructural morphologic correlates of acute kidney injury in an established model of ovine endotoxemic shock. Design: Randomized, controlled, experimental study. Setting: Animal research facility of a university hospital. Subjects: A total of 31 awake instrumented sheep. Interventions: The animals were subjected to continuous endotoxin infusion (Salmonella typhosa) at incremental doses until the mean arterial pressure was <65 mm Hg and arterial lactate was >= 2 mmol.L-1 or (if arterial hypotension was absent) arterial lactate was >= 4 mmol.L-1. The subjects were then randomized to receive no fluid resuscitation (control group, n = 5) or blinded infusion of a balanced crystalloid (n = 9), 0.9% saline-based (n = 8), or balanced 6% hydroxyethyl starch 130/0.4 (n = 9) up to a maximum dose of 50 mL.kg(-1), followed by open-label infusion of balanced crystalloid. Animals surviving the 12-hr intervention period were deeply anesthetized and killed. Kidney samples were taken immediately for transmission electron microscopic analyses. Additional specific experiments were performed to take kidney samples ex vivo. Measurements and Main Results: Endotoxemia was associated with arterial hypotension and capillary leakage. Fluid resuscitation established a hypotensive-hyperdynamic circulation in all resuscitated animals without significant hemodynamic differences among groups. Plasma creatinine and urea concentrations were higher in both hydroxyethyl starch groups as compared to the crystalloid group (creatinine, 1.2 +/- 0.1 and 1.4 +/- 0.3 vs. 0.8 +/- 0.1 mg.dL(-1); urea, 21 +/- 1 and 21 +/- 2 vs. 17 +/- 2 mg.dL(-1); p < .05 for 0.9% saline-based and balanced tetrastarch vs. crystalloids at 8 hrs). In contrast, kidney function, as measured by creatinine clearance and cumulative creatinine excretion, was similar between the colloid and crystalloid treatment groups (creatinine clearance at 8 hrs, 122 +/- 18 and 108 +/- 31 vs. 107 +/- 13 mL.min(-1).m(-2); creatinine excretion per hour alive, 283 +/- 29 and 264 +/- 19 vs. 291 +/- 24 mg.hr(-1); p > .05 for 0.9% saline-based and balanced tetrastarch vs. crystalloids), whereas kidney function deteriorated markedly in control animals. The electron microscopic tubular injury score was lower in hydroxyethyl starch-treated animals as compared to the crystalloid group. Vacuolar tubular cell alterations were present in all groups. The percentage of intact microvilli brush borders was significantly higher in sheep treated with either hydroxyethyl starch solution as compared to the other groups. Conclusions: The present study provides evidence that renal function, as measured by creatinine clearance and cumulative creatinine excretion as well as ultrastructural tubular integrity, is preserved with the use of 6% tetrastarch solutions despite increases in plasma levels of renal retention variables in ovine endotoxemic shock. (Crit Care Med 2011; 39:783-792)