Early diagnosis of acute kidney injury subsequent to severe hypotension and fluid resuscitation in anaesthetized dogs

ObjectivesTo document changes in urinary biomarker concentration and conventional diagnostic tests of acute kidney injury (AKI) following hypotension and fluid resuscitation in anaesthetized dogs.Study designExperimental, repeated measures, prospective study.AnimalsA group of six male adult Greyhound dogs.MethodsFollowing general anaesthesia, severe hypotension was induced by phlebotomy, maintaining mean arterial blood pressure (MAP) < 40 mmHg for 60 minutes, followed by resuscitation with intravenous gelatine solution to maintain MAP > 60 mmHg for 3 hours. Following euthanasia, renal tissue was examined by light microscopy (LM) and transmission electron microscopy (TEM). Urinary and serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), and gamma-glutamyl transpeptidase (GGT), serum creatinine and urine output were measured at baseline and hourly until euthanasia. Data are presented as mean and 95% confidence interval and analysed using repeated measures analysis of variance with Dunnett’s adjustment, p < 0.05.ResultsStructural damage to proximal renal tubular cells was evident on LM and TEM. Urinary biomarker concentrations were significantly elevated from baseline, peaking 2 hours after haemorrhage at 19.8 (15.1–25.9) ng mL^–1 NGAL (p = 0.002), 2.54 (1.64–3.43) mg mL^–1 CysC (p = 0.009) and 2043 (790–5458) U L^–1 GGT (p < 0.001). Serum creatinine remained within a breed-specific reference interval in all dogs. Urinary protein–creatinine ratio (UPC) was significantly elevated in all dogs from 1 hour following haemorrhage.Conclusions and clinical relevanceUrinary NGAL, CysC and GGT concentrations, and UPC were consistently elevated within 1 hour of severe hypotension, suggesting that proximal renal tubules are damaged in the earliest stage of ischaemia-reperfusion AKI. Measurement of urinary biomarkers may allow early diagnosis of AKI in anaesthetized dogs. Urinary GGT concentration and UPC are particularly useful as they can be measured on standard biochemistry analysers.     

Effects of isovolemic resuscitation with hemoglobin-based oxygen carrier Hemoglobin glutamer-200 (bovine) on systemic and mesenteric perfusion and oxygenation in a canine model of hemorrhagic shock: a comparison with 6% hetastarch solution and shed blood

OBJECTIVE: To study Hemoglobin glutamer-200 bovine (Hb-200), 6% hetastarch (HES) and shed whole blood (WB) resuscitation in canine hemorrhagic shock. STUDY DESIGN: Prospective laboratory investigation. Animals Twelve adult dogs [29 +/- 1 kg (mean +/- SD)]. METHODS: Anesthetized dogs were instrumented for recording systemic and mesenteric hemodynamic parameters and withdrawal of arterial, mixed and mesenteric venous blood, in which hematological, oxygenation, blood gas and acid-bases variables were determined. Recordings were made before [baseline (BL)], after 1 hour of hypovolemia and immediately and 3 hours post-resuscitation with 30 mL kg(-1) of either Hb-200, HES, or WB. RESULTS: Blood withdrawal (average 34 +/- 2 mL kg(-1)) caused significant hemodynamic changes, metabolic acidosis and hyperlactatemia characteristic for hemorrhagic shock. Only WB transfusion restored all variables. Hemoglobin glutamer-200 bovine infusion returned most hemodynamic parameters including cardiac output and mesenteric arterial blood flow to BL but increased mean arterial pressure above BL (p < 0.05). However, Hb-200 failed to restore total Hb and arterial oxygen content (CaO2), leaving systemic (DO2I) and mesenteric O2 delivery (DO2Im) below BL (p < 0.05). Nevertheless, acid-base variables recovered completely after Hb-200 resuscitation, and met-hemoglobin (Met-Hb) levels increased (p < 0.05). Hetastarch resuscitation returned hemodynamic variables to or above BL but further decreased total Hb and CaO2, preventing recovery of sDO2I and mDO2I (p < 0.05). Thus, systemic and mesenteric O2 extraction stayed above BL (p < 0.05) while acid-base variables recovered to BL, although slower than in Hb-200 and WB groups (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Resuscitation with Hb-200 seemed to resolve metabolic acidosis and lactatemia more rapidly than HES, but not WB; yet it is not superior to HES in improving DO2I and DO2Im. The hyperoncotic property of solutions like Hb-200 that results in rapid volume expansion with more homogenous microvascular perfusion and the ability to facilitate diffusive O2 transfer accelerating metabolic recovery may be the key mechanisms underlying their beneficial effects as resuscitants.