Endotoxic kidney injury in Beagle dogs assessed by serum creatinine and symmetric dimethylarginine, and urinary neutrophil gelatinase-associated lipocalin and clusterin.

Sepsis of Gram negative bacterial origin results in lipopolysaccharide-induced endotoxemia. This often leads to acute kidney injury (AKI) and its recognition remains a challenge and delays treatment. As renal damage occurs before a rise in serum creatinine is detected, new early biomarkers of kidney injury need to be explored. The aim of this study was to determine changes in serum parameters of renal function and urine biomarkers of renal injury. This was a descriptive study. Endotoxemia was induced intravenously in six anaesthetized Beagles (T1). To achieve normotension, dogs received fluids (T2), followed by a continuous infusion of noradrenaline and dexmedetomidine or 0.9% NaCl (T3). Ten minutes later, the dogs received fluids (T4) and noradrenaline and dexmedetomidine or 0.9% NaCl in a crossover manner (T5). At each timepoint, blood and urine were collected for serum creatinine, urea, symmetric dimethylarginine, urine protein/creatinine (UPC) ratio, urine neutrophil-gelatinase-associated lipocalin (U-NGAL), U-NGAL/creatinine ratio, urine clusterin (U-clusterin) and U-clusterin/creatinine ratio. Data were analyzed using a mixed-effect model taking into account time and stage of veterinary AKI (VAKI). Three of six dogs had a VAKI stage ≥1; one with anuria and elevated creatinine. Serum creatinine (P < 0.001), U-NGAL/creatinine ratio (P = 0.01) and U-clusterin/creatinine ratio increased over time (P < 0.01). The UPC ratio (mean (range) 0.68 (0.35-2.3) versus 0.39 (0.15-0.71) P < 0.01) and U-NGAL (3164 pg/mL (100-147,555) versus 100 (100-14,524), P = 0.01) were higher in VAKI stage ≥1 versus stage 0, respectively. Endotoxemia induced VAKI stage ≥1 in half of the dogs. Repeated measurement of selected parameters could detect AKI early.