Effect of administration of nonsteroidal anti-inflammatory drugs before surgery on renal function in clinically normal dogs

OBJECTIVES: To investigate renal function in clinically normal dogs undergoing general anesthesia for ovariohysterectomies that received nonsteriodal antiinflammatory drugs (NSAID) before surgery. ANIMALS: 40 clinically normal dogs. PROCEDURE: After induction of anesthesia, dogs were given an analgesic. Renal function was assessed before surgery and 24 and 48 hours after surgery by means of serum urea and creatinine concentrations, fractional clearance of sodium (FC(Na)), urine gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) activities, and urine analysis. Ten dogs in each of 4 groups received ketorolac tromethamine (0.5 mg/kg of body weight), ketoprofen (1 mg/kg), carprofen (4 mg/kg), or morphine (0.1 mg/kg; control group). RESULTS: Duration of general anesthesia ranged from 1.75 to 5 hours, with a mean of 3 hours. Two ketorolac- and 2 ketoprofen-treated dogs had transient azotemia. A significant decrease in the FC(Na) between before surgery and 24 hours after surgery, and between before surgery and 48 hours after surgery, was found in ketoprofen- and carprofen-treated dogs. Ketorolac-, ketoprofen-, and morphine-treated dogs had a decrease in urine specific gravity. Two ketorolac, 1 ketoprofen-, 1 carprofen-, and 4 morphine-treated dogs had increases in renal tubular epithelial cells on urine sediment examination 24 hours after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: In clinically normal dogs undergoing general anesthesia and elective surgery, the use of NSAID as analgesics is not contraindicated. Compared with ketorolac or ketoprofen, carprofen had the least effect on renal function and integrity.     

Renal effects of carprofen administered to healthy dogs anesthetized with propofol and isoflurane

OBJECTIVE: To evaluate renal effects of carprofen in healthy dogs following general anesthesia. DESIGN: Randomized clinical trial. ANIMALS: 10 English hound dogs (6 females and 4 males). PROCEDURE: Dogs were randomly assigned to control (n = 5) or carprofen (5) groups. Anesthesia was induced with propofol (6 to 8 mg/kg [2.7 to 3.6 mg/lb] of body weight, i.v.) and maintained with isoflurane (end-tidal concentration, 2.0%). Each dog underwent two 60-minute anesthetic episodes with 1 week between episodes, and mean arterial blood pressure was maintained between 60 and 90 mm Hg during each episode. Dogs in the carprofen group received carprofen (2.2 mg/kg [1 mg/lb], p.o.) at 9:00 AM and 6:00 PM the day before and at 7:00 AM the day of the second anesthetic episode. Glomerular filtration rates (GFR) were determined during each anesthetic episode by use of renal scintigraphy. Serum creatinine and BUN concentrations and the urine gamma-glutamyltransferase-to-creatinine concentration (urine GGT:creatinine) ratio were determined daily for 2 days before and 5 days after general anesthesia. RESULTS: Significant differences were not detected in BUN and serum creatinine concentrations, urine GGT:creatinine ratio, and GFR either between or within treatment groups over time. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen did not significantly alter renal function in healthy dogs anesthetized with propofol and isoflurane. These results suggest that carprofen may be safe to use for preemptive perioperative analgesia, provided that normal cardiorespiratory function is maintained.     

Hepatic effects of halothane and isoflurane anesthesia in goats

OBJECTIVE: To determine hepatic effects of halothane and isoflurane anesthesia in young healthy goats. DESIGN: Randomized prospective clinical trial. ANIMALS: 24 healthy 9-month-old female goats. PROCEDURE: Goats were sedated with xylazine hydrochloride and ketamine hydrochloride and anesthetized with halothane (n = 12) or isoflurane (12) while undergoing tendon surgery. End-tidal halothane and isoflurane concentrations were maintained at 0.9 and 1.2 times the minimal alveolar concentrations, respectively, and ventilation was controlled. Venous blood samples were collected approximately 15 minutes after xylazine was administered and 24 and 48 hours after anesthesia, and serum aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) activities and bilirubin concentration were measured. Goats were euthanatized 25 or 62 days after anesthesia, and postmortem liver specimens were submitted for histologic examination. RESULTS: All goats recovered from anesthesia and survived until euthanasia. Serum SDH, GGT, and ALP activities and bilirubin concentration did not increase after anesthesia, but serum AST activity was significantly increased. However, serum hepatic enzyme activities were within reference limits at all times in all except 1 goat in which serum AST activity was high 24 and 48 hours after anesthesia. This goat had been anesthetized with halothane and had the longest duration of anesthesia. No clinically important abnormalities were seen on histologic examination of liver specimens. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of halothane or isoflurane for anesthesia in young healthy goats is unlikely to cause hepatic injury.     

Serum gamma-glutamyl transpeptidase activity in healthy cats and cats with induced hepatic disease

Activities of serum gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) were determined in healthy cats and in cats before and after treatment: common bile duct ligation, carbon tetrachloride administration, sham surgery, or anesthesia only. Significant (P less than 0.01) increases in serum GGT, ALP, and ALT occurred in cats with ligated bile ducts. Significant (P less than 0.01) increases in serum ALT occurred in carbon tetrachloride-treated cats. Increases of serum GGT, ALP, or ALT were not observed in cats subjected to sham surgery or anesthesia only compared with these cats' baseline values and values in healthy cats. Tissue GGT activity was measured in liver, renal cortex, jejunal mucosa, and bile ducts. There was a 1.5-fold increase in GGT activity in livers of cats with ligated bile ducts, compared with that in livers of healthy cats.     

Effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing surgery for fracture repair

OBJECTIVE: To evaluate effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing general anesthesia for fracture repair. ANIMALS: 26 client-owned dogs. PROCEDURE: Anesthesia was induced with levomethadone, diazepam, and propofol and maintained by administration of isoflurane in oxygen-nitrous oxide. Carprofen (4 mg/kg, SC) was administered 1 hour before induction to 13 dogs (group 1) and after extubation to the other 13 dogs (group 2). All dogs also received carprofen (4 mg/kg, SC, q 24 h) for the first 4 days after surgery. Renal function (glomerular filtration rate [GFR], urinary protein-to-urinary creatinine ratio [UP:UC], and results of urinalysis and biochemical analysis of plasma), hemostatic variables (bleeding time, platelet aggregation, prothrombin time [PT], activated partial thromboplastin time [APTT], and platelet count), and Hct were assessed before and at various time points after surgery. RESULTS: Analysis of results for renal function tests, most of the hemostatic and plasma biochemical variables, and Hct did not reveal significant differences between treatment groups. Values for GFR, UP:UC, PT, APTT, and platelet aggregation were outside reference ranges in many dogs before surgery and during the first 6 hours after surgery. In most dogs, these trauma-induced pathologic changes returned to within reference ranges during the 4-day period after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen did not cause clinically relevant adverse effects in dogs anesthetized for fracture repair after 5 days of treatment, even when it was administered before surgery or given to patients with trauma-induced alterations in renal function or hemostasis.     

Renal biomarkers in domestic species

Current conventional tests of kidney damage and function in blood (serum creatinine and urea nitrogen) and urine (urine protein creatinine ratio and urine specific gravity) are widely used for diagnosis and monitoring of kidney disease. However, they all have important limitations, and additional markers of glomerular filtration rate and glomerular and tubular damage are desirable, particularly for earlier detection of renal disease when therapy is most effective. Additionally, urinary markers of kidney damage and function may help localize damage to the affected portion of the kidney. In general, the presence of high‐ and intermediate‐molecular weight proteins in the urine are indicative of glomerular damage, while low‐molecular weight proteins and enzymes in the urine suggest tubular damage due to decreased reabsorption of proteins, direct tubular damage, or both. This review aims to discuss many of these new blood and urinary biomarkers in domestic veterinary species, focusing primarily on dogs and cats, how they may be used for diagnosis of renal disease, and their limitations. Additionally, a brief discussion of serum creatinine is presented, highlighting its limitations and important considerations for its improved interpretation in domestic species based on past literature and recent studies.     

Evaluation of clinical status, renal function, and hematopoietic variables after unilateral nephrectomy in canine kidney donors

OBJECTIVE: To determine clinical status and renal and hematopoietic function after kidney donation and identify risks associated with kidney donation in dogs. DESIGN: Prospective study. ANIMALS: 14 dogs that underwent unilateral nephrectomy for kidney donation. PROCEDURES: Records were reviewed retrospectively to collect data regarding prenephrectomy clinicopathologic variables. Dogs were reexamined prospectively at various times after nephrectomy, and pre- and postnephrectomy CBC, serum biochemical analyses, urinalysis, and urine protein-to-urine creatinine ratio were compared. Six dogs had postnephrectomy renal volume determined ultrasonographically, and 4 of those dogs also underwent scintigraphic determination of glomerular filtration rate and renal biopsy. RESULTS: All dogs were clinically normal at the time of reevaluation. There were no significant differences between prenephrectomy and postnephrectomy values for BUN concentration or urine specific gravity. Mean postnephrectomy serum creatinine concentration was significantly greater than prenephrectomy concentration. Mean serum phosphorus concentration was significantly decreased after nephrectomy, and mean Hct, corpuscular volume, and corpuscular hemoglobin concentration were significantly increased after nephrectomy. Postnephrectomy renal volume was greatest in dogs < 12 months old at the time of surgery. Mean postnephrectomy glomerular filtration rate was 2.82 +/- 1.12 mL/kg/ min (1.28 +/- 0.51 mL/lb/min). Renal biopsy specimens obtained during and after nephrectomy were histologically normal. CONCLUSIONS AND CLINICAL RELEVANCE: Renal and hematopoietic variables were within reference ranges in dogs examined up to 2.5 years after unilateral nephrectomy. Compensatory renal hypertrophy was greatest in dogs < 1 year of age at donation. Donor age, along with histocompatability, may be an important factor in selecting dogs for kidney donation.     

Evaluation of a technique for measurement of gamma-glutamyltranspeptidase in equine urine

gamma-Glutamyltranspeptidase (GGT) activity in equine urine was measured, using an assay developed for use with serum and was found to be reproducible. The GGT activity was measured in samples prepared by serial dilution of exogenous GGT with equine urine, and the activity was determined to be linear between 21 IU/L and 407 IU/L. The behavior of exogenously added GGT was compared in equine serum and urine. The enzyme behaved similarly in both fluids. The GGT activity was measured in serum and urine samples after storage at -20, 4, and 25 C for 24 and/or 72 hours. Enzyme activity decreased after storage at all temperatures and times, but the decrease was greatest and most variable at -20 C. The urine GGT: urine creatinine ratio was calculated on serial urine samples collected over 24 hours. Although the urine GGT activity and creatinine concentration had significant variation, the ratio remained constant. The urine GGT: urine creatinine ratio was calculated from random urine samples collected from 27 clinically healthy adult horses and was found to be 10.52 +/- 4.78 (mean +/- SD).     

Analgesic effect of pre-operative etodolac and butorphanol administration in dogs undergoing ovariohysterectomy

The analgesic, bleeding, and renal effects of dogs pre‐medicated with etodolac with and without butorphanol were evaluated. Twenty‐four 1‐year‐old healthy dogs, weighing 19 ± 3 kg (mean ± SD) were randomly assigned to four treatment groups (n = 6): control (C), etodolac (E), butorphanol (B), and etodolac with butorphanol (EB). Etodolac (12–14 mg kg^?1 PO) was given 1 hour before propofol induction and isoflurane maintenance anesthesia. Butorphanol (0.4 mg kg^?1 IV) was given immediately following endotracheal intubation. Control dogs received only propofol (8 mg kg^?1 to effect) and isoflurane anesthesia. All dogs were mechanically ventilated to maintain Pe ′CO₂ between 35 and 45 mm Hg (4.7–6.0 kPa). Lactated Ringer's solution was given at 10 mL kg^?1 hour^?1 during anesthesia. Plasma cortisol concentrations were assessed 1 day prior to surgery (baseline), immediately prior to anesthesia induction, and every 30 minutes until 5 hours following extubation, and 1 day after surgery. Total duration of anesthesia was 50 minutes and total surgery duration was 30 minutes. Isoflurane concentration area under the curve (AUC) over time during the anesthesia was compared among treatment groups. Buccal mucosal bleeding time (BMBT) was assessed 1 day before E administration and during surgery. Urine GGT to urine creatinine ratio, BUN, and plasma creatinine were taken daily from 1 day before to 3 days after surgery. Behavioral pain scores (numerical rating scale) were assessed by two observers blinded to the treatment during the 5‐hour recovery period at 30 minute intervals until 3 hours, and again at 5 hours after extubation. All data were analyzed using anova . Multiple comparisons were performed if the anova was significant. Alpha value was set at 0.05. Plasma cortisol concentrations significantly increased from time of extubation in all the treatment groups. They did not return to the baseline until 5, 2.5, 1.5, and 1.5 hours after extubation in the C, B, E, and EB groups, respectively. Isoflurane AUC was not significantly different among treatment groups. Dogs treated with EB had significantly less behavioral pain than all other groups throughout the 5‐hour recovery period. No significant difference was found between treatment groups or within treatment groups over time in BMBT, or any renal variables. This study demonstrated that (i) pre‐operative administration of E provides profound analgesia during the post‐operative period without renal or bleeding side‐effects in dogs undergoing OHE; and (ii) a combination of butorphanol–etodolac provides the best analgesic effect during the post‐operative period based on the behavioral pain score.     

Effect of tepoxalin on renal function and hepatic enzymes in dogs exposed to hypotension with isoflurane

ObjectiveTo evaluate the possible renal and hepatic toxicity of tepoxalin in dogs exposed to hypotension during isoflurane anesthesia.Study designProspective, randomized experimental study.AnimalsTwenty adult mixed-breed dogs, weighing 18.8 ± 2.8 kg.MethodsThe animals received 10 mg kg^?1 tepoxalin orally 2 hours before the anesthetic procedure (PRE; n = 6), or 30 minutes after anesthesia (POST; n = 6), along with a control group (CON; n = 8), which were only anesthetized. The PRE and POST groups also received the same dose of tepoxalin for 5 days post-procedure. All dogs were anesthetized with propofol and maintained with isoflurane and the end-tidal isoflurane (Fe’Iso) was increased until mean arterial pressure decreased to 50–60 mmHg. These pressures were maintained for 60 minutes. Heart rate, arterial pressures and Fe’Iso were recorded at 0, 10 and every 10 minutes up to 60 minutes of hypotension. Blood gases, pH, electrolytes and bleeding time were analyzed before and at 30 and 60 minutes of hypotension. Renal and hepatic changes were quantified by serum and urinary biochemistry and creatinine clearance.ResultsSerum concentrations of alanine amino transferase (ALT), alkaline phosphatase (ALP) and σ-glutamyl transferase (GGT), blood urea nitrogen (BUN) and creatinine (Cr), and urinary output, urinary Cr, Cr clearance, and GGT:Cr ratio remained stable throughout the evaluations. During the anesthetic procedure there were no important variations in the physiological parameters. No side effects were observed in any of the groups.Conclusions and clinical relevanceTepoxalin did not cause significant effects on renal function or cause hepatic injury in healthy dogs exposed to hypotension with isoflurane, when administered pre- or postanesthetic and continued for five consecutive days.     

Clinical and clinicopathological changes in 6 healthy ponies following intramuscular administration of multiple doses of imidocarb dipropionate

Haematological variables and selected serum indices, particularly those affected by changes in renal and hepatic function, were examined in 6 healthy ponies following 4 intramuscular doses of 4 mg/kg imidocarb dipropionate administered every 72 hours. This treatment regime has been reported to sterilise experimental Babesia equi infections in horses and may have value in preventing the spread of this disease during exportation of possible carrier horses to non-endemic countries. Serum bile acids and serum gamma glutamyltransferase activity were measured to evaluate the effect of this treatment regime on hepatic function. Owing to the absence of any increase in these variables it was concluded that this treatment regime had no clinically detectable deleterious effect on hepatic function in healthy ponies. Urinary gamma glutamyltransferase : creatinine ratios (IU/g), serum creatinine and fractional clearance of sodium, potassium and phosphate (%) were calculated as a measure of renal function. Urinary GGT and urinary GGT : creatinine ratios were significantly elevated on Day 5 of the trial, with 2 of the trial animals also exhibiting mild azotaemia indicative of changes in renal function. The changes in urine GGT : urine creatinine ratios observed in this study also provides evidence of the value of this ratio for the early detection of renal toxicity, following exposure to nephrotoxic agents.     

Estimation of Quantitative Enzymuria in Dogs With Gentamicin-Induced Nephrotoxicosis Using Urine Enzyme/Creatinine Ratios From Spot Urine Samples

The correlation between 24-hour urinary excretion of N -acetyl-β- d -glucosaminidase (NAG) and γ-glutamyl transferase (GGT) with urine NAG and GGT/creatinine ratios was assessed in dogs with gentamicin-induced nephrotoxicosis. Eighteen 6-month-oid male Beagles with normal renal function were randomly divided into 3 groups of 6. Each group was fed a different concentration of protein (high protein, 27.3%; medium protein, 13.7%; and low protein, 9.4%) for 21 days. After dietary conditioning, gentamicin was administered at a dose of 10 mg/kg IM tid for 8 days and each group was continued on its respective diet. Endogenous creatinine clearance and 24-hour urinary excretion of NAG and GGT were determined after dietary conditioning (day 0) and on days 2, 4, 6, and 8 of gentamicin administration. In addition, urine NAG and GGT/creatinine ratios (IU/L ± mg/dL) were determined from catheterized spot urine samples obtained between 7 and 10 am on the same days. The correlation between 24-hour urinary enzyme excretion and urine enzyme/creatinine ratio in the spot urine samples was evaluated by simple linear regression analysis. Spot sample urine enzyme/creatinine ratios were significantly correlated with 24-hour urinary enzyme excretion through day 4 for dogs on low dietary protein, through day 6 for those on medium protein, and through day 8 for those on high dietary protein. Mean ± SD baseline values for urine NAG/creatinine ratio and 24-hour urinary NAG excretion were 0.06 ± 0.04 and 0.19 ± 0.14 IU/kg/24 hr, respectively. Baseline values for urine GGT/creatinine ratio and 24-hour urinary GGT excretion were 0.39 ± 0.18 and 1.42 ± 0.82 IU/kg/24 hr, respectively.     

Effects of oral administration of furosemide and torsemide in healthy dogs

OBJECTIVE: To investigate the diuretic effects, tolerability, and adverse effects of furosemide and torsemide after short- and long-term administration in healthy dogs. ANIMALS: 8 mixed-breed dogs. PROCEDURES: In a crossover study, furosemide (2 mg/kg), torsemide (0.2 mg/kg), or placebo (bifidobacterium [1 mg/kg]) was administered orally to each dog every 12 hours for 14 days. Blood and urine samples were collected before the study (baseline data) and at intervals on the 1st (short-term administration) and 14th day (long-term administration) of treatment for assessment of urine volume and specific gravity and selected clinicopathologic variables including BUN, creatinine, and aldosterone concentrations, and creatinine clearance. RESULTS: Compared with the baseline value, short-term administration of furosemide or torsemide immediately increased urine volume significantly; after long-term administration of either drug, urine specific gravity decreased significantly. Compared with the effect of placebo, the 24-hour urine volume was significantly increased after short-term administra-tion of furosemide or torsemide. In addition, it was significantly increased after long-term administration of torsemide, compared with that of short-term administration. Long-term administration of furosemide or torsemide increased the BUN and plasma creatinine con-centrations, compared with the baseline value. Compared with the baseline value, plasma aldosterone concentration was significantly increased after long-term administration of either drug and was significantly higher after torsemide treatment than after furosemide treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, diuretic resistance developed after 14 days of furosemide, but not torsemide, administration; however, both loop diuretics were associated with increased BUN and plasma creatinine concentrations, compared with values before treatment.     

Renal involvement in dogs with babesiosis

Proteinuria, and renal tubular casts and epithelial cells in urine sediment, are commonly observed in both complicated and uncomplicated babesiosis, but do not necessarily reflect or predict renal failure. This study investigated the presence and degree of renal damage in canine babesiosis. Renal function and integrity were evaluated using serum urea and creatinine, serum electrolytes (sodium and potassium), fractional clearance of sodium (FcNa) and potassium (FcK), urine enzyme activity of gamma-glutamyl transpeptidase and alkaline phosphatase, urine protein:creatinine ratio, and urinalysis. One control group (n = 10) and 3 groups of babesiosis cases were studied: mild uncomplicated (n = 10), severe uncomplicated (n = 11), and complicated (n = 9). All babesiosis groups showed well-concentrated urine. Mean serum urea was elevated in the severe and complicated groups, and was significantly different from the control group. There was no statistically significant difference between the groups for creatinine, although the complicated group had a mean value above the normal reference range. Hypokalaemia was uncommon in all the groups. Hyperkalaemia was present in only 2 dogs in the complicated group. Marginal hyponatraemia was present in a minority of dogs in all groups. The serum electrolytes were not significantly different between groups. There was no overall elevation, nor any statistically significant difference in both the FcNa and FcK between the groups. Only 1 dog, in the complicated group, showed marked enzymuria. Proteinuria was a common finding and was significantly different between the severe and complicated groups and the control group. Some dogs in all groups had renal tubular epithelial cells in the urinary sediment, which increased in severity from the mild to the complicated groups and was significantly different from the control group. This study demonstrated that minimal renal damage occurs more often in canine babesiosis than significant damage or acute renal failure.     

Diuretic effects of fenoldopam in healthy cats

Objective: To determine the effect of fenoldopam infusion on urine output, sodium excretion, creatinine clearance, and indirect blood pressure in healthy cats. Design: Prospective study. Setting: Veterinary medical teaching hospital. Animals: Eight purpose‐bred cats, 2–4 years old. Interventions: None. Measurements: Urine output was measured hourly for 12 hours before and after fenoldopam administration. Sodium excretion, modified creatinine clearance, and fractional sodium excretion were measured before and following fenoldopam administration. Urine specific gravity, central venous pressure, and systolic blood pressure were measured every 4 hours during the experiment. Main results: Compared with pre‐infusion values, urine output, sodium excretion, and fractional excretion of sodium increased significantly 6 hours after initiation of fenoldopam infusion. This increase was sustained throughout the observation period. The modified creatinine clearance decreased significantly following 2 hours of fenoldopam infusion, but increased significantly by 6 hours after infusion, the time of peak urine output. Changes in urine specific gravity mirrored changes in fractional sodium excretion, whereas the central venous pressure mirrored changes in modified creatinine clearance. The diuretic effect in cats was prevented when a dopamine receptor blocking agent was administered before fenoldopam infusion. Conclusion: Fenoldopam at a dose of 0.5 μg/kg/min induces diuresis in cats in a delayed manner. This increase appears to be due, in part, to dopamine receptor‐induced natriuresis. Changes in glomerular filtration rate may also occur.     

Calculation of urinary enzyme excretion, with renal structure and function in dogs with pyometra

The urinary enzyme markers of renal damage, alkaline phosphatase (AP), gamma-glutamyl transferase (GGT) and N-acetyl-beta-glucosaminidase (NAG), glomerular filtration rate (GFR) and renal biopsies were studied to evaluate renal status in dogs with pyometra. After ovariohysterectomy, urinary enzymes were measured daily for 12 days in 55 dogs, and again at a later follow-up visit. Thirteen dogs had high levels of at least one enzyme at initial presentation. Seventeen dogs had a transient increase in urinary enzyme values between one and five days after surgery. Enzyme values usually declined to low activities within 12 post-operative days. Renal biopsies demonstrated tubular abnormalities in many dogs. Mean GFR was 2.4 and 2.0 ml min(-1) kg(-1), respectively on day 1 post-operatively and at the follow-up visit 1-4 months later. High urinary enzyme values often reflected extensive lesions in renal proximal tubular cells and sometimes reduced GFR.     

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.     

Kidney Injury Molecule-1 in the detection of early kidney injury in dogs with leptospirosis

Renal damage, a common feature in canine leptospirosis, ranges from a subclinical affection to kidney dysfunction and death. Chances of recovery can be improved by early intervention. However, traditional biomarkers (serum urea and creatinine) have limited relevance for precocity. Kidney Injury Molecule-1 (KIM-1) is a transmembrane protein upregulated in early stages of tubular injury. This study evaluated the use of urinary KIM-1 to detect early renal injury in naturally occurring canine leptospirosis. This exploratory research included 30 dogs divided into two groups: (1) dogs with leptospirosis (n = 25) and (2) healthy dogs (n = 5). Leptospira sp. infection was diagnosed through urine PCR and/or direct bacteriologic culture and/or serology (single MAT titters ≥800). Additionally, stage of infection was further characterized in acute and subacute phases based on the onset of clinical symptoms from 3 to 7 days. Urinary KIM-1 (uKIM-1) concentrations were measured in both groups with a commercial canine ELISA kit.uKIM-1 levels were statistically different (P < 0.01) between the studied groups, especially in non-azotemic dogs (P = 0.0042). The biomarker showed 88 % sensibility to diagnosis of kidney injury at> 1.49 ng/mL cut-off. Urine KIM-1 was negatively correlated with urine specific gravity (USG) but accompanied histopathological evidence of renal degeneration, necrosis and regeneration processes, extending information on kidney health. Measurement of KIM-1 in the urine of canine patients was able to detect naturally occurring acute and subacute leptospirosis accompanied by tubular injury in early non-azotemic infections.     

Evaluation of adverse effects of long-term orally administered carprofen in dogs

OBJECTIVE: To evaluate the adverse effects of carprofen in dogs after oral administration for 2 months. DESIGN: Prospective, randomized, blinded, placebo-controlled clinical trial. ANIMALS: 22 dogs with osteoarthritis in the hip or elbow joint. PROCEDURE: 13 dogs received orally administered carprofen daily for 2 months, and 9 dogs received a placebo for 2 months. Dogs were weighed, and serum and urine samples were collected before initiation of treatment and 4 and 8 weeks after initiation of treatment. Serum concentrations of total protein, albumin, urea, and creatinine and serum activities of alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were measured. Urinary ALP-to-creatinine, gamma-glutamyltransferase (GGT)-to-creatinine, and protein-to-creatinine ratios were calculated. Dogs were observed by owners for adverse effects. RESULTS: Serum protein and albumin concentrations were lower in treated dogs than in those that received placebo at 4 weeks, but not at 8 weeks. No changes were observed in serum urea or creatinine concentrations; ALP or ALT activity; or urinary ALP-to-creatinine, GGT-to-creatinine, or protein-to-creatinine ratios. Dogs' weights did not change. Severity of vomiting, diarrhea, and skin reactions did not differ between groups, but appetite was better in dogs receiving carprofen than in dogs in the placebo group. CONCLUSIONS AND CLINICAL RELEVANCE: It is possible that the transient decreases in serum protein and albumin concentrations in dogs that received carprofen were caused by altered mucosal permeability of the gastrointestinal tract because no indications of renal or hepatic toxicity were observed. Carprofen appeared to be well tolerated by dogs after 2 months of administration.     

Plasma exogenous creatinine clearance test in dogs: comparison with other methods and proposed limited sampling strategy

Plasma clearance of creatinine was evaluated for assessment of glomerular filtration rate (GFR) in dogs. In 6 healthy dogs (Experiment 1), we determined 24-hour urine clearance of endogenous creatinine, plasma, and urine clearances of exogenous creatinine administered at 40, 80, and 160 mg/kg in a crossover design (linearity study), plasma iothalamate clearance, and plasma and urine clearances of 14C-inulin. In Experiment 2, plasma creatinine and iothalamate clearances were compared, and a linearity study was performed as for Experiment 1 in 6 dogs with surgically induced renal impairment. Experiment 3 compared plasma creatinine clearance with plasma iothalamate clearance before and 3 weeks after induction of moderate renal impairment in 6 dogs. Plasma creatinine clearances were calculated by both noncompartmental and compartmental analyses. In Experiment 1, plasma inulin clearance was higher (P < .001) than other clearance values. Plasma creatinine clearances at the 3 dose rates did not differ from urine inulin clearance and each other. In Experiment 2, plasma creatinine clearances were about 14% lower than plasma iothalamate clearance (P < .05). In Experiment 3, decreases in GFR assessed by plasma clearances of iothalamate and creatinine were similar. Renal failure decreased the daily endogenous input rate of creatinine by 25%. Limiting sampling strategies for optimizing GFR calculation were proposed, allowing an error lower than 6.5% with 4 blood samples. These results suggest that determination of plasma creatinine clearance by a noncompartmental approach offers a reliable, inexpensive, rapid, and convenient means of estimating GFR in routine practice.