Effect of benazepril and robenacoxib and their combination on glomerular filtration rate in dogs

Combined use of angiotensin‐converting enzyme inhibitors and nonsteroidal anti‐inflammatory drugs may induce acute kidney injury, especially when combined with diuretics. The objective of this investigation was to evaluate the effect of benazepril, robenacoxib and their combination in healthy dogs. In each of two studies (studies 1 and 2), 32 beagle dogs were randomized into one of four groups in a parallel‐group design. Groups received once‐daily oral treatment for 7 days with placebo, benazepril, robenacoxib or benazepril plus robenacoxib. In study 2, all dogs received additionally 2 mg/kg furosemide orally twice daily. The primary endpoint was the glomerular filtration rate (GFR) estimated from the plasma clearance of iohexol. Secondary endpoints included standard clinical monitoring and, in study 2, plasma renin activity, urine volume, specific gravity and aldosterone concentration and water intake. Administration of furosemide induced diuresis, reduced GFR and activated the renin–aldosterone–angiotensin system. Benazepril and robenacoxib, administered alone or in combination, were tolerated well, did not decrease GFR with or without co‐administration of furosemide and significantly reduced urinary aldosterone concentrations. No increased risk of acute kidney injury was identified with the combination of benazepril and robenacoxib in healthy dogs. Different effects might occur in dogs with heart or renal disease.     

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.     

The pharmacokinetics and pharmacodynamics of furosemide in anesthetized dogs with normal and experimentally decreased renal function

The pharmacokinetics and the biliary and urinary excretions following intravenous administration of furosemide (5 mg/kg) were investigated in the anesthetized dogs with normal and experimentally reduced renal function. After the administration, furosemide caused diuretic and choleretic response, and was excreted into urine and bile at almost similar rate to plasma concentration decay in normal dogs. Half maximum diuretic response was obtained at 1.5 micrograms/ml of plasma concentration and 100 micrograms/min of urinary excretion rate of furosemide. Acute renal failure was produced in dogs by the intravenous administration of mercuric chloride (HgCl2, 2 mg/kg). In HgCl2-treated dogs, the prolongation of half life (T1/2 beta) and the decrease in plasma clearance were noted with the decreased diuretic response. These changes in parameters appeared to be associated with the decrease in excretion of furosemide into the urine, but not into the bile. Plasma level-diuretic response relationship was extensively shifted to the right in HgCl2-treated dogs, while urinary dose-response relationship did not change significantly between two groups. These results suggest that the decreased response to furosemide in HgCl2-treated dogs seems to be due to the decreased renal clearance rather than to the subsensitivity to furosemide on the site of action.     

Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs

OBJECTIVE: To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. ANIMALS: 36 adult dogs. PROCEDURES: Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. RESULTS: For serum gamma-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.     

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.     

Estimating glomerular filtration rate in healthy dogs using inulin without urine collection

The goals of this study were to determine if the glomerular filtration rate (GFR) in dogs could be estimated by plasma inulin clearance and/or infusion inulin clearance analyses without urine collection, and to compare these results with GFR values obtained by urinary inulin clearance analysis. The dogs included in this study were healthy 20 beagles. Inulin clearance values were obtained by urinary inulin clearance, infusion inulin clearance, and plasma inulin clearance techniques. Urinary inulin clearance was 4.09±0.52 ml min(-1) kg(-1) (body weight); infusion inulin clearance, 4.01±0.49 ml min(-1) kg(-1); and plasma inulin clearance, 4.14±0.66 ml min(-1) kg(-1). The urinary inulin clearance was strongly correlated with infusion inulin clearance and weakly correlated with plasma inulin clearance. The GFR for dogs can be estimated by infusion and plasma inulin clearance analyses by blood sampling alone, without urine collection.     

Effect of meloxicam and carprofen on renal function when administered to healthy dogs prior to anesthesia and painful stimulation

OBJECTIVE: To determine whether administration of the nonsteroidal anti-inflammatory drugs meloxicam or carprofen to healthy dogs that were subsequently anesthetized and subjected to painful electrical stimulation has adverse effects on renal function as measured by glomerular filtration rate (GFR) and evaluation of serum concentrations of urea and creatinine. ANIMALS: 6 male and 6 female healthy young-adult Beagles. PROCEDURE: A study was conducted in accordance with a randomized crossover Latin-square design. One of 3 treatments (saline [0.9% NaCl] solution, 0.2 mg of meloxicam/kg, or 4.0 mg of carprofen/kg) was administered i.v. 1 hour before anesthesia was induced by use of drugs in accordance with a standard anesthetic protocol (butorphanol tartrate and acepromazine maleate as preanesthetic medications, ketamine hydrochloride and diazepam for induction, and maintenance with isoflurane). Anesthetized dogs were subjected to intermittent electrical stimulation for 30 minutes. Direct, mean arterial blood pressure; heart rate; and respiratory rate were monitored. End-tidal isoflurane concentration was maintained at 1.5 times the minimum alveolar concentration. The GFR, as measured by plasma clearance of 99mTc-diethylenetriaminepentaacetic acid, and serum concentrations of serum and creatinine were determined 24 hours after induction of anesthesia. RESULTS: Neither meloxicam nor carprofen significantly affected GFR or serum concentrations of urea and creatinine, compared with values for the saline treatment. CONCLUSIONS AND CLINICAL RELEVANCE: When administered 1 hour before onset of anesthesia and painful electrical stimulation, meloxicam or carprofen did not cause clinically important alterations of renal function in young healthy dogs.     

Effect of diuresis on urinary excretion and creatinine clearance in the horse

Endogenous creatinine clearance and renal excretion of phenylbutazone, osmotically active material, and compounds contributing to the urinary refractive index were studied in 12 Thoroughbred mares after no treatment, after water administration, or after furosemide administration. Urine was quantitatively collected, using urinary bladder catheters. On average, urine flow of the mares was 9 microliters/min/kg without treatment and increased to about 50 microliters/min/kg after water administration and to about 70 microliters/min/kg after furosemide administration. Water administration increased creatinine clearance values and excretion of phenylbutazone. Furosemide administration increased urinary excretion of osmotically active compounds and compounds contributing to urinary refractive index and decreased excretion of phenylbutazone.     

Effect of carprofen on hemostatic variables in dogs

OBJECTIVE: To evaluate the effect of carprofen on hemostatic variables in clinically normal dogs. ANIMALS: 12 clinically normal Labrador Retrievers. PROCEDURE: 10 dogs (6 females, 4 males) received carprofen (2.2 mg/kg of body weight, PO, q 12 h) for 5 days. Two dogs (untreated control group; 1 female, 1 male) did not receive carprofen. Hemostatic variables (platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen, platelet aggregation, and bleeding time) were assessed for all dogs prior to treatment, on day 5 of treatment, and 2 and 7 days after discontinuation of the drug (days 7 and 12). Serum biochemical variables and Hct were assessed prior to treatment and on days 5 and 12. RESULTS: In dogs receiving carprofen, platelet aggregation was significantly decreased, and onset of aggregation was significantly delayed on days 5, 7, and 12, compared with pretreatment values. Activated partial thromboplastin time was significantly increased on days 5, 7, and 12 over pretreatment values in treated dogs, but values remained within reference ranges. Significant differences were not detected in buccal mucosal bleeding time, other serum biochemical and hemostatic variables, or Hct, compared with pretreatment values and the internal control group. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of carprofen for 5 days causes minor but not clinically important alterations in hemostatic and serum biochemical variables in clinically normal Labrador Retrievers. Carprofen is commonly used to treat osteoarthritis and chronic pain in dogs, but prior to this study, its effect on platelet aggregation and hemostatic variables was unknown.     

The Gastroduodenal Effects of Buffered Aspirin, Carprofen, and Etodolac in Healthy Dogs

Twenty-four healthy mixed-breed dogs were divided into 4 groups. Group 1 received a placebo p.o. q12h, group 2 received an average of 16.5 (15.1-17.8) mg/kg buffered aspirin p.o. q12h, group 3 received an average of 2.2 (2.0-2.4) mg/kg carprofen p.o. q12h, and group 4 received an average of 12.8 (11.7-13.8) mg/kg etodolac p.o. q24h (with a placebo in the PM). All treatments continued for 28 consecutive days. Gastroduodenal endoscopy was performed on days -9, 0, 5, 14, and 28. Multiple gastric biopsies were obtained endoscopically on day -9 to determine each dog's Helicobacter infection status. Four regions in the stomach and 1 region in the proximal duodenum were evaluated endoscopically, and each was assigned a score from 1 to 11. Scores for each region then were summed to give a total score for each endoscopic evaluation. Erosions and submucosal hemorrhages were seen in all dogs receiving aspirin. Only minor gastric lesions were observed in the carprofen, etodolac, and control groups. No adverse clinical signs were noted in any dog given any treatment. Median total score on days 0, 5, 14, and 28, respectively, were as follows: group 1: 5.0, 5.0, 5.0, 5.0; group 2: 5.0, 27.0, 26.0, 27.5; group 3: 5.0, 5.0, 6.0, 5.0, group 4: 5.0, 7.0, 5.0, 5.0. There was no significant difference among dogs receiving carprofen, etodolac, or placebo. The administration of carprofen, etodolac, or placebo to healthy dogs resulted in significantly less gastroduodenal lesion development than in dogs receiving buffered aspirin.     

Use of a three-blood-sample plasma clearance technique to measure GFR in horses

Measurement of renal function in horses poses a particular challenge because plasma creatinine is influenced by muscle mass which is highly developed and variable between individuals, while conventional clearance methods involve potentially daunting problems, particularly urine collection and bladder washout. This paper provides data which enable technetium-diethyleneaminopentacetic acid (Tc-DTPA) clearance to be used to calculate glomerular filtration rate (GFR)/extracellular fluid volume (ECFV) as an expression of GFR in horses, as previously validated in humans, dogs and calves. Apart from being arguably a more physiological expression of GFR than using derivatives of body weight, the use of GFR/ECFV eliminates a source of delay and error, namely measurement of the injected dose, and offers the convenience of requiring only three blood samples. It therefore has advantages for both research and clinical applications.     

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.     

Measurement of glomerular filtration rate via urinary clearance of inulin and plasma clearance of technetium Tc 99m pentetate and exogenous creatinine in dogs

OBJECTIVE: To compare glomerular filtration rate (GFR) measured via urinary clearance of inulin (UCI) with plasma clearance of technetium Tc 99m pentetate (99mTc-pentetate) and creatinine in dogs. ANIMALS: 6 healthy Beagles and 18 Beagles with reduced renal function. PROCEDURE: 13 blood samples were obtained between 5 and 600 minutes after i.v. bolus injections of (99m)Tc-pentetate and creatinine. Plasma clearance of (99m)Tc-pentetate was computed on the basis of 1, 2, or 13 samples, and plasma clearance of creatinine was computed on the basis of 2, 5, or 13 samples. During plasma clearance procedures, constant i.v. infusion of carboxyl carbon 14 inulin was begun and UCI was determined in urine collected from 90 to 120, 120 to 180, and 180 to 240 minutes. Clearance procedures were repeated in 12 dogs to evaluate reproducibility of results. RESULTS: Significant association between UCI and plasma clearance was determined via all methods. However, plasma clearances were moderately to markedly different from UCI, depending on test substance, GFR, and sample numbers used for plasma clearance computations. Comparisons were particularly discordant when some methods of limiting samples were used to define plasma clearance. CONCLUSIONS AND CLINICAL RELEVANCE: Values derived from plasma clearance methods for (99m)Tc-pentetate and creatinine were not interchangeable with UCI results, which raises questions about their reliability as clinical research tools for measurement of GFR. Plasma clearance methods that are relative indices of renal function should not be interpreted as accurate measures of GFR without validation.     

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.     

Effects of urine alkalization and activated charcoal on the pharmacokinetics of orally administered carprofen in dogs

OBJECTIVE: To investigate the effects of oral administration of activated charcoal (AC) and urine alkalinization via oral administration of sodium bicarbonate on the pharmacokinetics of orally administered carprofen in dogs. ANIMALS: 6 neutered male Beagles. PROCEDURES: Each dog underwent 3 experiments (6-week interval between experiments). The dogs received a single dose of carprofen (16 mg/kg) orally at the beginning of each experiment; after 30 minutes, sodium bicarbonate (40 mg/kg, PO), AC solution (2.5 g/kg, PO), or no other treatments were administered. Plasma concentrations of unchanged carprofen were determined via high-performance liquid chromatography at intervals until 48 hours after carprofen administration. Data were analyzed by use of a Student paired t test or Wilcoxon matched-pairs rank test. RESULTS: Compared with the control treatment, administration of AC decreased plasma carprofen concentrations (mean +/- SD maximum concentration was 85.9 +/- 11.9 mg/L and 58.1 +/- 17.6 mg/L, and area under the time-concentration curve was 960 +/- 233 mg/L x h and 373 +/- 133 mg/L x h after control and AC treatment, respectively). The elimination half-life remained constant. Administration of sodium bicarbonate had no effect on plasma drug concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: After oral administration of carprofen in dogs, administration of AC effectively decreased maximum plasma carprofen concentration, compared with the control treatment, probably by decreasing carprofen absorption. Results suggest that AC can be used to reduce systemic carprofen absorption in dogs receiving an overdose of carprofen. Oral administration of 1 dose of sodium bicarbonate had no apparent impact on carprofen kinetics in dogs.     

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.     

Effects of carprofen on renal function during medetomidine-propofol-isoflurane anesthesia in dogs

OBJECTIVE: To investigate effects of carprofen on indices of renal function and results of serum bio-chemical analyses and effects on cardiovascular variables during medetomidine-propofol-isoflurane anesthesia in dogs. ANIMALS: 8 healthy male Beagles. PROCEDURES: A randomized crossover study was conducted with treatments including saline (0.9% NaCl) solution (0.08 mL/kg) and carprofen (4 mg/kg) administered IV. Saline solution or carprofen was administered 30 minutes before induction of anesthesia and immediately before administration of medetomidine (20 microg/kg, IM). Anesthesia was induced with propofol and maintained with inspired isoflurane in oxygen. Blood gas concentrations and ventilation were measured. Cardiovascular variables were continuously monitored via pulse contour cardiac output (CO) measurement. Renal function was assessed via glomerular filtration rate (GFR), renal blood flow (RBF), scintigraphy, serum biochemical analyses, urinalysis, and continuous CO measurements. Hematologic analysis was performed. RESULTS: Values did not differ significantly between the carprofen and saline solution groups. For both treatments, sedation and anesthesia caused changes in results of serum biochemical and hematologic analyses; a transient, significant increase in urine alkaline phosphatase activity; and blood flow diversion to the kidneys. The GFR increased significantly in both groups despite decreased CO, mean arterial pressure, and absolute RBF variables during anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen administered IV before anesthesia did not cause detectable, significant adverse effects on renal function during medetomidine-propofol-isoflurane anesthesia in healthy Beagles.     

Effects of administration of fluids and diuretics on glomerular filtration rate, renal blood flow, and urine output in healthy awake cats

OBJECTIVES: To determine effects of commonly used diuretic treatments on glomerular filtration rate (GFR), renal blood flow (RBF), and urine output (UO) and compare 2 methods of GFR measurement in healthy awake cats. ANIMALS: 8 healthy cats. PROCEDURE: In a randomized crossover design, cats were randomly allocated to 4 groups: control; IV administration of fluids; IV administration of fluids and mannitol; and IV administration of fluids, dopamine, and furosemide. Inulin and para-aminohippuric acid were used for determination of plasma clearance for GFR and RBF, respectively. Plasma clearance of technetium-Tc-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) was also used for GFR determination. RESULTS: Furosemide-dopamine induced the largest UO, compared with other groups. Both mannitol and fluid therapy increased RBF, compared with the control group. Mannitol, and not fluid therapy, increased RBF, compared with furosemide-dopamine. There were significant differences in GFR values calculated from 99mTc-DTPA and inulin clearances between the 2 groups. In all groups, use of 99mTc-DTPA caused underestimation of GFR, compared with use of inulin. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy awake cats, administration of furosemide-dopamine did not increase GFR or RBF despite increased UO. Fluid therapy and fluid therapy plus mannitol improved RBF. Determination of GFR by use of 99mTc-DTPA cannot always be substituted for inulin clearance when accurate measurement is required.     

Relationship between plasma iohexol clearance and urinary exogenous creatinine clearance in dogs

The objective of this study was to determine if plasma iohexol clearance, computed by a 1-compartment model defined by 3 plasma samples. was an accurate measure of glomerular filtration rate (GFR) in dogs. Twenty-two adult Beagle dogs of both genders were studied. Ten dogs had intact kidneys, and 12 dogs had surgically reduced renal mass. A bolus injection of iohexol was made, and blood was obtained for plasma iohexol assay after 120, 180, and 240 minutes. Plasma was analyzed for iohexol concentration by means of 3 assay methods: chemical, high-performance liquid chromatography (HPLC), and inductively coupled plasma emission spectroscopy (ICP). Urinary clearance of exogenous creatinine was used to measure GFR for three 30-minute periods occurring between 150 and 240 minutes after iohexol injection. Plasma clearance of iohexol and renal clearance of creatinine were compared by linear regression analysis and by limits of agreement techniques. Plasma iohexol clearance and urinary exogenous creatinine clearance were significantly correlated (chemical R2 = .90; HPLC R2 = .96; and ICP R2 = .96). The 1-compartment iohexol clearance:exogenous creatinine clearance ratios were 1.04 +/- 0.17, 1.05 +/- 0.14, and 1.10 +/- 0.15 for the chemical, HPLC, and ICP methods of assay, respectively, indicating that plasma iohexol clearance slightly overestimated GFR. Assuming a +/- 2 standard deviation interval for error, corrected plasma iohexol clearance measured GFR with +/-34% accuracy for the chemical, +/-26% accuracy for the HPLC, and +/-27% accuracy for the ICP method. These results indicate that plasma iohexol clearance should have utility for detection of renal dysfunction earlier in the course of progressive renal disease than is possible with measurement of plasma creatinine or urea concentrations.     

A Comparison of Inulin, Paraaminohippuric Acid, and Endogenous Creatinine Clearances as Measures of Renal Function in Neonatal Foals

The glomerular filtration rate (GFR) was estimated in eight full-term neonatal foals by the single injection inulin plasma clearance method at two days of age, the continuous infusion plasma and urinary clearance methods at three days of age, and the 12-hour endogenous creatinine clearance method at four days of age. The effective renal plasma flow (ERPF) was estimated simultaneously by the single injection para-aminohippuric acid (PAH) plasma clearance method in the eight two-day old foals and the continuous PAH infusion plasma and urinary clearance method in the eight three-day old foals. The GFR (+/- 1 SEM), as determined from the single injection plasma clearance method, was 2.30 +/- 0.34 mL/kg/min; by continuous infusion plasma clearance 2.56 +/- 0.30 mL/kg/min; by continuous infusion urinary clearance 2.82 +/- 0.32 mL/kg/min; and by 12-hour endogenous creatinine clearance 2.81 +/- 0.55 mL/kg/min. Effective renal plasma flow (+/- 1 SEM) measured by the single injection plasma clearance method was 15.22 +/- 1.5 mL/kg/min, by continuous infusion plasma clearance was 18.21 +/- 2.0 mL/kg/min. and by continuous infusion urinary clearance it was 11.95 +/- 1.9 mL/kg/min. The results of these methods were not statistically different. On a per kilogram body weight basis, the full-term neonatal foal's GFR and ERPF was determined to be comparable with adult equine GFR and ERPF.