QUANTITATIVE AND QUALITATIVE SCINTIGRAPHIC MEASUREMENT OF RENAL FUNCTION IN DOGS EXPOSED TO TOXIC DOSES OF GENTAMICIN

Five, 3-month-old mongrel dogs weighing between 4.5 to 5.5 kg were studied to evaluate and compare the efficiency of 99mTc-DTPA, 99mTc-MAG3, and 99mTc-DMSA in detecting gentamicin-induced renal tubular injury. After baseline renograms using all three methods, all dogs received daily intramuscular injections of gentamicin at a dose of 30-45 mg/kg. Additional studies were obtained after a cumulative dose of 450, 1,575, and 2,250 mg of gentamicin was reached. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and percentage of total renal uptake measurements were calculated. Baseline and post-gentamicin injection blood urea nitrogen (BUN) and serum creatinine values were determined. A Duncan test revealed significant renal function impairment at 450 mgs of cumulated gentamicin with 99mTc-DMSA and at 1,575 mgs of cumulated gentamicin for 99mTc-DTPA and 99mTc-MAG3. There was no correlation between BUN and serum creatinine values when compared to gentamicin (p > 0.05). The images obtained with 99mTc-MAG3 were of better quality than those obtained with 99mTc-DTPA even under severe renal dysfunction. Percentage of 99mTc-DMSA uptake indicated renal damage, before than GFR and ERPF. BUN and serum creatinine measurements were poor indicators of gentamicin-induced renal failure.     

Ureteral obstruction after ureteroneocystostomy in dogs assessed by technetium TC 99m diethylenetriamine pentaacetic acid (DTPA) scintigraphy

OBJECTIVE: To use technetium Tc 99m diethylenetriamine pentaacetic acid (99mTc-DTPA) renal scintigraphy to monitor ureteral obstruction after ureteroneocystostomy in a canine model of partial ureteral obstruction. STUDY DESIGN: Experimental study. ANIMALS: Eight normal adult dogs. METHODS: Partial ureteral obstruction was created in 8 dogs by incomplete ligation of the terminal right ureter. Two weeks later, ureteroneocystostomy was performed in 7 dogs with unilateral partial ureteral obstruction and in 1 dog that had developed bilateral partial ureteral obstruction. 99mTc-DTPA scintigraphy was performed intermittently for 2 weeks after ureteroneocystostomy. Renal transit time of each kidney, as assessed by the time to maximal uptake (time of peak), and glomerular filtration rate, as assessed by percentage of kidney uptake of the radiopharmaceutical between 1 and 3 minutes, were estimated. Comparison between affected and nonaffected kidneys was performed with the Wilcoxon rank sum test. RESULTS: Unilateral partial ureteral obstruction was induced successfully in 7 dogs. In 1 dog, bilateral partial obstruction was induced inadvertently. After ureteroneocystostomy, percentage of kidney uptake of 99mTc-DTPA was low in 4 affected kidneys. The uptake returned to within normal limits in 2 of the kidneys during the observation period. The time activity curve had a more rounded appearance or was increasing continuously for all affected kidneys. A significant increase in renal transit time was observed 2 and 4 days after ureteroneocystostomy. Transit time progressively returned to normal by 4 to 11 days for all affected kidneys except 1. CONCLUSION: Ureteroneocystostomy resulted in persistent partial ureteral obstruction for 4 to 11 days as determined by 99mTc-DTPA scintigraphy. CLINICAL RELEVANCE: 99mTc-DTPA scintigraphy may be a useful procedure for monitoring renal function and ureteral obstruction after ureteroneocystostomy. Persistent partial ureteral obstruction may be seen 1 to 2 weeks after ureteral reimplantation in dogs with previously existing dilated ureters.     

Quantitative renal scintigraphic determination of the glomerular filtration rate in cats with normal and abnormal kidney function, using 99mTc-diethylenetriaminepentaacetic acid.

The nuclear imaging technique known as quantitative renal scintigraphy was validated as a means to assess the kidney function of cats. Renal function tests were performed in 6 healthy cats and 3 cats with clinical manifestations of kidney failure. In addition, the nephrotoxic drugs, gentamicin sulfate, or amphotericin B were used in an attempt to induce renal failure in 4 cats. Using linear regression analysis, equations were derived to estimate the glomerular filtration rate (GFR) on the basis of the renal percent uptake of 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). One-way ANOVA and Student's t test were used to evaluate treatment effects on clearances of inulin and creatinine, percent uptake of 99mTc-DTPA, and serum creatinine concentrations. The results show that the percent uptake of 99mTc-DTPA by the kidneys correlated well with the GFR obtained through the clearance of inulin. Thus, it was concluded that quantitative renal scintigraphy, using 99mTc-DTPA as a marker of kidney function, is an adequate technique to estimate the kidney function of healthy cats and cats with functional renal impairment. The best estimate of the GFR of cats, using the percentage dose of 99mTc-DTPA, was obtained on the 1- to 3-minute postinjection interval of the marker, using data that was background-subtracted, but not corrected for tissue absorption of gamma rays or binding of 99mTc-DTPA to plasma proteins. There was no significant difference in the mean inulin clearance, creatinine clearance, or percent uptake of 99mTc-DTPA between the 3 treatment groups of this study.(ABSTRACT TRUNCATED AT 250 WORDS)     

PRELIMINARY EVALUATION OF 99mTECHNETIUM DIETHYLENETRIAMINE PENTAACETIC ACID, 99mTECHNETIUM DIMERCAPTOSUCCINIC ACID, AND 99mTECHNETIUM MERCAPTOACETYLTRIGLYCINE FOR RENAL SCINTIGRAPHY IN CORN SNAKES (ELAPHE GUTTATA GUTTATA)

The efficacy of three radiopharmaceuticals, 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA), 99mTc-dimercaptosuccinic acid (99mTc-DMSA), and 99mTc-mercaptoacetyltriglycine (99mTc-MAG3), for renal imaging was examined in 16 corn snakes (Elaphe guttata guttata). All snakes received the radiopharmaceutical via an intracardiac injection. The kidneys could not be visualized in the three snakes that received 99mTc-DTPA or in the three snakes that received 99mTc-DMSA, but were well delineated in all 10 snakes receiving 99mTc-MAG3. These snakes were anesthetized and a dynamic frame mode acquisition was obtained for 30 min immediately following injection. A 60 s single static frame mode image was then obtained with the snake in a curled position. Two of the 10 snakes that received 99mTc-MAG3 were removed from further analysis because of suspected pericardial injections. Of the remaining eight snakes, the mean (+/- SD) renal uptake was 25 +/- 9.8% or 24 +/- 9.7%, with or without correction for residual injection site activity, respectively. Correction for remaining radioactivity in the heart does not appear to be necessary if it is less than 10% of the total dose. 99mTc-MAG3 provided consistently high quality images of the kidneys and further studies are warranted to evaluate its sensitivity for detecting decreased function in snakes with renal disease.     

Effect of tepoxalin on renal function in healthy dogs receiving an angiotensin-converting enzyme inhibitor

The objective of this study was to investigate renal function in clinically normal dogs receiving tepoxalin, a nonsteroidal inflammatory drug, either in association with or without an angiotensin-converting enzyme inhibitor (ACEI). Ten adult female Beagle dogs were used in the three phases of the study. The dogs were administered the drugs once daily for 7 days (experiment 1: placebo/tepoxalin/tepoxalin and benazepril; experiment 2: enalapril/tepoxalin and enalapril) or for 28 days (experiment 3: tepoxalin and benazepril together). Renal function was assessed by measurement of glomerular filtration rate (GFR) by renal scintigraphy [(renal uptake of 99mTc-diethylenetriaminepentacetic acid (DTPA)] and plasma clearance of 99mTc-DTPA. Compared with the placebo group, renal uptake and plasma clearance of 99mTc-DTPA were not significantly modified after a 7-day period of treatment with tepoxalin or enalapril alone, tepoxalin and benazepril or tepoxalin and enalapril together. No significant change was obtained in GFR after a 28-day period of dosing with tepoxalin and benazepril together. Therefore, it was concluded that tepoxalin did not alter renal function in healthy Beagle dogs receiving ACEI.     

Evaluation of the use of technetium Tc 99m diethylenetriamine pentaacetic acid and technetium Tc 99m dimercaptosuccinic acid for scintigraphic imaging of the kidneys in green iguanas (Iguana iguana)

OBJECTIVE: To evaluate the use of scintigraphy involving technetium Tc 99m diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) or technetium Tc 99m dimercaptosuccinic acid ((99m)Tc-DMSA) for the determination of kidney morphology and function in green iguanas (Iguana iguana). ANIMALS: 10 healthy iguanas weighing >1.6 kg. PROCEDURE: Renal scintigraphy was performed by use of (99m)Tc-DTPA in 6 of the iguanas and by use of (99m)Tc-DMSA in all 10 iguanas. After the injection of (99m)Tc-DMSA, scans were performed for each iguana at intervals during a 20-hour period. Renal biopsies were performed in all 10 iguanas after the final scintigraphic evaluation. RESULTS: In iguanas, the use of (99m)Tc-DTPA for renal scintigraphy was nondiagnostic because of serum protein binding and poor renal uptake of the isotope; mean +/- SD (99m)Tc-DTPA bound to serum proteins was 48.9 +/- 9.9%. Renal uptake of (99m)Tc-DMSA produced distinct visualization of both kidneys. Renal uptake and soft tissue clearance of (99m)Tc-DMSA increased over the 20-hour imaging period; mean +/- SD renal uptake of (99m)Tc-DMSA was 11.31 +/- 3.06% at 20 hours. In each of the 10 iguanas, ultrasonographic and histologic examinations of biopsy specimens from both kidneys revealed no abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that the kidneys of iguanas can be evaluated scintigraphically by use of (99m)Tc-DMSA; this technique may be potentially useful for the diagnosis of renal failure in iguanas.     

Investigation of pulmonary deposition of a nebulized radiopharmaceutical agent in awake cats

OBJECTIVE: To determine whether conscious, unsedated cats will inhale a nebulized material administered via a facemask and whether this material will reach the lower airways. ANIMALS: 20 healthy adult cats. PROCEDURE: Technetium Tc 99m-diaminetriaminopentaacetic acid (99mTc-DTPA) was nebulized into a spacer and administered to the cats via a closely fitting facemask. By use of a gamma camera, images were then immediately obtained to determine the distribution of 99mTc-DTPA within the lower airways. RESULTS: Images obtained by use of the gamma camera revealed that all 20 cats had inhaled 99mTc-DTPA from the facemask. In each cat, deposition of the radiopharmaceutical agent was evident throughout the lung fields. CONCLUSIONS AND CLINICAL RELEVANCE: Awake cats that were not used to the application of a facemask did inhale substances from such a device. Aerosolization of medications may be a feasible route of administration for cats with lower airway disease.     

Phenolsulfonphthalein pharmacokinetics and renal morphologic changes in adult pony mares with gentamicin-induced nephrotoxicosis

Changes in renal function, determined by pharmacokinetics of phenolsulfonphthalein (PSP), and renal morphologic features were examined in adult pony mares given 20 mg of gentamicin sulfate/kg of body weight, IV, q 8 h (group A) n = 7 or isotonic saline solution, IV, q 8 h, n = 5 (group B) for 14 days. Susceptibility of ponies to gentamicin-induced nephrotoxicosis was varied. Two group-A ponies developed acute renal failure and were euthanatized before treatment day 14, whereas 5 group-A A ponies did not develop physical or behavioral abnormalities after 14 days of gentamicin administration. All group-A ponies but none of group-B ponies developed ultrastructural abnormalities of the proximal tubular epithelium, consistent with gentamicin-induced nephrotoxicosis. Significant (P less than 0.05) differences were not detected in pharmacokinetic values of either group. Clearance of PSP was reduced in 4 group-A ponies that developed the most severe gentamicin-induced nephrotoxicosis. Changes in clearance of PSP were significantly (P less than 0.05) correlated with changes in the serum creatinine concentration.     

Glomerular Filtration Rate and Renal Volume in Dogs with Congenital Portosystemic Vascular Anomalies before and after Surgical Ligation

Glomerular filtration rate (GFR) and renal volume were evaluated in dogs with confirmed portosystemic vascular anomalies (PSVA) before and after surgical ligation of their PSVA. Pre- and postligation CBC, serum biochemistry, urinalysis, abdominal ultrasonography with measurement of renal volume, and per rectal scintigraphy were performed to document resolution of abnormalities consistent with portosystemic shunting. GFR was estimated by plasma 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) clearance before (n = 21) and after (n = 12) surgical correction of PSVA. Preligation 99mTc-DTPA GFR was increased (median, 5.64 mL/minute/kg; range, 3.53-8.49 mL/minute/kg; reference range, 2.83-4.47 mL/minute/kg) in 81% (17/21) of dogs. Postligation 99mTc-DTPA GFR decreased in all 12 evaluated dogs (median change = -42%; P < .001). Preligation renal volume was above the reference range for the left and right kidneys in 71% (10/14) and 69% (11/16) of dogs evaluated, respectively. Right renal volume decreased significantly (n = 5; median change, -45%; P = .03) after surgical ligation of PSVA. These findings document increased GFR and renal volume in dogs with PSVA, which may explain in part the low blood urea nitrogen and serum creatinine concentrations encountered in these dogs. Knowledge of changes in GFR associated with PSVA ligation may prove helpful in the anesthetic, drug, and dietary management of affected dogs.     

Effect of diet on gentamicin-induced nephrotoxicosis in horses.

Gentamicin sulfate-induced nephrotoxicosis was compared in 2 groups of horses fed different rations. Four horses were fed only alfalfa hay, and 4 other horses were fed only whole oats. Seven days after initiation of the diet, all horses were given gentamicin IV (5 mg/kg of body weight) every 12 hours for 22 days. Urinary gamma-glutamyl-transferase to urinary creatinine (UGGT:UCr) ratio was calculated daily, and serum concentration of gentamicin was measured at 1 and 12 hours after drug administration. Results indicated that horses fed oats had greater renal tubular damage than did horses fed alfalfa. Mean UGGT:UCr for horses fed alfalfa was 47.1 +/- 18.8 and was 100.0 +/- 19.0 for horses fed oats (P = 0.007). The UGGT:UCr in horses fed oats was greater than 100 for a total of 54 days; horses fed alfalfa had UGGT:UCr greater than 100 for only 7 days. Two horses not given gentamicin were fed only oats and 2 were fed only alfalfa. These horses had mean UGGT:UCr of 17.6 +/- 2.2 and 30.5 +/- 3.0, respectively. Mean peak and trough concentrations of gentamicin were statistically different for horses fed oats and those fed alfalfa (peak 23.16 +/- 1.87 and 14.07 +/- 1.79 micrograms/ml, respectively [P = 0.0001], and trough, 1.81 +/- 0.69 and 0.71 +/- 0.70 micrograms/ml, respectively [P = 0.0270]). Mean half-lives of gentamicin (estimated from peak and trough concentrations) for horses fed alfalfa (2.58 +/- 0.26 hours) and horses fed oats (2.88 +/- 0.27 hours) were not significantly different. Horses fed only oats had greater degree of gentamicin-induced nephrotoxicosis than did those fed only alfalfa.     

Single intravenous and multiple intramuscular dose pharmacokinetics and tissue residue profile of gentamicin in sheep

Single and multiple dose gentamicin regimens were compared in sheep to determine the relevant pharmacokinetic differences. Seven mature sheep were given 10 mg/kg of gentamicin by IV bolus. Serum concentrations were monitored for 19 days. Four weeks after the initial bolus, gentamicin was administered IM (3 mg/kg every 8 hours) for 7 days. Ewes were euthanatized and necropsied at 1, 8, and 15 days after termination of the IM regimen and the tissues were assayed for gentamicin. Serum concentrations were analyzed using a triexponential equation. The IV kinetic studies revealed an alpha half-life (t1/2) of 0.31 +/- 0.14 hours, beta t1/2 of 2.4 +/- 0.5 hours, and gamma t1/2 of 30.4 +/- 18.9 hours. Multiple IM dose kinetic studies revealed a beta t1/2 of 2.8 +/- 0.6 hours and gamma t1/2 of 82.1 +/- 17.8 hours. After multiple dosing, gamma t1/2 was significantly longer than after the single IV bolus (P less than 0.05). Twenty-four hour urine collection accounted for 75% to 80% of the total IV dose. Renal cortical gentamicin concentration reached 224 micrograms/g of tissue and then decreased, with a 90-hour t1/2. Renal medullary gentamicin concentration reached 18 micrograms/g with a 42-day t1/2. After multiple dosing, liver gentamicin concentration reached 11 micrograms/g and skeletal muscle concentrations were less than or equal to 0.6 micrograms/g. Route or duration of administration significantly affected the gamma-phase serum concentrations, which may influence gentamicin nephrotoxicosis. The present study also illustrated the complexities in predicting aminoglycoside withdrawal times for food-producing animals before slaughter.     

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.     

Evaluating the effects of 14-day oral vedaprofen and tolfenamic acid treatment on renal function, hematological and biochemical profiles in healthy cats

The objective of this study was to evaluate the effects of the nonsteroidal anti-inflammatory drugs vedaprofen and tolfenamic acid on renal function after oral administration for 2 weeks in healthy cats. Experiments were performed using nineteen domestic short-haired cats randomly divided into one control (n=6) and two treatment groups. All cats in the first (n=6) and second treatment groups (n=7) received vedaprofen (0.5 mg/kg/day) and tolfenamic acid (4 mg/kg/day), respectively. During the experiment, renal function was evaluated using percent renal uptakes of (99m)Technetium-diethylenetriamine-pentaacetic acid ((99m)Tc-DTPA) collected from renal scintigraphy and blood samples used to determine complete blood count and biochemical profiles. Renal scintigraphy and blood collections were performed at days 0, 5, 11, 15, and 45. The percent of renal uptake after the administration of vedaprofen and tolfenamic acid were not significantly different compared to pretreatment (day 0) and control group levels. In addition, significant changes were not observed in hematological and biochemical profiles within or between groups, with the exception of slightly lower numbers in red blood cell counts compared to the normal value on day 45 in the tolfenamic acid-treated group. Taken together, we conclude 14-day administration of vedaprofen and tolfenamic acid might not cause any adverse effects on renal function, hematological and serum biochemical variables.     

Evaluation of 99mTc-diethylenetriaminepentaacetic acid nuclear imaging for quantitative determination of the glomerular filtration rate of dogs

The suitability of 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) as an agent to assess glomerular filtration rate (GFR) in dogs was evaluated. Glomerular filtration rates of 12 healthy dogs were determined on the basis of creatinine and/or inulin clearance. Glomerular filtration rates also were determined in 7 dogs after induction of acute renal failure by administration of amphotericin B. The healthy dogs and the amphotericin B-treated dogs were given 99mTc-DTPA (1 to 2 mCi) IV. The percentage of the 99mTc-DTPA dose in the kidneys (percentage dose) was determined, with background activity subtracted from total activity at 15-s intervals 0 to 6 minutes after 99mTc-DTPA infusion. Linear regression analyses (LRA) were performed to determine whether the percentage dose at various time intervals after injection correlated with GFR calculated on the basis of creatinine and inulin clearance data. One to 3 minutes after 99mTc-DTPA administration appeared to be the best period for analysis of the data. The percentage dose of 99mTc-DTPA (corrected for kidney depth differences) was determined and LRA against GFR were performed. The percentage dose correlated better with inulin clearance (r = 0.94) than with endogenous creatinine clearance (r = 0.83). Only inulin clearance correlations improved with kidney depth correction. The LRA was used to derive an equation that could be used to calculate GFR on the basis of the percentage dose. The equation derived from inulin regression was: GFR (milliliter/minute/kilogram of body weight) = 0.194 (depth-corrected percentage dose)--0.37; the equation derived from the creatinine regression was: GFR (milliliter/minute/kilogram) = 0.171 (depth-corrected percentage dose)-0.15.(ABSTRACT TRUNCATED AT 250 WORDS)     

DIURETIC RENAL SCINTIGRAPHY IN NORMAL CATS

The purpose of this study was to develop a protocol for diuretic renal scintigraphy (renography) in cats and describe normal findings. ^99mTc‐DTPA renal scintigraphy was performed twice in 10 healthy cats. Furosemide or saline were injected 4.5 min after radiopharmaceutical administration for the diuretic or control scan, respectively. A dynamic acquisition was performed for 8 min. The following parameters were evaluated: (1) global and individual glomerular filtration rate (GFR); (2) shape of the time–activity curve (TAC); (3) time of peak (TOP); (4) individual kidney excretion half‐time (T_1/2) of the radiopharmaceutical; (5) percentage of maximum activity measured at the end of the study. Global GFR in the control studies (2.79±0.83 ml/min/kg, mean±SD) did not differ significantly from the diuretic scans (2.34±0.51 ml/min/kg). The shape of most (16/20) TAC of diuretic renograms was similar to those of control renograms. The TOP of the diuretic renogram curves was 3.06±0.58 min, and did not differ from that of the control scans (3.01±0.61 min). T_1/2 of the diuretic renograms was significantly shorter (5.15±0.83 min) than that of the control renograms (6.31±1.50 min). A significantly lower percentage of maximum activity was present at the end of the study in diuretic renograms (median: 47.25%; range: 33.60–59.60%) compared with control renograms (63.40%; 30.00–69.40%). Diuretic renal scintigraphy is a noninvasive and fast procedure to perform in cats. The applicability of this technique needs to be investigated in patients with significantly impaired renal function and obstructive uropathies.     

Evaluation of an implanted osmotic pump for delivery of amikacin to corn snakes (Elaphe guttata guttata).

The risk of accidental envenomation to the handler of venomous snakes during drug administration limits the ability to treat these animals. One commercially available osmotic pump is a miniature self-contained cylindrical implant that operates on the basis of an osmotic pressure difference between the extracellular fluid and the osmotic agent in the pump. Osmotic pumps loaded with amikacin were surgically placed into the coelomic cavity of five adult corn snakes (Elaphe guttata guttata) (group A). Four snakes (group B) received an intramuscular injection of amikacin at 5 mg/kg followed by 2.5 mg/kg q 72 hr for a total of four injections. Plasma concentrations of amikacin were measured in both groups. Renal function was evaluated pre- and posttreatment via scintigraphy with 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) and measurement of plasma uric acid concentrations. Mean (+/- SD) steady state amikacin concentration for group A was 6.9 +/- 1.7 microg/ml (predicted = 8.0 microg/ml), and the measured pump rate was 0.134 +/- 0.017 microl/hr (predicted = 0.130 microl/hr). Mean (+/- SD) peak and trough plasma amikacin concentrations for group B were 22.7 +/- 8.5 microg/ml and 14.3 +/- 7.0 microg/ml, respectively. While neither scintigraphy nor plasma uric acid concentrations indicated toxicity in either group, continuous administration of aminoglycosides may cause nephrotoxicity, and it is unknown whether this delivery method of amikacin would be efficacious in treating bacterial infections in snakes. In addition, due to migration of one pump into the trachea causing asphyxiation and death, these pumps may not be appropriate for intracoelomic placement in corn snakes. Nonetheless, the pumps delivered the drug at a predictable rate and were efficacious in achieving a constant plasma concentration of amikacin at the predicted level. Osmotic pumps may offer a safer alternative to periodic intramuscular injections for drug delivery in venomous or aggressive snakes.     

EVALUATION OF 99MTC-DIETHYLENETRIAMINEPENTAACETIC ACID RENAL SCINTIGRAM CURVES IN NORMAL DOGS AFTER INDUCTION OF DIURESIS

The normal 99mTc-diethylenetriaminepentaacetic acid (DTPA) renal scintigram curve has 3 distinct phases; an arterial phase followed by progressive uptake and subsequent excretion from the kidney. In dogs with X-linked hereditary nephritis, a distinct flattening of the renal scintigram curve has been observed prior to any decline in glomerular filtration rate (GFR). The cause of this shape change is not known, however, it coincided with decreased urine-specific gravity and thus might be related to polyuria. To further evaluate this possibility, we assessed whether diuresis without concurrent renal disease could flatten the 99mTc-DTPA renal scintigram curve. GFR scintigraphy was performed in six healthy dogs once as a baseline, and again after induction of diuresis by each of four different methods. Scintigram curves were evaluated subjectively as well as quantitatively by calculation of GFR estimates, mean renal transit times, time to peak activity and half-time clearance. Complete flattening of the renal scintigram curve did not occur with diuresis alone, and therefore, flattening of the scintigram curve may serve as an early indicator of renal dysfunction. However, during diuresis after intravenous saline administration, alterations in time to peak activity and mean renal transit time may create inaccuracies in GFR estimates based on the conventional regression formula that cause a false lowering of the resultant global GFR value.     

DIURETIC RENAL SCINTIGRAPHY IN NORMAL DOGS

Diuretic renal scintigraphy is commonly used in human medicine to differentiate obstructive from nonobstructive pyelectasia. In order to determine normal parameters, 99mTc-DTPA renal scintigraphy was performed twice in 20 healthy adult Mongrel dogs. Each dog was injected with either 3.0 mg/kg furosemide or an equivalent volume of saline 4.5 min following injection of the radiopharmaceutical. The following parameters were evaluated: (1) global and individual glomerular filtration rate (GFR); (2) time of peak (TOP) of the time-activity curve (TAC); (3) shape of the TAC; (4) individual kidney excretion half-time (T1/2); (5) proportion of maximum activity measured at end of study (8 min); (6) time of onset; and (7) duration of the effect of the diuretic. Most TAC in the diuretic renography group showed a steep drop in the curve following administration of the diuretic compared with a gradual slope in the saline control group. There was a statistically significant difference in T1/2 between the control renograms (median 10.25 min, range 4.41-18.07 min) and the diuretic renograms (median 4.16 min, range 3.62-5.90 min). There was a statistically significant difference in percentage maximum activity between the control renograms (median 65.25%, range 48.27-93.68%) and the diuretic renograms (median 48.54%, range 35.64-58.76%). Median time of onset of the diuretic effect was 1.10 min (0.20-2.40 min), and median duration was 0.83 min (0.30-2.35 min).     

Effect of short-term treatment with meloxicam and pimobendan on the renal function in healthy beagle dogs

The aim of the study was to investigate the renal function in clinically normal dogs receiving meloxicam and pimobendan alone or in combination. Ten adult female beagle dogs were administered the treatment for 7 days in a randomized crossover trial (control/meloxicam/pimobendan/meloxicam and pimobendan). Renal function was assessed by blood urea, creatinine, sodium, potassium and chloride concentrations and by glomerular filtration rate, measured by means of renal scintigraphy [renal uptake of ^99mTc-diethylenetriaminepentacetic acid (DTPA)] and plasma clearance of ^99mTc-DTPA. As compared with the control group, renal uptake and plasma clearance of ^99mTc-DTPA were not significantly modified after a 7-day period of treatment with meloxicam or pimobendan alone, or meloxicam and pimobendan in combination. Furthermore, urea, creatinine, sodium, potassium and chloride levels in the serum of the dogs during the 7-day period treatment were not significantly modified in relation to the treatments. It was therefore concluded that meloxicam and pimobendan alone or in combination did not alter renal function in healthy dogs.     

Gentamicin pharmacokinetics and nephrotoxicity in naturally acquired and experimentally induced disease in dogs

Pharmacokinetic disposition of gentamicin was studied in 69 dogs--12 control and 33 subtotally nephrectomized dogs representing combined data from previous experimental studies, and 24 dogs with a variety of diseases and degrees of renal dysfunction. Drug disposition varied considerably within and between diseases, and dosages had to be altered to achieve therapeutic drug concentrations and to minimize drug toxicosis. Decreased drug clearance when serum creatinine and urea nitrogen concentrations are normal may be indicative of subclinical renal disease and therefore may indicate a predisposition for development of nephrotoxicosis. Results of the study indicated the need to individualize aminoglycoside dosage regimens on the basis of pharmacokinetic disposition of drug, especially in dogs with preexisting subclinical renal dysfunction. Because of the large variability normally encountered in dogs with various diseases, monitoring of renal function alone is not sufficient to accurately predict gentamicin clearance, volume of distribution, or half-life.