REPEATABILITY AND RELIABILITY OF GLOMERULAR FILTRATION RATE DETERMINATION VIA GAMMA CAMERA UPTAKE OF TC-99M-DTPA IN CATS WITH CHRONIC KIDNEY DISEASE.

Measurement of glomerular filtration rate (GFR) via gamma camera uptake of 99mTc-diethylenetriaminepentaacetic acid is a standard method for quantifying renal function. Aims of this retrospective, observer agreement study were to determine intra- and interobserver variation in GFR values for cats with chronic kidney disease and to determine whether renal insufficiency classification changed between observers. Guideline cut-points were established for the difference in repeated GFRs to differentiate changes caused by therapeutic effect vs. inherent variation. Included cats had a diagnosis of chronic kidney disease and had undergone GFR examinations between the years of 2010 and 2013. Twenty-nine GFR studies were sampled. Each study was read twice, 6 months apart, by two veterinary radiologists and one radiology resident. Modified Bland-Altman plots were used to investigate differences between readings 1 and 2 by observer and between pairs of observers by reading. Reliability of clinical classification was assessed through comparisons between readings and observers. Measurements were not systematically different between readings for the experienced observers but were higher in reading 1 than reading 2 for the inexperienced observer. Measurements were not systematically different between the experienced observers in reading 1 or between any two observers in reading 2. Reliability for GFR measurements was high among experienced observers; variations in GFR measurements rarely led to differences in clinical classification. Results suggested that, for experienced observers, changes in GFR values following treatment in cats with chronic kidney disease between -0.4 and 0.4 mL/min/kg may be due to inherent variability rather than treatment effect.

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 (T1/2) 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). T1/2 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.

Effects of measurement of plasma activity input on normalization of glomerular filtration rate to plasma volume in dogs.

Glomerular filtration rate (GFR) normalized to body fluid volumes to adjust for differing body size and conformation is more physiologically correct than a relationship with body weight (BW). GFR can be normalized to plasma volume by a renographic method that uses the Rutland-Patlak plot with plasma activity and kidney activity inputs. A plasma time-activity curve is obtained from a region of interest (ROI) of the left ventricle (LV), the size of which is in theory not critical. The aims of the study were to evaluate the effect of different LV ROI sizes, the effect of extravascular activity in the thorax over the LV ROI, and different time intervals for the semilogarithmic LV plot. Seventy-two scintigrams were used, with three different-sized automatic and a manual LV ROI, all with and without subtracting extravascular activity, and with LV curve time intervals of 30-120 s and 60-240 s. GFR/plasma volume was not affected by LV ROI sizes but significantly affected by extravascular activity subtraction and different time intervals. Subtracting extravascular activity from the LV ROI did not improve precision, but increased variability caused by different LV ROI sizes and time intervals chosen for the LV plot. The ROI for measuring extravascular activity apparently contained a considerable and variable intravascular component, which when subtracted, created noisy and unreliable LV curves. Manual LV ROI, without extravascular subtraction, and a time interval for LV input between 1 and 4 min are recommended as they gave the least variability determined by statistical analysis. With these methods, normal individual GFR/plasma volume in normal beagle dogs was 29.2 +/- 6.5 ml/min/l.

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).

In vivo radionuclide uptake quantification using a multi-pinhole SPECT system to predict renal function in small animals.

PURPOSE: In vivo quantification of radiopharmaceuticals has great potential as a tool in developing new drugs. We investigated the accuracy of in vivo quantification with multi-pinhole single-photon emission computed tomography (SPECT) in rats. METHODS: Fifteen male Lewis rats with different stages of renal dysfunction were injected with 50 MBq 99mTc-dimercaptosuccinic acid. Four to six hours after injection, SPECT of the kidneys was acquired with a new four-headed multi-pinhole collimator camera. Immediately after imaging the rats were sacrificed and the kidneys were counted in a gamma-counter to determine the absorbed activity. SPECT data were reconstructed iteratively and regions of interest (ROIs) were drawn manually. The absolute activity in the ROIs was determined. RESULTS: Uptake values ranging from 0.71% to 21.87% of the injected activity were measured. A very strong linear correlation was found between the determined activity in vivo and ex vivo (r2=0.946; slope m=1.059). CONCLUSION: Quantification in vivo using this multi-pinhole SPECT system is highly accurate.

Determination of glomerular filtration rate in dogs using contrast-enhanced computed tomography.

The purpose of this project was to establish a procedure and reference values for glomerular filtration rate (GFR) using contrast-enhanced computed tomography (CT) in eight healthy dogs. A single section of the kidney was scanned sequentially after bolus injection (3 ml/s) of iohexol (300 mg/kg). Time-attenuation curves were constructed and the GFR per volume of kidney was calculated using Patlak graphical analysis software. The GFR was then converted from contrast clearance per unit volume (ml/min/ml) to contrast clearance per body weight (ml/min/kg). Individual kidney and global GFR were calculated using both CT and nuclear scintigraphy. Global GFR for each dog was also determined by plasma iohexol clearance. Contrast-enhanced CT underestimated the global GFR compared with the other two methods. The average global GFR was 2.57 +/- 0.33 ml/ min/kg using functional CT and 4.06 +/- 0.37 ml/min/kg using plasma iohexol clearance. There was significant (P < 0.05) interobserver variability of CT GFR of the right kidney and total GFR. There was decreased interobserver variability for the left kidney. There was no difference in the intraobserver variability for CT-determined individual kidney and global GFR. There was no difference between the motion corrected and nonmotion corrected values for individual and global CT GFR. Nuclear scintigraphy produced a slightly higher coefficient of variation than contrast-enhanced CT, 2.9% and 1.0%, respectively. It is hypothesized that altered renal blood flow, hematocrit of the small vessels, and nephrotoxicity play a role in the underestimation of GFR by contrast-enhanced CT.

Determination of extrarenal plasma clearance and hepatic uptake of technetium-99m-mercaptoacetyltriglycine in cats.

OBJECTIVE: To determine maximum extrarenal plasma clearance of technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) and maximum extrarenal hepatic uptake of 99mTc-MAG3 in cats. ANIMALS: 6 clinically normal adult cats. PROCEDURES: Simultaneously, baseline plasma clearance and camera-based uptake of 99mTc-MAG3 were determined in anesthetized cats. Double exponential curves were fitted to plasma clearance data. Injected dose was divided by area under the curve and body weight to determine 99mTc-MAG3 clearance. Regions of interest were drawn around kidneys and liver, and percentage dose uptake was determined 1 to 3 minutes after injection. After bilateral nephrectomy, simultaneous extrarenal plasma clearance and camera-based hepatic uptake of 99mTc-MAG3 were evaluated in each cat. RESULTS: Mean +/- SD baseline plasma clearance and extrarenal clearance were 5.29 +/- 0.77 and 0.84 +/- 0.47 mL/min/kg, respectively. Mean extrarenal clearance (as a percentage of baseline plasma clearance) was 16.06 +/- 7.64%. For right, left, and both kidneys, mean percentage dose uptake was 9.42 +/- 2.58, 9.37 +/- 0.86, and 18.79 +/- 2.47%, respectively. Mean hepatic percentage dose uptake before and after nephrectomy was 12.95 +/- 0.93 and 21.47 +/- 2.00%, respectively. Mean percentage change of hepatic uptake after nephrectomy was 166.89 +/- 23.19%. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, extrarenal clearance of 99mTc-MAG3 is higher than that of other species; therefore, 99mTc-MAG3 is not useful for estimation of renal function in felids. Evaluation of renal function in cats may be more accurate via camera-based versus plasma clearance-based methods because camera-based studies can discriminate specific organs.

Effect of region of interest selection and uptake measurement on glomerular filtration rate measured by 99mTc-DTPA scintigraphy in dogs.

Determinations of different methods of measurement of uptake of 99mTc-DTPA using scintigraphy of glomerular filtration rate (GFR) were made from 29 studies on 10 healthy beagle dogs. GFR was measured by calculating the percentage dose uptake (integral method) and rate of uptake (slope method) of 99mTc-DTPA using manual kidney regions of interest (ROI) and automatic kidney and background ROIs at different time periods of the uptake phase. These results were compared using linear regression analysis to the GFR obtained from 99mTc-DTPA plasma clearance using multiple blood samples. The best correlation coefficient between percentage DTPA uptake and GFR by DTPA clearance (r = 0.84, P < 0.001) was derived from time intervals between 30s-120s with a perirenal background ROI at 1 or 2 pixels out from the kidney ROI using automatic kidney ROI at 20% threshold. With the slope method, the best correlation coefficient (r = 0.85, P < 0.001) was obtained from time intervals between 30s-peak with the background ROI at 2 pixels out from the kidney ROI using automatic ROI at 35% threshold. The offset was higher, and the correlation varied more with different ROIs and the method was unreliable at time intervals extending beyond the peak radioactivity. Manual kidney ROIs with automatic background ROIs had slightly lower correlations. With DTPA renography both integral and slope uptake method with automatic kidney and background ROIs are accurate methods to estimate the GFR, but that the integral method is much more stable to variations in ROI size and the duration of the uptake phase of the renogram.

Renal transit time of 99mTc-diethylenetriaminepentacetic acid (DTPA) in normal dogs.

The transit time of 99mTc-DTPA in the kidneys is an indicator of renal function that has been used in humans for the diagnosis of renal obstruction, renal artery stenosis, and rejection of renal transplants. Its use, however, has not been reported in the dog. 99mTc-DTPA scintigraphy was performed in 8 normal dogs and the time of peak was calculated as the time between the injection and the maximum renal uptake. Deconvolution analysis was performed to estimate the renal retention function using 3 different techniques, i.e. the matrix method, the fast Fourier transform (FFT) method, and the constrained least square method. The parenchymal and whole kidney mean transit times were calculated from the deconvolved renogram using alternatively the thorax and the aorta as the input function. Average mean transit times ranged from 137 to 184 seconds. Parenchymal mean transit time was significantly shorter than whole kidney mean transit time (P<0.03). Mean transit time calculated with the thorax as the input function was significantly longer than mean transit time calculated with the aorta (P<0.001). No differences were observed between mean transit time calculated with the matrix, FFT and constrained least square methods.

A method for creating reversible ureteric obstruction in the primate.

A technique has been developed for the establishment of a state of reversible, ureteric obstruction in the primate. Ten adult males had baseline 99mTc-DTPA renogram studies. A randomly selected ureter was totally occluded and obstruction confirmed on renogram. The occlusion was reversed and subsequent renograms confirmed recovery of activity in the obstructed kidneys of the eight animals who survived the reversal procedure. Seven were alive on conclusion of the study. Prevention of ureteric strictures was achieved with an intra-ureteric silastic tube. Autopsies demonstrated patency of every previously occluded ureter. This is the first study to be reported in primates, and the second overall, in which complete ureteric obstruction and its successful reversal has been confirmed on renogram using this surgical method. The technique is suitable for the study of the effect of reversible ureteric obstruction on renal function.

Evaluation of kidney function in dogs suffering from canine encephalitozoonosis by standard clinical pathological and radiopharmaceutical techniques.

Canine encephalitozoonosis can be responsible for a severe renal disease in dogs which may develop into progressive, irreversible kidney failure. Three pure-bred Boxer littermates with confirmed encephalitozoonosis were subjected to sequential clinical pathological tests and renal biopsies. The endogenous serum creatinine and urea levels showed an initial temporary reduction but later increased steadily. The phenolsulphonphthalein retention test confirmed this end-stage renal disease. Initial hyper-gamma globulinaemia showed a rapid decline. Urinalysis was an indicator of chronic renal disease and the kidney biopsies confirmed progressive irreversible kidney lesions. Evaluation of sequential tests are advocated for the setting of a prognosis. The radiopharmaceutical techniques employed proved to be sensitive indicators of renal dysfunction and a means of evaluating the function of the left and right kidney separately.

Standardization of anaesthesia for radiorenography with primates under laboratory conditions.

The influence of thiopentone intravenous infusion or halothane inhalation on the results of radiorenography was evaluated using, in six chacma baboons (Papio ursinus), 99mTc-diethyltriamine-pentaacetic acid (DTPA) as scanning agent. The renogram parameters, which depend on the condition of the cardiovascular system, differed significantly for the two anaesthetic agents. Since anaesthesia is necessary in baboon studies for the duration of renogram acquisition, it is imperative to standardize an experimental procedure which will leave the cardiovascular system relatively stable. From this investigation it seemed most appropriate to use as an anaesthetic a constant intravenous infusion of thiopentone.

The feasibility of a renogram study in dogs with radiopharmaceutical 99mTc-DTPA.

The present study is one of in vivo 99mTc-DTPA renography, successively involving conscious healthy dogs under acepromazine maleate sedation and dogs under the narcotic sodium thiopental. It was found that during the running of the renogram the animal had to be kept completely immobile and that constant infusion narcosis with sodium thiopental produced this immobility without affecting the renograms unduly. However administration of a thiopental bolus did have an adverse effect on the renogram. Sedation with acepromazine maleate significantly increased the time to peak and the excretion phase as presented by the slope. These effects are thought to be due to a decreased blood pressure with concomitant renal bloodpooling and retarded bloodflow. The radioisotope renogram appears to hold great promise for both clinical and research applications. The equipment required for this application however, is so costly that it would only be financially feasible for major centres.

[Isotope nephrography in studying the nephrotoxicity of cisplatin in pigs]. / Izotopová nefrografie pri sledování nefrotoxicity cisplatiny u prasat.

The cis-DDP (Cisplatin) nephrotoxicity and its prevention by hydration in experimental pigs was studied by laboratory and patho-morphological examinations and by isotope nephrography (renography). In total, 33 nephrographic examinations were performed in 14 pigs. The comparison of these nephrographs with the laboratory and post-mortem patho-morphological examinations showed that all findings were in perfect accordance. Only in exceptional cases there was a discrepancy between the pathological nephrograph and the type of kidney damage. The possibility of using the isotope nephrography as a progressive complementary method of the kidney function examination, under the condition of securing suitable maximum immobility of pigs, was fully proved.