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Abstract

The purpose of this study was to evaluate results of diuretic renal scintigraphy in 32 feline kidneys with nephroureterolithiasis and variable degrees of renal pelvis/ureteral dilation. Six kidneys showed a non-obstructive scintigraphic pattern, with a downward slope of time-activity curves (TAC) and a median excretion half-time of radiopharmaceutical (T½) of 6.09 (5.08–8.43) min. Eight kidneys showed an obstructive pattern, with a continuous rise of TAC and median T½ of −7.91 (−43.13–0.00) min. In one kidney with presumptive partial obstruction scintigraphic results were equivocal. Seventeen kidneys, most of which had an individual kidney glomerular filtration rate below 0.5 ml/min/kg, had non-diagnostic studies. Diuretic renal scintigraphy may be a useful adjunct modality in the diagnosis of ureteral obstruction in some cats if renal function is maintained. However, the large number of non-diagnostic studies in animals with decreased renal function represents a clear limitation of the technique.

Urolithiasis ranks among the most important urinary tract disorders in cats.¹ Calculi within the renal pelvis or ureter can result in complete or partial obstruction of the urinary collecting system and subsequently cause hydronephrosis and/or hydroureter. Complete ureteral obstruction will cause irreversible damage to the renal parenchyma necessitating lifelong management or result in death of the affected patient.^2–4 Interventional procedures to relieve ureteral obstruction (lithotripsy, surgery or ureteral stenting) are costly, some may be associated with high morbidity (ureteral leakage, ureteral stricture, and anesthetic death), and treatment decisions are difficult and agonizing for veterinarians and owners.^5–7 As dilation of the urinary collecting system can be related to non-obstructive disorders such as vesicoureteral reflux, trauma, infection and congenital anomalies,^8–10 diagnosis of ureteral obstruction may be difficult but is crucial when making treatment decisions.

Abdominal radiographs, abdominal ultrasonography±determination of resistive index, excretory urography and percutaneous antegrade pyelography have been described in the evaluation of ureteral obstruction in animal patients. However, these imaging modalities have certain limitations. Radiographs may show radiopaque calculi, but in most instances are not useful in diagnosing the presence or degree of ureteral obstruction. They may, however, be useful in monitoring progression of ureteral calculi through the urinary tract when conservative treatment or lithotripsy are attempted.¹¹ Excretory urography may be used to visualize dilation of renal pelvis and ureter proximal to the obstructive lesion, but opacification of the affected kidney is often poor.¹² Percutaneous antegrade pyelography has been used successfully in the diagnosis of ureteral obstruction, but has the disadvantage of being invasive and requiring general anesthesia.¹³ Additionally, surgical intervention to prevent leakage from the injection site is needed following this procedure if ureteral obstruction is present. Ultrasonography has a high sensitivity for the detection of pyelectasia and obstructive ureteral calculi but lacks diagnostic information regarding renal function or ureteral patency.^9,11,14 Doppler sonography with determination of a resistive index has been investigated in dogs with ureteral obstruction but has low accuracy and is not commonly used in veterinary medicine.¹⁵ To the best of our knowledge, computed tomography and magnetic resonance imaging have not been described in the diagnosis of ureteral obstruction in animals.

Renal scintigraphy using an injection of a diuretic to clear the radiopharmaceutical from the renal collecting system (‘diuretic renal scintigraphy’, ‘diuretic renography’, ‘diuresis scintigraphy’) is considered by many the diagnostic imaging modality of choice to assess renal function and drainage in cases of upper urinary tract dilation in humans.^16–20 Indications include differentiation of obstructive from non-obstructive hydroureteronephrosis,^18,21 assessment of potential for renal recovery from urinary tract obstruction in children²² and prediction of surgical success following pyeloplasty.²³ Diagnosis of ureteral obstruction is based on an altered shape of a renal time-activity curve (TAC) derived from dynamic scintigraphic data and delayed excretion of radiopharmaceutical from the kidneys after injection of the diuretic, ie, prolonged excretion half-time (T_½). In normal subjects and in patients with non-obstructive renal pelvis dilation, the TAC shows a downward slope after injection of radiopharmaceutical. In obstructive uropathies, the TAC reaches a plateau or shows continuous rise. In humans, the excretion half-time of radiopharmaceutical <10 min is considered normal, 10–20 min is equivocal for ureteral obstruction, and >20 min is consistent with obstructive uropathy.^{17,18,24–26} In dogs diuretic renal scintigraphy has been proven successful in the diagnosis of complete or partial ureteral obstruction in both experimental animals^24,27 and clinical patients.^28,29 A diuretic renal scintigraphy protocol and findings in normal cats have been described.³⁰ TAC were characterized by either a steep drop or gradual downward slope of the curve after injection of furosemide. T_½ was 4.93 (4.16–6.95) min (median (range)), and time of peak (TOP) of TAC was 3.06±0.58 min. To the best of our knowledge, results of diuretic renal scintigraphy in cats with partial or complete ureteral obstruction have not been described. The goal of this study was to report initial experience with this method in feline patients presented with nephroureterolithiasis.

Materials and methods

Results from a previous study in normal research cats³⁰ were used as a baseline for comparison.

The radiology database of the University of Tennessee College of Veterinary Medicine was searched from January 2004 to June 2008 for all feline patients in which diuretic renal scintigraphy was performed. Patients with complete radiographic and ultrasonographic evaluation of the abdomen and a diagnosis of unilateral or bilateral nephroureterolithiasis were included in the study. Signalment, laboratory data, imaging findings, treatment and outcome were reviewed. Renal and ureteral abnormalities including the presence and location of calculi and dilation of renal pelvis and/or ureter were recorded.

Renal excretion scintigraphy was performed as described previously.³⁰ An intravenous catheter was placed in the cephalic vein. If necessary, animals were sedated. Sedation protocols were variable and based on primary clinician's recommendations. The cats were placed in right recumbency, with the gamma camera (GE Starport; GE Healthcare) fitted with a low-energy all purpose (LEAP) parallel hole collimator positioned dorsally. A multiphase, dynamic frame-mode acquisition was controlled by an imaging computer and was initiated simultaneously with intravenous injection of 112.4±14.8 MBq (3.0±0.4 mCi) ^99mTc-DTPA (time 0). A 128×128×16 matrix size was used with a frame rate of one frame every 6 s for 3 min, then one frame every 3 s for an additional 5 min. Furosemide (Equi-Phar Furosemide Injection 5%; IVX Animal Health) (3.0 mg/kg) was administered intravenously at 4.5 min. A composite image was created by summing the images from 1–2 min following injection of ^99mTc-DTPA. Regions of interest (ROIs) were drawn manually around each kidney, and background regions were drawn cranial and caudal to each kidney. A renal TAC was then created by applying the ROI to the dynamic data. Net kidney counts were determined by correction for background activity. The numeric data from the TAC were imported into a spreadsheet (Microsoft Excel; Microsoft Corp) to determine glomerular filtration rate (GFR) using the Gates' technique modified by Krawiec et al.^31–33 Renal excretion was measured by linear regression from the maximum slope of the renogram curves during the excretion phase. To standardize the slope of the excretion phase, all renograms curves were normalized to a peak value of 10,000 as described previously.³⁴

Evaluation included visual inspection of TAC, determination of individual kidney GFR, TOP of the TAC and individual excretion half-time of radiopharmaceutical (T_½). Shape of the curve was described as either ‘classic non-obstructive drainage pattern’ with a steep drop after onset of diuretic action starting after or at the point of peak maximum activity,^24,25 non-obstructive pattern with gradual and continuous down slope of the curve following administration of furosemide,^30,34 or obstructed pattern with continuous rise or initial rise to a plateau of the renal TAC.²⁴ A flat TAC was considered non-diagnostic.

Results of excretion scintigraphy in kidneys without renal pelvis/ureteral dilation were compared to results of excretion scintigraphy in kidneys with dilation of the collecting system. GFR, TOP of the TAC and individual excretion half-time of radiopharmaceutical (T_½) in kidneys with obstructive and non-obstructive pattern of TAC were compared to each other and to values reported in normal cats.³⁰ Statistical evaluation was performed using the Wilcoxon rank sum test (SigmaStat 3.1; Systat Software). A P-value of <0.05 was considered significant. Descriptive data are reported as mean±standard deviation (SD) for normally distributed values, and median and range for non-normally distributed values.

Results

Eighteen renal excretion scintigraphic studies were performed in 15 cats. There were 11 domestic shorthair cats, three mixed breed cats and one Himalayan. Mean age was 8.7±3.7 years. Ten cats were spayed females and five were neutered males. Eight cats were moderately to severely azotemic at presentation (blood urea nitrogen (BUN)>35 mg/dl; serum creatinine>2.1 mg/dl), and four cats were mildly azotemic (BUN 35–45 mg/dl; serum creatinine<2.1 mg/dl). Fourteen cats had one scintigraphic examination and one cat had four examinations performed, resulting in 36 individual renal scintigrams. In four cats only one kidney showed evidence of urolithiasis, and the contralateral kidney was excluded from evaluation. Therefore, 32 individual renal scintigrams were available for evaluation. There were seven kidneys/ureters without and 25 kidneys/ureters with renal pelvis/ureteral dilation. Results of excretion scintigraphy in kidneys without renal pelvis/ureteral dilation – if diagnostic – were consistent with a non-obstructive pattern. Results of excretion scintigraphy in kidneys with renal pelvis/ureteral dilation were variable (see Table 1). Excretion scintigraphic studies were diagnostic in 15 and non-diagnostic in 17 kidneys. Individual kidney GFR was below 0.5 ml/min/kg in 15/17 non-diagnostic but only in 2/15 diagnostic studies.

Table 1

Frequency of scintigraphic patterns observed in individual feline excretory renal scintigraphy studies (n=32*).

Scintigraphic pattern	Dilation of renal pelvis and/or ureter
	No (n=7)	Yes (n=25)
		Mild (n=9)	Moderate (n=11)	Severe (n=5)
Non-obstructive pattern (n=6)	3	3	0	0
Obstructive pattern (n=8)	0	1	5	2
Equivocal for obstruction (n=1)	0	0	1	0
Non-diagnostic (n=17)	4	5	5	3

Fifteen cats were included in the study, 14 of which had one scintigraphic examination and one of which had four scintigraphic examinations performed (total of 36 individual scintigraphic curves). Four kidneys without mineralization/calculi were excluded from evaluation, resulting in a total of 32 individual excretory renal scintigrams.

Results of GFR analysis, TOP of TAC and T_½ are shown in Table 2 and are compared to values reported in normal cats in a previous study.³⁰ Six kidneys had renal excretion scintigraphy results consistent with a non-obstructive pattern (Fig. 1). All TAC showed gradual and continuous down slope of the curve. There was no significant difference in individual kidney GFR and TOP of TAC compared to normal. T_½ was significantly increased compared to normal (P=0.031), but was below 8.5 min in all cases.

Table 2

Results of diuretic renal scintigraphy.

	Individual kidney GFR (ml/min/kg) Median (range)	Time of peak (min) Median (range)	Excretion half-time (min) Median (range)
Normal (n=20)*	1.23 (0.77–2.41)	3.10 (2.00–4.35)	4.93 (4.16–6.95)
Non-obstructive (n=6)	1.02 (0.53–1.76)	2.70 (1.90–5.25)	6.09 (5.08–8.43)†
Obstructive (n=8)	0.67 (0.14–1.51)	7.10 (4.60–8.00)†	−7.91 (−43.13–0.00)†
Non-diagnostic (n=17)	0.36 (0.00–0.65)‡
Equivocal (n=1)§	1.29	5.05	13.99

Hecht et al. 2008³⁰

†

Statistically significant difference (P<0.05) compared to normal.

‡

Statistically significant difference (P<0.001) compared to normal.

Due to low number of subjects no statistical comparison to normal.

Fig 1

Non-obstructive nephrolithiasis in a 5-year-old domestic shorthair cat. (A) Ultrasonographic image shows a linear hyperattenuating structure with distal sound beam attenuation (between cursors) associated with the left kidney. The kidney (between arrowheads) is small and has a triangular hyperintense area associated with the cranial pole, consistent with an infarct. There is no evidence of renal pelvis dilation. (B) TAC derived during diuretic renal scintigraphy. Furosemide was injected at 4.5 min (arrow). Gradual and continuous down slope of the curve following administration of furosemide is consistent with a non-obstructive pattern (T_½=8.54 min).

Eight kidneys had renal scintigraphy results consistent with an obstructive pattern (Fig. 2). Seven TAC showed continuous rise, resulting in a negative T_½, and one curve rose to peak and plateaued after reaching peak activity (T_½=0.00 min). T_½ was significantly increased compared to normal (P=0.008). There was no significant difference in individual kidney GFR compared to normal. TOP was significantly increased compared to normal (P=0.008). Ultrasonographically, there was mild to severe hydronephrosis and hydroureter in all cases. Treatment consisted of lithotripsy (n=3), surgery (ureteroneocystostomy; n=2) or conservative treatment. Stone analysis was performed in one case following surgical removal of an ureterolith, and a diagnosis of calcium oxalate monohydrate calculus was made.

Fig 2

Obstructive ureterolithiasis in a 4-year-old cat. (A) Lateral abdominal radiograph shows small size and irregularity of the right kidney, bilateral renal mineralization and a small mineral opacity in the plane of the retroperitoneal space (arrow), consistent with an ureterolith. (B) Transverse ultrasonographic image of the left kidney shows mild renal pelvis dilation (between cursors) and a small non-obstructive nephrolith. At this point, there was no evidence of hydroureter. (C) TAC derived during diuretic renal scintigraphic study on the same day. Furosemide was injected at 4.5 min (arrow). Continuous rise of the curve following administration of furosemide is consistent with an obstructive pattern (T_½=−31.35 min). (D) Recheck ultrasound 2 days later demonstrates progressive renal pelvis dilation (between cursors), consistent with scintigraphic diagnosis of obstruction. Hydroureter was also noted at this time.

The result of excretion scintigraphy in one kidney was equivocal for obstruction. The TAC showed only mild down slope following injection of furosemide, and T_½ was determined as 13.99 min (Fig. 3A). Repeat renal scintigraphy 1 month later demonstrated an obstructive pattern (Fig. 3B), and lithotripsy was performed for treatment of an ureterolith. Recheck renal scintigraphic studies were consistent with a non-obstructive pattern (Fig. 3C,D).

Fig 3

Suspected partial ureteral obstruction in a cat. (A) Initial scintigraphic study shows only mild down slope of TAC following injection of furosemide (T_½=13.99 min), which is considered equivocal for obstruction. (B) Repeat diuretic renal scintigraphy 1 month later demonstrates an obstructive pattern, with continuous rise of TAC. (C) Diuretic renal scintigraphy after lithotripsy is consistent with a non-obstructive pattern (T_½=5.08 min). (D) Recheck scintigraphy 1 month later still shows a non-obstructive pattern (T_½₌5.35 min).

Seventeen studies were non-diagnostic, with flat TAC throughout the course of the examination. Individual kidney GFR was significantly decreased compared to normal (P<0.001).

Discussion

The purpose of this study was to evaluate initial results of diuretic renal scintigraphy in feline patients presented to our hospital for evaluation of nephroureterolithiasis. We found the procedure to be helpful in some cats with concurrent renal pelvis/ureteral dilation of variable degrees and maintained renal function. However, the large number of non-diagnostic studies in animals with decreased renal function (either due to underlying chronic renal disease or secondary to ureteral obstruction) represents a clear limitation of the technique. As expected, scintigraphic results in animals without renal pelvis/ureteral dilation were – if diagnostic – consistent with a non-obstructive pattern. As the index of suspicion for ureteral obstruction is very low in patients without evidence of renal pelvis and/or ureteral dilation, diuretic renal scintigraphy does not appear to add additional information in the diagnostic workup of these cases. Renal TAC in cats with non-obstructive nephroureterolithiasis were characterized by a gradual downward slope after administration of furosemide, similar to curves seen in normal animals³⁰ and human patients with non-obstructive hydroureteronephrosis.^17,18,25,35 A significantly longer excretion half-time was noted in cats with non-obstructive nephroureterolithiasis compared to results derived in normal cats in a previous study.³⁰ The reason for this finding is unknown, and the result has to be interpreted with caution in light of the small number of subjects in this group. As the pattern of the curves was consistent with a non-obstructive pattern in these patients it is not likely that this increase in T_½ will cause a diagnostic problem.

In cats with renal pelvic or ureteral obstruction there was continuous upward slope of the TAC or rise to a plateau, with a significant difference in excretion half-time compared to normal. This was expected and corresponds to findings in obstructive hydroureteronephrosis in humans and (experimental) ureteral obstruction in dogs reported in previous studies.^{16–20,24,27,29,36}

Scintigraphic findings in one kidney in a cat were equivocal for ureteral obstruction. If diuretic renal scintigraphy is equivocal in a human patient with renal pelvis dilation, the result should be interpreted in light of renal function.¹⁷ If renal function is maintained, the delayed washout of radiopharmaceutical is considered indicative of partial obstruction. If renal function is impaired, further investigation is warranted to achieve a diagnosis of obstruction. In our study, there was adequate renal function of the single feline kidney with delayed transit time, and a follow-up scan 1 month later showed an obstructive pattern. It seems likely that this cat had partial ureteral obstruction when the first scan was performed.

The large number of non-diagnostic scans in our patient population was unexpected and was in most cases associated with a severe decrease in individual kidney GFR (<0.5 ml/min/kg). Traditionally, a global GFR of 2.56±0.61 ml/min/kg is considered normal in the cat.³⁷ A previous study at our institution yielded a median individual kidney GFR value of 1.23 (0.77–2.41) ml/min/kg in normal cats.³⁰ Poor renal function represents a recognized limitation in the value of diuretic renal scintigraphy for the diagnosis of ureteral obstruction in humans.^38,39 According to recent consensus reports results have to be interpreted with caution if individual kidney GFR is <32 ml/min,⁴⁰ and more invasive diagnostic procedures such as pressure flow studies involving perfusion of the upper urinary tract while simultaneously measuring pressure may be needed to establish a definitive diagnosis in these patients.^41,42 Although pressure flow studies have been proven useful in the diagnosis of experimental ureteral obstruction in dogs,⁴³ they have to our knowledge not been reported in cats and are not commonly used in veterinary medicine. At our institution, repeat radiographs and ultrasonographic examinations were performed to monitor the presence and degree of obstruction and progression of calculi through the collecting system to achieve a diagnosis, and to initiate appropriate treatment in animals with decreased renal function and resultant non-diagnostic scintigraphy studies. To the best of our knowledge, no prospective studies have been performed to assess the value of different imaging modalities in the diagnosis of ureteral obstruction in cats, and a decision on which imaging study to perform is based on equipment availability and comfort level of clinician/radiologist. Percutaneous antegrade pyelography¹³ is probably the best modality for a diagnosis or exclusion of ureteral obstruction in cats but has the disadvantage of being invasive and requiring general anesthesia.

It is important to note that GFR values derived during excretion scintigraphy in cats with ureteral obstruction have to be interpreted with caution. Complete or partial ureteral obstruction eventually produces a decrease of glomerular filtration because of a decrease in renal blood flow and urine output, which will in turn result in decreased uptake of the radiopharmaceutical.^3,44 Due to the retrospective nature of this study, duration of obstruction at time of presentation and renal function prior to obstruction are not known. Additionally, it is likely that significant decrease in renal function secondary to obstruction may have resulted in non-diagnostic curves in some cases.

One problem when deciding which imaging procedure to pursue is that renal function usually is not known when an animal is first presented for evaluation of potential ureteral obstruction. If individual kidney GFR was known and was <0.5 ml/min/kg, excretion scintigraphy would not be useful as a diagnostic test based on the results of this study. As the majority of cats with ureterolithiasis are azotemic at presentation,¹¹ it would be advantageous if an increase in BUN and creatinine could be used as a criterion to decide on merit of diuretic renal scintigraphy. Azotemia indicates that global GFR is decreased to 1.0–1.2 ml/min/kg.⁴⁵ However, this does not reflect individual renal contribution to total renal function. If the entire or majority of renal function in one cat is derived from one particular kidney, and the other kidney is non-functional, the cat may have a diagnostic scan for the functional kidney and a non-diagnostic scan for the non-functional kidney. Of the 14 cats undergoing one scintigraphic examination in the frame of our study seven were moderately to severely azotemic at presentation. Of these seven cats three had unilateral obstruction with a contralateral non-functioning kidney (Fig. 4). The cat undergoing four scintigraphic studies was azotemic only at first presentation, where scintigraphic results were equivocal for one kidney and non-diagnostic for the other. Based on these findings azotemia cannot be used as an exclusion criterion when considering scintigraphy in a cat with potential ureteral obstruction.

Fig 4

Diuretic renal scintigraphy curves from a cat with bilateral ureterolithiasis, hydronephrosis and hydroureter. The cat was azotemic at presentation (BUN 72 mg/dl; serum creatinine 5.8 mg/dl). The curve for the left kidney was considered non-diagnostic, while the curve for the right kidney was consistent with obstruction. Individual kidney GFR as determined by scintigraphy was 0.17 ml/min/kg for the left kidney and 0.57 ml/min/kg for the right kidney. Low total GFR (0.74 ml/min/kg) is consistent with azotemia. The majority of total renal function (77%) was derived from the right kidney, and renal function on this side was still sufficient to generate a diagnostic curve. The cat underwent surgical exploration, and right-sided ureteral obstruction was confirmed.

Lack of a true gold standard represents a limitation of this study. Animals in which an ultimate diagnosis of non-obstructive nephroureterolithiasis was made did not undergo surgical exploration, and ureteral obstruction may have been missed in some instances. Additionally, in some cats a diagnosis of ureteral obstruction had to be based on a combination of clinical and imaging findings without surgical or post mortem confirmation. Like in most studies performed in clinical patients, diagnostic workup and treatment were determined by owner compliance, patient response to initial treatment and clinician preference. Our goal was not to determine sensitivity and specificity of this method but present initial experiences in cats with nephroureterolithiasis. Follow-up studies might include use of different radiopharmaceuticals such as ^99mTc-MAG3 to improve tracer-to background ratio, determination of sensitivity and specificity of diuretic renal scintigraphy in the diagnosis of ureteral obstruction in experimental animals, comparison of scintigraphic findings before and after treatment of obstructive nephroureterolithiasis, and comparison of diuretic renal scintigraphy to other imaging modalities, especially antegrade pyelography, in the diagnosis of renal pelvis or ureteral obstruction.

Conclusion

Based on the results of this study diuretic renal scintigraphy may be helpful in some cats with concurrent renal pelvis/ureteral dilation of variable degrees and maintained renal function. However, the large number of non-diagnostic studies in animals with decreased renal function (either due to underlying chronic renal disease or secondary to ureteral obstruction) represents a clear limitation of the technique.

Footnotes

Acknowledgements

Partial funding for this project was provided by the Center of Excellence Summer Research and Student Scholar Program of the University of Tennessee College of Veterinary Medicine.

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99m Tc-DTPA diuretic renal scintigraphy in cats with nephroureterolithiasis

Abstract

Materials and methods

Results

Discussion

Conclusion

Footnotes

Acknowledgements

References