Duplex Doppler Estimation of Intrarenal Pourcelot Resistive Index in Dogs and Cats With Renal Disease


Bill J. Rivers, Patricia A. Walter, David J. Polzin, and Vickie L. King  "Duplex  Doppler Estimation of Intrarenal Pourcelot Resistive Index in Dogs  and  Cats With  Renal  Disease"


In  human  beings,  intrarenal  blood  flow  impedance,  ex-pressed as the resistive index (RI) and obtained by duplex
Doppler ultrasonography, has been used to aid in diagnosisand prognosis of renal failure. Higher than normal  values for RI were obtained in 3 of 4 dogs with acute tubular necrosis (ATN) and in 5  of  10 dogs with  glomerulonephrosis (GNI. Normalization of RI was observed in 2 dogs with ATN evaluated serially during treatment. Increased RI values were obtained in 9 of 10 cats with nonobstructive renal disease and in 2 of 5 cats with obstructive renal disease. Normalization of RI was observed  in 3 cats with renal failure in  which treatment was effective (1 with obstruction; 2 with nonobstructive disease).  The magnitude of increase in RI did not correlate with  the  magnitude  of  concurrent renal  dysfunction. These results suggest that duplex Doppler evaluation of intrarenal  RI  is more  useful as  an  ancillary diagnostic technique  in  azotemic  dogs  with ATN than  in those  with  GN and in azotemic cats with nonobstructive  than in  those with obstructive disease.

 

 

Renal failure is an important cause of morbidity and mortality in dogs and cats.'.'  Often, renal biopsy is needed
for further clarification of cause and ~everity,'.~ but this procedure  is  relatively  invasive  and  potentially  is  associated with  complication^.^^^ Additional noninvasive methods to aid in the diagnosis and prognosis of  renal diseases in dogs and cats would be beneficial. B-mode  ultrasonography provides  noninvasive  morpho-
logic evaluation of organs without use of ionizing radiation. It  has  become  a  widely  accepted  diagnostic  technique  in veterinary practice and has  proved useful in the evaluation of  patients  with  renal  disease ? ~ ~ * ~  Duplex  Doppler  ultrasonography adds noninvasive real-time quantitative determination of organ blood flow in addition to morphologic evaluation. Diseases that alter organ blood flow have the potential to be further characterized by  duplex Doppler ultrasonography.

In  human patients, intrarenal blood flow  values obtained with duplex Doppler ultrasonography have been used to aid in diagnosis of renal disease and to monitor therapeutic response and prognosi ~ . ~ ~ ' ~  In human patients, duplex Doppler evaluation of  intrarenal blood flow  commonly is performed using resistive index (RI) (also known as Pourcelot index," resistivity index,I2  and resistance indexI3),  an expression of intrarenal blood flow impedance."  In human beings, the upper  limit of  normal for intrarenal RI  is 0.70;  values above 0.70  are  considered  abn ~ rmal .' ~ ~ ' ~  In  human  beings,  increased intrarenal RI has been used as an aid in the diagnosis of renal disease, and normalization of RI after effective treatment has been used to monitor therapeutic response.
Intrarenal RI values for normal dogs have been  described as  0.62 i   0.05 (mean t  standard  deviation  [SD]) for  the
right  kidney  and  0.63 t  0.05  (mean i  SD)  for  the  left kidney, with no statistically significant difference observed
between the right and left kidney.15 Intrarenal RI values for normal cats  have  been  described as 0.59 t  0.05 (mean  5SD) for the right kidney  and 0.56 i   0.06 (mean i   SD) for the  left kidney,  with  no  statistically  significant differences observed between  right  and  left  kidney.16 Mean  intrarenal RI vaIue plus 2 SD has been  used to describe the upper limit of normal in human beings."  Based on the aforementioned value^,'^.'^ 0.73 is proposed as the upper limit for intrarenal RI in normal dogs and 0.71 in normal cats.
Increased intrarenal RI values have been reported in dogs with obstructive ~ropathy.'~.'~ There are few reports of duplex Doppler-derived values for intrarenal blood flow impedance in dogs with spontaneous nonobstructive renal disease. Intrarenal RI values greater than 0.73 were observed in a dog with acute tubular necrosis, with normalization of intrarenal RI after effective treatment." A retrospective study examined intrarenal RI findings in 67 dogs with spontaneous nonobstructive renal disease." Histopathologic or cytologic findings were available in 12 of these dogs, of which 4 had tubulointerstitial disease with or without glomerular disease, and 3 had glomerular disease alone. Intrarenal RI values greater than 0.73 were observed in 3 of the 4 dogs with tubulointerstitial disease; values less than 0.73 were observed in all 3 dogs with glomerular disease alone. Based on these results, the authors suggested that increased intrarenal RI was compatible with tubulointerstitial rather than glomerular disease. For these 12 dogs, B-mode grayscale sonographic findings were not reported, and the number of dogs with increased intrarenal RI and normal B-mode gray-scale sonographic study was not described. The potential for normalization of intrarenal RI after effective therapy was not addressed in this study.

The purposes of the present study were to (1) describe RI findings in cats with renal failure and further document such findings in dogs with nonobstructive renal disease, including correlation with histopathologic and B-mode gray-scale sonographic findings in nonobstructive disease, and (2) determine if normalization of intrarenal RI is observed after effective treatment.

 

Materials and Methods
Duplex Doppler-derived values for intrarenal RI were obtained from dogs and cats with nonobstructive renal disease and from cats with obstructive renal disease presented to the University of Minnesota Veterinary Teaching Hospital. Histologic characterization of renal disease within 2 weeks of intrarenal RI evaluation was required for inclusion in animals with nonobstructive disease, unless recovery from azotemia was observed during the period of hospitalization. Case selection for obstructive renal disease was restricted to patients for which obstruction was suspected based on historical grounds or survey radiographs” obtained at presentation and those that underwent either intravenous excretory urography (IVU)” or ultrasoundguided antegrade pyelography (UAP)” within 24 hours after initial intrarenal R1 evaluation. Cases were classified as acute versus chronic renal failure according to published criteria.22 Acute renal failure (ARF) was defined as rapid onset of azotemia within 2 weeks of presentation.*’Chronic renal failure (CRF) was defined as primary renal failure persistent for months to years.22 Acute-on-chronic renal
failure (ACRF) was defined as progression of previously stable azotemia, occurring within 2 weeks of presentation.

                                                                          CBC (Coulter S-Plus, Coulter Electronics Inc, Hialeah, FL), automated serum biochemical profile (urea nitrogen, creatinine, glucose, phosphorus, sodium, potassium, calcium, chloride, total carbon dioxide [Astra-8 Automated StaVRoutine Analyzer, Beckman Instruments Inc, Brea, CAI; albumin, total bilirubin, total protein, amylase, alkaline phosphatase, alanine transaminase [Synchron Cx4 Automated Analyzer; Beckman Instruments]), complete urinalysisz3 and quantitative urine culturez4 (urine obtained by antepubic cystocentesis), survey abdominal radiographs” (XMA 325 x-ray machine, Universal X-Ray Inc, Chicago, IL; Dupont 4L film and Quanta Fast Detail intensifying screens, El duPont de Nemours and Co, Eden Prairie, MN), and real-time abdominal B-mode ultrasonographyz“ and duplex Doppler interrogation of intrarenal RI“ (Opus 1, with 7.5
MHz real-time sector transducer; Ausonics Corp, Sydney, Australia) using acoustic coupling gel (Aquasonic 100 Ultrasound Transmission Gel, Parker Labs Inc, Orange, NJ) were performed on all patients at presentation. Sonographic images were recorded on radiographic film (Dupont 4L film, El duPont de Nemours and Co, Eden
Prairie, MN) with a multiformat camera (MP 400 Series I1 formatting camera, International Imaging Electronics, Addison, IL). Interpretation of survey abdominal radiographs, IVU, UAP, and real-time B-mode renal ultrasonography was based on established criteria.20,2’ Urine output status for cases of nonobstructive disease at time of duplex Doppler ultrasonography was categorized according to published criteria.26

Indirect systemic arterial blood pressurez7 was determined on all 4 dogs with CRF (dogs 3, 5, 8, and 9; Table 1). in 2 of 10 dogs with ARF (dogs 6 and 12, Table 1) (Dinamap Vital Signs Monitor model 1846, Critikon Inc, Tampa, FL; with appropriately sized Blood Pressure Cuff, Baxter Healthcare Corp, Deerfield, IL), and in all 4 cats with ACRF (cats 4 through 6 and 8, Table 2) (Ultrasonic Doppler Flow Detector Model 8 ILL, Parks Medical Electronics Inc, Beaverton, OR; with Blood Pressure Cuff Neonatal #2, Baxter Healthcare Corp, Deerfield, IL). Urine protein-to-creatinine ratios”
(Astra-8 Automated StatlRoutine Analyzer, Beckman Instruments Inc, Brea, CA) were performed in dogs with excessive proteinuria” (dogs 3 through 5, 7 through 12, Table I). In 2 dogs (dogs 13 and 14, Table 1) and in 4 cats (cats 4, 9, and 10, Table 2, and cat 5, Table 3), serial sonographic examination. hematocrit, and serum creatinine concentrations were performed. Urine output, results of urinalysis, and serum creatinine concentration, urine protein-to-creatinine ratio, hematocrit, and systemic arterial blood pressure were not known by the sonographer performing sonography including duplex Doppler evaluation of intrarenal RI (BJR).

Ultrasound-guided renal biopsy” specimens (Monopty Biopsy Instrument, 1 8-gauge needle, 22-mm penetration length; Bard Urological Division, CR Bard Inc, Covington, GA) were obtained for histologic characterization of renal failure4 in 4 dogs (dogs 1, 4, 8, and 11, Table 1) and in 2 cats (cats 3 and 7, Table 2) with nonobstructive disease within 24 hours of initial sonography (by BJR). Anesthesia for biopsy in dogs was achieved with propofol (Diprivan 1 % injection; 10 mg/mL) (6 mgkg body weight IV).’” Anesthesia for biopsy in cats was achieved with ketamine hydrochloride (Ketaset; 100 mg/ mL) (10 mgkg body weight IV).” In 8 of the remaining 10 dogs (dogs 2, 3, 5 through 7, 9, 10, and 12, Table 1) and in 6 of the remaining 10 cats (cats 1, 2, 4 through 6, and 8, Table 2) with nonobstructive disease, histologic characterization of renal disease was made using specimens obtained by necropsy within 2 weeks of initial sonography. Renal tissue sections were prepared and interpreted using established methods5 In 2 dogs with nonobstructive disease (dogs 13 and 14, Table 1) and in 2 cats with nonobstructive disease (cats 9 and 10, Table 2), recovery from azotemia was observed during the period of hospitalization, and histologic characterization of renal failure was not obtained.

Distal intrarenal (distal interlobar or arcuate artery) R1 values were derived from duplex Doppler flow spectra obtained without sedation using previously established method~logy.‘”~~.~~ Distal intrarenal RI determination and rationale for its use in renal disease have been described previously.16 Normal intrarenal RI was defined as a value
within 2 SD of the mean” previously reported for the normal dog (ie, 0.52-0.73)’5 and cat (ie, 0.44-0.71).’6 Increased intrarenal RI was defined as a value greater than 0.73 for dogs and greater than 0.71 for cats. Flow spectra were recorded on radiographic film (Dupont 4L film, El duPont de Nemours and Co, Eden Prairie, MN) with a multiformat camera (MP 400 Series 11 formatting camera, International Imaging Electronics, Addison, IL). Accuracy of Doppler measurements was verified with a flow control phantom (RMI Doppler PhantodFlow Control System Model 425, Radiation Measurements Inc, Middleton, WI) using established methods.”

Individual patient intrarenal RI values were compared to concurrent serum creatinine concentration and to urine protein-to-creatinine ratio in the following fashion. R1 values for each individual kidney were averaged, and the resulting value was used for correlation analysis with the following exception: If only one individual kidney
RI value was increased, only this value was used for correlation analysis. Pearson correlation analysis” was performed to determine if a statistically significant (P < .05) correlation existed between individual dog intrarenal RI values and concurrent serum creatinine concentration and urine protein-to-creatinine ratio. Individual intrarenal RI values for cats were compared to serum creatinine concentration in the same fashion. In cats with nonobstructive renal disease,
the small number of oliguric and anuric animals precluded adequate statistical analysis of correlation between individual intrarenal RI values and urine output status.

 

Results
Clinicopathologic, sonographic, and histologic findings in dogs with nonobstructive renal disease are summarized in
Table 1. Results of serum creatinine concentration and sonography are listed chronologically for cases 13 and 14. No
sonographic evidence of obstruction2’ was observed in any dog. Systemic arterial blood pressure was measured” in dogs 3, 5, 6, 8, 9, and 12, and results were within normal limits.” All but dog 10 had abnormal urine protein-to-creatinine ratios. No evidence of infection was detected on quantitative urine cultures24 or histologic examination of renal biopsy specimens.' No evidence of obstructive uropathy was observed in dogs that underwent necropsy (dogs 2,3,5 through 7, 9, 10, and 12). Technically adequate Doppler flow spectra were obtained from both kidneys of each dog within 30 minutes of duplex Doppler interrogation of the corticomedullary junction. Although in some dogs values for mean intrarenal RI of individual kidneys differed by 2 or more SD (dogs 3 and lo), all intrarenal RI measurements obtained within each individual kidney were within 2 SD of the mean value obtained for that kidney. Acute tubular necrosis (ATN) was observed in renal biopsy specimens from dogs 1 and 2. Dogs 13 and 14 also were assumed to have ATN owing to resolution of azotemia after diuretic fluid therapy and absence of excessive proteinuria on routine urinalysis. Glomerular disease as well as ATN were observed in dog 2. Glomerulonephropathy (GN) was observed on histologic examination of renal biopsy specimens in the remaining 10 dogs, 6 of which had concurrent tubulointerstitial nephritis and 4 had GN alone. Increased intrarenal RI values were observed in 8 of the 14 dogs overall, in 3 of the 4 dogs with ATN, and in 5 of the 10 dogs with GN. Increased intrarenal RI was observed in 2 of the 4 dogs in which GN alone was present. Intrarenal RI value normalization was observed in 2 dogs presumed to have ATN (dogs 13 and 14) that recovered after treatment. Increased intrarenal RI was observed in 6 of 10 dogs in which the results of B-mode gray-scale sonographic examination were abnormal. Two of these 6 cases had GN alone. Increased intrarenal RI was observed in 2 of 4 dogs in which the results of B-mode gray-scale sonographic examination were normal.

 

Table 1. Summary of Clinicopathologic, Sonographic, and Histologic Findings in 14 Dogs With Nonobstructive Renal Disease

Note: Range of normal serum creatinine concentration = 0.4-1.5 mg/dL. Abbreviations: MRI. mean distal intrarenal artery resistive index value 2 standard deviation; RK, right kidney: LK, left kidney; P/C, protein-tocreatinine ratio; X, cross; M, intact male; F, intact female; FS, female spayed; MC, male castrated; ARF, acute renal failure; CRF, chronic renal failure; RCE, relative renal cortex echogenicity; ATN, acute tubular necrosis; GN, glomerulonephritis; TIN, tubulointerstitial nephritis; N.O., not obtained.

 

Fig 1.    Scatterplot  of individual  dog intrarenal resistive  index value versus concurrent serum creatinine concentration. A statistically  significant  correlation was not identified (P  = ,4352; Pearson correlation coefficient rho = .2100).

 

Fig 2. Scatterplot of individual dog intrarenal resistive index value versus concurrent urine protein-to-creatinine ratio. A statistically significant correlation was not identified (P = .6681; Pearson correlation coefficient rho = -.1670).

 

A scatterplot of individual dog intrarenal RI versus serum creatinine concentration is presented in Fig 1. Pearson correlation analysis3' did not demonstrate a statistically significant correlation between individual dog intrarenal RI values and concurrent serum creatinine concentration (P = ,4352; Pearson correlation coefficient rho = ,2100). A scatterplot of individual dog intrarenal RI versus urine protein-to-creatinine ratio is presented in Fig 2. Pearson correlation analysis" did not demonstrate a statistically significant correlation between individual dog intrarenal RI values and urine proteinto-creatinine ratio (P = .668 1; Pearson correlation coefficient rho = -.1670). A scatterplot of individual dog intrarenal RI versus histologic diagnosis is presented in Fig 3. A broad overlap was observed in intrarenal R1 values compared to histologic diagnosis of ATN versus GN without ATN. A greater percentage of dogs with ATN cases, however, had abnormal intrarenal RI values as compared with dogs with GN without ATN. The small number of cases precluded statistical analysis of the observed percentage difference. Clinicopathologic, sonographic, and histologic findings in the cats with nonobstructive renal disease are summarized in Table 2. Systemic arterial blood pressure" was normal" in cats with ACRF. Results of serum creatinine concentration, ultrasonography, and urine output assessment are listed chronologically. No sonographic evidence of obstruction'" was observed in any cat. No evidence of infection was detected on quantitative urine cultures24 or histologic examination of renal biopsy specimens5 for any cat. Increased intrarenal RI values were observed in 9 of 10 cats. Normalization of intrarenal RI was observed in the 2 cats that recovered during treatment (cats 9 and lo).

 

Fig 3. Scatterplot of individual dog intrarenal resistive index value versus histologic diagnosis of acute tubular necrosis IATNf compared to histologic diagnosis of glomerular disease without ATN (GN). Horizontal line demarcates upper limit of normal intrarenal resistive index (0.731).

 

Table 2. Summary of Clinicopathologic, Sonographic, and Histologic Findings in 10 Cats With Nonobstructive Renal Disease

Note: Normal serum creatinine concentration range = 0.1-2.1   mg/dL.Abbreviations: MRI. mean distal intrarenal artery resistive index value t   standard deviation; RK,  right kidney; LK, left kidney; ARF,  acute renal failure; ACRF.  acute-on-chronic  renal failure;  Ad,  adequate; 01 ,   oliguric;  An,  anuric; DLH,  domestic long-haired;  DSH, domestic short-haired; FS, female spayed;  MC, male castrated;  RCE,  relative renal cortex echogenicity;  ATN,  acute tubular necrosis;  TIN,  tubulointerstitial nephritis;  N.O., not obtained;  FNA, fine needle aspirate.

 

Clinicopathologic, sonographic, and IVU or UAP findings in cats with obstructive renal disease are summarized in
Table 3. In all cats, no evidence of infection was detected on quantitative urine cultures.24 In 3 of the 5 cats (cats 1
through 3), obstruction of the ureter was partial, defined as proximal pelvicoureteral dilation with distal ureteral patency observed on IVU or UAP. In the remaining 2 cats (cats 4 and 5), obstruction of the ureter was complete. In cat 2, a urolith was removed from the right ureter at surgery. In cat 5, a blood clot was removed from the left ureter at surgery. Intrarenal RI values were increased for the obstructed kidney in 2 of 5 cats (cats 2 and 5). In one cat with obstructive renal disease in which intrarenal RI values were obtained after surgical relief of obstruction (cat 5), normalization of RI was observed in the affected kidney.

 

Table 3. Summary of Clinicopathologic, Sonographic, and Intravenous Excretory Urogram (IVU) or Ultrasound Guided Antegrade Pyelogram (UAP) Findings in 5 Cats With Obstructive Renal Disease

Note:  Normal serum creatinine concentration range =  0.1 -2.1  mg/dL.Abbreviations: MRI.  mean distal intrarenal artery resistive index value 2  standard deviation;  RK,  right kidney;  LK,  left kidney; DLH, domestic long-haired;  DSH.  domestic short-haired;  FS, female spayed;  MC, male castrated;  ARF,  acute renal failure;  N.O.  = not obtained.

Fig 4. Scatterplot of individual cat intrarenal resistive index value versus concurrent serum creatinine concentration. A statistically significant correlation was not identified (P = .471; Pearson correlation coefficient rho = .162).

 

Technically adequate Doppler flow spectra were obtained from both kidneys from each cat within 40 minutes of duplex Doppler interrogation of the corticomedullary junction. Although in some cats with nonobstructive renal disease values for mean intrarenal RI of individual kidneys differed by 2 or more SD (cats 4, 8, 9, and 10, Table 2), all intrarenal RI measurements obtained within each individual kidney were within 2 SD of the mean value obtained for that kidney. A scatterplot of individual cat intrarenal RI versus serum creatinine concentration is presented in Fig 4. Pearson correlation analysis3’ did not demonstrate a statistically significant correlation between individual cat intrarenal RI values and concurrent serum creatinine concentration (P = .47 1 ; Pearson correlation coefficient rho = .162). A scatterplot of individual cat intrarenal RI versus urine output for the cats with nonobstructive renal disease is presented in Fig 5. A broad overlap was observed in intrarenal RI values compared with concurrent urine output status.

An example of a duplex Doppler image and accompanying distal intrarenal artery flow spectrum with increased intrarenal RI is presented in Fig 6. An example of a duplex Doppler image and accompanying distal intrarenal artery flow spectrum in an animal with normal intrarenal RI is presented in Fig 7. An example of normalization of mean intrarenal RI after treatment is presented in Fig 8.

 

Fig 5. Scatterplot of individual cat intrarenal resistive index value versus concurrent urine output status.

 

Fig 6. Duplex Doppler image illustrating 6-mode sonogram of kidney with Doppler sample volume placed at corticomedullary junction and accompanying Doppler flow spectrum with increased intrarenal resistive index, obtained from left kidney of Dog 11, Table 1. Note disparity between systolic peak and diastolic trough magnitude compared to Doppler flow spectrum illustrating normal intrarenal resistive index as shown in Fig 7.

 

Fig 7. Duplex Doppler image illustrating B-mode sonogram of kidney with Doppler sample volume placed at corticomedullary junction and accompanying Doppler flow spectrum with intrarenal resistive index within normal limits, obtained from left kidney of dog 8, Table 1.

 

Discussion
Motion of the interrogated vessel relative to the Doppler sample volume can hinder acquisition of technically satisfactory Doppler flow spectra.34 In human beings, difficulty may be encountered because of excessive patient motion and respiration.” In the present study, sedation was not employed during ultrasonography, and excessive patient motion and respiration required duplex Doppler interrogation of distal intrarenal arteries for up to 40 minutes to obtain technically adequate Doppler flow spectra from both kidneys. Identification of intrarenal vessels with color flow Doppler imaging prior to duplex Doppler interrogation may have permitted more rapid acquisition of technically adequate Doppler flow spectra, but it was not available.

Normalization of intrarenal RI after effective treatment has been used in human beings with both obstructive and
nonobstructive renal disease to aid in monitoring therapeutic response. ’’ Normalization of intrarenal RI values after effective treatment of radiographic contrast medium-induced ATN in a dog has been reported.” In the present report, normalization of intrarenal RI values was observed in 2 dogs (dogs 13 and 14, Table 1) and in 3 cats (cats 9 and 10, Table 2, and cat 5, Table 3) evaluated serially in which treatment was effective. Additional clinical studies with larger numbers of animals are needed, but results of the present report suggest that the values of 0.73 and 0.71 represent a clinically useful upper limit of normal for intrarenal RI in the dog and cat.

The physiologic basis for intrarenal RI has been described in detail elsewhere.’ ‘J~,~~ Doppler spectral waveforms from which RI is derived are affected by blood pressure, cardiac output, and vascular blood flow In human
beings, diseases affecting the renal interstitium, tubules, glomeruli, and vessels are associated with an increase in renal vascular impedance and decrease in renal diastolic as compared with systolic blood flow velocity, detected as an in crease in intrarenal RI.'" Increased intrarenal RI values also have been reported in human beings with obstructive uropathy.'" Significant hypotension, marked extremes of heart rate, and perinephric or subcapsular fluid accumulation have been associated with increased RI in the absence of renal disease in human beings.'

 

Fig 8. Doppler flow spectra obtained serially from left kidney of dog 14, Table 1, demonstrating normalization of intrarenal resistive index after treatment. Upper flow spectrum with mean intrarenal resistive index value of 0.87 was obtained at presentation with concurrent serum creatinine concentration of 6.9 mgldL and adequate urine output. Lower flow spectrum with mean intrarenal resistive index value of 0.66 was obtained after 2 days of diuretic fluid therapy with concurrent serum creatinine concentration 1.5 mgldL and adequate urine output. Note disparity between systolic versus diastolic flow in upper versus lower flow spectra,

 

Prior to ultrasonographic examination, there was no evidence of sodium depletion in the animals of the present
study. Hydration status was considered normal based on physical examination (eg, skin turgor) and hematocrit. Heart
rates were within the normal range. Vasoactive drugs were not administered prior to ultrasonographic examination. Arterial blood pressure measurements were within normal limits in all animals in which they were obtained.

                                         In some of the animals with nonobstructive renal disease in the present study, values for mean intrarenal RI of individual kidneys differed by 2 or more SD (dogs 3 and 10, Table 1, and cats 4, 7, 8, and 10, Table 2). In 1 cat (cat 4, Table 2), a disparity in severity of renal tubular histopathology was observed, which may have contributed to the observed disparity in individual kidney intrarenal RI values. In another cat (cat 10, Table 2), unilateral perinephric fluid was present, which may have contributed to the observed disparity in individual kidney intrarenal RI values. In the remaining animals with nonobstructive renal disease, no factors that may have contributed to differences in individual intrarenal RI values were identified. The observed differences in individual kidney intrarenal RI in these remaining animals presumably were due to differences in individual renal perfusion associated with renal pathology rather than an artifact of Doppler flow spectra acquisition. Prior studies in normal human beings,'" and cats"' have not demonstrated statistically significant differences between individual kidney intrarenal RI. Evaluation of intrarenal blood flow with duplex Doppler waveform indices such as RI has been described as an accurate and reliable technique in human beings." In the present study, accuracy of Doppler flow spectra
measurements was evaluated by a medical physicist with a flow control phantom (ER Ritenour, University of Minne- ~ota).~' Renal scintigraphy may have provided confirmation of differential renal perfusion and changes in renal perfusion over time,"." but it was not performed.

Real-time B-mode gray-scale sonographic examination of patients with parenchymal renal disease is limited to detection of abnormal architecture and relative echogeni~ity.'~~~~ Increased relative renal cortex echogenicity may be observed in both tubulointerstitial and glomerular diseases of the kidney.'" Increased relative renal cortex echogenicity also may be a normal variant in neonates and infants, with usage of higher-resolution, electronically focused transducers in human beings and dogs and as a result of increased renal fat deposition in ~ats.~',~' In human beings, conventional B-scan sonography is insensitive in the diagnosis of parenchymal renal disease,j' and the majority of gray-scale examinations in affected patients are normal.'" Increased intrarenal RI has been used in such instances as an aid in the diagnosis of renal failure.'"

In 2 of 14 dogs (dogs 5 and 13, Table I) and in 2 of 10 cats (cats 6 and 10, Table 2) with nonobstructive renal disease,increased intrarenal RI values were observed in kidneys for which the gray-scale sonographic appearance was unremarkable. Increased relative renal cortex echogenicity was observed as the sole renal parenchymal abnormality in 10 of 14 dogs with nonobstructive renal disease (dogs 1 through 3, 6, 7, 9 through 12, and 14, Table 1). Increased intrarenal RI was observed in 6 of these 10 dogs (dogs 1,3, 10 through 12, and 14, Table 1). Likewise, increased relative renal cortex echogenicity was observed as the sole renal parenchymal abnormality in 4 of 10 cats with nonobstructive renal disease (cats 1, 5, 8, and 9, Table 2). Increased intrarenal RI was observed in all 4 cats. In 1 of these 4 cats (cat 9, Table 2), the increased relative renal cortex echogenicity persisted unchanged despite recovery after treatment. Duplex Doppler evaluation of intrarenal RI may be useful as an aid in confirmation of renal disease in dogs and cats in which the grayscale sonographic appearance of the kidney is unremarkable or when increased relative renal cortex echogenicity is the sole renal parenchymal abnormality observed.

The use of intrarenal RI in the diagnosis of nonobstructive renal disease in human beings is limited.'" Intrarenal RI
values are age dependent, which may limit diagnostic utility in children and geriatric patients." Not all forms of renal
disease alter renal vascular resistance to the same degree.I4 Glomerular disease is less likely to produce increased RI.'" Increased intrarenal RI is not specific for the site of the disease process within the kidney, occumng in both tubulointerstitial and glomerular disease. Thus, this technique cannot replace renal biopsy in diagnostic Intrarenal RI evaluation alone is not recommended as a screening test for the presence of renal disease but rather as an ancillary diagnostic aid.'4

Similar limitations in the usage of intrarenal RI in the diagnosis of nonobstructive renal disease were observed in the present report. Normal intrarenal RI values were observed in 6 of 14 dogs (dogs 2, 4, and 6 through 9, Table
1) and in 1 of the 10 cats (cat 2, Table 2) with nonobstructive renal disease. Fewer dogs with glomerular disease without ATN (5 of 10 dogs: 3, 5, and 10 through 12, Table I) had increased intrarenal RI values as compared with dogs with ATN (3 of 4 dogs: 1, 13, and 14, Table 1). Increased intrarenal RI was observed both in dogs with tubular disease alone (dogs 1, 13, and 14, Table 1) and in dogs with glomerular disease alone (dogs 8, 9, 11, and 12, Table 1). In a recent study," increased intrarenal RI values were not observed in 3 dogs with glomerular disease alone. The authors therefore suggested that increased intrarenal RI is compatible with tubulointerstitial rather than glomerular disease. Based on the results of the present study, observation of increased intrarenal RI in an azotemic dog does not preclude the presence of glomerular disease alone.

Observation of pelvicoureteral dilation with gray-scale ultrasonography is suggestive of obstru~tion.~'.~~ Pelvicoureteral dilation, however, also may be due to pyelonephritis, congenital malformation, or di~resis.~',~' Differentiation of these potential causes may not be possible with gray-scale sonography al~ne.~'.~' Increased intrarenal RI has been reported in human beings'" and with obstructive uropathy.

The use of intrarenal RI in the diagnosis of obstructive renal disease in human beings also is limited.'" Increased
intrarenal RI may occur both in obstructive and nonobstructive renal disease.",I3 It may precede development of pelvicoureteral dilation in acute obstruction.'",44 Furthermore, not all patients with obstruction have increased RI." In acute or partial obstruction, RI values may be normal.'",44 After surgical relief of obstruction, intrarenal RI may normalize before serum creatinine concentration returns to normal. If obstruction has been present for 18 to 24 hours or more, normalization of RI after relief of obstruction may require days or weeks.''

In the present study, pelvicoureteral dilation was observed by gray-scale ultrasonography in 6 kidneys of the 5 cats with obstructive renal disease (Table 3). In 1 of these 5 cats (cat 5, Table 3), although bilateral pelvicoureteral dilation was observed by gray-scale ultrasonography, increased intrarenal RI was observed only in the obstructed kidney, and normalization of RI occurred after surgical relief of the obstruction. Increased intrarenal RI was observed in only 2 of 5 kidneys in which pelvicoureteral dilation was observed during grayscale ultrasonography and which were later shown to be obstructed by IVU or UAP (cats 2 and 5, Table 3). Increased intrarenal R1 was not observed in 2 of the 3 cats with partial obstruction (cats 1 and 3, Table 3) or in 1 of the 2 cats with complete obstruction (cat 4, Table 3). No gray-scale sonographic evidence of focal or diffuse renal parenchymal disease'" was observed in any of the cats with obstructive renal disease, but renal histopathology was not performed. Based on results of the present study, increased intrarenal RI in cats in which pelvicoureteral dilation is observed by gray-scale ultrasonography may be associated with obstruction, but lack of intrarenal RI increase does not preclude the presence of obstruction. Intravenous excretory urography or UAP should be considered for further diagnostic clarification in cats in which obstructive renal disease is s~spected.~' Increased intrarenal RI appears to have limited clinical utility
in the diagnosis of obstructive uropathy in the Duplex Doppler evaluation of intrarenal RI also appears to have
limited clinical utility in the diagnosis of obstructive renal disease in the cat. Additional clinical studies are needed for
further confirmation.

In human beings, there is a positive but weak correlation between serum creatinine concentration and intrarenal
RI.1",46 Proteinuria has not been associated with increased intrarenal RI in human beings.46 In the present study, a statistically significant correlation between individual dog intrarenal RI and serum creatinine concentration was not identified. A statistically significant correlation between individual dog intrarenal RI and urine protein-to-creatinine ratio also was not identified. Our results are in agreement with a recent study" of 67 dogs with spontaneous nonobstructive renal disease. In the present study, a statistically significant correlation between individual cat intrarenal RI and serum creatinine concentration was not identified. Broad overlap was observed in intrarenal RI values compared with urine output in cats with nonobstructive renal disease. The number of cats with nonobstructive disease in various urine output states precluded adequate statistical analysis. The magnitude of increase in intrarenal RI is of limited value in assessing the severity of concurrent renal dysfunction because the magnitude of intrarenal RI increase does not appear to correlate with concurrent urine protein-to-creatinine ratio, urine output status, or magnitude of azotemia.

The sensitivity47 of increased intrarenal RI in detection of nonobstructive renal disease (tubulointerstitial or glomerular disease) in the dogs of the present study was 57%. In a recent study," the sensitivity of increased intrarenal RI (defined as >0.70) in detection of nonobstructive renal disease in 67 dogs was 38%, but histopathologic or cytologic findings were available in only 12 dogs, of which 4 had tubulointerstitial disease with or without glomerular disease, and 3 had glomerular disease alone. Of these 7 dogs with tubulointerstitial or glomerular disease, increased intrarenal RI values (>0.73) were observed in 3. The resulting sensitivity4' in these animals, 43%, is similar to that observed in the present study. Human patients with glomerular disease are less likely to have increased intrarenal RI than those with renal tubular disease." The results of the present study suggest that the ~ensitivity~~ of increased intrarenal RI in detection of ATN is greater than the sensitivity for detection of glomerular disease without ATN. Similarly, in the study" described previously, increased intrarenal RI (>0.73) was observed in 3 of 4 dogs with tubulointerstitial disease with or without glomerular disease but was not observed in all 3 dogs with glomerular disease alone. At present, the small number of cases in the veterinary literature describing intrarenal RI values in correlation with histologic findings precludes adequate statistical analysis of the observed difference in sensitivity of detection of tubulointerstitial versus glomerular disease. Additional clinical studies with greater numbers of
animals are needed to assess sensitivity more precisely and provide further clarification of potential differential sensitivity in detection of tubulointerstitial versus glomerular disease. A recent study19 described the specificity of increased intrarenal RI (defined as >0.70) in detection of nonobstructive renal disease in dogs as 96%. We did not obtain intrarenal RI values in dogs without renal disease, and conclusions regarding specificity, positive predictive value, and negative predictive value47 of increased intrarenal RI in detection of nonobstructive renal disease in azotemic dogs cannot be made on the basis of the present study.

Based on the results of this study, it appears that the ~ensitivity~~ of increased intrarenal RI in detection of non- obstructive renal disease in azotemic cats is 90%. As a measure of the precision of this estimate of sensitivity based on the sample size of 10 cats, the 95% confidence interval4' for the obtained sensitivity is 72% to 100%. We did not obtain intrarenal RI values in cats without renal disease, and conclusions regarding specificity, positive predictive value, and negative predictive value4' of increased intrarenal RI in detection of nonobstructive renal disease in azotemic cats cannot be made on the basis of this study. Based on the results of this study, it appears that the sensitivity4' of increased intrarenal RI in detection of obstruction in the kidneys of cats in which pelvicoureteral dilation is observed during gray-scale ultrasonography is 40%. The precision of this estimate of sensitivity expressed as 95% confidence interva147 based on the sample size of 6 kidneys is 1% to 80%; thus, additional clinical studies with greater numbers of cats are needed to assess sensitivity more precisely. Pelvicoureteral dilation was observed during ultrasonography in the absence of obstruction in only 1 of the 6 kidneys studied (cat 5, Table 3). Additional clinical studies are needed to assess sensitivity, specificity, positive predictive value, and negative predictive value4’ of increased intrarenal RI in detection of obstructive renal disease in cats.

Based on the results of the present study, the following conclusions may be made: (1) Increased intrarenal Rl in
dogs and cats with increased relative renal cortex echogenicity may be due to renal disease rather than normal variation; further clinicopathologic evaluation in such patients is warranted. (2) Increased intrarenal RI values observed in azotemic dogs with spontaneous nonobstructive renal disease are more likely to be associated with active tubulointerstitial rather than glomerular disease, but increased intrarenal RI does not preclude presence of glomerular disease alone. (3) Duplex Doppler evaluation of intrarenal RI is useful as an ancillary diagnostic technique in azotemic dogs and cats with nonobstmctive renal disease, especially when the results of gray-scale ultrasonography are not definitive. (4) Duplex Doppler evaluation of intrarenal RI appears to have limited
utility as an ancillary diagnostic technique in cats with obstructive renal disease. (5) Increased intrarenal RI is of limited value in assessment of the severity of concurrent renal dysfunction. (6) Normalization of intrarenal RI may be observed after effective treatment in dogs with nonobstructive renal disease and in cats with both nonobstructive and obstructive disease.

 

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