Idiopathic renal hematuria, or benign essential renal hematuria, is a rare condition of chronic severe upper urinary tract bleeding. This condition typically results in gross hematuria that is not associated with trauma, stone disease, neoplasia, or other obvious causes.1–7 In humans, it is defined as acute, intermittent, or chronic gross hematuria for which radiologic and hematologic evaluation reveals no source.8,9 Other names given to this condition include lateralizing essential hematuria, chronic unilateral hematuria, upper tract hematuria, and benign lateralizing hematuria.8–10 Although it has been described in the human literature for decades, it is considered a rare condition.8–11 The first report in humans was in 1959 by Wallach et al,12 in which a small hemangioma of the renal pelvis causing severe hematuria was described. In veterinary medicine, there have been few cases reported for the literature and, rarely, lesions detected on histologic evaluation.2,7,13 The earliest reports of the condition were in the early 1980s: Meyer and Senior3 and Stone et al1 described benign, nontraumatic renal bleeding.
In veterinary medicine, IRH is typically seen in otherwise healthy large-breed dogs1–7,14–16 and has also been seen in cats, in the authors' experience, most commonly associated with dried solidified blood stones. Affected dogs have been described as being young, ranging in age from 2 months to 11 years, and are most commonly < 2 years of age.1,2,6,7 There does not seem to be a sex predilection. Hydronephrosis and hydroureter have been reported for approximately half of the cases, and this is suspected to be because of the accumulation of blood clots resulting in a partial or complete ureteral obstruction.1,2 Left-sided lesions appear to be more common (approx 75% reported); however, with few cases reported, this is hard to discern.1–7,14–16 The condition has been reported to occur bilaterally as well (cumulatively 21% of patients),1,2,4,5 and this can occur at the time of original diagnosis or within months to years after initial diagnosis.
In humans, renal vascular abnormalities that rupture, like hemangiomas and papillary angiomas found inside the renal pelvis, are typically the cause of this condition.8–11 This has not been clearly documented in the veterinary literature, hence the term IRH. Although the long-term course appears to be benign, anemia, iron deficiency, and ureteral and urethral obstructions can ensue.1,2,5 Obstructive uropathy may be associated with both upper urinary tract signs of ureteral pain and lower urinary tract signs of dysuria. With the advent of ureteropyeloscopy, the diagnosis of renal pelvic lesions has been documented in both human9–11 and veterinary patients,17,18 encouraging the use of renal-sparing treatments like ureteropyeloscopic-guided electrocautery17,18 or retrograde sclerotherapy infusions. Traditional treatment in veterinary medicine has focused on ureteronephrectomy. Because the lesions are not typically considered of renal parenchymal origin and because > 20% are, or can become, bilateral, nephrectomy is no longer recommended. Because of the small size of a canine ureter (0.5 to 2.0 mm),19 which does not easily accommodate ureteroscopes (2.7 mm) without prior manual or passive dilation, the use of retrograde sclerotherapy for hemostasis was investigated. The objective of the study reported here was to describe the use of endoscopic-, fluoroscopic-guided sclerotherapy in a series of dogs for the treatment of IRH and to determine the clinical short- and long-term outcomes.
Materials and Methods
Case selection—Medical records were reviewed for any dog that had presumptive IRH in which renal pelvic sclerotherapy was performed by the authors between August 1, 2010, and January 31, 2012. Patients were included if a presumptive diagnosis of IRH was made in which no concurrent cause for bleeding could be determined, a procedural report was available for review, and both short- and long-term follow-up were available.
Medical records review—Information regarding historical findings, signalment, clinical signs, diagnostic imaging (abdominal ultrasonography, abdominal radiography, renal angiography, or CT), laboratory biochemical findings (CBC, serum biochemical analysis, coagulation profile, buccal mucosal bleeding time, thromboelastography, urinalysis, or bacterial culture of urine), procedural report, method of treatment, hospitalization time, complications, and short- (< 1 month) and long-term (> 1 month) outcomes were recorded. Follow-up was obtained through serial reevaluations on the basis of urinalysis, biochemical findings, imaging (abdominal ultrasonography with or without cystoscopy), and clinical signs. All owners were contacted to assess degree of macroscopic hematuria (minimal, moderate, or severe), frequency of macroscopic hematuria (daily, weekly, or monthly), and overall urinary and systemic health of their dog.
Preprocedural diagnostic cystoscopya–d for full evaluation of the urethra, prepuce, vulva, vagina, UVJ, and bladder wall were completed on a day when gross hematuria was present. Renal angiograms were offered to owners for evaluation of gross vascular anomalies. This was performed with fluoroscopic guidancee from femoral arterial access. Each kidney was evaluated in both lateral and ventrodorsal projection to assess both the arterial and venous phase of the angiogram with a ≤ 2 mL/kg (0.9 mL/lb) total dose of an iodinated contrast agent.f
Procedures—Each dog had a cystoscopy performed while in dorsal recumbency. The vulva or prepuce and perineal region were aseptically prepared and flushed with a dilute chlorhexidine solution. For female dogs, a rigid cystoscope with a 30° anglea–c was used to evaluate the vestibule, vagina, urethra, bladder, and each UVJ. In male dogs, a 2.7-mm flexible ureteroscoped was used for evaluation of the prepuce, penile urethra, prostatic urethra, and each UVJ. In male dogs, once the hematuria was identified by means of flexible urethrocystoscopy, percutaneous perineal urethral access was obtained using fluoroscopic guidance to allow the use of a 2.7-mm rigid cystoscope for UVJ access. This procedure was performed as previously reported with fluoroscopic guidance with or without ultrasound guidance.g In 1 dog, an antegrade percutaneous cystoscopy approach was used as previously reported20 to obtain rigid cystoscopic visibility of the UVJ. This was performed instead of perineal urethral access because of the small size of the dog (10 kg [22 lb]).
By use of the rigid cystoscope, each UVJ was identified and monitored for at least 30 seconds to see ≥ 2 urine jets to assess for hematuria (Figure 1). The irrigation fluids were then changed from saline (0.9% NaCl) solution to 5% dextrose in water, which aids to prevent hemolysis and improves visibility of a bleeding lesion. This is also recommended to prevent formation of silver salts (when silver nitrate is mixed with sodium chloride) in the renal pelvis or ureter, which could ultimately result in a ureteral obstruction after infusion.21,22 Once the hematuric UVJ was identified, a 0.035-inch angled tipped guidewireh was advanced into the UVJ and up the affected ureter with the aid of cystoscopic and fluoroscopic guidance. A 5F open-ended ureteral catheteri was then advanced over the guidewire with fluoroscopic guidance to perform a retrograde ureteropyelogram and confirm there were no gross lesions present in the ureter or renal pelvis. The contrast agent used was 76% meglumine diatrozoatej and was chosen because this is the recommended mixture with povidone iodinek to accomplish appropriate sclerotherapy in humans.23–25 The wire was then advanced into the renal pelvis, and the catheter was advanced to the UPJ. The guidewire was then exchanged for a J-tipped stiffened wire,l and the cystoscope was removed over the guidewire while the wire remained inside the proximal portion of the ureter, at the UPJ. Then, over the guidewire, a UPJ balloon catheterm was placed to the level of the UPJ or proximal aspect of the ureter. The wire was subsequently removed. The balloon was then filled with air to allow a compliant occlusion of the proximal portion of the ureter. The patient was tilted into a 20° Trendelenburg position to allow dwelling of material into the renal pelvis (hind limbs higher than kidneys). Contrast material (76% meglumine diatrozoatej) was used in a 50% mixture with 5% dextrose in water to determine the volume it takes to fill the ipsilateral occluded renal pelvis and all associated calices without renal backfilling (Figure 2). This volume was then used for dwelling of the sclerotherapy materials. The contrast was then removed via passive draining.
Cystoscopic image of a female dog during evaluation for severe hematuria. The patient is in dorsal recumbency. A rigid cystoscope is used to visualize the left UVJ. Notice the jet of blood-tinged urine coming from the left ureter.
Citation: Journal of the American Veterinary Medical Association 242, 11; 10.2460/javma.242.11.1556
Cystoscopic image of a female dog during evaluation for severe hematuria. The patient is in dorsal recumbency. A rigid cystoscope is used to visualize the left UVJ. Notice the jet of blood-tinged urine coming from the left ureter.
Citation: Journal of the American Veterinary Medical Association 242, 11; 10.2460/javma.242.11.1556
Cystoscopic image of a female dog during evaluation for severe hematuria. The patient is in dorsal recumbency. A rigid cystoscope is used to visualize the left UVJ. Notice the jet of blood-tinged urine coming from the left ureter.
Citation: Journal of the American Veterinary Medical Association 242, 11; 10.2460/javma.242.11.1556
Fluoroscopic image of the upper portion of the urinary tract of a female dog taken during sclerotherapy. A UPJ balloon (black arrow) is placed up the left ureter by use of cystoscopic and fluoroscopic guidance. Notice the balloon is inflated with air, causing proximal ureteral occlusion. Contrast is being used to fill the renal pelvis, and filling volume was calculated to determine an appropriate volume of the sclerosing agent.
Citation: Journal of the American Veterinary Medical Association 242, 11; 10.2460/javma.242.11.1556
Fluoroscopic image of the upper portion of the urinary tract of a female dog taken during sclerotherapy. A UPJ balloon (black arrow) is placed up the left ureter by use of cystoscopic and fluoroscopic guidance. Notice the balloon is inflated with air, causing proximal ureteral occlusion. Contrast is being used to fill the renal pelvis, and filling volume was calculated to determine an appropriate volume of the sclerosing agent.
Citation: Journal of the American Veterinary Medical Association 242, 11; 10.2460/javma.242.11.1556
Fluoroscopic image of the upper portion of the urinary tract of a female dog taken during sclerotherapy. A UPJ balloon (black arrow) is placed up the left ureter by use of cystoscopic and fluoroscopic guidance. Notice the balloon is inflated with air, causing proximal ureteral occlusion. Contrast is being used to fill the renal pelvis, and filling volume was calculated to determine an appropriate volume of the sclerosing agent.
Citation: Journal of the American Veterinary Medical Association 242, 11; 10.2460/javma.242.11.1556
Finally, once occlusion of the ureter was obtained with the UPJ balloon, 2 dwell times (of 10 to 20 minutes each) were provided within the renal pelvis with the predetermined volume of a povidone iodine mixture (5% povidone iodine,k 76% meglumine diatrizoate, and 5% dextrose in water [1:1:3]). Then, this was passively drained to empty the renal pelvis and flushed with 5% dextrose in water,m and an additional 2 dwell times of 15 to 20 minutes each with a sterilized liquid 0.5% to 1% silver nitrate solutionn were performed with the same predetermined volume. Once the procedure was complete, the patient was removed from the Trendelenburg position back into dorsal recumbency, and the solution was left to passively drain out of the UPJ balloon catheter. Finally, the guidewire was reintroduced through the UPJ balloon catheter and curled inside the renal pelvis with fluoroscopic guidance. The catheter was removed over the wire, and the cystoscope was placed over the guidewire to the level of the UVJ. An appropriately sized double pigtail ureteral stento–r was placed over the guidewire with 1 loop curled inside the renal pelvis and the other inside the urinary bladder. All fluid was drained out of the bladder and urethra, and the cystoscope was subsequently removed. Dogs in which perineal urethral access was obtained had the sheaths removed, and the incision was left to heal by second intension. The dog with the percutaneous antegrade cystoscopy approach had the incision closed routinely with absorbable suture material.
Postprocedural management—Dogs were allowed to recover from anesthesia and were administered medications for pain management, typically including buprenorphine (0.01 mg/kg [0.005 mg/lb], IV, q 4 to 6 h) and tramadol (3 to 5 mg/kg [1.4 to 2.3 mg/lb], PO, q 8 h) for 1 to 3 days as needed and amoxicillin clavulanate (13 to 18 mg/kg [5.9 to 8.2 mg/lb], PO, q 12 h for 5 days). This was based on clinician preference. For dogs in which perineal urethral access was obtained, the site was kept covered and clean for 3 days and monitored by the owner daily for swelling, redness, or discharge. Most patients were discharged from the hospital within 6 to 24 hours after surgery.
Follow-up—Bacterial culture of urine, hematologic evaluation (CBC and serum biochemical analysis), and urinary tract ultrasonography were recommended at 2 weeks and 2 months after the procedure and then every 3 to 6 months for 1 year. For patients in which hematuria resolved, the stent was recommended to be cystoscopically removed 4 to 6 weeks after sclerotherapy. For patients in which the hematuria did not resolve, ureteroscopy with electrocautery treatment of the bleeding lesion was recommended.
Results
Clinical data—Review of medical records revealed 7 dogs (9 renal pelvises) that had sclerotherapy performed for upper urinary tract hematuria. One dog was excluded from the study because of concurrent systemic abnormalities, including thrombocytopenia, hepatic cirrhosis, and a splenic mass. The remaining 6 dogs (8 renal pelvises that were treated) were included in the study. Five male dogs (2 neutered and 2 sexually intact) and 1 spayed female dog were included, with a median age of 3 years (range, 0.9 to 12 years) and weight of 42.4 kg (93.28 lb; range, 10 to 45 kg [22 to 99 lb]). Dogs included 2 mixed-breed dogs and 1 each of an Australian Shepherd Dog, Great Pyrenees, Labrador Retriever, and Mastiff. Concurrent medical problems were documented as follows: recurrent grade 2 mast cell tumor, hypothyroidism, and an adrenal mass (1 dog); bilateral ectopic ureters without associated urinary incontinence (1); diffuse demodicosis (1); severe atopy (1); and bilateral grade 4 luxating patellas (1). The duration of hematuria was a median of 3.5 months (range, 2 to 5 months) and was intermittent in 1 dog. All dogs had blood pressure measurements within the reference limits at the time of initial evaluation.
Previous treatments included Yunnan baiyao, a traditional Chinese herbal remedy (1 capsule/10 kg [1 capsule/22 lb], PO, q 8 to 12 h), in 3 dogs; the remedy was unsuccessful in all 3. Various courses of antimicrobial treatment for a presumptive urinary tract infection were attempted in all dogs prior to sclerotherapy without resolution of the hematuria. Only 1 dog had a urine sample with a positive bacterial culture result 2 months prior to treatment, and treatment of the urinary tract infection also did not resolve the severe hematuria in this dog. Two dogs had frequent and intermittent pollakiuria and stranguria associated with blood clot passage during urination.
None of the dogs were azotemic. The median PCV was 35% (range, 29% to 47.7%), with a median total protein concentration of 5.3 g/dL (range, 4.4 to 6.6 g/dL) and a median reticulocyte count of 159,000 reticulocytes/μL (range, 74,000 to 213,000 reticulocytes/μL). Three dogs had a mild to moderate macrocytic normochromic regenerative anemia. The median platelet count was 389,000 platelets/μL (range, 287,000 to 636,000 platelets/μL). All dogs had gross hematuria with > 100 RBCs/hpf on urinalysis. The median urine specific gravity was 1.030 (range, 1.012 to 1.055). All dogs had urine samples with negative bacterial culture results within 2 weeks after the time of initial evaluation for their procedure. For all dogs, no abnormalities were detected in a coagulation profile; 4 of 6 dogs had buccal mucosal bleeding time measured, and results were within reference limits (median, 1.5 minutes [range, 1.2 to 2.5 minutes]; reference limits, < 4 minutes) for all 4. Blood pressure was evaluated in all dogs and was within reference limits in all patients (median systolic arterial blood pressure, 130 mm Hg [range, 115 to 150 mm Hg]).
Diagnostic imaging—Abdominal ultrasonography was performed in all dogs, and the abnormalities detected included a large mobile mass suspected to be a blood clot in the urinary bladder of 2 dogs, mild pyelectasis with a suspected blood clot in the renal pelvis of 1 dog, and a 1.5-cm noninvasive mass in the left adrenal gland in 1 dog. Four dogs underwent abdominal radiography, and no abnormalities were detected. Thoracic radiographs were taken in a 12-year-old dog, and findings were within reference limits. Two dogs had a cystoscopy performed by a referring internal medicine specialist and had documented hematuria from 1 UVJ. One dog had a cystotomy performed and had large blood clots removed from the urinary bladder. At that time, both ureters were documented to have normal yellow-colored urine from the UVJ. This dog had a bladder biopsy performed, and a histopathologic diagnosis of moderate acute erosive cystitis with edema was made. Two dogs had renal angiograms performed via femoral arterial access, and findings were considered within reference limits in all views. None of the dogs underwent abdominal CT.
All dogs had a cystourethroscopy performed at the time of the procedure. Five dogs had blood clots detected in the urinary bladder (clot diameter, 3 to 15 cm). All blood clots ultimately resolved without the need for removal. Both UVJs were evaluated in all patients, and 1 dog had bilateral hematuria, 2 dogs had left-sided hematuria, and 3 dogs had right-sided hematuria. One dog that had left-sided hematuria at initial examination developed right-sided hematuria 4.5 months later. One dog had bilateral ectopic ureters found during the cystoscopy. The 5 male dogs initially had flexible cystourethroscopy performed, and then all 5 had rigid cystoscopy performed for better observation and access for endourologic treatment (4 via perineal urethral accessj and 1 via antegrade percutaneous cystoscopy24).
Procedures—Once rigid endoscopy access was obtained and the hematuric UVJ was identified, the distal ureter was cannulated in a retrograde manner, with both endoscopic and fluoroscopic guidance. Once the UPJ balloon (5F in 3 ureters and 6F in 4 ureters) was at the proximal portion of the ureter, the balloon was inflated and the ureter was occluded. Renal pelvis volume was determined (median, 2.5 mL [range, 1.5 to 2.5 mL]). Each affected renal pelvis was infused twice with povidone iodine, and 7 of 8 were filled twice with silver nitrate (1/8 pelvises was filled once with silver nitrate), with dwell times ranging from 15 to 20 minutes each. One dog that had the percutaneous antegrade approach did not have a UPJ balloon used but instead had a 5F open-ended ureteral catheter used and the distal ureter manually occluded with a 1/4-inch Penrose drain.t After the final dwell in 7 of 8 ureters, a double-pigtail ureteral stent was placed over the guidewire. The various sizes included 6F × 26 cm (n = 3), 5F × 22 cm (1), 4.7F × 22 to 32 cm variable length (2), and 4.7F × 22 cm (1). One dog did not have a ureteral stent placed following the procedure. Median procedure and hospitalization times were 150 minutes (range, 65 to 185 minutes) and 18 hours (range, 6 to 96 hours), respectively.
Complications—One dog developed severe signs of ipsilateral renal pain with any pressure placed in the area of this kidney. This started immediately upon recovery, and this was the only dog that did not have a concurrent ureteral stent placed and was the only dog that had the procedure performed with surgical assistance via antegrade cystoscopy, having manual ureteral occlusion rather than proximal UPJ occlusion. This patient also developed mild ipsilateral pyelectasis (6 mm in transverse view on ultrasonography). Both the pyelectasis and signs of renal pain improved within 36 hours. One dog developed pollakiuria 1 week after the procedure, and the ureteral stent was documented to have migrated into the proximal portion of the urethra. This resolved once the stent was endoscopically retrieved. One dog did not return for stent removal after the hematuria resolved. On the 3-month reevaluation, the ureteral stent was found to have migrated into the renal pelvis. This patient remained nonhematuric, and the owner declined stent retrieval. One patient urinated out the stent 2 weeks after sclerotherapy treatment. The remainder of the dogs had stent retrieval by cystoscopic guidance.
Postoperative clinical data—Improvement in PCV was documented in all dogs, with the median PCV after sclerotherapy being 46% (vs 35% prior to sclerotherapy). Findings on hematologic evaluation, bacterial culture of urine, urinalysis (free catch), and urinary tract ultrasonography performed at 2 to 6 weeks and 3 to 6 months after sclerotherapy were all within reference limits, with no evidence of anemia, urinary tract infection, or pyelectasis. On urinalysis at 2 weeks after sclerotherapy, 2 of 6 dogs evaluated had microscopic hematuria (5 to 10 RBCs/hpf), and 1 had macroscopic hematuria (25 to 50 RBCs/hpf). At the time of last follow-up, 1 dog had macroscopic hematuria, and 1 dog had microscopic hematuria. All others had no evidence of hematuria.
Outcome—Cessation of gross hematuria was documented in 5 of 6 dogs (6/8 renal pelvises) within 1 week (median, 6 hours; range, 0 to 7 days). One dog had reduced severity of the hematuria, of which the owner reported moderate improvement (urine was mildly pink on some days and normal yellow on others). This was the dog with bilateral hematuria, a grade 2 mast cell tumor, and evidence of an adrenal mass on abdominal ultrasonography, with no evidence of hypertension or functional adrenal hyperactivity and with evidence of hypothyroidism. This dog was treated with repeated bilateral ureteroscopy 4 weeks after first treatment, and no distinct lesion was found in either renal pelvis. Instead, multiple calices were seen to have evidence of blood-tinged urine being produced. Topical sclerotherapy was repeated, and it was again unsuccessful, maintaining a static improvement from baseline. This dog was anemic on initial evaluation, and the anemia resolved after the first treatment. Another dog was found to have recurrence of hematuria 2 weeks after sclerotherapy, although the recurrence was considered mild and sporadic, with no recurrence of anemia (owner considered dramatic improvement from baseline because of days of normal yellow urine and intermittent urinations with slight blood tinge). The owner declined repeated treatment. Another dog had complete resolution of hematuria for 24 hours and then intermittent recurrence until stent removal. After 3 weeks, the stent was removed, and from that time, the hematuria completely resolved. Overall, long-term success was considered in 5 of 8 renal pelvises (4/6 dogs), with dramatic improvement in hematuria in 5 of 6 dogs (6/8 renal pelvises), and some improvement in hematuria in all dogs, with no recurrence of anemia, pollakiuria, or stranguria. Median follow-up time was 8 months (range, 3.5 to 20.5 months). No patient died of complications of the hematuria, such as anemia, or related to the procedure. Ureteronephrectomy was not required in any of the dogs. One dog died of a mast cell tumor 13 months after the first procedure, and the remaining 5 dogs were alive at last follow-up. All owners were pleased with the procedure and would consider its use again if necessary.
Discussion
Results of the present study supported the use of topical sclerotherapy as a safe, effective, minimally invasive, and renal-sparing treatment for the rare condition of IRH. Typically, IRH is considered a condition of young large-breed dogs,1,2,4–6 but it has only been reported in a small number of cases (approx 17 dogs cumulatively). The present study included an additional 6 dogs, including an older 12-year-old dog with concurrent diseases (grade 2 mast cell tumor, hypothyroidism, and an adrenal mass) as well as a small- or medium-breed dog weighing only 10 kg. The study also had 2 of 6 dogs with bilateral disease (one with bilateral disease at the time of diagnosis and another with bilateral disease that developed 4.5 months later). Previously, once a diagnosis of upper urinary tract bleeding, or IRH, had been made on the basis of cystoscopy or ureteral catheterization, an ureteronephrectomy was recommended if the hematuria was associated with lower urinary tract signs, anemia, chronic bone marrow regeneration, iron deficiency, or a ureteral obstruction. This philosophy has changed over the past few decades in human medicine and the past few years in veterinary medicine. With the concern that the hematuria is or can become bilateral (approx 21% to 33%),1–6 as confirmed in this series, as well as knowing that the lesion is typically found in the renal pelvis, rather than the kidney itself, preservation of the renal parenchyma is considered ideal and appropriate, particularly in young dogs. This series documents an overall long-term success for cessation of hematuria with topical sclerotherapy in 4 of 6 dogs (5/8 renal pelvises), with dramatic improvement in hematuria in 6 of 8 renal pelvises and > 50% improvement seen in all renal pelvises, with resolution of anemia, pollakiuria, and stranguria in all patients. This treatment avoided the need for ureteronephrectomy in all patients of this report.
The present study did not reveal a predisposition to having a predominance of left-sided hematuria, as described in previous reports,1–6 and most of the dogs in this series were males (5/6). For a diagnosis of IRH, no biochemical, coagulation, blood pressure, or imaging abnormalities could be found that could explain or contribute to the hematuria. All dogs in this study fit the criteria for IRH except 1 dog with concurrent disease (a recurrent grade 2 mast cell tumor, hypothyroidism, and an adrenal mass detected on abdominal ultrasonography). Because we could not correlate these individual abnormalities with resulting hematuria, we decided to include this patient. Unfortunately, this was the only treatment failure. Both sclerotherapy and ureteroscopy and electrocautery failed in this patient, and no distinct lesion was found in either renal pelvis of this patient. It is possible that this dog may not have had true IRH.
Anemia was present in 3 of 6 dogs prior to sclerotherapy and resolved in all dogs after treatment. Imaging included abdominal ultrasonography, abdominal radiography, renal angiography, and cystourethroscopy. Results of imaging were considered normal, other than some blood clots found in the urinary bladder in 2 dogs on ultrasonography and in 5 dogs on cystoscopy. A blood clot was found in the renal pelvis in 1 dog on ultrasonography. A definitive diagnosis of upper urinary tract hematuria was documented via cystoscopy in all dogs.
In male dogs, the percutaneous perineal access procedure made the endoscopic approach to the UVJ much easier. This was accomplished with fluoroscopic guidance, with or without ultrasound guidance, and with an access sheath. This procedure allowed better imaging with a rigid cystoscope and easier UVJ access for appropriate endoscopic catheterization. This procedure is routinely used in the authors' practice for the treatment of IRH and cystoscopic-guided laser ablation of ectopic ureters in male dogs.
The procedure was well tolerated in 5 of 6 dogs. One dog in which a ureteral stent was not placed and that did not have a UPJ balloon used required manual ureteral occlusion with a small surgical approach. This patient had severe signs of renal pain and postprocedural pyelectasis. This resulted in a prolonged hospitalization (4 days) for pain management, but the hematuria resolved immediately. It is currently recommended that ureteral stents be placed in all patients following sclerotherapy to avoid ureteral spasm or associated ureteritis associated with chemical irritation, which is a potential risk described in humans and which occurred in 1 patient of this report. Also, if possible, the ureteral occlusion should occur as proximal as possible to prevent the sclerotherapy from contacting the ureter or urinary bladder and causing irritation of the ureter or bladder. If this procedure is done with surgical assistance, care should be taken to prevent abdominal contamination with the mixture as well, considering that this can be irritating. Use of fluoroscopy is highly recommended for quantification of renal pelvis filling measurements to avoid backfilling of the renal parenchyma with any caustic agents.
A ureteral stent was placed in 7 of 8 ureters after sclerotherapy in the dogs of this report, and there were more complications with the stents (3/7) than is typically seen for routine ureteral stenting for obstructive ureteral disease. The complication seen in this series was ureteral stent migration in all 3 of these ureters. It is possible that this occurred as a result of excessive ureteral peristalsis, which can occur with ureteritis. No signs of ureteral pain were documented in any of these dogs that would explain why the stents moved. In > 150 stents placed in dogs in the authors' practice, typically for other reasons (eg, stones, tumors, or strictures), ureteral stent migration is seen in < 3% of cases. Further investigation into the cause of stent migration is necessary. Because of the pyelectasis with severe signs of renal pain that developed after the procedure in the 1 dog that did not have a stent placed, the authors now recommend ureteral stenting after sclerotherapy. It is the authors' opinion that, ideally, the stent should be removed 2 to 4 weeks after treatment to prevent migration.
In humans, sclerotherapy is used mainly in developing nations where ureteroscopic equipment is not available.21,22 Silver nitrate is considered a coagulating and chemical cauterization agent, and use has been reported for a small number of people, with successful treatment of renal hematuria in all patients.21,22 The treatment is often repeated 2 to 3 times/d until the cessation of hematuria is documented (2 to 4 days). This is typically done by leaving an indwelling ureteral catheter inside the renal pelvis, where a predetermined volume is allowed to dwell for various time periods, with patients placed in a Trendelenburg position in a hospital bed. This approach was considered in our patients, but maintaining a ureteral catheter in a renal pelvis in an unanesthetized canine patient holds the risk of ureteral perforation with any activity. Instead, serial dwells with patients under anesthesia were attempted. A more common condition in human medicine in which sclerotherapy has been used is for a condition called chyluria.23–26 This is most commonly associated with malaria-like diseases, in which multiple lymphatic communications develop within the renal pelvis, resulting in chyle-tinged urine. Sclerotherapy with the use of silver nitrate solution or povidone iodine solution has been successfully reported to treat chyluria in 75% to 90% of patients.23–26 In combination, these chemicals are thought to work synergistically. Iodine is considered a corrosive agent because of its oxidizing potential, and povidone is a thickening and granulating agent. Together, silver nitrate or povidone iodine may have chemocauterization effects, resulting in cessation of bleeding and antisepsis.27 Because we had 1 chance of renal pelvic access in these dogs, the authors elected to try both povidone iodine and silver nitrate infusions serially, with a goal to have a synergistic effect. Because it was successful in the first few patients, both agents were consistently used.
In humans, reported complications associated with silver nitrate infusions into the renal pelvis for either IRH or chyluria are rare. Acute necrotizing ureteritis with ureteral obstruction (in an unstented patient), bladder wall fibrosis, arterial hemorrhage, and hepatic dysfunction have been individually reported with silver nitrate infusions.28–30 These are not reported with the use of povidone iodine. With use of the UPJ balloon, preventing ureteral and bladder wall contact with the silver nitrate as well as use of a ureteral stent after infusion, these local complications can be avoided. Care also needs to be taken to avoid overfilling of the renal pelvis because backfilling into the renal parenchyma could cause damage to the renal tubular cells. This is why use of fluoroscopy and contrast to accurately measure renal pelvis filling volume is highly recommended. A ureteral stent was placed after the procedure to prevent the risk of ureteritis and is recommended by the authors, understanding the risk of stent migration, dislodgement, and irritation. The stent should be removed 2 to 4 weeks after the procedure if possible. If topical sclerotherapy fails and a ureteral stent is in place, the ureter will passively dilate over a few days to a few weeks.31 This will allow the passage of a ureteroscope up the canine ureter for retrograde ureteropyeloscopy and electrocautery to be performed, which is considered the treatment of choice for IRH in humans.8,9,32 Electrocautery is effective in > 90% of human patients when a lesion is identified.8,32 Additionally, a phenomenon in humans has been reported where patients in whom no abnormality is found endoscopically will often stop having gross hematuria after the procedure.8,9 This is postulated to be due to the increased intraluminal renal pelvic pressure associated with the ureteroscopy and irrigation, resulting in back pressure and inflammation and ultimately the cessation of the bleeding. In approximately 80% of patients, a lesion can be found in the renal pelvis or renal calyx.8–10,32–34 Typically in humans, if a lesion is found and treated with ureteroscopic electrocautery, it is expected that the hematuria will stop in > 90% of cases. In 1 report,32 recurrence occurred in approximately 12% of patients a median of 7 months following the procedure. In humans, multiple bleeding lesions (hemangiomas) are rarely documented endoscopically, and these are more likely to recur over time. When multiple hemangiomas are identified or bleeding is seen without a specific lesion from various calices, topical silver nitrate sclerotherapy is advocated, but the bleeding may be of parenchymal origin, and topical treatment may not work,8 as in 1 dog of this series.
Options reported for the treatment of IRH, other than ureteronephrectomy, sclerotherapy (silver nitrate or povidone iodine infusions), and ureteroscopic electrocautery, include partial occlusion of the renal artery (use of either surgical attenuation7 or endovascular occlusion [in the authors' experience]) and medical supplementation with a Chinese herb called Yunnan baiyao or aminocaproic acid. Temporary occlusion of the dorsal and ventral rami of the renal artery until hematuria from the ipsilateral UVJ resolves can allow for partial renal parenchymal loss (approx 50%) without a full nephrectomy. This would not be effective if multiple lesions were present or developed and is only partially renal sparing. With the endovascular technique, more selective renal arterial branches can be occluded, preserving more of the renal parenchyma, but this can also result in nontargeted renal arterial embolization, and selectivity can be very difficult, in the authors' experience.
Yunnan baiyao is a Chinese herbal medicine, and a formula that is commonly used to stop bleeding, promote wound healing, and relieve pain was first described > 80 years ago. It was used prior to sclerotherapy in 3 patients of this report. There is some evidence that Yunnan baiyao augments hemostasis by shortening bleeding times and increasing the permeability of platelet membranes.35–37 In rats, use of this formulation has been shown to shorten the time of platelet plug formation when applied both topically and systemically.36 It has also been documented to cause peripheral vasoconstriction.36,37 The positive hemostatic effects are well documented in the Chinese literature, but the exact mechanism remains unclear, and augmented platelet function seems to play a major role. Yunnan baiyao is also thought to have both anti-inflammatory and antimicrobial properties. Administration of Yunnan baiyao appeared to have no effect on the renal hematuria in the cases described in this report, and use was discontinued before sclerotherapy.
Use of aminocaproic acid to treat IRH in humans has also been reported.38 There are no known reports of use of aminocaproic acid in veterinary medicine for this condition. Aminocaproic acid is a derivative and analogue of the amino acid lysine, an inhibitor of proteolytic enzymes such as plasmin, which is responsible for fibrinolysis, potentially making this effective in the treatment of bleeding disorders. Adverse effects that have been reported include gastrointestinal upset, fever, liver disease, and thrombosis.
The limitations of the present study include the small number of cases, the retrospective nature, and the presumptive diagnosis of IRH in each patient. With concurrent disease in 1 dog, which could, in theory, contribute to a bleeding tendency, the success rate could have been considered higher had this patient been excluded. Another limitation is the use of both silver nitrate and povidone iodine concurrently in these patients, not allowing determination of which agent was the cause for the high success rate of hemostasis. Because obtaining renal access was considered a 1-time opportunity in most cases and because of the suggested synergistic potential of both agents, the authors elected to use both materials. A future study would involve the use of each agent separately to assess success. In addition, the renal-sparing nature of this treatment was based on postprocedural hematologic evaluation and imaging findings (ultrasonography). Without knowledge of pre- and postprocedural differential glomerular filtration rates, the renal-sparing nature of the treatment is presumptive. It is recommended to avoid overfilling of the renal pelvis, to use proximal ureteral occlusion to avoid ureteral and bladder contamination, and to place a ureteral stent after the procedure, to prevent signs of ureteral pain and obstruction from irritation of the sclerotherapy.
In conclusion, IRH is considered to be a benign condition of the upper urinary tract and, in up to one-third of cases, can be found bilaterally. Topical sclerotherapy can be safe, effective, and renal sparing and should be considered prior to ureteronephrectomy. To our knowledge, this report is the first to describe the use of local sclerotherapy for IRH in veterinary patients, which could be considered a valuable treatment that can be performed in a minimally invasive manner. Further investigation into this technique is needed prior to routine recommendation.
ABBREVIATIONS
| IRH | Idiopathic renal hematuria |
| UPJ | Ureteropelvic junction |
| UVJ | Ureterovesicular junction |
Rigid endoscope, 2.7-mm 30° lens, Richard Wolf, Vernon Hills, Ill.
Rigid endoscope, 2.7-mm 30° lens, Karl Storz Endoscopy-America, Culver City, Calif.
Rigid endoscope, 4.0-mm 30° lens, Karl Storz Endoscopy-America, Culver City, Calif.
Flexible endoscope Flex X2, 2.7-mm, Karl Storz Endoscopy-America, Culver City, Calif.
Artis Zee Fluoroscopic C-arm, Siemens, Malvern, Pa.
Omnipaque, iohexol (240 mg/mL), GE Healthcare, Princeton, NY.
Weisse C, Berent A. Percutaneous fluoroscopic-assisted perineal approach for rigid cystoscopy in male dogs (abstr). J Vet Intern Med 2012;26:1535.
Weasel Wire 0.035-inch hydrophilic angle-tipped guidewire, Infiniti Medical LLC, Menlo Park, Calif.
5F open-ended ureteral catheter, Bard Medical, Covington, Ga.
MD 76R, diatrizoate meglumine and diatrizoate sodium injection, USP Mallinckrodt Inc, St Louis, Mo.
Povidone iodine (10%) solution, Aplicare Inc, Meriden, Conn.
Amplatz super stiff J-tipped 0.035-inch, 150-cm guidewire, Cook Medical, Bloomington, Ill.
5F and 6F UPJ balloon catheter, Cook Medical, Bloomington, Ill.
0.5% silver nitrate solution, TEVA Pharmaceuticals, Sellersville, Pa.
4.7F × 20-cm double-pigtail ureteral stent, Infiniti Medical LLC, Menlo Park, Calif.
4.7F × 22- to 32-cm variable-length double-pigtail ureteral stent, Bard Medical, Covington, Ga.
5F × 22- to 32-cm variable-length double-pigtail ureteral stent, Cook Medical, Bloomington, Ill.
6F × 26-cm double-pigtail ureteral stent, Cook Medical, Bloomington, Ill.
Peel-away 16F sheath, Cook Medical, Bloomington, Ill.
Penrose drain, 1/4 inch, Bard Medical, Covington, Ga.
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