Introduction
Urate uroliths are a common urolith type in the canine population,1,2 associated with 2 distinct disease entities. The first is a mutation of the urate transporter, which is commonly seen in breeds such as Dalmatians.3,4 Secondly, ammonium urate uroliths are seen in dogs with a portosystemic shunt (PSS), or sporadically other liver disorders, due to reduced hepatic conversion of ammonia to urea and uric acid to allantoin.3 PSS are vascular anomalies that connect the portal vein to the systemic venous circulation, bypassing the hepatic circulation.5 Clinical signs involve the central nervous system and gastrointestinal and urinary tracts.5 Urolith formation is seen in 20% to 70% of dogs with a congenital extrahepatic PSS (cEHPSS), with ammonium urate reported in 36% to 100% of those cases.5–7 Surgical treatment of cEHPSS accounts for longer survival and is preferred over medical treatment,8 but the incidence of ammonium urate urolithiasis in dogs following complete closure of cEHPSS without the development of multiple acquired PSS (MAPSS) is currently unknown. Only 1 study9 describes the presence of ammonium urate cystoliths in a cat, 3 years after surgical attenuation of a cEHPSS using thin film banding. In this study, the cEHPSS was presumed to be closed on the basis of the presence of within-reference-interval postprandial serum bile acid concentrations 1 and 3 months postoperatively, yet absence of portosystemic shunting was not confirmed using medical imaging. Although urolithiasis can be asymptomatic, lower urinary tract signs such as hematuria, stranguria, and pollakiuria can occur, especially in the presence of a concurrent urinary tract infection.5,7,10 Besides, obstructive disease can be life-threatening.10 Urinary tract signs related to urolithiasis have been documented in 21% to 45% of dogs diagnosed with cEHPSS.6,7,11
Currently, it is unclear whether dogs are still vulnerable to developing ammonium urate uroliths following successful cEHPSS surgery and whether nephroliths remain or dissolve over time in the absence of portosystemic shunting. Furthermore, it is unclear whether dogs that develop MAPSS after cEHPSS attenuation are at greater risk of recurrent urolithiasis. Our study aimed to document the presence of urolithiasis in dogs long-term after cEHPSS attenuation.
Materials and Methods
A retrospective study with a prospective long-term follow-up was set up and approved by the local ethical and deontological committee (EC 2018-77, DWZ/ER/19/1.15/28). Records of the clinic were searched for dogs that underwent surgical attenuation of a cEHPSS between January 2012 and December 2018. Dogs were eligible for inclusion if the postoperative PSS status was determined by transsplenic portal scintigraphy or CT angiography a minimum of 3 months postoperatively and if the surgery was performed at least 6 months prior to study inclusion. Dogs with MAPSS (pU+/−) were only included if they developed these following surgical attenuation of a cEHPSS. As only a limited number of dogs with MAPSS were available that met the inclusion criteria, owners of all these dogs were contacted by phone and invited for a prospective follow-up visit. Subsequently, a number of dogs with closed cEHPSS with (cU+) and without urolithiasis (cU–) before or at the time of cEHPSS attenuation were listed. It was decided to include a similar number of dogs with closed cEHPSS with and without a history of preoperative urolithiasis. As the minority of these dogs did not have urolithiasis before or at the time of cEHPSS attenuation, all owners of these dogs were contacted by phone and invited for a prospective follow-up visit. Finally, dogs with closed cEHPSS that had a history of preoperative urolithiasis were matched to the previous dogs included, based on the time between the cEHPSS attenuation and the prospective follow-up visit, to achieve a comparable average follow-up time between all dogs. Owners of the latter dogs were contacted by phone and invited for a prospective follow-up visit. All owners that came for the prospective follow-up visit signed an informed consent that contained all details about the study, and hence all owners gave consent to analyze all retrospectively available data and perform all prospective investigations that were part of the current study (for details, see below).
Retrospective data of enrolled dogs were collected from medical records and included details about clinical signs before cEHPSS attenuation, surgical details, and postoperative follow-up. As most dogs were already included in previous prospective studies (EC2012/164 and DC211728/13_21_04; EC2014/179-27 and DC2015N03; and EC2017/49 and DC2017N06), standardized questionnaires regarding clinical signs were available for review at diagnosis, surgery, and follow-up until 6 months postoperatively. For the prospective follow-up visit, this questionnaire was adapted by adding questions focusing on the presence and severity of urinary tract signs both preoperatively and postoperatively until the examination date at the prospective follow-up visit, diet history, and medical history between cEHPSS attenuation and the prospective follow-up visit (Supplementary Appendix S1). Owners of dogs were invited for a prospective follow-up visit between June 2019 and January 2020, and a thorough history was taken by the primary author, who filled out the questionnaire together with the owners. If urinary tract disease occurred during the period between cEHPSS attenuation and the prospective follow-up visit, the referring veterinarian was contacted to obtain the results of the investigations. To quantify the severity of urinary complaints, a urinary score (0 to 18) was calculated for each dog before cEHPSS attenuation and at time of the prospective follow-up visit based on answers available in the questionnaires. Urinary signs that occurred often were assigned 2 points, and those that occurred occasionally were assigned 1 point. Hematuria, stranguria, and dysuria were multiplied by 2, whereas polyuria, polydipsia, and periuria were not multiplied.
At the prospective follow-up visit, physical examination and blood analyses, including CBC, serum biochemistry, and fasting ammonia concentration, were performed. Ammonia was measured immediately after blood sampling using a portable laboratory device (PocketChem BA; A Menarini Diagnostics srl). Ultrasonography of the urinary tract was performed in all dogs by a European College of Veterinary Diagnostic Imaging diplomate (ES) to assess the presence of urolithiasis and echogenicity of urine and reassess cEHPSS closure. In case uroliths were detected, the size and location were recorded and abdominal plain radiographs were performed to assess radiopacity. Ultrasound-guided cystocentesis and in-house urinalyses were performed in all dogs, including urine-specific gravity, manual semiquantitative dipstick urinalysis and microscopic native, and diff-quick stained sediment examination, completed within 30 minutes after collection. In case uroliths were removed, they were sent for quantitative analysis.
Statistical analysis
Due to the small number of dogs included, it was decided to report results as nonparametric data. Statistical analysis was performed using SPSS Statistics (version 26; IBM). Kruskal-Wallis tests were performed to assess differences between groups (cU+, cU–, and pU+/−) in age, body weight, body condition score, fasting ammonia concentrations, urinary scores, the presence of urolithiasis at the time of surgical attenuation of the cEHPSS and the prospective follow-up visit, and the time between cEHPSS attenuation and the prospective follow-up visit. In case of statistical significance, pairwise comparisons were performed with the Bonferroni correction. To assess urinary scores over time, Wilcoxon matched-pair signed rank tests were performed. Results with a P ≤ .05 were considered significant.
Results
Signalment, history, and clinical findings
Owners of 26 dogs were contacted. The owner of 1 dog with MAPSS elected not to participate in the study because of the anxious nature of the dog, and thus a total of 25 dogs were included, of which 17 dogs had urolithiasis before or at the time of cEHPSS attenuation (12/19 dogs in which surgical attenuation resulted in a closed cEHPSS and 5/6 dogs that developed MAPSS; Table 1). Breeds of dogs included the following: Yorkshire Terrier (n = 5); Chihuahua, Dachshund, and Maltese (3 each); Bichon Frise and mixed-breed dog (2 each); and Border Collie, Jack Russell Terrier, Keeshond, Norwich Terrier, Pug, Miniature Schnauzer, and Standard Schnauzer (1 each). There was no difference between the groups in age (P = .340), body weight (P = .256), body condition score (P = .900), and time between cEHPSS attenuation and the prospective follow-up visit (P = .851). In 3 of 25 (12%) dogs, uroliths were previously diagnosed and removed by the referring veterinarian, and in 10 of 25 (40%) dogs, cystotomy was performed at the time of cEHPSS attenuation. An ameroid constrictor was placed in 17 of 25 (68%) dogs, and in 8 of 25 (32%) dogs, thin film banding was used.
Demographic data of included dogs in this study with a history of a surgical attenuation of congenital extrahepatic portosystemic shunts (cEHPSS).
| Variable | Complete study population (n = 25) | Closed cEHPSS (n = 19) | Closed cEHPSS | MAPSS (n = 6) | MAPSS | ||
|---|---|---|---|---|---|---|---|
| U+ (n = 12) | U– (n = 7) | U+ (n = 5) | U– (n = 1) | ||||
| Age (mo)a | 73 (18–115) | 82 (22–115) | 77.5 (22–115) | 83 (38–111) | 51.5 (18–86) | 47 (18–86) | 56 |
| Body weight (kg)a | 5.8 (2.2–14.9) | 6.3 (2.2–14.9) | 7.7 (2.4–14.9) | 3.8 (2.2–7.9) | 5.1 (2.5–9.2) | 5.6 (3.7–9.2) | 2.5 |
| BCSa | 5/9 (4/9–7/9) | 5/9 (4/9–7/9) | 5/9 (4/9–7/9) | 5/9 (4/9–6/9) | 5/9 (4/9–6/9) | 5/9 (4/9–6/9) | 5/9 |
| Time between cEHPSS attenuation and the prospective follow-up visit (mo)a | 36 (13–103) | 34 (14–103) | 41 (14–61) | 34 (18–103) | 38.5 (13–71) | 36 (13–71) | 41 |
| Sex (F, FN, M, MN) | 0, 15, 1, 9 | 0, 11, 1, 7 | 0, 6, 0, 6 | 0, 5, 1, 1, | 0, 4, 0, 2 | 0, 3, 0, 2 | 0, 1, 0, 0 |
| Type of cEHPSS (PA, PC, PP) | 4, 17, 4 | 4, 12, 3 | 3, 6, 3 | 1, 6, 0 | 0, 5, 1 | 0, 4, 1 | 0, 1, 0 |
| Surgical attenuation method (AC, TFB) | 17, 8 | 14, 5 | 9, 3 | 5, 2 | 3, 3 | 2, 3 | 1, 0 |
aData are reported as median and range
AC = Ameroid ring constrictor. BCS = Body condition score. F = Female sexually intact. FN = Female neutered. M = Male sexually intact. MAPSS = Multiple acquired portosystemic shunts. MN = Male neutered. PA = Portoazygos. PC = Portocaval. PP = Portophrenic. TFB = Thin film banding. U+ = Dogs with confirmed urolithiasis before or at the time of cEHPSS attenuation. U– = Dogs with no history of urolithiasis before or at the time of cEHPSS attenuation.
One dog with closed cEHPSS was diagnosed with idiopathic epilepsy 7 months after cEHPSS attenuation and showed marked alopecia and a decreased mental status at the time of the prospective follow-up visit (4 years after cEHPSS attenuation). The dog was subsequently diagnosed with hypothyroidism. None of the other dogs showed significant abnormalities on physical examination at the time of the prospective follow-up visit. Irrespective of the surgical outcome, occasional gastrointestinal complaints were reported at the time of the prospective follow-up visit, mainly consisting of episodes of vomiting, diarrhea, hypersalivation, melena, and/or decreased appetite. Neurological complaints encountered after cEHPSS attenuation were mainly periodically dullness and hyperactivity (Table 2).
Number of dogs with gastrointestinal, neurological, or urinary signs a median of 36 months (13 to 103 months) after cEHPSS attenuation.
| Group | n | Gastrointestinal signs | Neurological signs | Urinary signs | Liver-supportive treatment (n) |
|---|---|---|---|---|---|
| Closed cEHPSS | 19 | 15 (79%) | 9 (47%) | 6 (32%) | Diet (1), diet and lactulose (1), none (17) |
| U+ | 12 | 8 (67%) | 5 (42%) | 4 (33%) | Diet and lactulose (1), none (11) |
| U– | 7 | 7 (100%) | 4 (57%) | 2 (29%) | Diet (1), none (6) |
| MAPSS | 6 | 5 (83%) | 4 (67%) | 6 (100%) | Diet (1), diet and lactulose (2), diet and metronidazole (1), lactulose (1), none (1) |
| U+ | 5 | 4 (80%) | 3 (60%) | 5 (100%) | Diet (1), diet and lactulose (1), diet and metronidazole (1), lactulose (1), none (1) |
| U– | 1 | 1 | 1 | 1 | Diet and lactulose |
See Table 1 for key.
Seven dogs still received a liver-supportive treatment (Table 2). All dogs but one received a liver-supportive diet. One dog with MAPSS received a liver-supportive diet until 12 months after cEHPSS attenuation when ammonium urate cystoliths were surgically removed and after which the diet was changed to a urolithiasis-prevention diet.
Urinary complaints
At the time of cEHPSS attenuation, 23 of 25 (92%) dogs showed urinary complaints, and at the time of the prospective follow-up visit, 12 of 25 (48%) dogs had a history of urinary complaints in the period from 3 months postoperatively to the prospective follow-up visit. Six of those dogs had a closed cEHPSS (6/19 [32%]) and the other 6 had MAPSS (6/6 [100%]; Tables 2 and 3). One of the dogs with MAPSS suffered from recurrent clinical bacterial cystitis. At the time of cEHPSS diagnosis as well as the prospective follow-up visit, the urinary scores were not different between the different groups (P = .347 and P = .082, respectively). However, over time, urinary scores of cU+ dogs significantly decreased (P = .005 vs P = .223 for cU– and P = .248 for pU+/−).
Number of dogs presented with urinary complaints at the time of cEHPSS diagnosis compared to the period between the time of cEHPSS attenuation and the time of the prospective follow-up visit with a median time of 36 months (13 to 103 months).
| Group | n | Pollakiuria | Polyuria | Hematuria | Stranguria | Dysuria | Periuria | Median urinary score (range) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| cEHPSS diagnosis | Follow-up | cEHPSS diagnosis | Follow-up | cEHPSS diagnosis | Follow-up | cEHPSS Diagnosis | Follow-up | cEHPSS diagnosis | Follow-up | cEHPSS diagnosis | Follow-up | cEHPSS diagnosis | Follow-up | ||
| Closed cEHPSS | 19 | 15 (79%) | 7 (37%) | 9 (47%) | 7 (37%) | 7 (37%) | 1 (5%) | 7 (37%) | 0 (0%) | 6 (32%) | 0 (0%) | 10 (53%) | 3 (16%) | 4 (0–17) | 0 (0–6) |
| U+ | 12 | 10 (83%) | 2 (17%) | 6 (50%) | 3 (25%) | 5 (42%) | 1 (8%) | 7 (58%) | 0 (0%) | 5 (42%) | 0 (0%) | 7 (58%) | 2 (17%) | 7.5 (0–17) | 0 (0–4) |
| U- | 7 | 5 (71%) | 5 (71%) | 3 (43%) | 4 (57%) | 2 (29%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (14%) | 0 (0%) | 3 (43%) | 1 (14%) | 3 (0–11) | 2 (0–6) |
| MAPSS | 6 | 5 (83%) | 5 (83%) | 4 (67%) | 2 (33%) | 2 (33%) | 2 (33%) | 1 (17%) | 1 (17%) | 1 (17%) | 0 (0%) | 5 (83%) | 4 (67%) | 5 (2–18) | 3 (1–10) |
| U+ | 5 | 4 (80%) | 4 (80%) | 3 (60%) | 2 (40%) | 2 (40%) | 2 (40%) | 1 (20%) | 1 (20%) | 1 (20%) | 0 (0%) | 4 (80%) | 3 (60%) | 3 (2–18) | 2 (1–10) |
| U- | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 7 | 4 |
Follow-up = At time of prospective follow-up visit.
See Table 1 for remainder of key.
Blood analyses
Blood examinations were performed at the time of the prospective follow-up visit (Table 4). One (5%) dog with closed cEHPSS had hyperammonemia; nevertheless, neither MAPSS nor clear indications for recanalization of the cEHPSS were found on the basis of abdominal ultrasonography. Unfortunately, further medical imaging was refused by the owner as the dog was clinically doing very well. Hyperammonemia was present in 4 of 6 (67%) dogs with MAPSS. A statistically significant difference in fasting ammonia concentrations was present between pU+/− and both cU+ and cU– (P = .018 and P = .014, respectively).
Median (range) of selected blood and urine variables a median of 36 months (13 to 103 months) after cEHPSS attenuation.
| Variables | Closed cEHPSS (range) | MAPSS (range) | Reference interval |
|---|---|---|---|
| n | 19 | 6 | |
| Hematocrit (%)a | 50.3 (35.8–62.1) | 44.8 (29.4–49.2) | 37.3–61.7 |
| Mean corpuscular volume (fL)a | 65.2 (60.3–71.2) | 57.2 (52.7–63.5) | 61.6–73.5 |
| Albumin (g/L)a | 32 (28–41) | 26 (17–33) | 23–40 |
| Alkaline phosphatase (U/L)a | 42 (< 10–235) | 99.5 (48–220) | 23–212 |
| Alanine transaminase (U/L)a | 51 (22–131) | 66 (31–299) | 10–125 |
| Urea (mmol/L)a | 4.7 (2–9.6) | 1.7 (0.9–3.2) | 2.5–9.6 |
| Glucose (mmol/L)a | 5.93 (4.58–7.19) | 5.64 (4.97–7.54) | 4.11–7.95 |
| Total protein (g/L)a | 62 (55–72) | 56 (50–70) | 52–82 |
| Fasting ammonia concentration (µmol/L)a | 14 (low-84) | 49.5 (20–79) | < 45 |
| Urinary pH (range)a | 7 (5–9) | 6.75 (5–8) | 7.0–7.5 |
| Urine specific gravity (range)a | 1.035 (1.009–1.046) | 1.022 (1.011–1.041) | 1.016–1.060 |
| Urinary proteins | |||
| No | n = 6 (32%) | n = 3 (50%) | NA |
| Trace | n = 9 (47%) | n = 2 (33%) | NA |
| 30 mg/dL | n = 3 (16%) | n = 0 (0%) | NA |
| 100 mg/dL | n = 1 (5%) | n = 1 (17%) | NA |
| Urinary bilirubin | |||
| No | n = 14 (74%) | n = 3 (50%) | NA |
| 1 mg/dL | n = 2 (11%) | n = 2 (33%) | NA |
| 3 mg/dL | n = 3 (16%) | n = 1 (17%) | NA |
| Microscopic analysis of the urinary sediment | |||
| No crystals | n = 16 (84%) | n = 4 (67%) | NA |
| Slide artifacts | n = 1 (5%) | n = 0 (0%) | NA |
| Mild struvite crystalluria | n = 1 (5%) | n = 0 (0%) | NA |
| Moderate amorphous crystalluria | n = 1 (5%) | n = 0 (0%) | NA |
| Moderate amorphous crystalluria | n = 0 (0%) | n = 1 (17%) | NA |
| Mild amount of amorphous crystalluria | n = 0 (0%) | n = 1 (17%) | NA |
aData are reported as median and range.
See Table 1 for remainder of key. NA = Not applicable.
Urinalysis
Urinalysis was performed at the time of the prospective follow-up visit (Table 4). Microscopic hematuria was found in 13 of 25 (52%) dogs. Nonetheless, all dogs had an inactive sediment. Microscopic analysis of the sediment revealed some artifacts in 1 dog with closed cEHPSS, most likely due to dirty slides or staining, although the presence of ammonium biurate crystals could not be completely ruled out. One dog with MAPSS had a previous episode of bacterial cystitis (Escherichia coli, treated with amoxicillin–clavulanic acid) but was asymptomatic at the time of the prospective follow-up visit. Nevertheless, a moderate number of amorphous crystals and a large number of rods were present, although only a small number of erythrocytes and leukocytes were seen. Urine culture and sensitivity testing revealed the presence of multiresistent E coli. Of the 4 dogs with crystalluria at the time of the prospective follow-up visit, 2 had concomitant urolithiasis. Only in 1 dog quantitative urolith analysis was performed because the dog showed clinical signs (urinary score 10) and revealed the presence of calcium oxalate crystals, which did not match the type of crystalluria (amorphous) at the time of the prospective follow-up visit.
Ultrasonographic and radiographic assessment of the urinary tract
Before cEHPSS attenuation, uroliths were visible on abdominal ultrasonography in 17 of 25 (68%) dogs, with 5 dogs having uroliths in > 1 location. In 15 of 25 (60%) dogs, echoic foci were present in the urinary bladder. In 3 dogs, echoic foci were seen in the absence of urolithiasis (Table 5). At cEHPSS attenuation, the median urinary score of dogs with echoic foci was 5 (2 to 18) and the median urinary score of dogs with urolithiasis was 5.5 (0 to 18).
Presence of urinary complaints, echoic foci, cystoliths, urethroliths, nephroliths, and urinary crystals in 25 dogs a median of 36 months (13 to 103 months) after cEHPSS attenuation.
| Group | Dogs | Echoic foci (n) | Ureteroliths (n) | Cystoliths, urethroliths (n) | Nephroliths (n) | Crystals on urinary sediment (n) | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| n | cEHPSS diagnosis | Prospective follow-up visit | cEHPSS diagnosis | Prospective follow-up visit | cEHPSS diagnosis | Prospective follow-up visit | cEHPSS diagnosis | Prospective follow-up visit | Prospective follow-up visit | ||
| Closed cEHPSS | 19 | 10 | 3 | 1 | 0 | 10 | 1 | 4 | 1 | 2 | |
| U+ | 12 | 7 | 1 | 1 | 0 | 10 | 1 | 4 | 1 | 0* | |
| AU (6) | UN (1) | ||||||||||
| AU with struvite (2) | |||||||||||
| UN (2) | |||||||||||
| U– | 7 | 3 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | |
| AM (1) | |||||||||||
| Struvite (1) | |||||||||||
| MAPSS | 6 | 5 | 2 | 0 | 0 | 5 | 4 | 1 | 3 | 2 | |
| U+ | 5 | 5 | 2 | 0 | 0 | 5 | 4 | 1 | 3 | 2 | |
| AU (2) | AU (1) | AM (2) | |||||||||
| UN (3) | Ca-Ox and struvite (1) | ||||||||||
| UN (2) | |||||||||||
| U– | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Total | 25 | 15 | 5 | 1 | 0 | 15 | 5 | 5 | 4 | 4 | |
*The presence of ammonium biurate crystals could not be completely ruled out in 1 dog because of the presence of artifacts.
AM = Amorphous crystals. AU = Ammonia urate uroliths. Ca-Ox = Calcium oxalate uroliths. UN = unknown.
See Table 1 for remainder of key.
At time of the prospective follow-up visit, uroliths were seen in 5 of 25 (20%) dogs (Table 5), of which 4 dogs had uroliths in multiple locations. One of the 19 (5%) dogs with closed cEHPSS had urolithiasis, whereas 4 of 6 (67%) dogs with MAPSS had urolithiasis. In the dog with the closed cEHPSS and long-term urolithiasis, small cystoliths (up to 2.0 mm), nephroliths (< 1.0 mm), and urethral uroliths (< 1.0 mm) were detected via ultrasound. Additional plain radiographs revealed very small, faint mineralizations (< 1.0 mm) in both kidneys and a mineral opaque structure of 2.6 mm in length at the level of the prostatic part of the urethra. In this dog, multiple nephroliths had already been reported on ultrasound 1 month before cEHPSS attenuation. However, at that time, they were ranging from 1.5 to 4.0 mm. At the time of the prospective follow-up visit, the dog had a urinary score of 4 and unremarkable blood and urinalysis. One of the dogs with MAPSS had very small cystoliths preoperatively, which were not removed at the time of cEHPSS attenuation because of their small size. At the prospective follow-up visit, cystoliths (1.0 to 2.0 mm) were still observed. The remaining 3 dogs with MAPSS and long-term urolithiasis developed new uroliths. One dog had ammonium urate cystoliths that were removed at the time of the cEHPSS attenuation and had 60 months prior to the prospective follow-up visit calcium oxalate and struvite cystoliths removed. However, at the time of the prospective follow-up visit, new small nephroliths (1.0 to 2.0 mm), cystoliths (4.3 mm), as well as urethroliths (1.1 mm) were diagnosed by ultrasound. Based on plain radiography, only the cystoliths were radiopaque (3.5 X 2.7 mm), and urinalysis revealed amorphous crystalluria. The fasting ammonia concentration of that dog was normal. As the urinary score was 10, voiding urohydropropulsion was performed, but the obtained sediment was not sufficient to allow quantitative analysis, although it revealed calcium oxalate crystals. In the second dog, only cystoliths had been present initially, and those were removed at the time of cEHPSS attenuation. The dog had a second cystotomy for removal of multiple newly formed ammonium urate cystoliths 15 months after cEHPSS attenuation. At the time of the prospective follow-up visit 16 months after surgery, the dog presented with hyperammonemia and very small mineralizations (< 1 mm) were detected in the left renal pelvis. The last dog had nephroliths (2.5 mm) and cystoliths (1.0 mm) at the time of cEHPSS attenuation that were removed. At the follow-up visit, the dog had hyperammonemia, the nephroliths (< 1.0 mm) were still present, and, additionally, new cystoliths (< 1.0 mm) had formed.
Urinary bladder echoic foci were observed in 5 of 25 (20%) dogs. Three of these dogs had closed cEHPSS and no urolithiasis (one dog had struvite crystalluria, another one amorphous crystalluria, and the last one did not have crystalluria). Two dogs had MAPSS and concurrent urolithiasis (one dog without crystalluria and the other with amorphous crystalluria).
In 3 of the 4 dogs with closed cEHPSS that presented with nephrolithiasis at time of diagnosis, nephrolithiases were absent at the time of the prospective follow-up visit. In 1 dog, echoic foci were visible at the level of the renal pelvis (initial nephrolith was 8.7 X 4.7 X 8.3 mm), whereas in the other 2 dogs (initial nephroliths were 2.0 and 3.0 mm in one dog and 4.4 and 6.0 mm in the other dog) no echoic foci were observed. The remaining dog with closed cEHPSS and preoperative nephrolithiasis developed postoperative cystolithiasis. Although there was persistent nephrolithiasis, at long-term the nephroliths were smaller compared to before.
At the time of the prospective follow-up visit, dogs in cU+ and dogs in cU– had significantly less urolithiasis compared to dogs in pU+/− (P = .013, and P = .010, respectively). No statistical significance in urolithiasis was present between dogs of cU+ and cU– (P = 1.000). Dogs in cU+ had significantly less urolithiasis at the time of the prospective follow-up visit compared to the time of cEHPSS attenuation (P = .001), whereas no significant difference was present over time in dogs of pU+/− (P = .317).
Discussion
To our knowledge, this was the first study that documented the presence of urolithiasis long-term after surgical attenuation of a cEHPSS in dogs, with known postoperative PSS status. This study revealed that dogs with closed cEHPSS that had urolithiasis at the time of surgical attenuation did not have a higher risk to have recurrent urolithiasis compared to dogs that did not have urolithiasis at the time of cEHPSS surgery. In the only dog with a confirmed closed cEHPSS and long-term urolithiasis, small, nonradiopaque cystoliths were detected at long-term follow-up, while the radiopaque nephroliths that were present at the time of cEHPSS diagnosis decreased in size. Also, the nephroliths that were present at the time of surgical attenuation in the other dogs with closed cEHPSS decreased in size or even disappeared over time. In contrast, half of the dogs that developed MAPSS following surgical attenuation of cEHPSS were diagnosed with uroliths that were either not yet present or in which previous cystoliths had been removed at the time of surgical attenuation of the cEHPSS.
At the time of the prospective follow-up visit, ammonium biurate crystals were not detected in any of the dogs. Two of the dogs with MAPSS and long-term urolithiasis had amorphous crystalluria. The presence of amorphous crystals is a nonspecific finding, and although these crystals were not consistent with ammonium urate crystals, the presence of ammonium urate uroliths could not be excluded. Hyperammonemia was present in 4 of 6 dogs with MAPSS, and 3 of 4 dogs had uroliths. However, only in 1 dog there was definite proof of ammonium urate urolithiasis. Radiographic examination was performed in one of the remaining dogs and revealed radiopaque uroliths. As ammonium urate uroliths are usually radiolucent7 and no crystalluria was present, it was considered unlikely that the uroliths in that particular dog were composed of ammonium urate. No radiographic examination was performed in the third dog with hyperammonemia that also presented with nonobstructive uroliths. Only 1 of 19 dogs with a confirmed closed cEHPSS in our study was diagnosed with mineral-opaque lithiasis in the kidneys and prostatic urethra and radiolucent cystoliths at the time of the prospective follow-up visit. No crystalluria was present, and uroliths were not removed to determine the urolith composition.
A remarkable finding in dogs with confirmed absence of postoperative portosystemic shunting is that nephroliths detected at the time of cEHPSS attenuation were no longer present at the time of the prospective follow-up visit in 3 of 4 dogs. In the fourth dog, the nephroliths decreased in size over time. It should be acknowledged that only a small number of dogs were included and that no information was available regarding the composition of the nephroliths. Nevertheless, our findings suggest that ammonium urate uroliths can dissolve over time following successful surgery. One dog with MAPSS developed cysto- and small nephroliths 1 year after cEHPSS attenuation while receiving a liver-supportive diet. Cystotomy was performed and confirmed ammonium urate cystolithiasis. Lactulose and metronidazole treatment were reinstalled, and the diet was adapted in an attempt to prevent recurrence. At the time of the prospective follow-up visit (16 months postcystotomy), the small nephroliths were no longer seen, either due to dissolution as a result of the medical therapy or due to passage through the ureter and subsequent excretion. At the time of the prospective follow-up visit, 3 other dogs that developed MAPSS after surgical attenuation of cEHPSS presented with nephrolithiasis, while nephroliths were not identified at the time of cEHPSS attenuation. In total, 4 of 6 (67%) dogs that developed MAPSS had urolithiasis long-term after cEHPSS surgery. The development of urolithiasis might be due to the persistent elevated blood ammonia concentrations, although in 3 of those dogs, ammonium urate urolithiasis could only be assumed but not proven due to the impossibility to perform quantitative stone analysis. The goal of medical treatment for cEHPSS is to decrease blood ammonium concentration, subsequently decreasing the number and severity of clinical signs5 and reducing the formation and excretion of uric acid, which is an essential component for urolith development.3 A liver-supportive diet combined with lactulose is superior to a liver-supportive diet alone.12
In the current study, a urinary scoring system was used to quantify the number of urinary signs. Uroliths that solely contain ammonium urate typically have a smooth surface, which limits irritation to the bladder mucosa3; consequently, dogs with ammonium urate urolithiasis might be asymptomatic. Up to 67% of dogs with cEHPSS are reported to have urinary complaints.6 In our study, 32% (6/19) of dogs with cEHPSS had 1 or more urinary complaints between cEHPSS surgery and the prospective follow-up visit, but only 5% (1/19) of dogs with closed cEHPSS had urolithiasis. All dogs that developed MAPSS after cEHPSS surgery were reported to have urinary complaints between the cEHPSS attenuation and the prospective follow-up visit, whereas only 67% (4/6) of dogs presented with long-term urolithiasis. Quantification of urinary signs helps to determine their effect on the quality of life of affected dogs.
The present study clearly revealed that the presence of bladder echoic foci did not mean that crystalluria was present, and neither the presence of bladder echoic foci nor the presence or absence of crystalluria corresponded with the presence of urolithiasis. The type of crystalluria was also not necessarily compatible with the type of urolithiasis present. It has been documented previously that the type of crystals found in urine does not always correspond to the type of uroliths and that urolithiasis can occur without concurrent crystalluria.3,13
The current study had some limitations. The selected study population was relatively small; especially, the number of dogs that developed MAPSS following surgical attenuation of cEHPSS was limited. As only dogs with cEHPSS were included, no statement can be made about dogs that underwent surgery for congenital intrahepatic portosystemic shunts or for dogs that develop MAPSS unrelated to cEHPSS surgery. Nevertheless, based on the results of the current study, it is to be expected that any type of portosystemic shunting increases the risk of development of urolithiasis. Furthermore, the length of the postoperative follow-up periods varied considerably (median, 36 months; range, 13 to 103 months); nevertheless, no significant difference was present between groups. Obviously, nephroliths could not be analyzed, and consequently it remained uncertain whether these were composed of ammonium urate. Unfortunately, in one of the dogs with postoperative urolithiasis, abdominal radiographs were not performed, whereas radiopacity could have given a hint toward ammonium urate urolithiasis. In addition, the accuracy of detecting ammonium urate urolithiasis using ultrasonography is lower compared to other types of uroliths.14 The sensitivity to detect urolithiasis using ultrasonography is further influenced by patient motion, the presence of intestinal gas, and the degree of bladder distention.15 Despite the fact that all ultrasound exams focused on the urinary tract with the aim to identify potential uroliths and were performed by a European College of Veterinary Diagnostic Imaging diplomate, it cannot be entirely excluded that some small uroliths remained undetected. Although the area of the cEHPSS was visualized in all dogs, shunting through the cEHPSS due to recanalization was difficult to assess due to artifacts caused by metallic devices used for cEHPSS attenuation (ameroid ring constrictor and vascular staples to secure thin film bands). Furthermore, MAPSS can be missed with abdominal ultrasonography even if it is performed by experienced ultrasonographers.16 Of another note, the dogs in this study did not receive a standardized medical treatment (including diet), which might have influenced the outcome, especially in dogs with MAPSS. The data on urinary signs in the period from 3 months postoperatively to the prospective follow-up visit was obtained by owner questionnaire. Questionnaires are useful tools to determine the presence of clinical signs17–19; however, accurateness of the answers is based on the owners’ memory and observation competence. As the owners of most dogs participated in previous studies, questionnaires about the presence of clinical signs at the time of the cEHPSS diagnosis were already available. Finally, ideally a negative control group would have been added to compare the prevalence of urolithiasis long-term in dogs following cEHPSS to those that never had vascular anomalies.
In conclusion, in this study, dogs with successful cEHPSS closure seemed no longer prone to develop urolithiasis and associated urinary complaints in contrast to dogs that developed MAPSS following cEHPSS surgery. Noteworthy, nephroliths (partially) dissolved after successful surgical attenuation of cEHPSS.
Supplementary Materials
Supplementary materials are posted online at the journal website: avmajournals.avma.org
Acknowledgments
No third-party funding or support was received in connection with this study or the writing or publication of the manuscript. The authors have nothing to declare.
The authors wish to thank all dog owners for participating in the study and all referring veterinarians for their help in providing data of the dogs and thereby enabling this study.
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