Unusual canine urolithiasis cases

Haematuria and cystic calculi are a common presentation in practice, and the profession is familiar with the approach to treatment when the analysis of struvite or oxalate is confirmed by the lab. Recently, in their small animal practice, the author’s team encountered two more unusual cases of urolithiasis.

Byrti the Dorset olde tyme bulldogge and Vince the Dalmatian are both lovely patients, and have proven to be interesting and challenging cases to treat.

The author wanted to share her practice’s experiences in the diagnosis and treatment of these unusual cases with other small animal vets.

Urolithiasis in practice

Overall prevalence of urolithiasis in dogs has been estimated to be between 0.25% to 1%^1,2.

Within those overall figures, much variation exists in cases depending on their geographical location, gender, neuter status, breed and body size^1-3.

Trends in urolithiasis also appear to shift through the years³.

The urolith centre at the University of Minnesota, Twin Cities analyses samples for patients across six continents, giving them a great opportunity to look at patterns in urolithiasis^3,4.

Looking at nearly 100,000 submissions from 2009-10 suggested that urolithiasis is most common in females around seven years of age³.

Calcium oxalate and struvite stones made up a large proportion of the samples (Table 1)³.

Table 1. Urolith percentages (Minnesota Urolith Center, University of Minnesota, Twin Cities submissions, 2009-10)3
Urolith composition	Percentage of submissions (N=99,598)
Calcium oxalate	45.2
Struvite	42.5
Purine (including urate and xanthine)	5.1
Cystine	1.2
Calcium phosphate carbonate	1
Silica	0.7
Calcium phosphate	0.5
Other	3.4

Seeing two young male dogs such as Byrti and Vince with urolithiasis was unusual within the general dog population, but on researching further, the author’s team realised the conditions they suffer from are not unexpected in their breeds^1-8.

Cystinuria in Byrti

Byrti is a two-year-old, male, Dorset olde tyme bulldogge (Figure 1), presented to the author’s practice in June 2021 with haematuria and stranguria.

After his clinical signs failed to respond fully to a course of NSAID and antibiotics, Byrti was admitted for further investigation.

An ultrasound scan of his bladder revealed multiple small hyperechoic structures within the lumen of the bladder, creating acoustic shadows suggestive of cystoliths (Figure 2).

As Byrti was an entire male at this point, his prostate was examined on scan, and found to be uniform and of normal size. A lateral abdominal x-ray confirmed multiple small calculi within the bladder, but without the familiar radiopaque appearance of struvite or oxalate stones (Figure 3).

After removal of the calculi by cystotomy, they were confirmed as cystine uroliths (Figure 4).

On further reading, evidence became apparent that this type of urolith not only has specific requirements for dietary management, but also has several predisposing factors that need to be considered in treatment^4-8.

Causes of cystinuria

In most dogs, several amino acids pass into glomerular filtrate in the nephron and are then reabsorbed in the renal tubules by the cystine, ornithine, lysine and arginine (COLA) transporter^4,6-8. A proportion of dogs have an inherited defect in this transporter, leading to high concentrations of COLA in urine^4,6-8.

Cystine has a low solubility in urine, leading to high risk of urolith formation in affected dogs^4,6-8. Studies suggest that this is much more common in males^2-7. Predisposed breeds include the Labrador retriever, Newfoundland, basset hound, dachshund and bulldog, but the condition has been seen in up to 170 breeds of dog^1-8. Genetic tests are available to detect the condition in the Labrador retriever and Newfoundland^4,7.

The amount of cystine in urine is highest in younger dogs and starts to decrease beyond five years of age^4-7. This could explain why urolith formation is most common in young adult dogs of four to six years of age^3,4,6,7. For some dogs with the condition, androgens appear to increase the degree of cystinuria^4-8.

Treating cystinuria

In treating cystinuria, the ongoing output of cystine into urine means that urolith removal is not likely to be curative. Studies also suggest that complete removal of cystine stones from the bladder is very difficult, even for experienced surgeons, with a proportion of stones left behind in 15% of cases⁴.

Dietary and medical management relies on reducing excretion of cystine into urine, and increasing solubility of any of that which remains (Panel 1)^4-8.

Monitoring success

The success of medical treatment can be monitored in many ways^4,7,8:

• Repeat urinalysis – aiming for pH more than 7.5, specific gravity (SG) less than 1.020 and haematuria may suggest new stone formation.
• Urine microscopy – to identify cystine crystals (Figure 5).
• Bladder imaging – cystine uroliths are not markedly radiopaque so ultrasound of the bladder is more useful for monitoring than plain radiographs. Regular scans can identify reforming of uroliths.
• Quantitative cystine analysis – urine cystine:creatinine ratio is the best quantitative test. Although readily available in the US, the author’s team found this harder to access in the UK. Laboklin in Manchester can analyse quantities of several amino acids in urine, including cystine, with the COLA test.

Treating Byrti

The complex nature of cystinuria means the treatment approach needs to be adjusted for each patient^4-8.

Following surgery, the author’s team started Byrti’s treatment plan (summary in Table 2). He was changed to Hill’s u/d diet, and urine pH and SG were monitored.

Table 2. Summary of Byrti’s treatment
Treatment	Details
Cystotomy	Initial management of urolithiasis and gave diagnosis of cystinuria
Hill’s u/d diet	Low protein, urine alkalinising diet
Potassium citrate supplement (75mg/kg twice daily)	Urinary alkaliniser to maintain urine pH consistently more than 7.5
Deslorelin implant	To remove androgen influence and assess if this reduced cystinuria
Increased water intake	Needed to reduce urine specific gravity to less than 1.020
Scrotal urethrostomy (and castration with scrotal ablation)	To reduce risk of repeat urethral obstruction (castration will reduce androgen-dependent cystinuria)
Phenoxybenzamine (0.5mg/kg twice daily) and dantrolene (1mg/kg twice daily; both off licence).	Urethral relaxants to manage urethral spasm post partial obstruction

Having found that his urine pH was not consistently above 7.5, the author’s team also added potassium citrate supplement as a urinary alkaliniser.

Byrti’s u/d diet was only available in a dried form (though it is now also available in wet as well) and, even with his owners adding extra water to his diet, the author’s team has found the urine dilution goal difficult to achieve. To assess whether his condition was androgen dependent, the author’s team sent urine for cystine:creatinine assay before using a deslorelin implant as a temporary chemical castration. The level of cystinuria was assessed again later on post-castration.

Cystine levels in urine had not reduced after castration showing that, unfortunately, Byrti’s condition was not androgen linked (Panel 2).

Despite medical management of his condition, Byrti had several further episodes of haematuria and showed evidence of some stones reforming in the bladder.

He went on to develop partial urethral obstruction, and was unable to void the urolith with the help of urethral relaxants phenoxybenzamine and dantrolene.

At this stage, surgical management was needed to relieve the obstruction and reduce risk of further obstruction.

Byrti underwent castration with scrotal ablation to allow a scrotal urethrostomy. The author’s team’s experiences with Byrti certainly highlighted the recurrent nature of this condition.

The author’s team hopes this surgery, along with continuing medical treatment and the benefits of castration, will allow Byrti to live comfortably with his condition.

If he continues with repeated episodes of urolithiasis, the next step in treatment would be to introduce a cystine binder, such as tiopronin.

This is available by prescription from human pharmacies for off-licence use, and has been found to have a beneficial role in the dissolution and prevention of uroliths in recurrent cases^4,6-8.

Studies suggest this drug is generally well tolerated in long-term use, but a small proportion of dogs developed side effects^6-8. The most notable adverse effects were mild proteinuria, aggression and myopathy, all of which stopped on cessation of the drug^6-8.

Several other drug therapies are being looked at for the future, to help both humans and dogs with this condition, but currently they are only in the early stages of research⁷.

Urate urolithiasis in Vince the Dalmatian

Vince is a two-year-old male, entire Dalmatian (Figure 6) presented with haematuria and dysuria in August 2021.

As he was showing significant difficulty in passing a stream of urine, the author’s team began investigations immediately.

A catheter was passed easily, suggesting no urethral obstruction, but bladder ultrasound revealed acoustic shadowing consistent with a large cystolith (Figure 2). This was shown to be radiolucent on plain abdominal radiography (Figure 7).

Removal of the urolith at cystotomy confirmed it to be of urate origin (Figure 8), prompting further research into the treatment options for Vince.

Causes of urate urolithiasis

Purine metabolism in the body produces uric acid. This is usually removed from the bloodstream and metabolised by the liver into highly soluble allantoin^4,8.

Some dogs – particularly the Dalmatian and bulldog – have a genetic mutation that leads to the failure of transportation of uric acid into the liver cells^4,8.

As a result, high concentrations of poorly soluble uric acid are excreted in urine, leading to a risk of urolith formation^4,8. The same problem can be seen in portosystemic shunts due to a failure of urate delivery to the hepatocytes^4,8.

In the Dalmatian, the formation of uroliths is much more common in males, with females in one study only making up 3% of cases^3-5,8.

Treating urate urolithiasis

Identifying the cause of the hyperuricosuria is important to deciding on a treatment plan. Patients with a portosystemic shunt will need treatment of this condition, so it is important to assess bile acid levels in dog breeds other than the Dalmatian or bulldog^4,8.

As Vince was a Dalmatian, the author’s team’s research focused on methods to treat dogs with the genetically induced condition. Treatments are based around increasing the solubility of urate in the urine and reducing the excretion of uric acid (Panel 3)^4,8.

Medical treatment can be successful for dissolving bladder stones – in some cases within four weeks⁸.

One study showed full medical dissolution in 40% of cases, reduction in urolith size in 30% of cases and no change on 30%⁸. For cases with severe signs or urethral obstruction, surgical treatment is needed.

Monitoring treatment

Monitoring for success of dietary changes and for signs of recurrence is important^4,8.

• Urinalysis to check pH is more than 7, SG is less than 1.020 and to detect haematuria.
• Urine microscopy for urate crystals.
• Bladder imaging – urate stones are usually translucent so ultrasound is more useful than plain radiographs for detecting new cystoliths.

Treating Vince

Vince had significant dysuria due to his cystolith, so a cystotomy was needed to quickly alleviate his clinical signs.

Although he was previously on a Dalmatian-specific diet, his urine pH at diagnosis was 6.

Postoperatively, the author’s team started him on Hill’s u/d, which has managed to maintain urine pH of more than 7 and SG of 1.010. He is not currently on allopurinol.

The author’s team will continue to monitor his urine and carry out periodic bladder ultrasound scans.

Conclusion

The author’s team look forward to seeing Byrti and Vince for their monitoring visits as they are real characters. Byrti always insists on watching the screen during his ultrasound scans.

The author’s team hopes both dogs continue to cope with their conditions and that sharing their cases may help manage other similar patients.

• The author thanks the University of Minnesota Urolith Center and Hill’s Pet Nutrition for their resources, providing a wide range of information and support for treatment of these patients.
• Some of the drugs mentioned in this article are used under the cascade.
• This article was updated on 24 May 2022 to point out Hill’s Prescription Diet u/d Dog Food is available as wet and dried.