Page 1192 - Clinical Small Animal Internal Medicine

1130 Section 10 Renal and Genitourinary Disease

Epidemiology and Risk Factors Epidemiology
VetBooks.ir prising only 0.3–0.6% of uroliths submitted to the MUC the prevalence of cystine urolithiasis. In the USA, urolith
Geographic location of the dog or cat plays a large role in
Pure calcium phosphate uroliths are rare in dogs, com­
prevalence has been reported as 1–2%. This is in con­
per year and 2% of uroliths submitted to the CVUC (see
Table 123.2). Most calcium phosphate uroliths are mixed trast to parts of Europe where cystine urolithiasis has
in composition and are predominantly (≥70%) struvite or been reported as 8% in Sweden and 26% in central Spain.
calcium oxalate. Mixed stones are very common in cats In Canada, cystine uroliths submitted to the CVUC rep­
and dogs. resented 0.6% and 0.1% of all canine and feline stones,
Risk factors for these uroliths vary based on stone con­ respectively, between 2009 and 2012 (see Table 123.2).
tent and sex, as pure hydroxyapatite uroliths occur Risk factors for cystine urolithiasis in dogs include age,
slightly more in male dogs (52%) than female dogs (48%) breed, and sex. Most affected dogs are males (98%),
whereas with brushite uroliths, male dogs (75%) are although the disease is not genetically sex linked, and
more commonly affected than female dogs (24%). young to middle‐aged (3–8 years). The exception to
these risk factors is the Newfoundland breed, where
Etiopathogenesis these stones occur in both genders and often at a younger
Several factors may influence urine calcium phosphate age. Newfoundland dogs also appear to have an increased
saturation including urine concentration of calcium and incidence of cystine nephroliths.
phosphate, urine pH, and the presence or absence of Breed predisposition has varied widely over the last
inhibitors of calcium phosphate crystal formation. 15 years and urolith risk may depend on the dog’s geo­
Alkaline urine pH decreases the solubility of hydroxyapa­ graphic location. Unfortunately, most studies do not
tite and likely contributes to calcium phosphate uroliths. compare breed distribution to the national registry for
Excessive urinary excretion of calcium (hypercalciuria) dog breeds, nor are dog health insurance numbers,
and phosphate (hyperphosphaturia) may also induce cal­ which have provided the information for these studies,
cium phosphate urolith formation. common everywhere. Bull mastiff, Scottish deerhound,
Co‐morbidities such as primary hyperparathyroidism English bulldog, Newfoundland, Chihuahua and dachs­
and hypercalcemia may influence stone formation, and hund are the most common breeds affected in North
up to 30–40% of dogs with primary hyperparathyroidism America, while terrier breeds (Yorkshire, Jack Russell,
present with calcium‐containing uroliths. However, and West Highland white) are the most affected in
hypercalcemic cats are more likely to have calcium oxa­ the UK.
late rather than calcium phosphate uroliths.
It has been reported that some dogs with urinary tract Etiopathogenesis
hemorrhage can develop blood clots mineralized with In normal dogs, cystine is freely filtered at the glomeru­
calcium phosphate. These stones are not considered true lus and then actively reabsorbed in the proximal tubules.
calcium phosphate uroliths as they do not contain the Cystinuria is a limited hereditary renal transport disorder
same matrix proteins or ultrastructure as typical calcium involving cystine and the dibasic amino acids ornithine,
phosphate uroliths. lysine, and arginine, collectively known as COLA.
Instead of the normal >99% reabsorption in the proximal
renal tubules, these amino acids are lost in the urine;
Cystine Urolithiasis
however, only cystine causes a problem. In cystinuric
Dogs that develop cystine uroliths excrete an increased patients, the carrier proteins responsible for reabsorp­
amount of cystine (and to a variable extent other amino tion are defective. The type of amino acids lost and their
acids) in their urine, a condition called cystinuria. quantity vary depending on the case. The low solubility
Cystine is composed of two cysteine amino acid mole­ of cystine in acidic urine predisposes to the formation of
cules linked by a disulfide bond. Urine solubility of cys­ cystine crystals and uroliths in the urinary tract.
tine is low, and dogs with cystinuria are predisposed to Cystinuria in humans and dogs is classified into several
urolith formation. distinct types depending on age of onset, severity, sex,
Canine cystine uroliths are typically pure, but a few inheritance, and mutant gene. In dogs, type I‐a cystinu­
contain struvite, urate, silicate, oxalate or calcium apa­ ria is an autosomal recessive disease caused by a SLC3A1
tite. Typically, urolith appearance is smooth, oval and gene mutation common in the Newfoundland, Landseer,
light yellow to reddish‐brown. The size of cystine uro­ and Labrador retriever breeds.
liths varies, but small and multiple stones are common. A nonsense mutation in exon 2 of the SLC3A1 (amino
The cystine uroliths submitted to urolith centers have acid – aa‐transport) gene has been identified as a
usually been retrieved from the LUT. molecular basis of the defect but the underlying genetic