Canine and Feline Urolithiasis Updates and Challenges India F. Lane, DVM, MS, EdD, DACVIM Elizabeth M. Lennon, DVM, PhD, DACVIM The University of Tennessee College of Veterinary Medicine Urolithiasis - General Urolithiasis is common in both dogs and cats. Urolithiasis likely results from a constellation of predisposing factors that ultimately results in precipitation of excretory metabolites in the urine. These precipitates form crystals which can eventually aggregate into stones. The most common uroliths in dogs include struvite (magnesium ammonium phosphate), calcium oxalate, cystine, urate, and silica. The most common feline uroliths include feline calcium oxalate and struvite. In addition to being comprised solely of one type, uroliths can also be composed of multiple stone types, which is referred to as a compound stone. For example, the core of a urolith could be formed of calcium oxalate with a struvite urolith shell. The majority of uroliths are present in the urinary bladder at diagnosis (84%). Other sites include the urethra (7%), the kidney (3%), and less than 1% are present in the ureters, although that number has been increasing in recent years. Urine pH has a significant determining factor on the presence of uroliths. Certain uroliths form in acidic urine, while others form in more basic urine. Calcium oxalate, purine, cystine, silica, and calcium phosphate uroliths form in acidic urine, while infection-induced struvite stones form in basic urine. It is important to recognize that crystalluria (presence of microcrystals in the urine that are observed on urine sediment examination) is not abnormal. Normal individuals can have crystals present in their urine and this does not mean that this animal will form stones. Therefore, it is inappropriate to begin an animal on a prescription diet when crystals alone are noted. However, certain types of crystals can be of diagnostic significance – for example, if ammonium urate crystals are seen on urinalysis, this can be indicative of a portosystemic shunt or other hepatic abnormality. Updates – Urolith Types Struvite Uroliths Struvite uroliths, otherwise known as magnesium ammonium phosphate, are radioopaque stones that are often large in size and there may be many stones. They tend to have a smooth contour and are a variety of shapes. In dogs, struvite uroliths are most commonly infection-induced. Therefore, they occur more commonly in females. They tend to be more common in young adult animals. In cats, struvite stones are most often sterile. They occur equally in males and females, and because they tend to form in alkaline urine, they are associated with a high protein diet. Infection-induced struvite uroliths occur secondary to urease producing bacteria. These bacteria contain the enzyme urease, which cleaves urea, as a survival mechanism to be able to live in the unfavorable environment of urine. Staphylococcus are the most common urease-producing bacteria that results in urinary tract infection in dogs, but other bacteria such as Proteus, Klebsiella, Pseudomonas, Corynebacterium, and Ureaplasma can produce urease as well. The urease enzyme cleaves urea into ammonia, bicarbonate, and carbonate ion. The bicarbonate and ammonia that is produced are responsible for increasing urine pH, and the ammonia is one of the components of the urolith. Treatment of struvite uroliths includes elimination of existing uroliths and treatment of urinary tract infection. This can be accomplished by surgical removal, minimally invasive techniques, or by medical dissolution through diet, modification of water intake, and treatment of a urinary tract infection if one is 328 present. If struvite uroliths are highly suspected, medical dissolution is often attempted first since it is a non-invasive method of control. Antibiotics that are appropriate for treatment of the UTI, based on culture, should be administered throughout the course of dissolution. Important components of dietary therapy of struvite uroliths includes a low protein diet to decrease the urinary ammonia, low magnesium, low phosphorus, acidifying diet (to cause acidification of the urine). A high salt diet may also be helpful to increase water intake and create more dilute urine, but this is unproven. The average time to medical dissolution of struvite uroliths is 8-10 weeks. During the dissolution period, the animal should be monitored every 4 weeks, with a urinalysis, culture, and radiographs performed. The urine specific gravity should be maintained at less than 1.015 in dogs and less than 1.035 in cats. Urine cultures should be considered, especially if the stones do not appear to be getting smaller. Treatment should be continued 2- 4 weeks past radiographic resolution, since some smaller stones may not be visible radiographically and could serve as a nidus for further stone growth if not completely dissolved. There are several potential complications of medical dissolution of struvite uroliths, including urethral obstruction, continuing urinary tract signs, side effects of the antimicrobial, failure to dissolve, and problems with the diet. Urethral obstruction can occur if the stones get to a size in which they can enter the urethra, so owners should be warned about the symptoms and emergent nature of urethral obstruction. If the animal was originally presented with lower urinary tract symptoms, these could continue for the duration of treatment. Long-term antibiotic treatment can have unwanted medication side effects. Struvite uroliths can fail to dissolve with medical dissolution, and the therapeutic approach should be reconsidered if the stones are not smaller in 4-6 weeks. Failure of dissolution can include owner noncompliance, persistent urinary tract infection, or a compound stone in which part of the stone is not a type can be dissolved. Lastly, some animals may have an intolerance to the diet. By nature, these diets tend to be high fat to replace the restricted protein, so could cause weight gain or potentially contribute to pancreatitis in a predisposed animal. Prevention of struvite uroliths includes controlling infection and factors that predispose to urinary tract infection, as well as increasing water intake to maintain more dilute urine that will not favor crystal formation. Calcium oxalate uroliths Calcium oxalate uroliths are increasing in incidence and comprise 40-50% of all uroliths. They are > 85% of all nephroliths and ureteroliths. Calcium oxalate uroliths are radiodense, usually small and round, and can have an irregular surface. There are often not more than a dozen stones. Increased calcium in the urine is a risk factor for calcium oxalate uroliths. This can result from 1) bone resorption of calcium, 2) hyperabsorption from the gastrointestinal tract, 3) hypercalcemia, or 4) renal leak calciuria, in which increased amounts of calcium are lost into the urine because of a defect in tubular resorption. Breeds that are predisposed to calcium oxalate urolithiasis include miniature Schnauzers, Lhasa apsos, Yorkshire terriers, and Bichon frises. In cats, Siamese and Ragdoll cats are predisposed. In cats, aciduria is a common finding. Crystals are not present in about half of patients with calcium oxalate uroliths. Cats often have chronic kidney disease concurrently. Treatment of calcium oxalate uroliths is limited to surgical or minimally invasive removal (see below). Medical dissolution is not effective. Urate uroliths Urate urolithiasis (ammonium urate) comprise 5-8% of all uroliths. They are composed of ammonium urate. Dalmatians have a strong genetic predisposition, and 60% of all urate uroliths occur in Dalmatians. English bulldogs are also predisposed. Urate uroliths are also more common in puppies less than one year. Urate uroliths can also occur secondary to liver disease and portosystemic shunt, so liver function should be investigated in animals that are found to have urate uroliths. Urate uroliths are usually 329 radiolucent, so contrast radiography or ultrasound is necessary to detect them. They are usually small, smooth, green or brown, and round, and multiple stones are often present. Dalmatians have defective transporters for uric acid, so they cannot reabsorb it in the proximal tubule and they cannot transport it to the liver for breakdown, so they end up with higher levels of uric acid in their blood and urine than other dogs. This results in increased risk of ammonium urate uroliths. Dogs with severe hepatic disease or portosystemic shunts are also at risk of formation of urate uroliths. Uric acid is normally broken down to allantoin in the liver, but if the hepatic enzyme uricase is not able to break this down, due to loss of hepatic mass or portosystemic shunt, increased uric acid in the serum and urine can result. In the case of portosystemic shunt, urate uroliths are usually seen prior to one year of age and other signs of portosystemic shunt are usually present (small breed dog, poor doer, +/- hepatic encephalopathy). Dogs with urate urolithiasis will usually have acidic urine on urinalysis. Urate or amorphous crystals may be present on urine sediment examination. Treatment of urate uroliths includes removal of the stones either through surgery, a minimally invasive approach, or by medical dissolution. Results of medical dissolution are variable. Roughly 1/3 will have complete dissolution, 1/3 will have partial dissolution, of which 50% are then small enough to retrieve nonsurgically, and the remaining 1/3 will have an increase in the size or number of stones. Medical dissolution