Canine Urolithiasis - The Merck Veterinary Manual

Canine Urolithiasis

Struvite Stones

Dissolution Protocol

Prevention Protocol

Calcium Oxalate Stones

Dissolution and Prevention Protocols

Silica Stones

The most common canine uroliths are magnesium ammonium phosphate, calcium oxalate, or urate; less common uroliths include cystine, silica, calcium phosphate, and xanthine.

Struvite Stones:

The most common urinary stones in dogs are composed of struvite. The mineral composition is mostly struvite (MgNH₄ PO₄•6H₂ O), but frequently, small amounts of carbonate-apatite and ammonium urate are present. In most cases, struvite uroliths form in association with urinary tract infections with urease-producing Staphylococcus or Proteus spp . Unlike in cats, in which they are frequent, sterile struvite uroliths rarely form in dogs. They have been detected in a family of English Cocker Spaniels, suggesting a genetic predisposition.

Struvite calculi removed from bladder

Struvite stone

Medical management involves dissolution and prevention of stone formation. In both instances, the aim of treatment is to reduce the concentrations of NH4+, Mg²⁺ , and PO4-3 in urine. For dissolution, urine should be extremely undersaturated for struvite; for prevention, the degree of struvite saturation should be sufficiently low to make crystallization unlikely. The choice between surgery, lithotripsy, and medical treatment may not be easy. Owner compliance, the animal’s acceptance of the diet, availability of lithotripsy, practice philosophy, and knowledge of the indications and contraindications are necessary to make a decision. If stone dissolution is prolonged or fails, it may be more costly than surgical treatment. Surgical removal of uroliths is often incomplete, with small, hidden uroliths often inadvertently left in the urinary tract serving as a nidus for recurrence.

Before beginning stone dissolution by medical therapy, a physical examination, CBC, serum chemistry profile, urinalysis, urine culture and sensitivity, abdominal radiographs to document stone size, and blood pressure measurement (if possible) should be performed. Contraindications to stone dissolution include heart failure, edema, ascites, pleural effusion, hypertension, hepatic failure, renal failure, and hypoalbuminemia. Renal failure is not always a contraindication for dissolution of struvite nephroliths, however.

Dissolution Protocol:

While the use of urinary acidification to reduce urine pH <6 and other individualized dietary maneuvers may prove effective, a few commercially available diets that are generally nutritionally balanced promote struvite stone dissolution. Dogs fed these rations generally have reduced intake of protein, phosphate, and magnesium and a high intake of sodium. This results in osmotic diuresis, reduced daily urea output, and enhanced urine volume. The low urinary urea concentration is one of the most important features of such diets and also reduces ammonia production by the action of urease-producing bacteria. No other food, including treats, should be fed, and adequate fresh water should be available at all times.

Urease-producing urinary tract infections must be treated. The choice of antibacterial should be based on sensitivity testing when possible. Most Staphylococcus and Proteus infections are sensitive to levels of amoxicillin or ampicillin achieved in the urine of normal dogs. A urease inhibitor can be given but is not usually necessary. Concurrent treatment with a urease inhibitor such as acetohydroxamic acid enhances the rate of struvite stone dissolution, particularly when antibiotic resistance precludes effective antibacterial sterilization of the urine. A reasonably safe dose of acetohydroxamic acid appears to be 12.5 mg/kg, PO, bid. A reversible, mild hemolytic anemia has been seen in dogs given higher doses.

After ~4 wk of treatment, a physical examination, serum chemistry profile, urinalysis, and abdominal radiographs or ultrasonography should be repeated. The stone dissolution protocol should be discontinued if severe side effects develop, although a mild degree of hypoalbuminemia is to be expected and can be tolerated. With good compliance, the following results can be anticipated: urine pH <6.5; urine specific gravity <1.025; serum urea <10 mg/dL. The radiographic stone size should be compared with the size on previous radiographs. Routine testing should be repeated every 4 wk until 4 wk after the stone is no longer visible radiographically; this generally takes 8-12 wk but may take up to 20 wk. Stones that fail to reduce in size after 8 wk of treatment are probably not composed of struvite and should be treated another way, although failure could also result from poor treatment compliance. Renal stones tend to dissolve more slowly than bladder stones.

The recurrence rate after surgical treatment of struvite uroliths has been reported to be ~20-25%, with most recurrences within 1 yr. When surgery is performed to remove multiple small struvite calculi, removing all stone material is often difficult. In such cases, a 4-wk dissolution protocol starting at the time of suture removal aids in preventing recurrence due to residual crystalline material. Once the urinary tract is free of stones, prevention strategies are much more likely to be successful.

Prevention Protocol:

The key to prevention of recurrence in animals with a struvite stone associated with infection is achieving and maintaining sterile urine. Routine testing of urine pH by the owner is important. If fresh urine is alkaline, a urinalysis and culture should be done, and the dog treated appropriately if an infection is present.

Once stone dissolution is completed, a prevention program can be considered. The aim is to prevent urinary tract infections with urease-producing microbes. The concentration of major struvite solutes in urine should also be reduced. A commercially available diet may be fed to lower urinary phosphate and magnesium and to maintain an acidic urine. Urease-producing infections should be eliminated, after which owners should regularly check the pH of the first voided urine in the morning after an overnight fast; in most dogs on a normal diet, the urine will be acidic. Checking urine pH weekly is sufficient.

Calcium Oxalate Stones:

Calcium oxalate uroliths have been increasing in frequency in dogs. While they may develop in any breed, Miniature Schnauzers, Lhasa Apsos, Yorkshire Terriers, Bichon Frise, Shih Tzus, and Miniature Poodles may be predisposed. Most affected dogs are 2-10 yr old. Hypercalciuria leading to calcium oxalate stone formation can result from increased renal clearance of calcium due to excessive intestinal absorption of calcium (absorptive hypercalciuria), to impaired renal conservation of calcium (renal leak hypercalciuria), or to excessive skeletal mobilization of calcium (resorptive hypercalciuria).

Absorptive hypercalciuria is characterized by increased urine calcium excretion, normal serum calcium concentration, and normal or low serum parathormone concentration. Because absorptive hypercalciuria depends on dietary calcium, the amount of calcium excreted in the urine during fasting is normal or significantly reduced when compared with nonfasting levels. Renal leak hypercalciuria has been recognized in dogs less frequently than absorptive hypercalciuria. In dogs, renal leak hypercalciuria is characterized by normal serum calcium concentration, increased urine calcium excretion, and increased serum parathormone concentration. During fasting, these dogs do not show a decline in urinary calcium loss. The underlying cause of renal leak hypercalciuria in dogs is not known. Resorptive hypercalciuria is characterized by excessive filtration and excretion of calcium in urine as a result of hypercalcemia. Hypercalcemic disorders have been associated only infrequently with calcium oxalate uroliths in dogs.

Routine laboratory determinations should include serum calcium, phosphate, total CO₂, and chloride to eliminate the possibility of hyperparathyroidism and renal tubular acidosis. Dissolution of calcium oxalate stones by medical means has not been established at present. Treatment requires surgical removal or lithotripsy followed by preventive strategies.

Prevention Protocol:

Recurrence is a major problem with calcium oxalate uroliths. An “ideal” diet is considered to be low oxalate, low protein, and low sodium, and would maintain urine pH at 6.5-7.5 and urine specific gravity <1.020. A few commercially available canned foods achieve these goals and may minimize the risk of recurrence. Potassium citrate may be added as needed to assure the urine pH is within the desired range; water may be used to provide appropriate reduction in urine concentration. If these urine conditions are achieved and calcium oxalate crystals are still observed in warm, fresh urine, then vitamin B₆ and/or thiazide diuretics can be considered (although of unproven efficacy). Effectiveness of therapy should be reevaluated at 1- to 4-mo intervals by urinalysis. Chlorothiazide diuretics may also be of value.

Urate Stones:

Ammonium urate stones are most common in Dalmatians and in dogs with congenital portosystemic vascular shunts. The formation of ammonium urate calculi depends on the urine concentrations of urate and ammonium and on other poorly understood factors. Dalmatians fail to convert most of their metabolic urate to allantoin and thus excrete the bulk of nucleic acid metabolites as relatively insoluble urate. The biologic mechanism responsible for decreased hepatic conversion of urate to allantoin lies not in reduced uricase activity, but in reduced hepatic transport of urate; the rate of urate hepatic transport is about 3 times faster in breeds other than Dalmatians. The net result is only 30-40% of urate is converted to allantoin in Dalmatians compared with ~90% in other breeds.

Urate bladder stones, Dalmatian

Urethral calculi, Dalmatian

Dalmatians fed a diet high in animal protein excrete a net acid load in the urine, and urinary ammonium output is subsequently increased. The combined high concentration of ammonium and urate in urine increases the risk of formation of ammonium urate stones. The excretion of acidic metabolites of an animal protein diet is believed to be important in this process because urinary ammonium excretion is enhanced and ammonium urate is insoluble. Urate output has been reported to be the same in Dalmatians that form stones and in those that do not, although in some studies the methods used to determine urine uric acid concentrations were unreliable; ammonium output has not been determined. In dogs with a portosystemic vascular anastomosis, increased urinary ammonium output may partially be due to the increased filtered load of ammonia, because plasma levels of ammonia tend to be increased.

Dissolution Protocol:

Urine alkalinization minimizes renal ammonia production; the goal is to achieve a urine pH >7. If required, urine alkalinization can be achieved by administering NaHCO₃, 1 g (1/4 tsp)/5 kg, PO, tid, with food. Potassium citrate, administered to effect (25-50 mg/kg/day) is an alternative, more palatable alkalinizing agent.

Urinary urate output should be reduced. This can be accomplished by feeding a low purine, low-protein commercial diet. In addition, the xanthine oxidase inhibitor allopurinol (15 mg/kg, PO, bid) may be administered to ensure the nucleic acid metabolite load is excreted as a combination of xanthine, hypoxanthine, uric acid, and allantoin, rather than almost entirely as urate. However, the effectiveness of allopurinol in reducing urinary urate output is variable, and urinary urate levels should be measured (although this may be difficult). Allopurinol must be used cautiously in dogs with hepatic disease or primary renal failure because it is metabolized to its active form in the liver and is excreted via the kidneys. It is important that diets high in purines not be fed to dogs receiving allopurinol because xanthine uroliths may result.

Urine volume should be increased to reduce the concentration of all dissolved solutes in urine. This can be achieved by feeding canned diets restricted in protein. By reducing formation of urea, renal medullary urea concentration declines, interfering with the countercurrent system of urine concentration. Adding salt, 1 g (1/4 tsp)/5 kg, daily to the diet, or mixing water with the food are additional methods. Salt should not be given to animals with hypertension but otherwise poses little risk in normotensive dogs without chronic kidney disease, proteinuria, or hypoalbuminemia.

Prevention Protocol:

Prevention strategies aim to reduce the concentration of ammonium and urate in urine to levels unlikely to induce flocculation.

A low-protein, low-purine diet should be fed to reduce urinary urate output. Alkalinization should be used as needed to ensure alkalinuria. Treatment with allopurinol (10 mg/kg, PO, sid) can be considered. Ideally, allopurinol is not needed as a supplement to dietary management; however, if urate crystals persist, a low maintenance dose of allopurinol is appropriate.

These dissolution and prevention strategies were developed for use in Dalmatians in which hepatic conversion of urate to allantoin is reduced, but the liver is otherwise normal. They may not be safe for use in dogs with portosystemic vascular shunts. Such dogs tend to develop hypoalbuminemia, edema, and ascites when fed a low-protein diet. The safety of allopurinol in these dogs has not been established. In addition, alkalinization can predispose to hepatic encephalopathy because of increased GI absorption of dietary protein metabolites.

Cystine Stones:

Stones composed almost entirely of cystine form in dogs that have a renal tubular amino acid reabsorption defect known as cystinuria. Healthy dogs demonstrate 97% fractional reabsorption of cystine, while affected dogs excrete a much greater proportion of the filtered cystine load and may even exhibit net cystine secretion. Cystine is a relatively insoluble amino acid; therefore, in high concentration it may precipitate and form stones. Despite excessive urinary loss of cystine in cystinuric dogs, plasma cystine levels remain the same as in healthy dogs; in fact, the only morbidity or mortality associated with the inherited defect of cystine reabsorption is the sequela of urolith formation. Identification of cystine crystals by urinalysis indicates the dog is at risk of forming cystine uroliths. For poorly understood reasons, not all cystinuric dogs develop uroliths. However, the absence of uroliths does not preclude their future development, and preventive measures are indicated.

Cystinuria is thought to be inherited as a sex-linked trait. However, in Newfoundlands it is transmitted as a simple autosomal recessive trait. The defect has also been reported in Dachshunds, Basset Hounds, English Bulldogs, Chihuahuas, Yorkshire Terriers, Irish Terriers, and mixed-breed dogs. Except for Newfoundlands, cystinuria has been recognized almost exclusively in male dogs. A urine cystine concentration of >75 mg/g creatinine in nonfasted dogs is predictive of susceptibility to cystine urolithiasis.

Cystine solubility depends on urine pH, with solubility increasing rapidly when urinary pH is >7.5. Dogs fed meat-based diets tend to excrete acidic urine, which leads to urine cystine supersaturation.

Cystinuria is a lifelong defect of tubular reabsorption and cannot be cured. Cystine stones tend to recur within 1 yr without management to prevent recurrence, and they often recur despite attempts at prevention.

Dissolution and Prevention Protocols:

Urinary cystine output should be reduced. Protein-restricted alkalinizing diets have been associated with reducing the size of cystine urocystoliths. Urinary cystine concentration can also be reduced by administering N-(2-mercaptoproprionyl)-glycine (2-MPG, tiopronin) or penicillamine. 2-MPG should be given at 15-20 mg/kg, PO, bid, for dissolution, and at 10-15 mg/kg, PO, bid, for prevention. Penicillamine (15 mg/kg, PO, bid) can be substituted for 2-MPG; unfortunately, ~40% of dogs treated with penicillamine exhibit anorexia and vomiting. The vomiting may be partially resolved by giving the medication with meals; however, a severe reduction in dosage or complete withdrawal is often necessary.

The urine should be alkalinized to a pH >7.5. Sodium bicarbonate added to the diet at 1 g (1/4 tsp)/5 kg, tid, readily accomplishes this, but because sodium supplementation may enhance cystinuria, potassium citrate (20-75 mg/kg, PO, bid) is preferred.

Urine volume can be increased by mixing water with the food. Salt should not be added to the diet because increased sodium excretion may cause increased cystine excretion. Provided urine volume is adequate and the urine pH is maintained above 7.5, most cystinuric dogs will pass urine that is only slightly supersaturated or undersaturated for cystine. Under such conditions, only relatively small doses of 2-MPG or penicillamine may be necessary to achieve 24-hr undersaturation.

Silica Stones:

Early reports indicated a predominance of silica stones in German Shepherds, but many breeds have now been implicated. Urethral obstruction in males is the most common presenting problem, but signs similar to those associated with other types of uroliths also may be noted. The mean age at occurrence is ~6 yr. The stones are usually multiple and develop in the bladder and urethra. Silica uroliths are radio-opaque. They frequently, but not always, have a characteristic “jack-stone” appearance. Identification requires spectrographic analysis and cannot be made with kits for qualitative stone analysis.

The role of diet in spontaneously occurring silica urolithiasis has not been determined, although plants are often an abundant source of silica. If the diet of an affected dog is known to be high in silica, or if silica urolithiasis has been recurrent, a dietary change should be recommended. Only general management principles can be suggested for silicate urolithiasis. Additional salt and/or water should be added to the diet to induce diuresis and to lower the urine solute concentration. When present, urinary tract infections should be eliminated. Diets high in plant proteins should be avoided.