Managing urolithiasis (Proceedings)

Epidemiology

The majority of uroliths submitted for analysis are retrieved from the lower urinary tract (primarily bladder, occasionally urethra). Upper urinary tract uroliths (kidney and ureter) are increasing in frequency in cats, although these stones are retrieved and submitted less often, so it is difficult to know the exact incidence of occurrence.

The majority of submitted stones (80-90%) are calcium oxalate or struvite. In cats, the proportions of calcium oxalate and struvite uroliths from the bladder are approximately equal. Upper urinary tract uroliths are almost always calcium oxalate in cats. In female dogs, stones retrieved from the bladder are usually struvite. In male dogs, calcium oxalate uroliths are the predominant bladder urolith. There are breeds predisposed to producing certain urolith types. Upper urinary tract uroliths in dogs are equally split between calcium oxalate, struvite, and other types.

Urate uroliths are uncommon, except in the Dalmatian breed and dogs with portosystemic shunts. English bulldogs, Yorkshire terrier, Miniature Schnauzers, Shih tzus, Russian black terriers, and Siamese cats have an increased incidence of urate urolithiasis. English bulldogs, Newfoundlands, Mastiffs, and Staffordshire Bull Terriers are predisposed to cystine urolithiasis.

Diagnosis

Signs of lower urinary tract uroliths include pollakiuria, dysuria, stranguria, and hematuria. These signs cannot be distinguished from signs of other lower urinary tract diseases, including neoplasia, urinary tract infection, idiopathic cystitis, etc. Signs of upper urinary tract infection may include signs from uremia if obstructive nephropathy is present. Abdominal pain is not commonly reported with ureteroliths, but may occur more commonly than is recognized.

Calcium oxalate and struvite uroliths are generally radioopaque, whereas urate and cystine are variably radiolucent. Uroliths generally need to be at least 3 mm to be detected by survey radiography. The false negative rate for detecting uroliths for survey radiography is 13%. Double contrast cystography decreases the false negative rate to 4.5%, and can detect radiolucent uroliths. Abdominal ultrasonography is also a good method for detecting both radioopaque and radiolucent uroliths, with a false negative rate of 3.5%. Excretory urography may be needed to identify upper urinary tract uroliths and determine if they are obstructing urine flow.

Urinalysis may provide clues to the mineral content. Struvite uroliths are more likely to form in alkaline urine; calcium phosphate in alkaline to neutral urine; calcium oxalate and silica in neutral to acidic urine, and urate, xanthine, cystine, and brushite in acidic urine. Crystals in the urine sediment must be evaluated within 6-8 hours of collection or the results may be misleading. Blood tests may provide some information about etiology, such as the association of hypercalcemia with calcium oxalate uroliths.

Methods of Removal

Nephroliths are common in cats with chronic kidney disease, affecting about 50% of cats with CKD. They do not seem to accelerate progression of CKD and do not need to be removed in all cases. Reasons for removal of nephroliths and ureteroliths include obstruction to urine flow, progressive deterioration in renal function, recurrent urinary tract infection, or enlargement despite preventative measures. Cystic calculi are generally removed by some method. Physical removal of cystic calculi provides benefits including rapid resolution, definitive diagnosis of urolith type (via quantitative urolith analysis) and reduced risk of urinary obstruction. In asymptomatic patients, removal of cystic calculi is not mandatory, particularly if there are relative contraindications to anesthesia or surgery. Ureteroliths should always be removed (or flushed retrograde into the bladder).

Struvite, urate, and cystine stones can be dissolved with medical therapy. Calcium oxalate and calcium phosphate stones cannot be dissolved.

There are a variety of non-surgical methods of urolith removal. Small stones may be removed by aspiration through a large urethral catheter. Although this method is unlikely to completely remove all calculi, it may provide calculi for analysis to direct future therapy. Voiding urohydropropulsion attempts to flush calculi out through the urethra. By holding the animal in a vertical position, uroliths settle to the neck of the bladder, and the force of expressing the bladder may flush the calculi out. This technique is best for small stones in female patients. Retrograde hydropulsion does not remove uroliths, but can flush a urolith in the urethra back into the bladder for easier surgical removal. All of these techniques can be performed with minimal equipment in a sedated patient. However, they are limited to addressing small stones.

Slightly larger uroliths may be able to be removed with a basket forceps with cystoscopy. Laser lithotripsy can fragment uroliths into pieces small enough to be aspirated or flushed through the urethra. The laser is placed in direct contact with the urolith with cystoscopic guidance.

Extracorporeal shock-wave lithotripsy can fragment nephroliths or ureteroliths into pieces small enough to pass through the ureter. Recent advances in technology now allow this technique to be used in cats with less renal damage than previously. Because of the risk of fragments of nephroliths obstructing the ureter, percutaneous nephrolithiotomy may be a better technique for very large nephroliths. This technique involves placing the cystoscope (laparoscope) sheath directly into the renal pelvis percutaneously, inserting the lithotripsy probe (laser or ultrasound) to fragment the nephrolith, and aspirating the fragments rather than having them pass though the ureter. These techniques require general anesthesia and are currently limited in availability.

Surgical techniques to remove uroliths include cystotomy, permanent urethrostomy or temporary urethrotomy, ureterotomy or ureteral resection and reimplantation (for distal ureteroliths), and nephrotomy or pyelotomy.

Cystotomy is a common surgery in small animal practice, and may be a more expedient method of removing a large stone burden than laser lithotripsy or other non-surgical techniques. In dogs that are recurrent stone formers (such as male Dalmatians), a permanent urethrostomy may allow small stones to pass rather than causing obstruction. Ureterotomy in cats generally requires either an operating microscopy or magnifying loupes because of the small diameter of the cat ureter. Nephrotomy causes a 10-20% decrease in long-term renal function in healthy kidneys, and thus pyelotomy would be preferred if the renal pelvis is sufficiently dilated to allow the procedure.

Calcium Oxalate Uroliths

Calcium oxalate uroliths increased over the past 20 years, and seem to have reached a plateau in the past 2 years. Speculative reasons for this change in incidence in cats include changes in diet formulations, as acidifying feline diets were in widespread use until the past few years. In dogs, perhaps more dogs with struvite uroliths are being managed with medical dissolution protocols without collecting and submitting the uroliths for analysis, thus skewing the ratio of calcium oxalate to struvite.

Certain breeds are predisposed to developing oxalate uroliths (Standard Schnauzer, Miniature Schnauzer, Lhasa Apso, Jack Russell Terrier, Papillon, Yorkshire Terrier, Bichon Frise, Keeshond, Pomeranian, Samoyed, Shih Tzu, Chihuahua, Cairn Terrier, Maltese, Miniature and Toy Poodle, West Highland White Terrier, Dachshund, Ragdoll, British Shorthair, Foreign Shorthair, Himalayan, Havana Brown, Scottish Fold, Persian, and Exotic Shorthair). Certain diseases predispose to calcium oxalate urolith formation (hypercalcemia, hyperparathyroidism, and hyperadrenocorticism).

Calcium oxalate crystals are more likely to precipitate in acidic urine. These uroliths are the most radio-opaque and are likely to be apparent on survey radiographs if over 3 mm in diameter.

Calcium oxalate uroliths cannot be dissolved with medical therapy and therefore must be physically removed with methods described above.

Characteristics of a diet to prevent calcium oxalate uroliths include increased calcium, phosphorus, sodium, and potassium, moderate magnesium, and restricted carbohydrate. However, canned food to increase water intake is the most effective dietary measure. If diet alone is insufficient to prevent urolith recurrence and to keep the urine pH above 6.4 in cats and 7.0 in dogs, potassium citrate (40-75 mg/kg PO BID) can be administered. Thiazide diuretics (i.e., hydrochlorthiazide 2 mg/kg PO BID) can be used to decrease urinary calcium excretion. Despite these measures, calcium oxalate uroliths frequently recur within 3 years. Radiographic monitoring every 3 to 6 months may allow detection when uroliths are small and may be removed by non-surgical means.

Struvite Uroliths

Struvite uroliths in dogs are almost always caused by infection with urease producing organisms. Urease acts to convert urea into ammonia, bicarbonate and carbonate. Ammonia is one component of struvite, with phosphate and magnesium contributed by diet. Alkaline urine increases struvite crystal precipitation, followed by aggregation into a calculus. The most common urease-producing organisms in dogs are S. intermedius, Proteus spp., and occasional strains of Pseudomonas, Klebsiella, or E. coli. Female dogs are 15 times more likely to have struvite uroliths than male dogs. This may be a reflection of the propensity for female dogs to develop urinary tract infection. Struvite uroliths in cats are usually sterile.

Struvite uroliths are radio-opaque. They are frequently smooth, round or pyramidal, and may be large. Uroliths over 1 cm in diameter are usually struvite. Alkaline urine increases suspicion of struvite urolithiasis and urinary tract infection.

Medical therapy effectively dissolves struvite uroliths. Restricted protein, sodium supplemented diets help decrease ammonia production from protein metabolism while diluting urinary calculogenic materials by sodium dieresis. In dogs, antibiotic therapy is necessary during the entire dissolution period, as bacteria and mineral are layered together during urolith formation, and entrapped bacteria are released as the outer mineral layers dissolve. Therapy should be continued for one month past radiographic resolution because uroliths smaller than 3 mm are unlikely to be detected. Dissolution in dogs is dependant on urolith size, with smaller uroliths dissolving faster due to a relatively larger surface area. Average time for dissolution in dogs is about 3 months. Struvite uroliths in cats tend to dissolve faster, with an average dissolution time of 1 month.

Prevention of struvite uroliths in dogs is based on eradication of urinary tract infection, which may involve correction of any predisposing causes. Surveillance and early treatment of infection before uroliths form is also prudent. Because struvite uroliths in dogs are caused by infection, dietary therapy is of minimal benefit. In cats however, diet has been considered the main method of prevention. The target urine pH is around 6.3 to decrease struvite precipitation without excessive acidification that might promote calcium oxalate precipitation. Clinical data is still needed to determine the optimal diet composition, although several diets promoted to decrease formation of both struvite and calcium oxalate uroliths in cats are available (Royal Canin Urinary SO Formula, Hill's C/D Multicare).

Urate Uroliths

Purine uroliths include urate and xanthine. Dalmatians are predisposed to urate formation. Purine from protein metabolism is metabolized to hypoxanthine. Hypoxanthine is then converted to xanthine then uric acid. Most mammals convert uric acid to allantoin for excretion in the urine. Uric acid is poorly soluble. Dalmatians excrete large amounts of uric acid in the urine due to a defect in conversion of xanthine to uric acid (from decreased transport into the hepatic cells for biotransformation) and a defect in uric acid reabsorption in the renal tubules. Although both male and female Dalmatians have the genetic problem, clinical disease is far more common in male Dalmatians, affecting 25-33% of them. This is likely due to anatomic differences, in that the shorter wider urethra of female dogs may allow passage of the generally small urate uroliths, whereas the narrow urethra of male dogs increases the risk of obstructive disease.

English Bulldogs are also predisposed to urate urolithiasis. Hepatic disease, most notably portosystemic shunts, also predispose to urate urolithiasis. Evaluation of hepatic function (usually with bile acid determination) is recommended for any animal other than Dalmatian with urate crystals or uroliths. Cats rarely get urate uroliths.

Urate uroliths can be dissolved medically. A diet restricted in purines (protein-restricted) is the foundation of therapy. Allopurinol (15 mg/kg PO BID) inhibits xanthine oxidase, thus decreasing conversion of xanthine to uric acid. Dissolution usually takes about 3 months. Hill's U/D diet can be used for long-term therapy and may be sufficient to prevent urate urolith formation. If diet does not substantially decrease urinary uric acid excretion, allopurinol (10 mg/kg PO SID to BID) can be used for long-term preventive therapy. Allopurinol should be used only in conjunction with a restricted purine diet to decrease the risk of xanthine urolith formation.

Dilated cardiomyopathy has been reported in English Bulldogs on a purine-restricted diet. Carnitine and taurine deficiencies can develop due to the combination of decreased intake and increased urinary loss and are presumed to play a role in the development of cardiac disease.

Cystine Uroliths

Cystine uroliths are most common in English Bulldogs, Dachshunds, Mastiffs, Basset Hounds, and Newfoundlands. In the Newfoundland, cystinuria is inherited in a simple autosomal recessive pattern. Other amino acids are present in the urine of cystinuric dogs, but the pattern of amino acid loss is variable. Cystine uroliths are variably radiolucent. They can be dissolved with a combination of low protein diet (i.e., Hill's U/D), N-(2-mercaptopropionyl)-glycine (2-MPG, Thiola), and urinary alkalinization (i.e., potassium citrate).

Silica Uroliths

Breeds predisposed to silica uroliths include German Shepherds, Yorkshire Terriers, Shih Tzus, Lhasa Apsos, Golden Retrievers, Miniature Schnauzers, and Old English Sheepdogs. Most silica uroliths have a jackstone appearance. There is no method to dissolve these uroliths.