Feline nephroliths and ureteroliths (Proceedings)

Nephroliths are uroliths (calculi) located in the renal pelvis and/or collecting diverticula of the kidney and ureteroliths are calculi located in the ureter. Although only 5 to 7% of all feline uroliths submitted to stone centers for analysis are nephroliths, the true incidence of nephroliths may be higher because many animals with nephroliths are asymptomatic. Also because removal of uroliths from the upper urinary tract is inherently more difficult, nephroliths and ureteroliths are less likely to be submitted to stone centers than are lower tract uroliths. Furthermore, nephroliths are an important clinical problem because of their potential complications. Nephroliths may obstruct the renal pelvis or ureter, may predispose to pyelonephritis, and may result in compressive injury of the renal parenchyma leading to renal failure. Nephroliths may be considered "inactive" if they are not causing any complications. Inactive nephroliths may not require removal, but they should be monitored periodically by urinalysis, urine culture, and radiography. Indications for removal of nephroliths in cats include obstruction and recurrent infection. We have observed spontaneous retrograde movement of ureteroliths five cats. Furthermore, we have also documented uroliths moving from the renal pelvis into the proximal ureter, and back into the renal pelvis in some animals. This observation indicates that even so-called 'inactive' nephroliths may cause intermittent obstruction and subsequent renal injury.

Calcium oxalate was the most common composition (70.5%) of feline nephroliths and ureteroliths submitted to the Minnesota Urolith Center, followed by matrix (8%), struvite (8%), calcium phosphate (4.5%), compound (5%), purine (2%), and mixed (2%).7 Feline ureteroliths are much more common than 20 years ago. One study showed a 50-fold increase in the frequency of calcium oxalate uroliths in the upper urinary tract of cats from 1981 to 2000.

Clinical Signs

Many dogs and cats with nephroliths are asymptomatic and the nephroliths are diagnosed during work up of other problems. Clinical signs noted in some patients include hematuria, recurrent urinary tract infection (UTI), vomiting, abdominal or lumbar pain (uncommon), and uremia due to either bilateral ureteral obstruction or progressive renal injury resulting in renal failure. Cats with ureteroliths may also present with acute or chronic renal failure. Ureteroliths may be bilateral at the time of presentation, or one kidney may be non-functional from prior ureteral obstruction when a subsequent ureterolith obstructs the contralateral kidney.

Diagnosis

Radiodense nephroliths and ureteroliths are usually diagnosed by abdominal radiography. Ultrasonography or excretory urography may be used to confirm the presence, size, and number of nephroliths and ureteroliths; however, ultrasonographic confirmation of ureteroliths is not always possible. Cats with ureteral obstruction may have poor excretion of dye during excretory urography and identification of the cause of ureteral obstruction may be facilitated by antegrade pyelography via nephropyelocentesis. In cats, mineralization of the renal pelvis and/or collecting diverticula must be differentiated from true nephrolithiasis. Sometimes this distinction is difficult to definitively determine. Definitive identification of nephrolith mineral type requires quantitative analysis of nephroliths or nephrolith fragments,although nephrolith composition can frequently be predicted on the basis of signalment, radiographic appearance, and urinalysis findings.

Urinalysis results from cats with nephroliths or ureteroliths may reveal hematuria and crystalluria. Crystal identification and urine pH may be helpful in predicting nephrolith composition. Pyuria and bacteriuria may be noted in patients with concomitant UTI. Urine culture should be performed on urine obtained by cystocentesis from all cats with nephrolithiasis or ureteroliths. Serum chemistry profile and CBC may indicate systemic abnormalities that have resulted from or contributed to nephrolithiasis. An inflammatory leukogram may be noted with concurrent pyelonephritis especially if ureteral obstruction is also present. Azotemia may be present with bilateral renal disease and/or obstruction. Hypercalcemia is occasionally noted as a predisposing factor to calcium oxalate urolithiasis.

Treatment

Treatment options for nephroliths include monitoring of inactive nephroliths, surgery, medical dissolution, and extracorporeal shock wave lithotripsy. Calcium oxalate, calcium phosphate and matrix nephroliths, the most common types of nephroliths in cats, are not amenable to dissolution. Ureteroliths are also not amenable to medical dissolution because they are not bathed in under-saturated urine. In veterinary medicine, the time-honored method of treatment of nephroliths has been surgical removal by nephrotomy or pyelolithotomy. In most dogs and cats, because the nephroliths are surrounded by renal tissue, nephrotomy is required. In one study, nephrotomy resulted in a 27 to 52% reduction in glomerular filtration rate (GFR) 3 weeks post surgery, which improved to 22 to 34% reduction in GFR 6 weeks post surgery. A more recent study neither intersegmental nor bisection nephrostomy adversely affected GFR. Percutaneous nephrolithomy is standardly used to remove large staghorn nephroliths in humans. Percutaneous nephrolithomy has been performed experimentally in dogs, and we have performed it once in an English Bulldog. However, given the small size of the renal pelvis in cats, this approach would be much more difficult in cats.

Temporary diversion of urine via nephrostomy tube placement may be used preoperatively and postoperatively to assist with management of ureteral obstruction in cats. Because the diameter of the ureteral lumen is only approximately 0.4 mm, even minor mucosal edema may cause ureteral obstruction after ureteral surgery, so urinary diversion via nephrostomy tubes is sometimes recommended. Movement or displacement of nephrostomy tubes can be minimized by using locking loop-design nephrostomy catheters. Although not commonly performed, percutaneous or surgical placement of nephrostomy tubes prior to prolonged surgery is useful to stabilize cats with severe uremia. Alternatively, placement of ureteral stents either via cystoscopy (female cats) or surgery may also be used to bypass obstructive ureteroliths. Ureteral stent placement is technically demanding and is not possible in every cat. Hemodialysis, if available, may be used prior to surgery to medically manage oliguric patients.

Medical dissolution protocols for cats are limited to struvite nephroliths which are unfortunately uncommon. Medical dissolution protocols should always include appropriate monitoring. Medical dissolution protocols for struvite nephroliths include a calculolytic diet (Prescription Diet Feline s/d, Hill's) and appropriate antibiotic therapy if UTI is present for the duration of therapy.2 Renal failure and obstruction are contraindications to medical dissolution of struvite nephroliths. Because nephroliths can move into the ureter as they dissolve, frequent monitoring with radiographs and ultrasound to monitor for obstruction from ureteroliths.

Microsurgical techniques have recently been used successfully to surgically remove ureteroliths in cats. Ureterotomy and primary closure of the ureter requires microsurgical expertise. For stones in the middle and distal ureter, some authors recommend transection of the ureter and reimplantation of the healthy proximal ureter into the bladder (ureteroneocystostomy). Other authors prefer to attempt ureterotomy for removal of ureteroliths regardless of location.

Extracorporeal shock wave lithotripsy (SWL) is fragmentation of uroliths using shock waves are generated outside the body. SWL uses repeated shock-waves to fragment the nephrolith into many small fragments that can pass spontaneously through the excretory system. Preliminary research with SWL in cats revealed that the shock wave dose must be reduced in cats compared to dogs to prevent shock wave induced injury to the kidney. Using the Dornier HM3, shock wave doses greater than 750 shock waves at an energy level of 13 kilovolts result in renal parenchyma injury and reduction in renal function. We have treated 5 cats with spontaneously occurring calcium oxalate ureteroliths and chronic renal failure. Four of these cats also had unilateral (1) or bilateral (3) nephroliths. We were only successful in SWL treatment of one of these 5 cats (complete resolution of the ureterolith). We were unsuccessful in the other four cats. Partial fragmentation of the nephroliths occurred in two of four cats. Serum creatinine concentrations were transient increased after SWL treatment in two cats. One additional cat had marked decline in renal function after SWL for greater than 1 month. Because of these poor initial results, we discontinued lithotripsy treatment of cats using the Dornier HM3.

Recent reports indicate that dry lithotriptors with small focal spots can be safely used to treat cats without compromising renal function. Treatment of normal cats with the Dornier MFL-5000 did not cause significant renal injury or renal functional problems.23 A few cats have been successfully treated by shock wave lithotripsy with dry lithotriptors.24 In an in vitro study, we demonstrated that feline calcium oxalate uroliths are significantly more difficult to fragment using SWL than canine calcium oxalate uroliths. Shock wave lithotripsy is unlikely to be as effective in cats as in dogs because the small diameter of the feline ureter requires that all fragments be fine sand. Even with sand-like fragments, ureteral obstruction is likely to occur in some cats. Therefore, more effective techniques are needed for removal of nephroliths and ureteroliths in cats.

Medical Management of Ureteral Obstruction

Conservative medical management by serial monitoring of ureteroliths along with administration of intravenous fluids and diuretics has been recommended provided there is minimal renal functional compromise and no infection, renal colic, or progressive ureteral dilation. Typically, dogs and cats with evidence of complete obstruction, worsening azotemia, or evidence of pyelonephritis should be treated by either surgical intervention or shock wave lithotripsy (SWL). Size and location of the ureterolith may help determine if intervention is required. In humans, up to 98% of ureteroliths < 5 mm in diameter and 71% of ureteroliths in the distal third of the ureter will pass spontaneously. It is difficult to apply these specific criteria to dogs and cats because of the wide variation in weight. In humans, if a ureterolith remains in the same location for 2 weeks, interventional techniques should be considered, and this information can probably be applied to dogs and cats with ureteroliths. If an animal is monitored for 2 weeks and the ureterolith is not moving distally, intervention should be considered.

In one recent report, 52 cats were managed medically (IV fluid administration and diuretics). Serial radiographs were monitored in 14 of these cats and the ureterolith passed spontaneously to the urinary bladder in 9 of them. However, 17 of the 52 cats did not respond to medical management and they were either euthanatized or they died within 1 month. The optimal time to allow for passage of ureteroliths by medical management prior to surgical intervention is unknown. In this retrospective study, the time from initial diagnosis to surgery decreased from 19 days early in the study in 11 cats to 2 days for cats later in the study.

Expulsive therapy may have a role in management of cats with obstructive ureteroliths. Suggested therapy includes IV fluid administration with diuretics (eg, mannitol), calcium channel-blocking agents, alpha-adrenergic antagonists, amitriptyline, and glucagon. The medical therapy that most agree on is IV fluid administration with diuretics to increase urine flow to facilitate ureterolith passage with serial monitoring of the ureterolith position by radiographs or ultrasonography.

Although there are anecdotal clinical reports that glucagon facilitates passage of ureteral calculi in cats, the only clinical study of glucagon administration in cats did not demonstrate any benefits for management of obstructive ureteroliths and an unacceptably high incidence of side-effects occurred. Some potential benefits of glucagon combined with diuresis for expulsive therapy of ureteroliths have been reported in humans and research models in dogs; however, glucagon administration for ureteroliths is no longer utilized in humans. Given the unacceptable number of side effects and lack of documented efficacy, glucagon administration is not recommended.

In one report, amitriptyline facilitated passage of urethral plugs in male cats with urethral obstruction. Although the article title implies urethral calculi, the cats in the report all appeared to have urethral plugs rather than actual uroliths. Amitriptyline also inhibited contraction of urinary tract smooth muscle from rats, pigs, and humans in vitro and was suggested as a potential therapy for promoting passage of ureteroliths. There are no other reports supporting the use of amitriptyline for expulsive therapy of ureteroliths.

In humans, multiple clinical studies have confirmed that the alpha-adrenergic antagonist tamsulosin (Flowmax® ) better facilitates passage of ureteral calculi compared with other medications. Calcium channel-blocking agents like nifedipine also facilitate passage of ureteroliths in humans. In some clinical trials, tamsulosin appeared to be superior to calcium channel-blocking agents such as nifedipine, but not in other studies.

Impaction of ureteroliths causes inflammation and edema of the ureteral mucosa, which may further impair passage of the ureterolith. In humans, the use of steroids or nonsteroidal, antiinflammatory medications in addition to other expulsive therapy is sometimes advocated, but the potential role of these medications in dogs and cats with ureteroliths has not been studied.

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