Management of uroliths in the upper tract Larry G. Adams, DVM, PhD, Diplomate ACVIM (SAIM) Purdue University College of Veterinary Medicine, West Lafayette, Indiana, USA Key points: The most common composition of upper tract uroliths in dogs and cats is calcium oxalate. The second most common composition of upper tract uroliths in dogs is struvite associated with urease-producing bacterial UTI. Ureteral stents are useful for management of obstructive ureteroliths in dogs. Infection-induced struvite ureteroliths in dogs may be dissolved by cystoscopic placement of ureteral stent, administration of antibiotics, and feeding a dissolution diet. Shock wave lithotripsy is effective for treatment of nephroliths and ureteroliths in dogs. Subcutaneous ureteral bypass (SUB) may be the preferred treatment option for management of obstructive ureteroliths in cats. Introduction Nephroliths and ureteroliths pose unique challenges to the clinician compared to lower tract uroliths. Nephroliths may obstruct the renal pelvis or ureter, may predispose to pyelonephritis, may result in compressive injury of the renal parenchyma leading to progressive CKD, and may cause acute uremia from complete ureteral obstruction. Nephroliths may be considered incidental if they are not causing any of these complications. Incidental nephroliths do not require removal, but they should be monitored periodically by urinalysis, urine culture, radiography and ultrasonography. Indications for intervention for nephroliths and ureteroliths in dogs include obstruction of the ureteral pelvic junction (UPJ) or ureter, relapsing UTI from infected uroliths, progressive nephrolith enlargement, and nephroliths located near the UPJ of a solitary functional kidney.1-3 The major indication for treatment of upper tract uroliths in cats is obstructive ureteroliths.3-5 Unlike humans with ureteroliths that tend to move in an antegrade fashion due to the effects of gravity, spontaneous retrograde movement of ureteroliths in dogs and cats that may result in relief of ureteral obstruction.6 Furthermore, we have also documented uroliths moving from the renal pelvis into the proximal ureter, and back into the renal pelvis in some animals.6 Calcium oxalate is the most common composition of nephroliths in dogs and cats. The second most common composition of upper tract uroliths in dogs is struvite associated with urease-producing bacterial UTI. The second most common nephrolith composition in cats is dried solidified blood calculi.7-8 Dried solidified blood calculi may be radiolucent and approximately 40% of DSB calculi in cats are located in the upper urinary tract.7 Feline ureteroliths have become more common with changes in urinary diets to prevent struvite uroliths.8 Calcium oxalate and dried solidified blood calculi are not amendable to medical dissolution thereby limiting the treatment options for these uroliths.

Clinical Signs Many dogs with nephroliths are asymptomatic and the nephroliths are diagnosed during work up of other problems. Potential clinical signs associated with upper tract uroliths in dogs include hematuria, recurrent UTI, fever, vomiting, abdominal or lumbar pain, and uremia from bilateral ureteral obstruction or progressive renal injury resulting in renal damage.3-5 Ureteroliths may be bilateral, or one kidney may be non-functional from prior ureteral obstruction when a subsequent ureterolith obstructs the contralateral kidney resulting in an acute uremic crisis. Acute ureteral obstruction secondary to ureteroliths has become a common clinical syndrome in cats.3-4 Many cats with acute uremia from ureteral obstruction have one enlarged kidney and one small kidney. The small kidney may be fibrotic and non- functional from prior ureteral obstruction. The cat may be asymptomatic until an acute uremic crisis develops from ureteral obstruction of the contralateral enlarged kidney. Renal enlargement may be from compensatory hypertrophy, hydronephrosis or a combination of the two. Cats may also present with bilateral ureteral calculi; relative renal function of both kidneys should be determined before deciding on treatment plan. Urine output in patients with ureteroliths may be anuric, oliguric, polyuric or normal urine output depending on severity of ureteral obstruction. Cats with distal ureteral obstruction may also have signs suggestive of lower urinary tract disease (e.g., dysuria and pollakiuria). 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. Documentation of upper tract uroliths accompanied by progressive renal pelvic dilation is highly suggestive of obstructive ureteroliths even if the ureterolith is not documented directly by ultrasonography.5 Animals 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. The author prefers to perform contrast ureterogram via nephropyelocentesis as part of an interventional procedure rather than as an isolated diagnostic procedure. Another imaging modality to confirm upper tract uroliths is CT scan performed before and after contrast administration. Urinalysis results from animals with nephroliths or ureteroliths may reveal hematuria and crystalluria. Crystal identification and urine pH may be helpful in predicting urolith composition. Likewise, collection of small uroliths from the urinary bladder may be used to determine likely composition of concurrent upper tract uroliths. Pyuria and bacteriuria may be noted in dogs with concomitant UTI and infection-induced struvite uroliths. Urine culture should be performed on urine obtained by cystocentesis because concurrent UTI is relatively common.5 Serum chemistry profile and CBC may indicate systemic abnormalities that have resulted from or contributed to formation of nephrolithiasis. Dogs with pyelonephritis or pyonephrosis and concurrent ureteral obstruction may have an inflammatory leukogram and thrombocytopenia.9 Anemia is also common in animals with CKD from obstructive ureteroliths. Azotemia may be present with bilateral renal disease or bilateral obstruction. Dogs that have alkaline urine pH, UTI, struvite crystalluria and staghorn-shaped radiodense nephroliths most likely have struvite nephroliths. Ionized calcium should also be measured in dogs and cats with calcium oxalate nephroliths or ureteroliths to evaluate for potential underlying causes of the uroliths. Treatment of nephroliths and ureteroliths Treatment options for nephroliths include monitoring of inactive nephroliths, open surgery, medical dissolution, ureteral stent placement, and extracorporeal shock wave lithotripsy (SWL).1,3,5 Calcium oxalate, calcium phosphate and matrix nephroliths are not amenable to dissolution. Ureteroliths and obstructive nephroliths are also not amenable to medical dissolution because they are not bathed in under-saturated urine unless the obstruction is bypassed with a ureteral stent.9 Medical dissolution of ureteroliths may be facilitated by placement of a ureteral stent to induce passive ureteral dilation.9-10 In most dogs, the nephroliths are surrounded by renal tissue such that pyelolithotomy is not possible, so nephrotomy is the only open surgical option.11-12 In one study, neither intersegmental nor bisection nephrotomy adversely affected GFR; however complete nephrolith removal via nephrotomy is challenging.12 Percutaneous nephrolithomy (PCNL) is used to remove large staghorn nephroliths in humans, and PCNL and surgically- assisted endoscopic nephrolithomy (SENL) have been performed in dogs for removal of large nephroliths.3 For obstructive ureteroliths, ureterotomy may be performed in dogs but is associated with a number of potential complications. Ureterotomy in cats requires microsurgical experience and post-operative complications are common compared to ureteral stents.4,5 Ureteral Stent Placement for Ureteroliths in Dogs Ureteral stents are useful for management of obstructive ureteroliths in dogs.4,5,9 Ureteral stents can be placed retrograde via cystoscopy in female dogs and induce passive ureteral dilation within 2-4 weeks.10 In male dogs, ureteral stent placement may require open cystotomy, laparoscopic-assisted cystostomy or temporary perineal access.13 Placement of a ureteral stent bypasses the ureteral obstruction created by the stone and the stent causes passive dilation of the ureter.10 Once the ureter has dilated, the ureteral stone may pass around the ureteral stent. Infection-induced struvite ureteroliths may be dissolved by placement of ureteral stent, administration of antibiotics (selected based on urine culture and sensitivity testing) and feeding a dissolution diet.9 Ureteral stents may be left in place long-term to bypass calcium oxalate ureteroliths; however, there is a risk of stent mineralization (encrustation) that may occlude the stent. If this occurs and the obstruction is detected early, then the stent can be exchanged for a new stent either by cystoscopy or surgery. Once the ureter passively dilates from the ureteral stent, ureterorenoscopy using flexible digital ureteroscope is possible in medium sized or larger dogs.10 Ureterorenoscopy for removal of nephroliths is possible with use of appropriately sized urologic guidewires, ureteral access sheath placement, flexible stone baskets, and concurrent fluoroscopy. Extracorporeal shock wave lithotripsy in dogs Extracorporeal shock wave lithotripsy (SWL) is fragmentation of uroliths using shock waves are generated outside the body.1 SWL uses repeated shock-waves to fragment the nephrolith into many small fragments that can pass spontaneously through the excretory system. We originally reported the safety and efficacy of SWL for the treatment of canine nephroliths and ureteroliths from our first 5 cases.2 The author has treated more than 200 dogs with SWL for fragmentation and removal of nephroliths and ureteroliths. SWL treatment was successful in approximately 85% of the dogs with calcium containing nephroliths.1 Overall approximately 30% of dogs required more than one SWL treatment for complete fragmentation of their nephroliths. For dogs with obstructed ureteroliths, success rates were slightly lower (76%), with over 50% requiring more than 1 SWL treatment to achieve adequate fragmentation of ureteroliths.1 Considering our experience, SWL is a safe and effective method of treating nephroliths and ureteroliths in dogs. Unlike dogs, SWL is not effective in cats. Uroliths from cats are more resistant to fragmentation than uroliths from dogs.14 We have seen several complications from SWL treatment. The most common complication has been the developed transient ureteroliths that partially obstructed the ureter in approximately 10% of dogs treated for nephroliths, although only about 10% of these dogs require additional treatment to facilitate removal of these fragments.1 Pre- placement of a ureteral stent before SWL may be useful to prevent ureteral obstruction in dogs with nephroliths larger than 1-1.5 cm.1,3 Lithotripsy treatment of the right kidney in small dogs often results in mild asymptomatic increases in amylase, lipase and TLI suggestive of pancreatic injury. Approximately 2% of dogs develop clinical acute pancreatitis following SWL treatment of the right kidney.15 Large nephroliths (> 1.5-2 cm) are not ideal candidates for SWL treatment.3,5 PCNL or SENL are preferred over SWL for larger nephroliths because of the risk of ureteral obstruction by nephrolith fragments.3,5 Cystoscopic-assisted placement of a ureteral stent with periodic stent exchange is an alternative to SWL treatment of obstructive ureteroliths.3 Recurrence is a potential problem in dogs with nephroliths. Because nephrotomy results in reduced renal function, repeated surgery for may result in progressive loss of renal function and renal failure. Therefore, SWL is preferable to nephrotomy for treatment of nephroliths.1,3,5 Repeated SWL treatments have been successfully performed in dogs with highly recurrent nephroliths. Medical Management of Ureteral Obstruction Conservative medical management by serial monitoring of ureteroliths along with administration of intravenous fluids and diuretics may initially be attempted provided there is minimal renal functional compromise and no infection, renal colic, or progressive ureteral dilation.3,5 Typically, dogs and cats with evidence of complete obstruction, worsening azotemia, or evidence of pyelonephritis should be treated via surgical intervention, ureteral stent placement, subcutaneous ureteral bypass, or SWL (dogs). The optimal time to allow for passage of ureteroliths by medical management prior to surgical intervention is unknown. Subcutaneous ureteral bypass placement in cats Subcutaneous ureteral bypass (SUB) is a new option for management of obstructive ureteroliths.16 A SUB is a nephrostomy tube connected to a cystostomy tube by a subcutaneous port. There is a substantial learning curve associated with SUB placement. Most complications are associated with leakage or kinking of the tubing in the immediate post-operative period. One advantage of the SUB over ureteral stents is the ability to flush the SUB system to remove transient occlusions by cellular debris and help maintain patency. The urine from the bladder and renal pelvis may be sampled for urinalysis and urine culture by insertion of a Huber needle into the SUB port. Another advantage of the SUB is the much larger diameter (6.5 Fr) compared to ureteral stents (2.2 Fr), such that occlusion due to encrustation of the lumen is much less likely with a SUB than with ureteral stents. In our hospital, SUB placement is currently the preferred technique for intervention for majority of cats with ureteroliths. SUBs are sampled and flushed every 3 months using aseptic technique followed by infusion of sterile 2-4% tetra-EDTA solution. Long-term survival in cats treated with ureteral stent or SUB placement is dependent on the degree of recovery of renal function after relief of the ureteral obstruction. On the basis of renal function following relief of obstruction, cats with Stage 1-2 CKD had more prolonged survival than cats with stage 3-4 CKD.17 Therefore, earlier intervention should be considered in cats with complete ureteral obstruction to preserve as much renal function as possible. The optimal time wait to allow for passage of ureteroliths using medical management prior to intervention should be determined for each individual cat. Factors indicating need for quicker intervention include multiple ureteroliths, hyperkalemia, refractory metabolic acidosis, severe azotemia and marked distention of the renal pelvis and ureter. Hemodialysis may be used for medical management of oliguric patients prior to surgical intervention. References 1. Adams LG, Goldman CK. Extracorporeal shock wave lithotripsy. In Nephrology and urology of small animals. Edited by Polzin DJ, Bartges J. Ames, Iowa, Blackwell Publishing, 2011, p. 340-348 2. Block G, Adams LG, et al. Use of extracorporeal shock wave lithotripsy for treatment of spontaneous nephrolithiasis and ureterolithiasis in dogs, J Am Vet Med Assoc 1996, 208:531-536 3. Berent AC, Adams LG. Interventional management of complicated nephrolithiasis. In: Weisse CW, Berent AC, eds. Veterinary Imaging-Guided Interventions. Ames, IA. Wiley- Blackwell Publishing: 2015:289-300. 4. Berent AC. Ureteral obstructions in dogs and cats: a review of traditional and new interventional diagnostic and therapeutic options, J Vet Emerg Critical Care 2011, 21:86- 103. 5. Lulich JP, Berent AC, Adams LG, et al. ACVIM Small Animal Consensus Recommendations on the Treatment and Prevention of Uroliths in Dogs and Cats. J Vet Intern Med 2016;30:1564-1574. 6. Dalby AM, Adams LG, et al. Spontaneous retrograde movement of ureteroliths in three dogs and five cats, J Am Vet Med Assoc 2006, 229:1118-1121 7. Westropp JL, Ruby AL, et al. Dried solidified blood calculi in the urinary tract of cats, J Vet Intern Med 2006, 20:828-834 8. Cannon AB, Ruby AL, et al. Evaluation of trends in urolith composition in cats: 5,230 cases (1985-2004), J Am Vet Med Assoc 2007, 231:570-576 9. Kuntz JA, Berent AC, Weisse CW, et al. Double pigtail ureteral stenting and renal pelvic lavage for renal-sparing treatment of obstructive pyonephrosis in dogs: 13 cases (2008- 2012). J Am Vet Med Assoc 2015;246:216-225 10. Vachon C, Defarges A, Brisson B, et al. Passive ureteral dilation and ureteroscopy after ureteral stent placement in five healthy Beagles. Am J Vet Res 2017;78:381-392. 11. Greenwood KM, Rawlings CA. Removal of canine renal calculi by pyelolithotomy, Veterinary Surgery 1981, 10:12-21 12. Stone EA, Robertson JL, et al. The effect of nephrotomy on renal function and morphology in dogs, Veterinary Surgery 2002, 31:391-397 13. Tong K, Weisse C, Berent AC. Rigid urethrocystoscopy via a percutaneous fluoroscopic- assisted perineal approach in male dogs: 19 cases (2005-2014). J Am Vet Med Assoc 2016;249:918-925. 14. Adams LG, Williams JC, Jr., McAteer JA, et al. In vitro evaluation of canine and feline urolith fragility by shock wave lithotripsy. American Journal of Veterinary Research 2005;66:1651-1654. 15. Daugherty MA, Adams LG, et al. Acute pancreatitis in two dogs associated with shock wave lithotripsy, J Vet Intern Med 2004, 18:441-441. 16. Berent AC, Weisse CW, Bagley DH, et al. Use of a subcutaneous ureteral bypass device for treatment of benign ureteral obstruction in cats: 174 ureters in 134 cats (2009-2015). J Am Vet Med Assoc 2018; 253:1309-1327.