Objectives of Presentation:

Following this presentation, the attendee should be able to

• Describe role of nephroureterolithiasis with CKD
• Outline diagnostic workup for patients with nephroureterolithiasis
• Describe complications associated with nephroureterolithiasis
• Outline therapeutic approach to patients with nephroureterolithiasis

Introduction

Nephroureterolithiasis is being recognized more frequently; however, they account for <2% of urolithiasis occurring in dogs and cats.¹ Many patients are asymptomatic and nephroureteroliths may not be discovered until abdominal imaging is performed for any reason. There appears to be an association of nephroureterolithiasis with chronic kidney disease, especially in cats. Nephroureteroliths can lead to ureteral obstruction, deterioration of renal function, serve as a nidus for bacterial urinary tract infection, or cause hematuria or pain. Clinical signs, when present, include systemic signs associated with acute kidney injury (oftentimes associated with underlying chronic kidney disease), or vague signs such as abdominal pain, arched back, anorexia, or vomiting. Sometimes patients present for an abrupt change in behavior or an acute onset of abdominal pain or vomiting when acute ureteral obstruction occurs. This may be mistaken for intervertebral disk disease or acute pancreatitis. Approximately15% of cats with nephroureteroliths had urocystoliths. When unilateral nephroureteroliths are present, they often occur in the larger and more functional kidney. Most (> 70%) of nephroureteroliths are composed of calcium oxalate, although struvite (particularly infection-induced) and other mineral types (such as urate and cysteine) do occur.

Treatment¹

The decision to surgically treat nephroureteroliths can be difficult to make. Not all nephroureteroliths require surgical treatment. In one study, presence of nephroliths without ureteral obstruction was not associated with progression of chronic kidney disease. In another study, cats with ureteroliths that were managed surgically lived longer than cats with ureteroliths that were managed medically. If nephroureteroliths are composed of minerals amenable to medical dissolution (e.g., struvite, urate, and cysteine), then medical dissolution may be attempted. Indications for surgical management of nephroureteroliths include ureteral obstruction, increase in urolith size and/or number despite appropriate medical treatment, recurrent or persistent urinary tract infection proven or presumed secondary to nephroureteroliths, compromise of renal function, recurrent or persistent clinical signs, or severe hematuria that is renal in origin.

Intervention

Surgical removal is not necessary for all upper urinary tract uroliths and may not be indicated for relatively small, non-obstructive upper urinary tract uroliths as these may pass into the urinary bladder. It is unknown what a safe time period to allow for ureteroliths passing without resulting in irreversible renal damage.

Renal function does not recover in dogs with unilateral ureteral ligation for 40 days. If a dog or cat is ill due to ureteral obstruction, it is not appropriate to wait for the ureteroliths to pass or to medically manage them for a prolonged period of time if renal function is to be preserved. If bilateral upper urinary tract surgery is required, the procedures should be staged with an approximate separation of 4 weeks in order to re­evaluate renal function and to allow recovery from the first procedure if possible. In general, the side with the most renal function should be operated first in order to preserve as much renal function as possible. Intervention is indicated if nephroliths are growing in size or number despite appropriate medical therapy or if ureteroliths are causing obstruction with presence of renal pelvic dilation of 5 mm.

Medical Management

At present, there is no means to medically dissolve calcium oxalate nephroliths. Infection­induced struvite, sterile struvite, urate, and cysteine uroliths may be dissolved by dietary modification and use of certain drugs. Medical dissolution therapy should not be attempted with ureteroliths unless urinary diversion (e.g., ureteral stent or subcutaneous bypass device) is performed. Medical expulsion therapy may be tried to facilitate passage of the ureteroliths into the urinary bladder. In human beings, alpha blocking agents have been shown to promote movement of ureteroliths into the bladder, especially if the uroliths are in the distal 1/3 of the ureter; however, the effectiveness in dogs and cats has not been evaluated. Glucagon has also been used to facilitate passage of ureteroliths after fragmentation by lithotripsy; however, its efficacy and safety has not been reported in dogs and cats although it has been attempted. Alpha-blocking agents and anti­inflammatory drugs may facilitate passage with fluid therapy. Amitriptyline has been shown to relax ureteral smooth muscle and facilitate expulsion of ureteroliths in humans. Spontaneous passage of ureteroliths has been shown to occur. Ureteroliths have also been reported to move retrograde up to 4 cm in the ureter, even back into the renal pelvis resulting in improvement of urine flow and azotemia.

Dialysis^2,3

In some patients dialysis may be required for stabilization. Dialysis is the process of removing solutes and/or water from one solution (plasma) to another solution (dialysate) by an osmotic gradient through a semipermeable membrane. The 2 types of dialysis are peritoneal dialysis and hemodialysis. Dialysis involves the use of one type of semipermeable membrane that allows the passage of small molecules while preventing the transfer and loss of large molecules. In peritoneal dialysis, the peritoneal membrane, interstitial tissue, and capillary endothelium act as the membrane. In hemodialysis, blood is circulated outside of the body through a dialyzer.

The foundation of peritoneal dialysis is the dynamics of fluid and solute exchange across a semipermeable membrane. Large molecules such as proteins pass slowly through such a membrane. Smaller molecules (urea and glucose) and ions (sodium and potassium) move easily across the membrane down a concentration gradient until equilibrium is reached on either side of the membrane. Water moves across the membrane from the solution of lower osmolality to that of higher osmolality until equilibrium is reached. Hemodialysis is a renal replacement therapy that provides a bridge of metabolic stability to patients who would otherwise die from the systemic effects of severe uremia. The principles of hemodialysis are similar to those of peritoneal dialysis, except that blood is shunted outside of the body, passed through a dialyzer ("purified"), and returned to the body. The composition of uremic blood is normalized by exposure to a contrived solution, the dialysate, across a semipermeable membrane in a device called a hemodialyzer. During hemodialysis, water and small-molecular-weight solutes and uremic toxins pass readily through the membrane pores (diffusion channels), along diffusive and hydrostatic gradients, but the movement of larger solutes (such as plasma proteins and cells) is limited by the size of the pores. Excessive body water and additional solute can be forced through the membrane by ultrafiltration produced by hydrostatic or osmotic forces imposed across the dialysis membrane. Net removal of uremic solutes is influenced by: (a) the concentration gradient for diffusion, (b) the diffusivity of the solute, (c) permeability characteristics and surface area of the membrane, (d) blood and dialysate flow within the dialyzer, (e) duration of dialysis, (f) distribution volume of the solutes, and (g) amount of ultrafiltration (convective transfer).

Nephrostomy Tubes

A nephrostomy tube may be placed for urinary diversion in order to relieve pressure on obstructed kidney. One end is curled (pig-tailed) that has a locking mechanism to maintain it in the dilated renal pelvis. Tubing exits the body wall and is connected to external urine collection bag. This requires anesthesia and either surgery or use of interventional radiology and usually is not performed in lieu of more definitive intervention.

Surgical Management

Surgical removal is not necessary for all nephroureteroliths. Surgery is not indicated for relatively small, non-obstructive upper urinary tract uroliths. Small upper urinary uroliths may pass into the urinary bladder. It is unknown what a safe time period to allow for ureteroliths passing without resulting in irreversible renal damage. Renal function does not recover in dogs with unilateral ureteral ligation for 40 days. If a dog or cat is ill due to ureteral obstruction, it is not probably appropriate to wait for the ureteroliths to pass or to medically manage them for a prolonged period of time if renal function is to be preserved. If a urinary tract infection is present, removal of the upper urinary tract urolith may be necessary to control the infection; however, it is not possible to determine prior to surgery if the uroliths are the source of infection. If bilateral upper urinary tract surgery is required, the procedures should be staged with an approximate separation of 4 weeks in order to re-evaluate renal function and to allow recovery from the first procedure. In general, the side with the most renal function should be operated first in order to preserve as much renal function as possible. Nephroliths can be removed either nephrotomy or by pyelolithotomy; however with either technique, it is not always possible to retrieve all uroliths. Nephrotomy should be avoided, if possible, because it causes renal damage and loss of nephrons. Pyelolithotomy is preferred because renal parenchymal tissue is not incised and so loss of renal function is less likely to occur when compared with nephrotomy; however, pyelolithotomy cannot be performed unless the renal pelvis is dilated. Often it requires microsurgical technique. Ureterotomy is technically difficult to perform because of the diameter of the ureter, especially in cats and stricture formation often occurs. Ureterotomy can occasionally be performed if the ureter is dilated around the ureterolith. Nephrectomy and ureterectomy are indicated for a severely hydronephrotic, non-functional kidney, but is not recommended in most cases as functional renal tissue may be present.

Comparison of Medical vs. Surgical Management⁴

In a retrospective analysis of medically versus surgically managed patients with ureteroliths, surgically managed patients tended to do better over a longer time. Surgery, though, was associated with more complications primarily in the perioperative period. There was a recurrence rate of 40%.

Lithotripsy

Extracorporeal shock wave lithotripsy (ESWL) is a standard of care for many human patients with upper urinary tract uroliths, and has been performed successfully in dogs and cats.⁵ In the 1970s, it was recognized that when raindrops or small meteorites collided with aircraft surfaces, pits on the metal resulted from shock waves generated by the collision. Shock waves traveling through fluids create damage by creating a strong tensile force on the interface of solution and solid material. Struvite is most easily fragmented, followed by calcium oxalate, then urate, then cystine. When upper urinary tract uroliths fragment, the small fragments pass into the urinary bladder over several weeks; their passage is not instantaneous. Animals that have undergone ESWL should have periodic examinations including serum biochemical analysis, urinalysis, and radiographs to monitor for successful passage of fragments and to detect any compromise of renal function due to the lithotripsy procedure. Acceptable canine candidates are those with nephroliths smaller than 2–3 cm in their greatest dimension or ureteroliths. With bilateral nephroliths, both kidneys are treated at the same time, unless there is concern about compromising renal function further. More than 100 dogs with nephroliths or ureteroliths have been treated at 3 institutions. Most of the uroliths were composed of calcium oxalate and most nephroliths fragment with 1 or 2 treatments. Feline nephroureteroliths appear to be more difficult to fragment with ESWL than in dogs, and renal function is more likely to be compromised. Successful fragmentation has been reported to occur in <20–25% of feline cases. Although renal function was normal in 4 healthy cats undergoing lithotripsy, lithotripsy of clinical cases of upper urinary tract urolithiasis in cats suggests that many cats, particularly those with preexisting renal disease, experience renal function compromise or worsening of their renal failure. While lithotripsy is considered safer and less invasive than surgical removal of upper urinary tract uroliths, there are risks. Abdominal pain, hemorrhage, and bruising of the kidneys occur, and hematuria may be observed immediately after the procedure. More significant hemorrhage within or around the kidney may occur in some cases. Residual stone fragments often take several weeks to move from the kidney into the urinary bladder. Transient or permanent ureteral obstruction can occur. If permanent and progressive ureteral obstruction occurs, it requires re-treatment by lithotripsy or surgical intervention. Uncommon complications include pancreatitis, bowel irritation, hemolysis, and systemic hypertension.

Intracorporeal laser lithotripsy is not often possible due to the inability to access the ureter via the urinary bladder in cats and most dogs. The smallest flexible ureteronephroscope is 2.2 mm in diameter and feline ureters are approximately 0.5 mm in diameter and canine ureters are approximately 0.5 to 1.5 mm in diameter. One option is to perform endoscopic nephrolithotomy. Placement of a ureteral stent (described below) results in ureteral dilation over time and ureters may dilate to approximately 4 mm around a ureteral stent, which could allow for passage of a flexible ureteronephroscope through the urinary bladder and into the ureter if the scope can be inserted through the ureterovesical junction.

Endoscopic Nephrolithotomy

A rigid scope can be inserted through the renal parenchyma into the dilated renal pelvis. The nephrolith is visualized and either retrieved or fragmented using laser lithotripsy or fragments retrieved. Usually a rigid cystoscope (1.9 mm or 2.7 mm) is used as human nephroscopes are too large to use in cats and dogs. There are no large studies of efficacy and complications in dogs and cats and this technique requires a surgical approach to the kidney.

Ureteral Stent⁶

In patients where nephroureteroliths cannot be managed surgically, urinary diversion may be accomplished by placing a ureteral stent. Usually a double pig-tailed stent is placed surgically, fluoroscopically, or via cystoscopy. One of the pig-tails is placed so that it is within the dilated renal pelvis and the other pig-tail is placed so that it is within the urinary bladder. The body of the stent connects the 2 pigtails and provides diversion of urine flow around the obstructive ureteroliths.

Subcutaneous Ureteral Bypass Device (SUB)⁷

A subcutaneous ureteral bypass device is used to divert urine from renal pelvis to urinary bladder bypassing the ureter. It is similar to a nephrostomy tube; however, it can be used long term and implanted subcutaneously. A locking pig-tail catheter is inserted surgically into the renal pelvis and the kidney is sutured to the body wall (nephropexy). The tube is tunneled subcutaneously to a metallic port that is implanted subcutaneously just off of ventral midline. The metallic port is used for collecting a urine sample using a special needle (Huber needle). A tube exits the other side of the port and re-enters the abdomen and is inserted near the apex of the urinary bladder, which may be sutured to the ventral abdominal wall (cystopexy).

Comparison of Ureteral Stent with SUB

Ureteral stenting is often performed in cats and more so than in dogs. There is a reported mortality of <2% for dogs and approximately 8% for cats. Success is highly dependent on the training and ability of the individual placing the ureteral stent. Dysuria from the urinary bladder pig tail occurs in approximately 40% of cats and less than 2% of dogs. Often this can be managed with anti-inflammatory drugs and antispasmodic. Re-occlusion may occur in up to 10% of dogs and 25% of cats. The advantage of a ureteral stent is that no additional management is required; however, stent encrustation may occur necessitating removal and possible replacement. The ureter often dilates around the ureteral stent and ureteroliths may subsequently pass into the urinary bladder. In many dogs, ureteral stents may be placed using interventional radiology, whereas in cats usually stents require surgical placement. SUBs are more often placed in cats than dogs. Mortality is <2% for dogs and approximately 6% in cats. Dysuria is uncommon occurring in <2% of dogs and cats. Re-occlusion may occur in approximately 20% of patients, especially cats. The advantage of SUB is that the ureteral obstruction is circumvented and additional clinical signs do not usually occur. Disadvantages include requirement of surgical placement and flushing of the SUB to prevent occlusion from small uroliths or encrustation.

Ureteral Ileal Graft

Recently, resection of an obstructed ureter and replacement with a vascularized ileal graft was described in a cat with ureteral obstruction and progressive renal azotemia.

Renal Transplantation⁸

A retrospective study of 19 cats with renal failure associated with calcium oxalate urolithiasis has been published. There were 13 females and 7 males; all cats were azotemic and 17 were anemic. Hypercalcemia was present in 7 cats. Mean duration of survival in all cats was 605 days; 8 cats were alive 282–1,005 days (median=1,305 days), 11 cats died 2–1,197 days (median=300 days), and 5 cats formed uroliths in their allograft kidney. Of these cats, 2 were hypercalcemic and 4 died following complications associated with urolith formation.

References

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2.  Langston C. Hemodialysis. In: Bartges J, Polzin DJ, eds. Nephrology and Urology of Small Animals. West Sussex, UK: Wiley-Blackwell; 2011:255–85.

3.  Labato MA. Peritoneal dialysis. In: Bartges J, Polzin DJ, eds. Nephrology and Urology of Small Animals. West Sussex, UK: Wiley-Blackwell; 2011:293–305.

4.  Kyles AE, Hardie EM, Wooden BG, Adin CA, Stone EA, Gregory CR, et al. Management and outcome of cats with ureteral calculi: 153 cases (1984–2002). J Am Vet Med Assoc. 2005;226(6):937–44.

5.  Adams LG, Goldman CK. Extracorporeal shock wave lithotripsy. In: Bartges JW, Polzin DJ, eds. Nephrology and Urology of Small Animals. Ames, IA: Wiley­ Blackwell; 2011:340–48.

6.  Berent A. Indwelling urinary catheters and stents. In: Bartges JW, Polzin DJ, eds. Nephrology and Urology of Small Animals. Ames, IA: Wiley-Blackwell; 2011:329–39.

7.  Berent AC. Interventional urology: endourology in small animal veterinary medicine. Vet Clin North Am Small Anim Pract. 2015;45(4):825–55.

8.  Adin CA. Renal transplantation. In: Bartges J, Polzin DJ, eds. Nephrology and Urology of Small Animals. West Sussex, UK: Wiley-Blackwell; 2011:306–28.