Minimally invasive removal of obstructive ureteral stones by intracorporeal lithotripsy in horses: 3 patients

Abstract

Three client-owned horses diagnosed with obstructive ureteral stones were referred and treated in a minimally invasive manner by retrograde ureteroscopy in conjunction with electrohydraulic lithotripsy (EHL) or laser Holmium:YAG lithotripsy (HYL). For all 3 horses, additional tests revealed variable degrees of azotemia and ureteral obstruction. Ultrasound examination (2 horses) revealed a loss of cortico-medullary distinction consistent with a chronic nephropathy. Ultrasound-guided biopsy of the right kidney in 1 horse revealed moderate glomerulosclerosis and lymphoplasmacytic nephritis. A standing anesthesia with a coccygeal epidural was done for each horse. A perineal urethrotomy was performed in 2 horses before the urethrocystoscopy. One horse was treated with Holmium:YAG laser lithotripsy and 2 others were treated using a electrohydraulic lithotripsy probe. Each procedure was successful. The ureteroscopy was successfully performed and visualization was excellent. Fragmentation of stones seemed easier with the electrohydraulic lithotripsy probe. No complications, pain, or signs of discomfort after the procedure were noticed. All 3 horses were discharged from the hospital.

Key clinical message:

Obstructive ureteral stones in horses can be successfully treated in a minimally invasive manner by retrograde ureteroscopy accompanied by lithotripsy. This technique is safe, not painful and did not require general anesthesia. Electrohydraulic lithotripsy appeared superior for stone fragmentation.

Urolithiasis is rare in horses with a reported prevalence of 0.1% (1). Cystoliths and urethroliths are more commonly recognized and represented 3/4 of all uroliths in 1 study of 68 horses, whereas ureteroliths occurred in < 4% (1). Equine ureterolithiasis is commonly bilateral and often associated with nephrolithiasis (2), with calcium carbonate being the predominant mineral type (1,3,4). Various surgical options to remove ureteroliths in the upper urinary tract have been described (5–8). The invasiveness of these techniques are in contrast with electrohydraulic lithotripsy (EHL) or Holmium:YAG laser lithotripsy (HYL), which have been described for fragmenting uroliths in horses (2,9–11). In humans, treatment of ureteroliths using HYL has a very high success rate, with some studies reporting a stone-free rate > 95% (12,13).

Three horses with obstructive ureteroliths were referred and treated in a minimally invasive manner by intracorporeal lithotripsy. The objective of our study was to describe retrograde ureteroscopy and nephroscopy in conjunction with intracorporeal lithotripsy in these 3 horses.

Case descriptions

Horse #1

A 5-year-old, 365 kg Arabian mare (Horse #1) was presented for treatment of unilateral obstructive ureteral calculi with a 2-year history of polyuria, polydipsia, suspected renal failure, and ureteroliths. On physical examination, the mare was bright with normal vital signs, dorsal reticulated leukotrichia, and mild ventral sternal edema. A complete blood (cell) count (CBC) revealed a normocytic normochromic anemia [25%; reference interval (RI): 31 to 51%] and biochemistry revealed an increased creatinine (3.9 mg/dL; RI: 0.8 to 1.5 mg/dL) and urea (30.2 mg/dL; RI: 11.5 to 21.3 mg/dL). A mild increase in alkaline phosphatase activity (192 U/L; RI: 67 to 185 U/L), gamma-glutamyl transferase activity (35 U/L; RI: 9 to 30 U/L), and lipase activity (45 U/L; RI: 10 to 19 U/L) were noted. Sodium was mildly decreased (310 mg/dL; RI: 310.5 to 328.9 mg/dL) associated with a mild hypophosphatemia (2.26 mg/dL; RI: 2.38 to 5.17 mg/dL). Urinalysis revealed hyposthenuria (specific gravity of 1.007), pH of 9, proteinuria (0.3 g/dL), and glucosuria (2.8 mmol/L). Urine sediment examination revealed 0–1 white blood cells/high power field (HPF), 2+ calcium carbonate crystals, and occasional to 1+ calcium oxalate dihydrate crystals. Urine culture was negative. Transrectal and transabdominal ultrasonography revealed a loss of renal cortico-medullary distinction with calculi in both kidneys (left: 7 and 17 mm; right: 24 and 16 mm). There was a right hydronephrosis and hydroureter with ureteroliths located in the proximal third of the ureter, ~60 cm from the vulva.

Horse #2

A 12-year-old Standardbred gelding (Horse #2) was presented for treatment of a cystolith with a 2-month history of polyuria, hematuria, and stranguria. Medical history reported 2 previous colic episodes that were medically managed. On physical examination, the gelding was bright with normal vital signs. Transrectal examination revealed a cystolith and an enlarged left ureter with a suspected ureterolith. A CBC revealed a normocytic normochromic anemia (29%; RI: 31 to 51%) and biochemistry revealed a mildly increased creatinine (1.6 mg/dL; RI: 0.8 to 1.5 mg/dL). The lipase activity was mildly elevated (23 U/L; RI: 10 to 19 U/L) and a mild hypoalbuminemia was noted (2.83 g/dL; RI: 3.1 to 3.9 g/dL). Transrectal and transabdominal ultrasonography revealed small focal mineralizations in the right kidney without evidence of hydronephrosis. A marked left hydronephrosis was noted with a loss of corticomedullary distinction and mineralizations and was suspected to be either nephroliths or mineralization of the parenchyma. Urinalysis revealed isosthenuria (1.008). Following routine perineal urethrotomy, a 5-cm cystolith was visualized endoscopically and removed using a laparoscopic retrieval bag after pneumatic lithotripsy, using a custom-made stainless-steel rod attached to an air compressor, as described (14). A cystolith fragment was submitted for bacterial culture and was positive for Escherichia coli that was sensitive to amikacin, ceftiofur, chloramphenicol, enrofloxacin, and gentamicin.

Horse #3

A 22-year-old Oldenburg gelding (Horse #3) was presented for treatment of bilateral obstructive ureteral calculi with a 1-month history of lethargy, loss of appetite, and increased creatinine (3.7 mg/dL; RI: 0.8 to 1.5 mg/dL). Physical examination was unremarkable. A CBC was unremarkable. Serum biochemistry revealed a marked increase in creatinine (4.3 mg/dL; RI: 0.8 to 1.5 mg/dL), as well as urea (40.7 mmol/L; RI: 11.5 to 21.3 mmol/L) and a mildly elevated lipase activity (33 U/L; RI: 10 to 19 U/L). The urine was isosthenuric (1.012) and sediment examination revealed 0 to 3 white blood cells/hpf, 10 to 20 red blood cells/hpf and 2+ calcium oxalate monohydrate crystals. Transrectal and transabdominal ultrasonography revealed bilateral nephrolithiasis (left kidney: 1 stone, 3 cm in diameter, plus other small stones; right kidney: several small stones), left renal pelvic dilatation (20 mm) and right renal pelvic dilatation (25 mm). Ultrasound-guided biopsy of the right kidney revealed moderate glomerulosclerosis and lymphoplasmacytic nephritis.

For each horse, standing anesthesia with a sacrococcygeal epidural was performed under the supervision of a veterinary anesthesiologist. For Horse #1, a sacrococcygeal epidural (morphine 0.1 mg/kg) was given before cystoscopy and the horse was restrained in a standing stock and sedated with xylazine (150 mg, IV), with ongoing sedation provided by detomidine (3 mg, IV) followed by CRI (0.03 mg/kg per hour) and butorphanol (3 mg, IV) as needed to restrict movement. For Horse #2, a sacrococcygeal epidural with a combination of 100 mg xylazine, 40 mg mepivacaine, and additional sedation with a CRI of detomidine and butorphanol titrated to effect (initially 500 mL of NaCl 0.9% with 10 mg detomidine and 10 mg butorphanol; subsequently, 500 mL of NaCl with 5 mg detomidine). Horse #3 was sedated with intravenous 5 mg butorphanol and 5 mg dexmedetomidine. A sacrococcygeal epidural (xylazine 0.17 mg/kg, lidocaine 0.2 mg/kg, and morphine 0.2 mg/kg) was then given. During the procedure, this horse also received intravenous detomidine CRI (0.005 to 0.03 mg/kg per hour).

For the mare (Horse #1), the vulva was aseptically prepared with 2% chlorhexidine. For the geldings (Horses #2 and #3), a silicone 2-way Foley balloon catheter (size 28 Fr 50 C.C. and length 1570 mm) was first placed using sterile technique; then, the perineal region was shaved and aseptically prepared with 2% chlorhexidine. A perineal urethrotomy was performed through an 8-cm vertical skin incision on the perineal raphe that started proximally 5 cm ventral to the anus. A single stay suture was placed on each side of the urethrostomy through the urethral mucosa, corpus spongiosum, bulbospongiosus muscle, and retractor penis muscle and anchored to the adjacent skin to retract the urethrostomy edges.

For each horse, urethrocystoscopy was conducted using a 1.1 m flexible videoendoscope (OLYMPUS EXER^A II GIF-Q180 diameter 8.8 mm, working channel 2.8 mm; Olympus America, Center Valley, Pennsylvania, USA). Lactated Ringer’s solution and air were infused continuously through the working channel of the endoscope throughout the cystoscopy, with only lactated Ringer’s solution for the ureteroscopy as well as during lithotripsy. First, cystoscopy was performed to evaluate the bladder mucosa and identify cystoliths. The ureteral papillae (right or left) were identified dorsally. Flushing lactated Ringer’s solution through the working channel of the endoscope helped open the ureteral papillae. Ureteral access was achieved using a 0.035-inch diameter, 260 cm, angled-tip hydrophilic wire (Cook Medical LLC, Bloomington, Indiana, USA) passed through the working channel of the flexible endoscope (HiWire 0.035 in, Straight/stiff taper 260 cm hydrophilic). Once the guidewire was blindly advanced into the distal third of the ureter, the endoscope was gently slid over the wire, allowing entry into the distal ureter. The guidewire was passed up the ureter and ureteroscopy was performed over the wire with continuous saline flush. The endoscope was advanced until the most distal ureterolith was identified (Figure 1). For Horse #1, marked ureteral mucosal proliferation around the stone was noted, reducing its mobility. The guidewire was then withdrawn and a 550 μm, 275-cm laser fiber (Cook Medical LLC), connected to the Holmium Laser System (Rapsody H-30 Holmium Laser System, Cook Medical LLC), was advanced, for Horse #1 through the working channel of the endoscope until 0.5 to 1 cm of the fiber was visible at the tip of the scope. Frequency and energy settings were modified (frequency range: 12 to 15 Hertz; energy range: 1.5 to 2.5 Joules) until successful fragmentation was obtained. The procedure was done in noncontact mode. For Horses #2 and #3, a 3.3FR WL 2500MM EHL probe (Riwolith probe 3.3 FR 2500 mm; Richard Wolf GmbH, Knittlingen, Germany) was introduced through the ureteroscope and positioned in contact with the ureterolith. The device setting was Power 3 // Pulse rate: 12 // Single Shot. Following stone fragmentation, larger fragments which could obstruct the ureteral lumen were removed using a 2-m pediatric endoscopic biopsy forceps (Cook Medical LLC).

Figure 1.

A large obstructive ureteral stone is visible (s) in the ureteral lumen. A guidewire passed through the working channel of the endoscope is seen (g). Ureteral mucosal edema and proliferation are visible (*) (Horse #3).

Other fragments were left in place to be evacuated by ureteral flow and peristalsis. If the duration of the procedure was considered excessive (> 3.5 h), the technique was repeated on subsequent days using a similar technique as described, to fragment and remove remaining ureteroliths. During the procedure, the ureteral mucosa was evaluated, and signs of ulceration, proliferations, or laser damage were recorded. Once ureteroliths were fragmented, the endoscope was advanced into the renal pelvis over the guidewire and nephroscopy was performed (Figure 2). The nephrolith was left in place if no obvious signs of obstruction were noted during the procedure, i.e., no luminal obstruction of the ureteropelvic junction.

Figure 2.

Antegrade nephroscopy of the renal pelvis and diverticula (Horse #3).

At the end of the procedure, success was defined as an appropriate urine flow from the ureteral papillae following lithotripsy. This was defined primarily as an improvement of the urine stream compared to that before the procedure and secondly by comparing streams between papillae. Bladder flushes were performed using 1 L of lactated Ringer’s solution to clear small fragments and debris from the bladder following lithotripsy. The duration of the procedure refers to the interval from the beginning of the anesthesia to the end of the lithotripsy procedure.

In Horse #1, a right ureterolith was fragmented and removed by HYL. Three procedures were necessary (total duration: 9.5 h). The presence of numerous embedded fragments, poor visibility, prolonged fragmentation time with perceived difficulty of the laser in fragmenting the stone, and ureteral mucosal edema were noted as reasons for the repeated procedures and extended interval. Several setting adjustments were required to successfully fragment the stone. Mild ureteritis was noted at the end of the procedures. Horses #2 and #3 were treated by EHL; the former for a left ureterolith and the latter for a left proximal ureterolith and a right nephrolith. In Horse #2, left ureteral access was achieved with the flexible endoscope. Only 1 EHL procedure was required to successfully fragment the ureterolith and relieve the ureteral obstruction (procedure time not recorded). Nephroscopy revealed a large amount of sediment; however, no nephroliths were identified. In Horse #3, only 1 EHL procedure was required to relieve the ureteral obstruction and procedural time was 2.2 h. Left ureteral access was achieved with a smaller flexible endoscope (OLYMPUS GIF N180 diameter 4.9 mm, working channel 2 mm). Application of the EHL successfully fragmented 2 large stones: 1 in the proximal ureter obstructing 80% of the lumen and the other in the right renal pelvis. No ureteral mucosal injuries were noted for Horses #2 and #3 following EHL.

Ureteral stone analysis in Horses #1 and #2 revealed a calcium carbonate stone with a minimal amount of magnesium in Horse #1 and with small amounts of magnesium and potassium in Horse #2.

All procedures were successful, and horses recovered well with no signs of urinary discomfort or colic. Postoperative treatments following lithotripsy and during hospitalization were under the attending clinician’s discretion. In Horse #1, dexamethasone (0.05 mg/kg, IV, q24h) and ceftiofur (2.2 mg/kg, IV, q12h) were administered for 2 d after the third procedure. Other treatments administered until discharge included intravenous fluids (LRS) and omeprazole (4.0 mg/kg, PO, q24h). Following the procedure, Horse #2 received a non-steroidal anti-inflammatory medication (firocoxib 0.1 mg/kg, PO, q24h) and trimethoprim-sulfadiazine (5 mg/kg on trimethoprim, PO, q12h) for 4 d. Intravenous fluids were also administered for 2 d at daily requirements. At discharge, the horse received an additional 10 d of firocoxib (0.1 mg/kg, PO, q24h). Following the procedure, Horse #3 received 4 d of ceftiofur (2.2 mg/kg, IV, q12h) following the renal biopsy and 2 d of dexamethasone (0.04 mg/kg, IV, q24h), due to the perineal urethrotomy. Intravenous fluids were also given for 7 d at daily requirements. Horses #2 and #3 were hospitalized until their creatinine reached a plateau (with 3 consecutive stable creatinine values). Horse #1 was discharged at the request of the owner, although the creatinine concentration had not stabilized.

Horse #1 was hospitalized for 26 d. Despite a mild improvement in creatinine following HYL (3.14 mg/dL; RI: 0.8 to 1.5 mg/dL), the creatinine slowly increased during hospitalization (4.59 mg/dL; RI: 0.8 to 1.5 mg/dL). She was re-admitted 6 mo later due to progressive azotemia. On admission, the creatinine was elevated (7.55 mg/dL; RI: 0.8 to 1.5 mg/dL). Ultrasound revealed a right-sided nephrolith and no significant renal pelvic dilation. The right ureter was not dilated and no ureteroliths were identified. Left nephrolithiasis was again noted, with no evidence of ureteral obstruction. Ureteroscopy was repeated and revealed a 1-cm ureterolith located in the mid ureter (~30 to 40 cm from the ureteral papillae). The ureterolith was mobile and therefore not appearing to cause obstruction. Using the same forceps previously described, multiple attempts were unsuccessful at removing the ureterolith. Due to ureteral wall edema, the procedure was aborted and repeated the next day but was once again unsuccessful. Considering the absence of significant pelvic dilation and the mobile ureterolith, it was decided to continue fluid diuresis and medical management. The mare was euthanized 2 mo later due to progressive azotemia and perceived poor quality of life.

Horse #2 was hospitalized for 11 d. The creatinine was stable after the procedure (1.51 mg/dL; RI: 0.8 to 1.5 mg/dL) and normalized 20 d later (1.43 mg/dL; RI: 0.8 to 1.5 mg/dL). At follow-up ultrasound examinations, there was a reduction in the left hydronephrosis and improvement of the appearance of the renal parenchyma.

Horse #3 was hospitalized for 25 d. A marked improvement of the creatinine was noted 3 d after the procedure (2.14 mg/dL; RI: 0.8 to 1.5 mg/dL) and remained stable until discharge (1.82 mg/dL; RI: 0.8 to 1.5 mg/dL). Only the left kidney had an improvement in pelvic dilatation following the procedure (1.2 versus 3.2 cm).

At the time of writing, Horses #2 and #3 (34- and 12-months post-procedure, respectively) were alive. Horse #3 was preparing for a competition season. Follow-up of creatinine was available for Horse #3; at 12 mo post-procedure, it was mildly elevated (1.57 mg/dL).

Discussion

To our knowledge, this is the largest case series documenting successful treatment of obstructive ureterolithiasis in horses by HYL or EHL. In humans, intracorporeal lithotripsy appears to have many advantages compared to other techniques (shorter procedural times and a better stone-free rate) (15). Intracorporeal lithotripsy for ureterolithiasis is not commonly performed in companion animals due to the small size of the ureter and difficulty in performing ureteroscopy. However, the large diameter of the equine ureter and relative ease of ureteroscopy in a standing horse makes this minimally invasive approach very attractive. In our patients, ureteral papillae were easily accessed by retrograde cysto-urethroscopy with the use of a guidewire. Visualization of the ureteral lumen, stone, and renal pelvis was considered excellent.

The ability to perform the procedure in a standing horse under sedation and epidural anesthesia is a substantial advantage, considering the morbidity associated with ureteral surgery and prolonged general anesthesia in horses. In a recent study, general anesthesia-related mortality rates were 1.4 and 0.96% for emergency and elective surgeries, respectively. There were complications associated with anesthesia in 17.5% of horses, 92% of which occurred during recovery (16).

For Horse #1, fragmentation of the ureteroliths by HYL was challenging and required changes in settings to be successful. The need for high settings for urolith fragmentation was attributed to the composition of equine uroliths, making them resistant to laser fragmentation. As described, some equine uroliths may be particularly resistant to lithotripsy with the Ho:YAG laser (10,11). This may be explained, at least in part, by the structure of the crystal lattice and the cementing substance (10,17). Further studies are required to determine if the microstructure and the gross appearance of the uroliths may help to determine fragility and susceptibility to fragmentation. Given the difficulties encountered with laser fragmentation, the authors chose EHL for Horses #2 and #3, as described in a previous report (2).

Fragmentation was faster with EHL as larger fragments broke off from the stone. In Horse #1, HYL tended to result in slow powdering of the stone and a longer procedure. The differences in stone fragmentation between HYL and EHL can be appreciated in Videos #1 and #2 (available online from www.canadianveterinarians.net). Intracorporeal EHL appeared to be superior to HYL for fragmentation of obstructive ureteroliths in our patients. These findings were in contrast to humans in whom intracorporeal laser lithotripsy was superior (17).

Damage to the surrounding tissue and risk of post-operative stricture following intracorporeal lithotripsy were of concern. In this study, despite mild inflammation of the ureteral mucosa at the end of the procedure by HYL, no substantial mucosal trauma or perforation were noted with HYL or EHL despite using high energy settings. For HYL, pulse energy ≤ 1 J at a pulse frequency rate up to 10 Hz has been described as an optimal power setting for urinary tract stone fragmentation in humans (18). No damage to the ureteral mucosa or complications related to the technique were noted for EHL. Increasing the energy density will help with fragmentation and decrease the total duration of the treatment but may be associated with greater soft tissue damage. Settings used for Horse #1 were not associated with gross ureteral damage or post-procedural complications.

Ureteral stricture has been reported as a rare complication of intracorporeal lithotripsy in humans with a prevalence of 0.3% (19). The risk of stricture appears to be higher with HYL (17,19). Stricture may be due to ureteral trauma from instrumentation or from stone impaction and encrustation into the mucosal surface (20). Although ureteroscopy was not consistently performed following lithotripsy, no postoperative ureteral stricture was detected in Horse #1 which had follow-up ureteroscopy 6 mo after lithotripsy.

No peri-operative complications occurred in our study; however, bladder rupture has been reported in a horse with cystic calculi that underwent shock wave lithotripsy (9). Lithotripsy, therefore, can be associated with complications and the procedure should be performed by an experienced operator familiar with the technique and settings.

All horses recovered rapidly from the procedure and were discharged. No dysuria, pollakiuria, or any signs of colic were noted during hospitalization. This is an important advantage compared to the standard surgical flank approach which sometimes requires general anesthesia, postoperative recovery, and increases the risk of colic (21).

There is no doubt that ureteral obstruction will cause damage to the kidney if the obstruction is not relieved; however, it is unclear whether the ureteral stones in these horses resulted from or caused the kidney disease (5,22). This limited case series did not provide clear evidence that relief of ureteral obstruction in horses improves kidney function.

As mentioned, neither kidney stones nor fragments (in the ureter or pelvis) were removed as they did not result in luminal obstruction and therefore did not impair urine flow. In human and veterinary medicine (especially in dogs and cats), it is only recommended that nephrolithiasis be removed if it contributes to outflow obstruction or results in recurrent infection or pain (23).

Nonobstructive nephrolithiasis does not significantly affect progression of renal disease, further supporting our decision to leave them in place (23,24). However, even nonobstructive ureteroliths have potential to cause morbidity and disease if they move into the ureter or remain in the bladder.

In conclusion, obstructive ureteral stones in horses were successfully removed by retrograde ureteroscopy in conjunction with HYL or EHL. Ureteral access was feasible using the method described. This technique was safe, well-tolerated and did not require general anesthesia. In our limited case series, ureteroscopy and nephoscopy enabled excellent visualization of the upper urinary tract. Application of EHL achieved quicker stone fragmentation and was associated with less mucosal trauma than HYL. Finally, despite removal of obstructive ureteroliths, some horses may experience further deterioration of kidney function. The main limitations of this study were the limited number of horses, along with its descriptive and retrospective nature.