Urinary calculi in a shih tzu dog with hyperadrenocorticism

Abstract

An 11-year-old spayed female shih tzu dog was presented with pollakiuria, stranguria, and hematuria. Radiographs revealed a large number of radiodense urinary calculi within the bladder. Physical examination, complete blood cell count, biochemistry and ACTH stimulation test suggested possible hyperadrenocorticism. A cystotomy was performed and the patient was treated for hyperadrenocorticism.

An 11-year-old, 10.3-kg spayed female shih tzu dog was presented to a small animal veterinary clinic for pollakiuria, inappropriate urination, stranguria, and gross hematuria which had progressed over the past few months. The owner reported the patient had a lifelong history of polydipsia and a history of urinary calculi 10 y earlier which had been managed medically with a dry, urinary-stone dissolution diet (Canine Urinary SO; Royal Canin Veterinary Diet, Guelph, Ontario). Urinary signs associated with the stones had resolved following switching to this diet until recently.

Physical examination revealed a body condition score (BCS) of 4.5/5 (AAHA Guidelines), keratoconjunctivitis sicca in the left eye, and a tense abdomen on palpation. The remainder of the physical examination was unremarkable. Analysis of a free-flow mid-stream urine sample revealed the urine was cloudy, light yellow in color, and isosthenuric (specific gravity of 1.012) with medium to large granular casts, markedly high numbers of red blood cells (RBCs), moderate numbers of white blood cells, a moderate concentration of cocci bacteria, and amorphous debris. Urine dipstick analysis (Chemstrip 10A; Roche, Mannheim, Germany) revealed a pH of 7.5, presence of moderate protein, and marked RBCs. The patient was prescribed marbofloxacin (Zeniquin; Zoetis, Kirkland, Quebec), 2.75 mg/kg body weight (BW), PO, q24h for 14 d, to treat possible urinary tract infection. A 2-week re-check was scheduled for repeat urinalysis with instructions to return sooner should clinical signs persist or worsen.

Three days following initial assessment, the dog was returned due to progression in the severity and frequency of incontinence, pollakiuria, stranguria, and hematuria. At home, the dog was almost constantly straining and urinating minute amounts of frank blood. On physical examination, a pendulous abdomen and thin hair coat were noted in addition to previous findings, suggestive of potential hyperadrenocorticism.

A complete blood (cell) count (CBC) (Vet Scan HM5; Abaxis, Budapest, Hungary) revealed a mildly elevated RBC count [9.0 × 10⁶/μL; reference interval (RI): 5.5 to 8.5 × 10⁶/μL], mildly elevated hemoglobin (HGB, 197 g/L; RI: 120 to 180 g/L), mildly elevated mean corpuscular hemoglobin concentration (MCHC, 358 g/L; RI: 310 to 340 g/L), and a mildly elevated platelet count (PLT, 553 × 10³/μL; RI: 200 to 500 × 10³/μL). A biochemistry panel (Catalyst One Chemical Analyzer; IDEXX, Westbrook, Maine, USA) showed elevated albumin (41 g/L; RI: 22 to 39 g/L), increased alanine aminotransferase (ALT; 168 U/L; RI: 10 to 125 U/L), markedly elevated alkaline phosphatase (ALKP; > 2000 U/L; RI: 23 to 212 U/L), mildly increased gamma-glutamyl transferase (GGT; 12 U/L; RI: 0 to 11 U/L), and increased cholesterol (8.91 mmol/L; RI: 2.84 to 8.26 mmol/L). Differential diagnoses for results seen on blood analysis included hyperadrenocorticism, liver disease, cholestatic disease, and portosystemic shunt.

Right lateral and ventrodorsal abdominal radiographs showed the urinary bladder filled with multiple radiodense uroliths (Figure 1). No uroliths were visible in the urethra, ureters, or kidneys, although superimposition with material within the small intestine made it difficult to evaluate the kidneys. There were no other abnormal radiographic findings.

Figure 1.

Ventrodorsal (a) and right lateral (b) abdominal radiographs of an 11-year-old spayed female shih tzu dog that was presented for pollakiuria, stranguria, and hematuria. The radiographs show large numbers of radiodense uroliths within the bladder (arrows). No other radiographic abnormalities were noted.

An ACTH stimulation test was performed with cosyntropin (Cortrosyn; Amphastar Pharmaceuticals, Rancho Cucamonga, California, USA), 0.06 mg/kg BW, IM, which showed elevated pre-cortisol concentration (174 nmol/L; RI: 28 to 120 nmol/L) and elevated 1 h post-cortisol concentration (737 nmol/L; RI: 220 to 550 nmol/L). The patient was diagnosed with hyperadrenocorticism and treatment with trilostane (Vetoryl; Dechra, Skipton, UK) was initiated at 2.91 mg/kg BW, PO, q24h until the time of a recheck in 14 d.

Meloxicam (Metacam Oral Suspension; Boehringer Ingelheim, Burlington, Ontario), 0.1 mg/kg BW, PO, q24h for 5 d, was prescribed for pain management, marbofloxacin was continued, and the patient received probiotics (Progut Plus Powder; Ceva Animal Health, Cambridge, Ontario), 2 g, PO, q12h to help the gastric flora to withstand the effects of antibiotic administration.

A cystotomy was performed 7 d following initial presentation. A retrograde urinary catheter was passed before surgery to check for patency and allow intraoperative flushing. A ventral midline incision was made from xiphoid to pubis, at which time the skin was noted to be thin and the abdominal wall appeared stretched. Urine was removed from the bladder by cystocentesis and submitted for urinalysis and culture and sensitivity (IDEXX Laboratories, Markham, Ontario). The lumen of the urinary bladder had innumerable uroliths, ranging from < 1 mm to > 3 cm in diameter. Stones were manually removed from the bladder and lavaged through the urinary catheter using warm saline. Urinary calculi were submitted for analysis (Canadian Veterinary Urolith Centre, Guelph, Ontario). A small section of the bladder wall was excised for aerobic and anaerobic culture and sensitivity. The bladder was closed with 2-layer simple continuous and Cushing patterns. Intra-operative radiographs revealed no stones remaining in the bladder and urethra. The abdomen was closed in 3 layers.

The patient was administered penicillin (Duplocillin; MSD Animal Health, Kirkland, Quebec), 0.1 mL/kg BW, IV, cefovecin (Convenia; Zoetis), 7.8 mg/kg BW, IV, hydromorphone (HYDROmorphone HP; Sandoz, Boucherville, Quebec), 0.1 mg/kg BW IV, and meloxicam (Metacam; Boehringer Ingelheim, Burlington, Ontario), 0.05 mg/kg BW, IV, during the surgery. Meloxicam was prescribed for postoperative pain.

Urinalysis of the submitted cystocentesis sample identified red turbid urine with a specific gravity of 1.020, pH of 8.0, large numbers of RBCs, and proteinuria. Urine sediment was composed of high numbers of neutrophils, few transitional epithelial cells, a moderate to high number of white blood cells, and triple phosphate crystals. Urine, bladder wall, and bladder stone swab culture yielded no bacterial growth.

Analysis of the calculi identified 2 types of stones: i) smooth irregular beige stones composed of approximately 50% struvite and 50% calcium phosphate carbonate at the nidus, stone, and shell; and ii) smooth, oval, and tan stones composed of approximately 95% calcium phosphate carbonate and 5% struvite.

On a follow-up visit to the clinic 14 d following cystotomy, the patient appeared to have fully recovered from surgery without complications and was urinating normally. An ACTH stimulation test performed 4 h following administration of trilostane (Vetoryl; Dechra), 2.91 mg/kg BW, PO, revealed low pre-cortisol levels (< 27.6, nmol/L; RI: 28 to 120 nmol/L), and post-cortisol levels (183 nmol/L; RI: 220 to 550 nmol/L). The dose of trilostane was reduced to 10 mg (0.97 mg/kg BW), q24h for 13 d, until the next re-check.

Discussion

In this patient, the development of urinary stones was likely multifactorial with hyperadrenocorticism and patient signalment as likely contributing factors to the development of mixed struvite and calcium phosphate stones.

An examination of urinary calculi samples submitted to the Canadian Veterinary Urolith Centre from 1998 to 2008 showed that 39% of canine calculi were struvite and only 2% calcium phosphate in composition (1). Of all samples analyzed, over half were accounted for by shih tzus, miniature schnauzers, bichon frises, lhasa apsos, and Yorkshire terriers (1). It has been proposed that small breed dogs are predisposed to urinary stone formation due to smaller urine volumes relative to bladder size, and a decreased frequency of micturition (2). This patient’s history of urolith development at a young age further suggests genetic predisposition to formation of urinary calculi (3).

Calcium phosphate uroliths are uncommon, and are usually promoted by an underlying metabolic disorder such as hyperparathyroidism, renal tubular acidosis, excess dietary calcium intake, and, as in this case, hyperadrenocorticism (1,4,5). One study showed that dogs with hyperadrenocorticism had a 10-fold higher likelihood of developing calcium-containing uroliths than do normal dogs (6). Elevated blood cortisol has been implicated in increasing glomerular filtration of calcium, thus promoting high urine calcium levels and likelihood of formation of calcium phosphate calculi (7,8).

Struvites in dogs are frequently a result of urinary tract infections by urease-producing bacteria, most notably, Staphylococcus pseudintermedius and Proteus spp. (9). By-products of urea metabolism by these organisms promote a neutral to alkaline urine environment. The basic urine pH decreases the solubility of struvite crystals and promotes calculus formation (9,10). This patient’s urine pH on presentation was 7.5, consistent with a struvite-promoting environment. In the described case, it is possible that elevated glucocorticoid levels from hyperadrenocorticism caused immunosuppression and increased susceptibility to urinary tract infection (11). Glucosuria, though not detected in this patient, may facilitate bacterial growth and reduce neutrophilic response to infection (11).

Despite lifelong maintenance on a struvite dissolution and calculus prevention diet, this patient had large quantities of mixed calculi composed of struvite and calcium phosphate. It is important to note that dietary control of struvites may fail in the presence of an uncontrolled urinary tract infection by urease-producing bacteria (12). While it was known that the patient had a history of calculi early in life, information on calculus type and course of treatment at that time is unknown. It is possible that dietary medical therapy was not effective in elimination of the previous urinary stones, which persisted as a nidus for infection and subsequent stone formation (13). Attempts to dissolve the stones through diet may also fail due to insufficient urine volume to bathe the stones; both small breed and presence of pre-existing urinary calculi are possible contributors (14). Additionally, mixed calculi with components not amenable to dietary dissolution may lead to failure (10). As such, a shell of calcium phosphate surrounding the struvite component may have reduced the effectiveness of therapy (10,13,15).