Abstract
Two feline littermates were diagnosed with calcium oxalate uroliths. Both had been maintained on a commercially available dry diet with reduced magnesium and urine acidifying properties. One female littermate was diagnosed by visualising the stones by radiographs while the second littermate, also female, became blocked when one of the uroliths lodged in the urethra. Two other, unrelated cats in the household, of similar age and raised under the same conditions, did not develop calcium oxalate uroliths.
The first of two littermates, a fourteen-year-old spayed female domestic short hair, presented with a primary complaint of weight loss. The cat weighed 3.9 kg at presentation (normal weight 5.4 kg). She resided in a multi-cat household and was fed on a low magnesium, urine-acidifying diet (Hill's Science Diet), Feline Maintenance (Hill's Prescription Diets), exclusively. All the cats were strictly indoor cats. This littermate was also experiencing intermittent vomiting and diarrhoea of 1-year duration that was responsive to prednisolone acetate (Upjohn Company). The presumptive diagnosis in this case was inflammatory bowel disease. Physical exam revealed a rapid heart rate (240 bpm), a normal temperature, and a thin conformation. The CBC showed a mild neutrophilia (12 692 cells/ul, reference 5 300 to 12 500 cells/ul), a monocytosis (1 169 cells/ul, reference less than 900 cells/ul), and a mild eosinophilia (835 cells/ul, reference less than 500 cells/ul). Serum chemistries revealed elevated ALT (93 iu/l, reference 30–80 iu/l), elevated AP (36 iu/l, reference 11–28 iu/l), elevated urea (10.9 mmol/l, reference 7.1–10.1 mmol/l), elevated creatinine (106.1 umol/l, reference 62–97 umol/l), hyperglycaemia (14.9 mmol/l, reference 3.7–6.9 mmol/l), reduced phosphorus (1.1 mmol/l, reference 1.2–1.7 mmol/l), and increased potassium (4.7 mmol/l, reference 3.2–4.4 mmol/l). Serum calcium was slightly elevated at 2.7 mmol/l (reference 2.2–2.6 mmol/l). T4 levels were within normal limits at 21 nmol/l (reference range 21–40 nmol/l). The bladder could not be palpated for cystocentesis, but a small amount of bloody urine was voided. Prednisolone acetate was discontinued and antibiotic therapy initiated (amoxicillin, 22 mg/kg bodyweight per os [PO] bid, SmithKline Beecham). Metronidazole (10 mg/kg PO bid, Searle) was also given for the diarrhoea.
After 2 weeks, the cat's condition continued to decline. The bladder could not be palpated for a cystocentesis. On urinalysis of a voided sample, the pH was 6.0 with a specific gravity of 1.026. Proteinuria (4+), and glucosuria (5+) were also present. Sediment examination revealed a haematuria (RBCs too numerous to count [TNTC]), 7–9 white blood cells (WBCs) per high-power field (hpf), bacteria (cocci, TNTC), 2–3 epithelial cells per hpf, and amorphous phosphate crystals. Antibiotics were changed to enrofloxacin (5 mg/kg bodyweight PO bid, Bayer) and cyproheptadine (1 mg PO bid, West Point) prescribed to stimulate the appetite.
After 3 weeks, the haematuria had not resolved and a second urinalysis was performed. Again, the bladder could not be palpated for a cystocentesis. The voided sample had a specific gravity of 1.028, a pH of 6.5, 2+ proteinuria, and negative to 1+ for glucose. Red blood cells were TNTC on sediment examination and there were 5–6 WBC/hpf, as well as bacteria. Epithelial cells were also present as cell aggregates. Urine cytology indicated a suppurative inflammatory response and transitional cell hyperplasia. No neoplastic cells were seen, but neoplasia could not be ruled out. The cat had continued to lose weight and was now 3.3 kg. A second CBC showed a lymphopenia (334 cells/ul, reference 1,500–7,000 cells/ul) and a low globulin level on serum chemistries (26 g/l, reference 34–44 g/l). Other abnormalities on serum chemistries included elevated ALT and AP (176 iu/l and 38 iu/l, respectively), elevated urea (13.9 mmol/l), elevated creatinine (124 umol/l), elevated potassium (5.0 mmol/l) and reduced total protein (61 g/l, reference 64–78 g/l). Serum calcium levels were within normal limits (2.5 mmol/l). Abdominal radiographs showed the presence of multiple bladder calculi. An exploratory laparotomy and cystotomy was performed. The cat was induced with pentobarbitone and maintained on isoflurane. Abnormal gross pathological findings included omental adhesions from a previous episode of peritonitis and exploratory laparotomy, icteric abdominal fat, chronic passive congestion of the liver, enlarged mesenteric lymph nodes and a thickened bladder wall. The intestine was active with peristalsis. Biopsies were taken of the pancreas, liver, mesenteric lymph node and jejunum. The bladder was isolated and an incision made on the dorsal aspect. Interior to the bladder were six gray uroliths ranging in size from 5 to 6 mm (Fig 1). The following day, the urine was clear and the frequency of urination reduced. The cat was started on cephadroxil (11 mg/kg PO bid, Fort Dodge) and a pancreatic enzyme supplement (1/4 teaspoon with meals, Pancreazyme, Daniels Pharmaceuticals), derived from porcine pancreas, was added to her post-surgery diet (Hill's Prescription Diet Canine/Feline A/D; Hill's Prescription Diets).
Calcium oxalate uroliths obtained from the first littermate (three stones, left) and the second littermate (single stone, right).
Histopathology was consistent with inflammatory bowel disease. The jejunum showed a lymphocytic/plasmacytic infiltrate in the lamina propria and submucosa. The villi were severely blunted and hypercellular. The pancreas was moderately fibrotic with connective tissue replacing pancreatic acini. The islet cells were replaced by amyloid. There was mild centrilobular swelling and degeneration of hepatocytes. The mesenteric lymph node was hyperplastic with germinal centres and numerous plasma cells.
After learning of the histopathology, the cat was subsequently placed on a novel protein diet (Limited Ingredient Diet, Venison and Potato, Innovative Veterinary Diets, Corona) as well as continuing the pancreatic enzyme supplement. Three of the six stones were sent for analysis to the Minnesota Urolith Center, St Paul. The stones consisted of 100% calcium oxalate monohydrate with a nidus of 90% calcium oxalate monohydrate and 10% calcium oxalate dihydrate. Two years later, the cat has remained asymptomatic for urinary tract and inflammatory bowel disease.
The second littermate, also a spayed female, presented on emergency with urinary tract obstruction, 3 months after her littermate's cystotomy. That evening, the owner had noticed the cat vocalising and attempting to urinate outside the litter box. However, no urine was voided. The cat was also vomiting. On presentation, the cat was panting and in distress. The physical exam revealed an enlarged, turgid bladder. Cystocentesis produced more than 100 ml of cloudy, red urine. Urinalysis showed a pH of 6.0, 4+ protein, RBCs TNTC, and 10–15 WBC/hpf. Serum chemistries showed an elevated urea (50.0 mmol/l), elevated glucose (13.2 mmol/l), elevated potassium (8.5 mmol/l), reduced sodium (142 mmol/l, reference 146–156 mmol/l), and increased chloride (122 mmol/l, reference 104–116 mmol/l). The cat was masked down with isoflurane anesthetic and a urinary catheter passed without meeting an obstruction. The catheter was sutured into place and the bladder flushed with sterile saline. The cat recovered from anaesthesia uneventfully and remained in the hospital for the next 3 days. During that time, the urine flow was unobstructed and the cat was sent home.
Four days later, the cat again presented on emergency with urinary obstruction. Serum chemistries showed a normal potassium level (4.0 mmol/l), increased chloride (121 mmol/l), increased glucose (8.3 mmol/l) and an increased urea (11.8 mmol/l). Urinalysis showed a specific gravity of 1.030, a pH of 6.0, 1+ protein, and the presence of non-haemolysed RBCs. The cat underwent a second mask induction with isoflurane and urinary catheter placement. Again, the catheter was passed easily without meeting an obstruction. Urine immediately flowed through and around the catheter. Since it was a spayed female, the primary rule-outs at this time were a neoplastic or inflammatory mass blocking the urethra.
After 2 days in intensive care, the cat underwent cystoscopy. Resistance was met shortly after entering the urethra where a ∼4 mm round yellow mass was found. The mass was hydropropulsed back into the bladder. An attempt was made to manually remove the mass without success. In addition, a second urolith could also be seen in the bladder lumen. At this point, a cystotomy was scheduled for the following day. Anaesthesia was induced by isoflurane. An incision was made into the bladder, whereupon two uroliths, one 6 mm and one 5 mm, were found within the lumen (Fig 1). A biopsy of the bladder showed a moderate mucosal hyperplasia and submucosal oedema. The bladder was also swabbed for culture. Upon receiving culture and sensitivity results, the antibiotic was changed to gentamicin (4 mg/kg subcutaneously sid) and ampicillin (20 mg/kg PO bid) to combat the
Discussion
The prevalence of calcium oxalate uroliths has been increasing. The increase in their occurrence parallels the introduction of acidifying diets low in magnesium. Correspondingly, the prevalence of struvite uroliths have declined from 78% in 1981 to 34% in 1994 (Osborne et al 1997), while in 1994, calcium oxalate uroliths accounted for 54% of the analysed stones. In human medicine, dietary and genetic factors contribute to the incidence of calcium oxalate stones (Goodman et al 1997, Leonetti et al 1998). In cats, there has been shown a breed predisposition for the development of calcium oxalate uroliths in Burmese, Himalayan and Persian breeds (Thumchai et al 1996).
We report the occurrence of calcium oxalate uroliths in two mixed-breed littermates. Both littermates presented within a 3-month period, while two other non-related cats in the same household did not develop uroliths. Genetic factors might have a role in the occurrence of these uroliths in these littermates. There were also other factors that may have contributed. All the cats in the household were fed a low magnesium, acidifying diet, exclusively. The presence of magnesium has been shown to act as an inhibitor of calcium oxalate urolith formation (Rattan et al 1994a b). In both cats, the urine pH was significantly low at ranges from 6.0 to 6.5. Previous studies have suggested that calcium oxalate crystals occur at urine pH of 6.3 to 6.7 (Osborne et al 1994). A history of being fed a single source diet, being neutered and being kept indoors may also have contributed (Osborne et al 1994, Kirk et al 1995).
Hyperparathyroidism could contribute to the formation of calcium oxalate stones by increasing blood concentrations of calcium and its urinary excretion. Parathyroid hormone levels in these littermates were not checked because calcium levels were normal over a 5-year period for one littermate, while the other had only slightly elevated calcium levels at initial presentation (2.7 mmol/l, reference 2.2–2.6 mmol/l). A previous study (McClain et al 1999) correlating the presence of hypercalcaemia and the incidence of calcium oxalate stones showed calcium ranges of 2.9–3.6 mmol/l (reference range 2.2–2.9 mmol/l) in cats. The cats were placed on high fibre diets and the calcium levels subsequently decreased to normal levels. In all of these cats, the parathyroid hormone levels were low to normal. Other reports have indicated that calcium levels of 2.8–3.4 mmol/l were prevalent in cats with calcium oxalate uroliths (Osborne et al 1994).
Both cats underwent cystotomies to remove the uroliths. A recent case report described the use of voiding urohydropropulsion to remove 37 calcium oxalate stones from a cat (Folger 1999). All of these uroliths measured less than 4 mm. In the two cats reported here, all of their uroliths were greater than 4 mm, and one of the litter-mates became blocked with a stone measuring 5 mm. This would confirm the previous report's assertion that in order to use voided urohydropropulsion, all of the stones must be less than 4 mm, and that a stone 5 mm would probably block the urethra. If the urethra is at all compromised by inflammation, even uroliths less than 4 mm may not be able to pass. Cystoscopy was used in this report to visualise the blockage and hydropropulse the urolith back into the bladder. A catheter was easily passed around the urolith on two occasions. Without cystoscopy, it would have been difficult to recognise the blockage as a urolith, and to gauge the correct position of a catheter for retrograde hydropropulsion.
The incidence of calcium oxalate has increased with the widespread use of low magnesium, urine-acidifying diets. Currently, there is no medical therapy that can be employed to dissolve existing calcium oxalate uroliths. Cystotomies are the current method of treatment, although voided urohydropropulsion is an alternative in cases where it can absolutely be determined that all existing uroliths are less than 4 mm.