Epidemiologic evaluation of canine urolithiasis in Thailand from 2009 to 2015.

The cross-sectional study described the epidemiology of 8560 canine urolith submissions from Thailand to the Minnesota Urolith Center between January 2009 and December 2015. The frequency of urolith types, the relationships between urolith type and breed, sex, and neutered status, and change of annual submission proportion over the study period were analyzed. Struvite was the most common canine urolith (44%), and was commonly found in intact females with a mean age of 6.3±3.1years. Calcium oxalate was the second most common (27%), more frequently found in intact males with a mean age of 8.8±3.3years. Compound, purine, cystine, calcium phosphate, and silica urolith were less common. During the study period, the proportion of struvite urolith significantly decreased from 48% in 2009 to 39% in 2015 (p<0.001). The proportion of CaOx increased from 21% in 2009 to 32% in 2015 (p<0.001). The results of this study can help veterinarians predict urolith composition to select diagnostic tests and to initiate therapy prior to urolith removal.

Cystinuria Associated with Different SLC7A9 Gene Variants in the Cat.

Cystinuria is a classical inborn error of metabolism characterized by a selective proximal renal tubular defect affecting cystine, ornithine, lysine, and arginine (COLA) reabsorption, which can lead to uroliths and urinary obstruction. In humans, dogs and mice, cystinuria is caused by variants in one of two genes, SLC3A1 and SLC7A9, which encode the rBAT and bo,+AT subunits of the bo,+ basic amino acid transporter system, respectively. In this study, exons and flanking regions of the SLC3A1 and SLC7A9 genes were sequenced from genomic DNA of cats (Felis catus) with COLAuria and cystine calculi. Relative to the Felis catus-6.2 reference genome sequence, DNA sequences from these affected cats revealed 3 unique homozygous SLC7A9 missense variants: one in exon 5 (p.Asp236Asn) from a non-purpose-bred medium-haired cat, one in exon 7 (p.Val294Glu) in a Maine Coon and a Sphinx cat, and one in exon 10 (p.Thr392Met) from a non-purpose-bred long-haired cat. A genotyping assay subsequently identified another cystinuric domestic medium-haired cat that was homozygous for the variant originally identified in the purebred cats. These missense variants result in deleterious amino acid substitutions of highly conserved residues in the bo,+AT protein. A limited population survey supported that the variants found were likely causative. The remaining 2 sequenced domestic short-haired cats had a heterozygous variant at a splice donor site in intron 10 and a homozygous single nucleotide variant at a branchpoint in intron 11 of SLC7A9, respectively. This study identifies the first SLC7A9 variants causing feline cystinuria and reveals that, as in humans and dogs, this disease is genetically heterogeneous in cats.

Comparison of foods with differing nutritional profiles for long-term management of acute nonobstructive idiopathic cystitis in cats.

OBJECTIVE: To evaluate the effect of nutrition on recurrent clinical signs of lower urinary tract (LUT) disease in cats with idiopathic cystitis. DESIGN: Randomized, controlled, masked clinical trial. ANIMALS: 31 cats with acute nonobstructive idiopathic cystitis. PROCEDURES: Cats were assigned to receive 1 of 2 foods (a cystitis prevention or control food) that differed in mineral (calcium, phosphorous, and magnesium), antioxidant, and fatty acid profiles. Owners documented LUT signs daily for up to 1 year. The primary endpoint was the number of recurrent episodes in which a cat had multiple (≥ 2 concurrent) LUT signs within a day (defined as multiple-sign day). Consecutive days in which a cat had multiple LUT signs were considered as a single episode. RESULTS: 4 cats fed prevention food and 2 cats fed control food were excluded from analysis because of noncompliance, gastrointestinal signs, food refusal, or owner voluntary withdrawal. The proportion of cats fed prevention food that had ≥ 1 recurrent episode of multiple-sign days (4/11) was not significantly lower than that of cats fed control food (9/14). However, cats fed prevention food had significantly lower mean incidence rates for recurrent episodes of multiple-sign days (0.7 episodes/1,000 cat-days) and episodes of hematuria (0.3 episodes/1,000 cat-days), dysuria (0.2 episodes/1,000 cat-days), and stranguria (0.2 episodes/1,000 cat-days) as single LUT signs, compared with cats fed control food (5.4, 3.4, 3.1, and 3.8 episodes/1,000 cat-days, respectively). Significantly fewer cats fed prevention food required analgesics (4/11), compared with cats fed control food (12/14). CONCLUSIONS AND CLINICAL RELEVANCE: Foods with differing nutritional profiles appeared to impact mean incidence rates of recurrent feline idiopathic cystitis-associated signs.

Risk factors for calcium carbonate urolithiasis in goats.

OBJECTIVE: To identify demographic or signalment factors associated with calcium carbonate urolith formation in goats. DESIGN: Retrospective case series and case-control study. ANIMALS: 354 goats with calcium carbonate uroliths (case animals) and 16,366 goats without urinary tract disease (control animals). PROCEDURES: Medical records of the Minnesota Urolith Center were reviewed to identify case goats for which samples were submitted between January 1, 1984, and December 31, 2012. Control goats evaluated at US veterinary teaching hospitals in the same time period were identified by searching Veterinary Medical Database records. Age, breed, sex, reproductive status, geographic location, season, and anatomic location of collected uroliths were analyzed to identify risk or protective factors associated with calcium carbonate urolithiasis. RESULTS: Nigerian dwarf goats had higher odds of developing calcium carbonate uroliths than did Pygmy goats (reference group). Several breeds had lower odds of this finding, compared with Pygmy goats; odds were lowest for mixed, Anglo-Nubian, and Toggenburg breeds. Breeds of African origin (Pygmy, Nigerian Dwarf, and Boer) comprised 146 of 275 (53%) case goats with data available. Goats of African descent had a higher risk of developing calcium carbonate uroliths than did goats of non-African descent (reference group). Males and neutered goats had higher odds of calcium carbonate urolithiasis, compared with females and sexually intact goats, respectively. Age category, geographic location, and season were associated with detection of calcium carbonate uroliths. CONCLUSIONS AND CLINICAL RELEVANCE: Goats with calcium carbonate uroliths were typically neutered males, > 1 year of age, and of African descent. This study identified factors associated with calcium carbonate urolithiasis in goats; however, these associations do not allow conclusions regarding cause-and-effect relationships.

An APRT mutation is strongly associated with and likely causative for 2,8-dihydroxyadenine urolithiasis in dogs.

2,8-Dihydroxyadenine (2,8-DHA) urolithiasis in people is caused by autosomal recessive mutations in the adenine phosphoribosyltransferase gene (APRT). 2,8-DHA urolithiasis has recently been reported in two dogs, but, to the authors' knowledge, no studies have yet investigated the genetic basis for susceptibility to the development of 2,8-DHA urolithiasis in this species. Our aim was to sequence APRT in dogs affected by 2,8-DHA urolithiasis and compare the results to clinically healthy dogs of similar ancestral lineages. Our hypothesis was that we would identify an autosomal recessive mutation in APRT that is associated with the disease. The case population consisted of six dogs with a history of 2,8-DHA urolithiasis: five Native American Indian Dogs (NAIDs) and a mixed breed. The control population consisted of adult NAIDs with no history of urolithiasis. We sequenced APRT and identified a missense mutation in a highly conserved codon of APRT (c.260G>A; p.Arg87Gln). The c.260A mutation was present in a homozygous state in all six dogs with 2,8-DHA urolithiasis, and it was strongly associated with the disease. This exact missense mutation has been previously reported to cause loss of APRT enzyme function in a human cell line, and it is likely a causative mutation in dogs. Therefore, the dog offers a naturally-occurring genetic animal model for 2,8-DHA urolithiasis.

Efficacy of two commercially available, low-magnesium, urine-acidifying dry foods for the dissolution of struvite uroliths in cats.

OBJECTIVE: To compare the efficacy and safety of using 2 commercially available, low-magnesium, urine-acidifying dry foods to dissolve sterile struvite uroliths in cats. DESIGN: Prospective, multicenter, randomized clinical trial . SAMPLE: 37 cats with presumed struvite uroliths. PROCEDURES: Cats were randomly assigned to be fed 1 of 2 low-magnesium, urine-acidifying dry foods (food A or B). For each cat, physical examination, urinalysis, and abdominal radiography were performed weekly to assess treatment response. RESULTS: 32 cats had complete urolith dissolution. Mean ± SD times for a 50% reduction in urolith size (0.69 ± 0.1 weeks) and complete urolith dissolution (13.0 ± 2.6 days) were significantly shorter for cats fed food A, compared with those (1.75 ± 0.27 weeks and 27.0 ± 2.6 days, respectively) for cats fed food B. At study termination, mean ± SD urine pH (6.083 ± 0.105) for cats fed food A was lower than that (6.431 ± 0.109) for cats fed food B. In 5 cats, uroliths did not dissolve and were subsequently determined to be composed of 100% ammonium urate (n = 4) or 100% calcium oxalate (1). Adverse events associated with diet were not observed in any of the cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dietary dissolution is safe and effective for eradication of sterile struvite uroliths in cats. Cats fed food A had faster urolith dissolution than did cats fed food B. Lack of a reduction in urolith size at 2 weeks after diet initiation was indicative of misdiagnosis or noncompliance.

Epidemiological evaluation of cystine urolithiasis in domestic ferrets (Mustela putorius furo): 70 cases (1992-2009).

OBJECTIVE: To determine the prevalence of cystine uroliths in domestic ferrets with urolithiasis and determine whether age, breed, sex, reproductive status, anatomic location, and season are risk factors associated with cystine urolith formation. DESIGN: Retrospective cross-sectional case-control study. SAMPLE: Records of 435 ferrets (Mustela putorius furo) with uroliths submitted for analyses between 1992 and 2009, of which 70 were cystine uroliths. PROCEDURES: Specific descriptive information was obtained about each ferret to determine whether specific risk factors were associated with the development of cystine uroliths. RESULTS: Cystine uroliths comprised 70 of the 435 (16%) uroliths. Cystine uroliths were more common in male (n = 54) than in female (16) ferrets. All cystine uroliths were retrieved from the lower portion of the urinary tract (bladder and urethra [n = 67]) or were voided (3); none of the uroliths were retrieved from the upper portion of the urinary tract (kidney and ureters). CONCLUSIONS AND CLINICAL RELEVANCE: Awareness of the prevalence of cystine uroliths along with knowledge of etiologic, demographic, and environmental risk and protective factors for urolithiasis may facilitate development of surveillance strategies that result in earlier detection of cystinuria. Genetic factors associated with this disease have not yet been reported in ferrets, but a familial pattern of inheritance determined to be a major underlying factor in cystine urolithiasis in dogs and humans suggests that this may be a factor in ferrets and that the parent stock of ferrets in the present study may have been inbred.

Effects of storage in formalin on composition of canine and feline uroliths.

OBJECTIVE: To determine whether storage in neutral-buffered 10% formalin in vitro has any effect on the composition of biogenic minerals of canine and feline uroliths. DESIGN: Prospective in vitro study. SAMPLE POPULATION: Canine and feline uroliths submitted to the Minnesota Urolith Center from 34 dogs and 27 cats. PROCEDURES: Submissions from each dog or cat consisted of multiple uroliths of a single mineral type. After retrieval from the urinary tract, none of the uroliths had been placed in a preservative before submission. Evaluated uroliths were exclusively composed of the following: only struvite (uroliths from 5 dogs and 5 cats), calcium oxalate (5 dogs and 5 cats), calcium phosphate apatite (5 dogs and 5 cats), cystine (5 dogs and 5 cats), ammonium urate (5 dogs and 5 cats), or silica (5 dogs). One urolith from each dog or cat was quantitatively analyzed by polarized light microscopy, infrared spectroscopy, or both. Another urolith from the same animal was immersed in 1 mL of neutral-buffered 10% formalin for 48 hours at room temperature (22.5°C). Uroliths exposed to formalin were then air-dried for 30 minutes, and the analysis was repeated. RESULTS: After exposure to formalin, a portion of every struvite urolith was transformed into newberyite. This was not observed with any other urolith mineral type. Quantitative mineral analysis of nonstruvite uroliths revealed no detectable change in mineral composition. However, 3 of 10 ammonium urate uroliths dissolved when placed in formalin. CONCLUSIONS AND CLINICAL RELEVANCE: To avoid misdiagnosis of mineral composition, uroliths should not be immersed in formalin prior to analysis.

Risk factors for urate uroliths in cats.

OBJECTIVE: To identify demographic factors associated with urate urolithiasis in cats and determine whether the rate of urolith submission to a laboratory had changed over time. DESIGN: Case series and case-control study. ANIMALS: Cases consisted of 5,072 cats with urate uroliths submitted to the Minnesota Urolith Center between January 1, 1981, and December 31, 2008. Controls consisted of 437,228 cats without urinary tract diseases identified in records of the Veterinary Medical Database during the same period. PROCEDURES: Information on cat breed, age, sex, reproductive status, and location of uroliths was used to identify risk factors. Changes in annual urolith submission rates were evaluated. RESULTS: Purebred cats had significantly higher odds of developing urate uroliths than did cats of mixed breeding (reference group). On the other hand, cats of the Abyssinian, American Shorthair, Himalayan, Manx, and Persian breeds had significantly lower odds of developing urate uroliths than did mixed breeds. Neutered cats were 12 times as likely to develop urate uroliths as were sexually intact cats. Cats in all age groups had significantly increased odds of developing urate uroliths, compared with cats < 1 year of age (reference group). Cats ≥ 4 but < 7 years of age had the highest odds of all groups and were 51 times as likely to develop urate uroliths as were cats < 1 year of age. Urolith submission rates did not change significantly with time. CONCLUSIONS AND CLINICAL RELEVANCE: Findings of this study suggested that the typical cat with urate uroliths was a purebred neutered cat, 4 to 7 years old, with uroliths in the bladder or urethra. This information may be helpful in predicting mineral composition of uroliths in vivo. However, no conclusions can be made regarding cause-and-effect relationships.

Effects of a urolith prevention diet on urine compositions of glycosaminoglycans, Tamm-Horsfall glycoprotein, and nephrocalcin in cats with calcium oxalate urolithiasis.

OBJECTIVE: To evaluate urine concentrations of glycosaminoglycans, Tamm-Horsfall glycoprotein, and nephrocalcin in cats fed a diet formulated to prevent calcium oxalate uroliths. ANIMALS: 10 cats with calcium oxalate urolithiasis. PROCEDURES: In a previous study conducted in accordance with a balanced crossover design, cats were sequentially fed 2 diets (the diet each cat was consuming prior to urolith detection and a diet formulated to prevent calcium oxalate uroliths). Each diet was fed for 8 weeks. At the end of each 8-week period, a 72-hour urine sample was collected. Concentrations of glycosaminoglycans, Tamm-Horsfall glycoprotein, and the 4 isoforms of nephrocalcin in urine samples collected during that previous study were measured in the study reported here. RESULTS; Diet had no effect on the quantity of Tamm-Horsfall glycoprotein and nephrocalcin in urine. However, the urine concentration of glycosaminoglycans was significantly higher during consumption of the urolith prevention diet. CONCLUSIONS AND CLINICAL RELEVANCE: Feeding a urolith prevention diet increased the urine concentration of glycosaminoglycans, which are glycoprotein inhibitors of growth and aggregation of calcium oxalate crystals.

Followership and leadership: promoting unity in academia.

As we plan our future in the twenty-first century, many believe that we face more problems than ever before, including the rising cost of sustaining teaching, research, and service programs in a climate in which state support for higher education is declining. Some commonly held opinions blame leaders and thus propose solutions that are based on the premise that leaders who are perceived to be ineffective should be replaced by those who promise to correct the situation. Leadership is a frequently discussed term, whereas the concept of followership is generally ignored. Followership, however, has been an unidentified facet of leadership in veterinary academia. The present article examines the premise that the primary way to solve the expanding list of problems facing academia is by zealously seeking, teaching, and encouraging leadership. Organizations such as universities succeed or fail on the basis of how well followers follow in addition to how well leaders lead. The truth is that without followers there would be no leaders. Yet the train of followers is almost nonexistent in most educational settings. Striving to recruit and entertain the proper balance of followers and leaders should be one of the goals of every college of veterinary medicine.

Epidemiology of struvite uroliths in ferrets: 272 cases (1981-2007).

OBJECTIVE: To confirm that the predominant mineral type in naturally occurring uroliths in ferrets is struvite; to determine whether age, breed, sex, reproductive status, geographic location, season, and anatomic location are risk factors associated with urolith formation in ferrets; to compare features of struvite uroliths in cats with those in ferrets; and to determine whether there is a logical evidence-based rationale for clinical trials of the safety and efficacy of diet-induced dissolution of struvite uroliths in ferrets. DESIGN: Retrospective case-control study. ANIMALS: 408 ferrets with uroliths (272 struvite uroliths) from the Minnesota Urolith Center, and 6,528 control ferrets from the Veterinary Medical Database. PROCEDURES: Historical information was obtained about each ferret. The association between proposed risk factors and outcome (struvite urolith formation) was assessed. RESULTS: Sterile struvite was the predominant mineral in uroliths in ferrets. Neutered male ferrets had a significantly increased risk of developing sterile struvite uroliths. A significant association was also found between increasing age and the detection of struvite uroliths. Struvite uroliths in ferrets were more likely to be retrieved from the lower urinary tract than from the upper urinary tract. CONCLUSIONS AND CLINICAL RELEVANCE: Knowledge of predominant mineral type in uroliths along with insight into etiologic, demographic, and environmental risk and protective factors for urolithiasis may facilitate development of surveillance strategies that result in earlier detection of uroliths in ferrets. Modification of risk factors, including dietary risk factors, may help to minimize urolith formation, dissolve existing uroliths, and minimize urolith recurrence.

Enterolith with a stingray spine nidus in an Atlantic bottlenose dolphin (Tursiops truncatus).

In March 2006, a dead, male bottlenose dolphin (Tursiops truncatus) was found in the salt marsh in Charleston, South Carolina, United States. During necropsy, an enterolith was found completely obstructing the intestinal lumen. Further examination of the enterolith revealed a stingray spine nidus. Most terrestrial enteroliths are composed primarily of struvite (magnesium ammonium phosphate); however, the majority of the enterolith discovered in the stranded dolphin was composed of calcium phosphate carbonate. This case provides an interesting comparison of the variation in the mineral composition between terrestrial and marine enteroliths.

Rate and frequency of recurrence of uroliths after an initial ammonium urate, calcium oxalate, or struvite urolith in cats.

OBJECTIVE: To determine frequency of and interval until recurrence after initial ammonium urate, calcium oxalate, and struvite uroliths in cats and whether breed, age, or sex was associated with increased risk for urolith recurrence. DESIGN: Case-control study. ANIMALS: 4,435 cats with recurrent uroliths. PROCEDURES: To identify recurrence of uroliths in cats for which uroliths were submitted for analysis at the Minnesota Urolith Center in 1998, the facility's database was searched for urolith resubmissions from the same cats between 1998 and 2003. Risk factors and differences in mean interval until recurrence were assessed. RESULTS: Of 221 cats with ammonium urate uroliths in 1998, 29 (13.1%) had a first and 9 (4.1%) had a second recurrence. Mean interval until recurrence was 22 and 43 months for the first and second recurrence, respectively. Of 2,393 cats with calcium oxalate uroliths in 1998, 169 (7.1%) had a first, 15 (0.6%) had a second, and 2 (0.1%) had a third recurrence. Mean interval until recurrence was 25, 38, and 48 months for the first, second, and third recurrence, respectively. Of 1,821 cats with struvite uroliths in 1998, 49 (2.7%) had a first and 3 (0.2%) had a second recurrence. Mean interval until recurrence was 29 months for first and 40 months for second recurrences. CONCLUSIONS AND CLINICAL RELEVANCE: These results provided insights into the frequency of urolith recurrence in cats. Because some uroliths associated with recurrent episodes probably were not submitted to our facility, our data likely represented an underestimation of the actual recurrence rate.

Efficacy and safety of laser lithotripsy in fragmentation of urocystoliths and urethroliths for removal in dogs.

OBJECTIVE: To characterize the efficacy and safety of laser lithotripsy in the fragmentation of urocystoliths and urethroliths for removal in dogs. DESIGN: Prospective case series. ANIMALS: 100 dogs with naturally occurring urocystoliths and urethroliths. PROCEDURES: Via cystoscopy, laser lithotripsy was performed to fragment uroliths. Basket retrieval and voiding urohydropropulsion were used to remove fragments. Postprocedural contrast cystography was performed to assess efficacy and safety. In 40 dogs, midstream urine samples were collected just prior to laser lithotripsy (day 0) and on days 1, 3, and 11 after laser lithotripsy to assess inflammation. RESULTS: Urolith removal was complete in 82% of dogs (52/66 with only urocystoliths, 17/17 with only urethroliths, and 13/17 with urocystoliths and urethroliths). Urolith removal was incomplete in 18 dogs; of these dogs, 9, 6, and 3 had urolith fragments >or= 3 mm, 1 to < 3 mm, and < 1 mm in diameter, respectively. Sex (female) was the most significant predictor for success. Median procedure time was 72 minutes. Two dogs developed urinary tract obstruction following laser lithotripsy. Hematuria was detected in 53% of dogs on day 0 and in 84%, 13%, and 3% of dogs on days 1, 3, and 11, respectively. Leukocyturia was detected in 13% of dogs on day 0 and in 47%, 0%, and 3% of dogs on days 1, 3, and 11, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that use of laser lithotripsy was a safe and effective alternative to surgical removal of urocystoliths and urethroliths in dogs.