First Reported Case of a Pyrophosphate Kidney Stone in a Human.

Urolithiasis composed of pyrophosphate salts has only been reported in animals, in the form of potassium magnesium pyrophosphate. However, there have been no reports of pyrophosphate stones in humans. Hypophosphatasia is an inherited disease characterized by low alkaline phosphatase activity and elevated levels of pyrophosphate in blood and urine. Urolithiasis is a part of the hypophosphatasia phenotype. The role of elevated urine pyrophosphate levels in the formation of stones in hypophosphatasia is unknown. Here, we report a case of a 60-year-old man with recurrent urolithiasis. The patient's most recent presentation was gross hematuria and his computed tomography scan showed bilateral kidney stones. Stones were removed via retrograde intrarenal surgery. Stone analysis revealed a composition of potassium magnesium pyrophosphate. The patient also has a long history of fracturing bone disease which led to the consideration of hypophosphatasia as the cause of both his bone disease and pyrophosphate stones. Hypophosphatasia was confirmed by genetic analysis. Pyrophosphate has been of interest in the fields of mineral metabolism because of its action as a crystallization inhibitor. However, pyrophosphate at elevated concentrations in the presence of divalent cations can exceed its solubility. Nephrocalcinosis and stone disease have been described in hypophosphatasia; stones have been assumed to be calcium phosphate but no compositional analysis has been reported. This is the first report of human stones composed of pyrophosphate salts, which led to the subsequent diagnosis of hypophosphatasia in this patient.

Development of a burst wave lithotripsy system for noninvasive fragmentation of ureteroliths in pet cats.

BACKGROUND: Upper urinary tract stones are increasingly prevalent in pet cats and are difficult to manage. Surgical procedures to address obstructing ureteroliths have short- and long-term complications, and medical therapies (e.g., fluid diuresis and smooth muscle relaxants) are infrequently effective. Burst wave lithotripsy is a non-invasive, ultrasound-guided, handheld focused ultrasound technology to disintegrate urinary stones, which is now undergoing human clinical trials in awake unanesthetized subjects. RESULTS: In this study, we designed and performed in vitro testing of a modified burst wave lithotripsy system to noninvasively fragment stones in cats. The design accounted for differences in anatomic scale, acoustic window, skin-to-stone depth, and stone size. Prototypes were fabricated and tested in a benchtop model using 35 natural calcium oxalate monohydrate stones from cats. In an initial experiment, burst wave lithotripsy was performed using peak ultrasound pressures of 7.3 (n = 10), 8.0 (n = 5), or 8.9 MPa (n = 10) for up to 30 min. Fourteen of 25 stones fragmented to < 1 mm within the 30 min. In a second experiment, burst wave lithotripsy was performed using a second transducer and peak ultrasound pressure of 8.0 MPa (n = 10) for up to 50 min. In the second experiment, 9 of 10 stones fragmented to < 1 mm within the 50 min. Across both experiments, an average of 73-97% of stone mass could be reduced to fragments < 1 mm. A third experiment found negligible injury with in vivo exposure of kidneys and ureters in a porcine animal model. CONCLUSIONS: These data support further evaluation of burst wave lithotripsy as a noninvasive intervention for obstructing ureteroliths in cats.

The impact of urine collection method on canine urinary microbiota detection: a cross-sectional study.

BACKGROUND: The urinary tract harbors unique microbial communities that play important roles in urogenital health and disease. Dogs naturally suffer from several of the same urological disorders as humans (e.g., urinary tract infections, neoplasia, urolithiasis) and represent a valuable translational model for studying the role of urinary microbiota in various disease states. Urine collection technique represents a critical component of urinary microbiota research study design. However, the impact of collection method on the characterization of the canine urinary microbiota remains unknown. Therefore, the objective of this study was to determine whether urine collection technique alters the microbial populations detected in canine urine samples. Urine was collected from asymptomatic dogs by both cystocentesis and midstream voiding. Microbial DNA was isolated from each sample and submitted for amplicon sequencing of the V4 region of the bacterial 16 S rRNA gene, followed by analyses to compare microbial diversity and composition between urine collection techniques. RESULTS: Samples collected via midstream voiding exhibited significantly higher sequence read counts (P = .036) and observed richness (P = .0024) than cystocentesis urine. Bray Curtis and Unweighted UniFrac measures of beta diversity showed distinct differences in microbial composition by collection method (P = .0050, R2 = 0.06 and P = .010, R2 = 0.07, respectively). Seven taxa were identified as differentially abundant between groups. Pasteurellaceae, Haemophilus, Friedmanniella, two variants of Streptococcus, and Fusobacterium were over-represented in voided urine, while a greater abundance of Burkholderia-Caballeronia-Paraburkholderia characterized cystocentesis samples. Analyses were performed at five thresholds for minimum sequence depth and using three data normalization strategies to validate results; patterns of alpha and beta diversity remained consistent regardless of minimum read count requirements or normalization method. CONCLUSION: Microbial composition differs in canine urine samples collected via cystocentesis as compared to those collected via midstream voiding. Future researchers should select a single urine collection method based on the biological question of interest when designing canine urinary microbiota studies. Additionally, the authors suggest caution when interpreting results across studies that did not utilize identical urine collection methods.

Resolution of urethral obstruction using temporary urethral stents in two female cats.

Case summary: The management of urethral obstructions is well documented in male cats but is less established for females. These cases describe two female cats that presented with non-dissolvable urocystoliths. Urocystoliths were removed by laser lithotripsy and basket retrieval. Following urolith removal, urethral obstruction occurred in both cats. Both cats were successfully managed using temporary urethral stents in lieu of indwelling urethral catheters permitting outpatient, spontaneous recovery of the urethra. Relevance and novel information: Use of temporary urethral stents has not been described in cats. These novel stents are constructed from materials available in most veterinary facilities, placed without advanced imaging and reside entirely within the urethra and vestibule. Temporary stents are used to bypass urethral disease, facilitating outpatient recovery, and are easily removed when no longer needed. For these reasons, temporary stents are a cost-efficient alternative to permanent stents or indwelling urinary catheters attached to closed urine-collection systems.

Frequency of histologic lesions in the kidneys of cats without kidney disease.

OBJECTIVES: In humans, renal aging is associated with an increased frequency of glomerulosclerosis, interstitial fibrosis, inflammation and tubular atrophy. The purpose of this study was to describe the frequency of renal histopathologic lesions in cats without kidney disease. METHODS: A cross-sectional study of archival kidney tissue from 74 cats without kidney disease (serum creatinine <1.6 mg/dl; urine specific gravity >1.035) was carried out: 0-4 years (young, n = 18); 5-9 years (mature, n = 16); 10-14 years (senior, n = 34), 15+ years (geriatric, n = 6). Glomerulosclerosis, tubular atrophy, interstitial inflammation and fibrosis, and the presence or absence of lipid in the interstitium and tubules were scored by a pathologist masked to clinical data. Statistical analyses were performed as appropriate. RESULTS: Geriatric cats had significantly more glomerulosclerosis than mature (P = 0.01) and young cats (P = 0.004). Senior cats had significantly more glomerulosclerosis than young cats (P = 0.006). Glomerulosclerosis was weakly positively correlated with age (r = 0.48; P <0.0001). Geriatric cats had significantly more tubular atrophy than mature (P = 0.02) and young cats (P <0.0001). Senior cats had significantly more tubular atrophy than young cats (P <0.0001). Geriatric cats had significantly more inflammation than senior cats (P = 0.02), mature cats (P = 0.01) and young cats (P <0.0001). Senior cats had significantly more inflammation than young cats (P = 0.004). Geriatric and senior cats had significantly more fibrosis than young cats (P = 0.01 and P = 0.04, respectively). Frequency of tubular lipid increased with age (young: 28%; mature: 56%; senior: 79%; geriatric: 100%) as did the frequency of interstitial lipid (young: 22%, mature: 56%, senior: 85%, geriatric: 100%). CONCLUSIONS AND RELEVANCE: Evidence of renal aging exists in cats. These changes imply that the aging kidney may be more susceptible to injury and impaired healing.

Characterization of the urogenital microbiome in Miniature Schnauzers with and without calcium oxalate urolithiasis.

BACKGROUND: Calcium oxalate (CaOx) uroliths are common in dogs. Humans with CaOx urolithiasis exhibit alterations of the urinary and urogenital microbiomes that might mediate urolith formation. Detection of urogenital microbes associated with CaOx in dogs could inform disease pathophysiology. OBJECTIVE: To identify compositional differences in the urogenital microbiome of Miniature Schnauzers with and without CaOx uroliths. ANIMALS: Nineteen midstream, voided urine samples from Miniature Schnauzers with (n = 9) and without (n = 10) a history of CaOx urolithiasis. METHODS: Analytical cross-sectional study. Microbial DNA was extracted from previously frozen urine samples and sequenced for the bacterial 16S rRNA V3-V4 hypervariable regions. Diversity and composition of microbial populations were compared between urolith formers and controls. RESULTS: Alpha and beta diversity measures were similar between groups. Five individual bacterial taxa differed in abundance (indicator values >0.5 and P < .05): Acinetobacter, 2 Geobacillus variants, and Hydrogenophaga were overrepresented in the urine of urolith formers, and Sphingopyxis was overrepresented in controls. Two distinct subtypes of urine microbial composition were observed based on beta diversity measures, independent of urolith status, and other clinical variables. CONCLUSIONS AND CLINICAL IMPORTANCE: Although we did not detect a difference in the overall urogenital microbial composition between groups, observed differences in individual bacterial taxa might be clinically relevant. For example, Acinetobacter was overrepresented in urolith formers and is associated with CaOx urolithiasis in humans. Two unique clusters of the microbiome were identified, independent of urolith status, which may represent distinct urotypes present in Miniature Schnauzers.

Prevalence and Predictors of Radiographically Apparent Upper Urinary Tract Urolithiasis in Eight Dog Breeds Predisposed to Calcium Oxalate Urolithiasis and Mixed Breed Dogs.

Data on upper urinary tract (UUT) uroliths in dogs are important to understanding their etiology. The aim of this retrospective case-control study was to determine the prevalence and identify predictors of radiographically apparent UUT uroliths in dog breeds at increased risk for calcium oxalate uroliths (CaOx risk breeds) and mixed breed dogs. Radiologist reports of three-view abdominal radiographs were reviewed from 251 purebred dogs of 8 CaOx risk breeds and 68 mixed breed dogs. UUT uroliths were more common in CaOx risk breeds than mixed breed dogs (23% versus 6%, respectively; OR = 4.8, 95% confidence interval [CI] 1.7−18.9, p < 0.001). UUT uroliths were more common in dogs with lower urinary tract (LUT) uroliths (predominantly calcium-containing) than those without (41% versus 5%, respectively; OR = 13.6, 95% CI 6.3−33.1, p < 0.001), and LUT uroliths predicted the presence of UUT uroliths in the multivariable regression (OR = 6.5, 95% CI 2.8−16.7, p < 0.001). Increasing age (p < 0.001) and lower body weight (p = 0.0016) were also predictors of UUT urolith presence in the multivariable regression. The high prevalence of UUT uroliths in dogs with LUT uroliths supports a shared mechanism for their formation.

Clinicopathologic findings and urolith composition for green iguanas (Iguana iguana) with urolithiasis: 21 cases and 132 stones (1996-2020).

OBJECTIVE: To document the clinical signs, diagnosis, and treatment of urolithiasis in green iguanas (Iguana iguana) and to report on the composition of uroliths from green iguanas submitted to the Minnesota Urolith Center for analysis. ANIMALS: 21 green iguanas with urolithiasis. PROCEDURES: Medical record databases of multiple veterinary teaching hospitals were searched from 1996 through 2020. Emails were sent to all facilities that submitted a urolith from a green iguana to the Minnesota Urolith Center from 1996 through 2020. Signalment; presenting complaint; physical examination findings; hematologic, biochemical, and diagnostic imaging findings; treatment; necropsy results; and survival times were described for each patient. RESULTS: Iguanas most commonly presented with nonspecific clinical signs, but 9 of the 21 iguanas had clinical signs associated with the urogenital tract. Twelve iguanas had a palpable mass in the caudal coelom. All uroliths were visible on radiographs. Surgery was performed on 15 iguanas; 3 died secondary to intra- or postoperative complications. Iguanas that underwent surgery had a median survival time of 39 months. Necropsy was performed on 5 iguanas, and urolithiasis contributed to the decision to euthanize or was the cause of death for 4. Uroliths from 132 iguanas were analyzed, and all were composed of 100% uric acid salts. CLINICAL RELEVANCE: Green iguanas with urolithiasis may not have clinical signs or physical examination findings associated with the urinary system, and hematologic and biochemical abnormalities are nonspecific. Green iguanas should be routinely examined for uroliths, and surgical treatment should be pursued.

Evaluation of Temporary Urethral Stents in the Management of Malignant and Nonmalignant Urethral Diseases in Dogs.

Urethral stent placement is a minimally invasive interventional procedure commonly performed by specialists to alleviate urethral obstruction. However, the availability of urethral stents is limited by their high cost and the need for special equipment. The aim of this retrospective study was to describe the construction and placement of an inexpensive temporary urethral stent and to report on its outcome in managing dogs with naturally occurring urethral disease. Temporary stents were placed in the urethra of 17 dogs with malignant and nonmalignant urethral pathologies. The most common indication for temporary stent placement was urethral obstruction. In this population, urethral patency was restored in all dogs. The most frequently reported complication was urinary incontinence. To manage this complication, dogs were diapered. Temporary urethral stents served as a durable and inexpensive alternative to expanding metallic stents. Because temporary stents were constructed from readily available materials and inserted without special equipment, practitioners capable of catheterizing the urethra can insert them on demand.

Variation in mineral types of uroliths from ferrets (Mustela putorius furo) submitted for analysis in North America, Europe, or Asia over an 8-year period.

OBJECTIVE: To compare mineral types of naturally occurring uroliths in ferrets (Mustela putorius furo) from North America, Europe, and Asia and to identify potential risk factors associated with cystine urolithiasis in ferrets. SAMPLES: 1,054 laboratory submission records of uroliths obtained from ferrets between January 1, 2010, and December 31, 2018. PROCEDURES: For this cross-sectional study, the medical records databases at 4 diagnostic laboratories were searched for records of submissions of uroliths obtained from ferrets. Data collection included submission date; ferret sex, neuter status, and age; receiving laboratory and continent; and urolith mineral type. Regression analyses were performed to identify variables associated with cystine uroliths. RESULTS: Of the 1,054 urolith submissions, 1,013 were from North America, with 92.6% (938/1,013; 95% CI, 90.8% to 94.1%) cystine uroliths, and 41 were from Europe and Asia, with only 26.8% (11/41; 95% CI, 15.7% to 41.9%) cystine uroliths. Median age was 2.0 years for ferrets with cystine urolithiasis versus 4.0 years for those with other types of uroliths. Submissions were more likely cystine uroliths for ferrets in North America versus Europe and Asia (adjusted OR [aOR], 59.5; 95% CI, 21.4 to 165.6), for ferrets that were younger (aOR, 0.67; 95% CI, 0.58 to 0.77), or for submissions in 2018 versus 2010 (aOR, 21.1; 95% CI, 5.1 to 87.9). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the proportion of submissions that were cystine uroliths dramatically increased in North America between 2010 and 2018. There is an urgent need to determine underlying causes and mitigate cystine urolithiasis in ferrets.

Multiple variants in XDH and MOCOS underlie xanthine urolithiasis in dogs.

Hereditary xanthinuria is a rare autosomal recessive disease caused by missense and loss of function variants in the xanthine dehydrogenase (XDH) or molybdenum cofactor sulfurase (MOCOS) genes. The aim of this study was to uncover variants underlying risk for xanthinuria in dogs. Affected dogs included two Manchester Terriers, three Cavalier King Charles Spaniels, an English Cocker Spaniel, a Dachshund, and a mixed-breed dog. Four putative causal variants were discovered: an XDH c.654G > A splice site variant that results in skipping of exon 8 (mixed-breed dog), a MOCOS c.232G > T splice site variant that results in skipping of exon 2 (Manchester Terriers), a MOCOS p.Leu46Pro missense variant (Dachshund), and a MOCOS p.Ala128Glyfs*30 frameshift variant that results in a premature stop codon (Cavalier King Charles Spaniels and English Cocker Spaniel). The two splice site variants suggest that the regions skipped are critical to the respective enzyme function, though protein misfolding is an alternative theory for loss of function. The MOCOS p.Leu46Pro variant has not been previously reported in human or other animal cases and provides novel data supporting this residue as critical to MOCOS function. All variants were present in the homozygous state in affected dogs, indicating an autosomal recessive mode of inheritance. Allele frequencies of these variants in breed-specific populations ranged from 0 to 0.18. In conclusion, multiple diverse variants appear to be responsible for hereditary xanthinuria in dogs.

Efficacy of medical dissolution for suspected struvite cystoliths in dogs.

BACKGROUND: Medical dissolution of struvite uroliths in dogs is commonly recommended, but data on success rates and complications are limited. OBJECTIVES: To evaluate the efficacy of medical dissolution for suspected struvite cystoliths in dogs. ANIMALS: Fifty client-owned dogs fed a therapeutic dissolution diet, with or without administration of antimicrobials, for treatment of suspected struvite cystoliths. METHODS: Single institution, retrospective case series. Medical records were reviewed for dogs with at least 1 follow-up visit. Dissolution success, complications, and possible predictors of success were evaluated. RESULTS: Full dissolution of cystoliths was achieved in 58% (29/50) of dogs within a median of 35 days (range, 13-167). Of 21 dogs without success, 7 each had partial dissolution, no dissolution, or undetermined outcome. Uroliths containing >10% nonstruvite mineral were common in the nonsuccess group (11/16 analyzed). Maximum urolith diameter, number of uroliths, and baseline urine pH did not differ significantly between dogs with and without success. Dissolution was more likely in dogs receiving antimicrobial therapy (OR = 16.3, 95% confidence interval 1.9-787.4, P = .002). Adverse events occurred in 9 dogs (18%); urethral obstructions were the most common, but 3 of 4 dogs with this complication were obstructed on presentation, before trial initiation. CONCLUSIONS AND CLINICAL IMPORTANCE: Results support a medical dissolution trial for dogs with suspected struvite cystoliths. If no reduction in urolith size or number occurs by 1 month, a nonstruvite composition is likely, and alternative interventions should be considered. Dogs presenting with urethral obstructions should not be considered candidates for medical dissolution.

Calcium oxalate urolithiasis in juvenile dogs.

BACKGROUND: The features of juvenile-onset calcium oxalate urolithiasis in dogs have not been previously reported. METHODS: Calcium oxalate urolith submissions to the Minnesota Urolith Center between 2012 and 2016 were analyzed to identify those originating from juvenile (≤2 years, n = 510) or mature (7-9 years, n = 39,093) dogs. Breed, sex, urolith salt type and urolith location were compared between groups. Breeds represented in both groups were also compared with respect to sex, urolith salt type and urolith location. RESULTS: French (odds ratios [OR] = 14.7, p < 0.001) and English (OR = 14.3, p < 0.001) Bulldogs were overrepresented in juvenile submissions. All juvenile French and English Bulldogs were male. Across all breeds, juvenile dogs were more likely to be male (89%, p < 0.001) than mature dogs (79%). Juvenile dogs were also more likely to form dihydrate stones compared to mature dogs (33% versus 14%, respectively; p < 0.001). Breed differences were discovered in sex, urolith salt type and stone location. CONCLUSIONS: French and English Bulldogs comprise a greater proportion of juvenile calcium oxalate urolith submissions than expected based on their rarity in mature submissions. Inherited risk factors, particularly X chromosome variants, should be investigated due to the strong breed and sex predispositions identified.

Canine Silica Urolithiasis in Mexico, Associated with the Concentration of Dissolved Silica in Tap Water.

Silica urolithiasis is infrequent in dogs, but in Mexico represents 12.9%. Our hypothesis is the consumption of high amounts of silicates in the diet, especially that dissolved in tap water. The objective of this study was to determine the concentrations of silica in the tap water in different geographical areas and their relationship with cases of silicate urolithiasis in dogs. From 179 cases of silicate urolithiasis, 98.9% were from dogs within a geographic area called the Trans-Mexican Volcanic Belt, which represents a cross shaft to the center of the country. Silica concentrations in tap water ranged between 3 and 76 mg/L, with a range of 27 to 76 mg/L, a mean of 49.9 ± 12 mg/L within the Trans-Mexican Volcanic Belt, and a concentration from 3 to 30 mg/L, with a mean of 16.4 ± 7 mg/L outside this area; these were significantly different (p < 0.001). These findings demonstrate that there is a geographic risk factor for silicate urolithiasis in urolith-forming dogs, related to the consumption of tap water with a high concentration of silica. Further studies are necessary to identify this same pathophysiological association in other species.

Determination of a serum total calcium concentration threshold for accurate prediction of ionized hypercalcemia in dogs with and without hyperphosphatemia.

BACKGROUND: Total serum calcium (tCa) concentrations are poorly predictive of ionized calcium (iCa) status in dogs. HYPOTHESIS: There is an optimal threshold of tCa concentration that is highly predictive of ionized hypercalcemia and this threshold is higher in hyperphosphatemic dogs as compared to nonhyperphosphatemic dogs. ANIMALS: Nonhyperphosphatemic (n = 1593) and hyperphosphatemic (n = 250) adult dogs. METHODS: Retrospective medical record review of paired tCa and iCa concentration measurements in dogs presented to a university teaching hospital over a 5-year period. Positive and negative predictive values, sensitivity, and specificity were calculated for tCa concentration thresholds of 11.0-15.0 mg/dL (upper limit of laboratory reference interval = 11.5 mg/dL) in nonhyperphosphatemic and hyperphosphatemic groups. RESULTS: In nonhyperphosphatemic dogs, an optimal tCa concentration threshold of 12.0 mg/dL resulted in a positive predictive value of 93% (95% confidence interval [CI], 84%-98%) and sensitivity of 52% (95% CI, 43%-61%) for ionized hypercalcemia. An optimal tCa concentration threshold was not identified for hyperphosphatemic dogs. The nonhyperphosphatemic dogs had a higher prevalence of ionized hypercalcemia than the hyperphosphatemic dogs (7 versus 3%, P = .04) and a lower prevalence of ionized hypocalcemia (23 versus 62%, respectively; P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: High tCa concentrations are strongly predictive of ionized hypercalcemia in nonhyperphosphatemic adult dogs and should prompt further diagnostic testing to determine the underlying cause of hypercalcemia. In this population, dogs without increased tCa concentrations rarely had ionized hypercalcemia, but iCa concentrations still should be evaluated in patients with tCa concentrations within the reference interval if there is clinical suspicion for calcium abnormalities.

Epidemiologic evaluation of calcium oxalate urolithiasis in dogs in the United States: 2010-2015.

BACKGROUND: Positive health implications of early recognition of calcium oxalate (CaOx) urolithiasis include increased opportunity for nonsurgical removal, early dietary modification to minimize urolith growth, early removal to avoid urinary obstruction, and early recognition of genetic and metabolic diseases before they contribute to additional morbidity. OBJECTIVES: To identify high- and low-risk dog breeds for CaOx uroliths and to determine the relationship of age and sex to the development of CaOx uroliths. ANIMALS: Calcium oxalate urolith submissions between 2010 and 2015. METHODS: A comparative cross-sectional study was conducted to identify high- and low-risk breeds for CaOx uroliths by comparing cases to multiple comparison groups. At-risk breeds were identified if odds ratios were significant (P value <.05) across all comparison groups. RESULTS: Of 258 898 urolith submissions, 124 285 were CaOx. Calcium oxalate was identified in 212 breeds. Twelve breeds were identified as high-risk breeds, and 14 breeds were identified as low-risk breeds. All high-risk breeds were small dog breeds, and all low-risk breeds were medium to large dog breeds. Overall, the mean age ± standard deviation of the first CaOx urolith was 8.4 ± 2.8 years. CONCLUSIONS AND CLINICAL IMPORTANCE: To achieve the health benefits of preclinical evaluation, breeds at high risk for CaOx urolithiasis should be screened at 5 to 6 years of age, which is 2 to 3 years before likely development of clinical urolithiasis.

Vitamin D metabolism in dogs with and without hypercalciuric calcium oxalate urolithiasis.

BACKGROUND: There are abnormalities in vitamin D metabolism in people with calcium nephrolithiasis, but limited data are available on vitamin D status in dogs with calcium oxalate (CaOx) urolithiasis. OBJECTIVE: To compare serum concentrations of vitamin D metabolites in dogs with and without hypercalciuric CaOx urolithiasis. ANIMALS: Thirty-eight dogs with (n = 19) and without (n = 19) a history of CaOx urolithiasis and hypercalciuria. METHODS: Retrospective cross-sectional study. Serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2 D], and 24,25-dihydroxyvitamin D [24,25(OH)2 D] were measured. The ratios of 25(OH)D/24,25(OH)2 D and 1,25(OH)2 D/25(OH)D were compared between cases and controls. RESULTS: There were no significant differences between cases and controls when comparing 25(OH)D, 24,25(OH)2 D, 1,25(OH)2 D, or 1,25(OH)2 D/25(OH)D. Cases had higher 25(OH)D/24,25(OH)2 D (median = 1.40, range = 0.98-1.58) compared to controls (median = 1.16, range = 0.92-2.75; P = .01). There was overlap in the ranges for 25(OH)D/24,25(OH)2 D between cases and controls, but 6 cases (32%) had ratios above the control dog range. There was a moderate positive correlation between the ratio of 25(OH)D/24,25(OH)2 D and urinary calcium-to-creatinine ratios (r = 0.40, 95% confidence interval = 0.10-0.64; P = .01). CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest that decreased conversion of 25(OH)D to 24,25(OH)2 D occurs in a subset of dogs with CaOx urolithiasis. Abnormalities in vitamin D metabolism might contribute to stone risk in dogs.

Bone resorption in dogs with calcium oxalate urolithiasis and idiopathic hypercalciuria.

People with calcium oxalate (CaOx) urolithiasis and idiopathic hypercalciuria (IH) often have evidence of increased bone resorption, but bone turnover has not previously been investigated in dogs with these conditions. The aim of this study was to determine whether a marker of bone resorption, ß-crosslaps, differs between dogs with CaOx urolithiasis and IH compared to controls. This retrospective, cross-sectional study used a canine specific ELISA to measure ß-crosslaps concentrations in stored frozen serum samples from 20 dogs with CaOx urolithiasis and IH and 20 breed-, sex-, and age-matched stone-free controls (18 Miniature Schnauzers, 14 Bichons Frise, and 8 Shih Tzus). Dogs with CaOx urolithiasis and IH had lower ß-crosslaps concentrations relative to controls (P = .0043), and ß-crosslaps had a moderate negative correlation with urinary calcium-to-creatinine ratios (r = -0.44, P = .0044). Miniature Schnauzers had lower ß-crosslaps concentrations than the other two breeds (P = .0035). The ELISA had acceptable intra-assay precision, but concentrations decreased when samples were repeatedly assayed over time. Assay recovery rates were also below acceptance criteria. In conclusion, Miniature Schnauzers, Bichons Frise, and Shih Tzus with CaOx urolithiasis and IH have evidence of decreased bone resorption compared to stone-free controls. This suggests that other causes of IH, such as intestinal hyperabsorption of calcium, underlie risk for CaOx urolithiasis in these breeds. Results should be confirmed in larger populations and with other ß-crosslaps assays and additional biomarkers of bone turnover. The stability of canine serum ß-crosslaps after freeze-thaw cycles and storage at various temperatures requires investigation.

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.

Urinary metals in a spontaneous canine model of calcium oxalate urolithiasis.

Calcium oxalate urolithiasis is a common and painful condition in people. The pathogenesis of this disease is complex and poorly understood. Laboratory animal and in vitro studies have demonstrated an effect of multiple trace metals in the crystallization process, and studies in humans have reported relationships between urinary metal concentrations and stone risk. Dogs are a spontaneous model of calcium oxalate urolithiasis, and the metal content of canine calcium oxalate stones mirrors that of human stones. The aim of this study was to test for a relationship between urinary metals and calcium oxalate urolithiasis in dogs. We hypothesized that urinary metals would differ between dogs with and without calcium oxalate urolithiasis. Urine from 122 dogs (71 cases and 51 stone-free controls) was analyzed for calcium and 12 other metals. The cases had higher urinary calcium, copper, iron, and vanadium and lower urinary cobalt. Higher urinary vanadium in the cases was associated with being fed a therapeutic stone-prevention diet. Urinary calcium had a strong positive correlation with strontium and moderate positive correlations with chromium, nickel, and zinc. The results of this study complement the findings of similar human studies and suggest a potential role of trace metals in calcium oxalate urolithiasis. Further investigation into how trace metals may affect stone formation is warranted.