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.

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.

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.

Comparison of laser lithotripsy and cystotomy for the management of dogs with urolithiasis.

OBJECTIVE: To compare efficacy, required resources, and perioperative complications between laser lithotripsy and cystotomy for urolith (ie, urocystoliths and urethroliths) removal in dogs. DESIGN: Retrospective case-control study. ANIMALS: 66 dogs with urolithiasis treated by laser lithotripsy (case dogs) and 66 dogs with urolithiasis treated by cystotomy (control dogs). PROCEDURES: Medical records were reviewed. Complete urolith removal rate, resources (ie, duration of hospitalization, procedure time, anesthesia time, procedure cost, and anesthesia cost), and complications (ie, hypotension, hypothermia, incomplete urolith removal, and requirement of an ancillary procedure) were compared between cystotomy group dogs and lithotripsy group dogs. RESULTS: Duration of hospitalization was significantly shorter for lithotripsy group dogs, compared with cystotomy group dogs. Procedure time was significantly shorter for cystotomy group dogs, compared with lithotripsy group dogs. Cost of anesthesia was significantly less for cystotomy group dogs, compared with lithotripsy group dogs. No significant differences were found between cystotomy group dogs and lithotripsy group dogs with regard to urolith removal rate, procedure cost, anesthesia time, or any of the evaluated complications. CONCLUSIONS AND CLINICAL RELEVANCE: Laser lithotripsy is a minimally invasive procedure that has been shown to be safe and effective in the removal of urocystoliths and urethroliths in dogs. No significant differences were found in the required resources or complications associated with laser lithotripsy, compared with cystotomy, for removal of uroliths from the lower portions of the urinary tract of dogs. Laser lithotripsy is a suitable, minimally invasive alternative to surgical removal of urethroliths and urocystoliths in dogs.

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.

Changing paradigms in the diagnosis of urolithiasis.

A paradigm shift is a fundamental change from a traditional model of thinking. This article presents four paradigm shifts in the diagnoses of urolithiasis, based on the experiences of the authors in the treatment of uroliths in dogs and cats. Case examples are provided to illustrate points regarding urine storage, ultrasonography, use of radiography to assure complete removal of uroliths, and the frequency of upper tract uroliths in cats.

Changing paradigms of feline idiopathic cystitis.

Since 1996, when the authors assembled the existing body of knowledge about lower urinary tract disease in cats, the understanding of the biological behavior and pathologic features of naturally occurring feline idiopathic cystitis has increased. No single model explains all the biological variability observed in cats with idiopathic cystitis. The authors' experience and available evidence indicate that feline idiopathic cystitis represents a syndrome resulting from a number of separate underlying but potentially interrelated mechanisms rather than a disease with a single cause. Identification of safe and effective treatment and prevention strategies of feline idiopathic cystitis will likely vary, depending on the underlying causes.

Paradigm changes in the role of nutrition for the management of canine and feline urolithiasis.

Results of experimental and clinical investigation have confirmed the importance of dietary modifications in medical protocols designed to promote dissolution and prevention of uroliths. The objectives of medical management of uroliths are to arrest further growth and to promote urolith dissolution by correcting or controlling underlying abnormalities. For therapy to be most effective, it must promote undersaturation of urine with lithogenic crystalloids by 1) increasing the urine solubility of crystalloids, 2) increasing the volume of urine in which crystalloids are dissolved or suspended, and 3) reducing the quantities of lithogenic crystalloids in urine. This article summarizes and applies evidence about nutritional management of urolithiasis derived from experimental and clinical studies of cats and dogs performed at the Minnesota Urolith Center.

Changing paradigms in the frequency and management of canine compound uroliths.

This article discusses the composition, formation, and treatment of canine compound uroliths and the importance of recognizing the unique causal factors that may be present in each individual patient. After first giving a detailed analysis of what compound uroliths are and how they form, the authors give examples and data from canine uroliths submitted between 1981 and 2007. Finally, the article discusses the importance of this data when formulating management strategies for individual patients to either dissolve existing stones or minimize urolith recurrence.

Drug-induced urolithiasis.

The prevalence of uroliths that contain drugs, their metabolites, or toxic ingredients in dogs, cats, and other animals is unknown. The authors examine specific drugs and their use in the animal population. They discuss these drugs in terms of uroliths and urolith formation in a variety of animals, making recommendations on which drugs can be safely used based on evidence from the authors' own studies and the literature.

Changing paradigms in ethical issues and urolithiasis.

This article defines the ethics involved in the medical treatment of patients. Using a case example, the authors discuss the treatment of uroliths from an ethical and medical perspective. Uroliths are defined, and treatment is discussed and explained.

Changing paradigms in the treatment of uroliths by lithotripsy.

Surgery remains a common procedure for removal of uroliths from the lower urinary tract of dogs. Incorporation of intracorporeal laser lithotripsy and extracorporeal shock wave lithotripsy has provided impetus for a paradigm shift in the way veterinarians manage urinary stones, however. These minimally invasive techniques provide a successful alternative to surgical urolith extraction.

Canine uroliths: frequently asked questions and their answers.

This article is devoted to answering frequently asked questions from veterinarians, veterinary technicians, and pet owners about urolithiasis and the detection, treatment, and prevention of various types of uroliths from various locations in the urinary tract. It has been divided into the following topics: urolith analysis, urolith types, diagnosis, treatment and prevention, urolith recurrence, urinalysis, diet, water, and miscellaneous. The information is geared toward both professionals (eg, the chemical analysis of uroliths) and pet owners (eg, the practical considerations of diet). It includes photographs of various stones and a checklist of factors that suggest the probable mineral composition of canine uroliths.

Melamine and cyanuric acid-induced crystalluria, uroliths, and nephrotoxicity in dogs and cats.

This article discusses the 2007 recall of canned pet food because of concerns about adverse effects on kidney function of cats and dogs. The discovery of melamine and cyanuric acid in the foods is detailed. Case studies, including clinical, pathology, histology, and toxicology findings, are presented. An attempt is being made to identify the minerals in the uroliths and kidney tissues of affected animals.

Quantitative analysis of 4468 uroliths retrieved from farm animals, exotic species, and wildlife submitted to the Minnesota Urolith Center: 1981 to 2007.

Knowledge of the mineral composition of uroliths in various species of animals can help veterinarians predict the mineral composition of stones in vivo. This information is important because dissolution of existing uroliths, or minimizing further growth of uroliths in situ, is dependent on knowledge of the mineral composition of uroliths. With this objective in mind, this report summarizes the results of quantitative mineral analysis of uroliths retrieved from 4468 animals sent to the Minnesota Urolith Center. It also encompasses the most extensive database about uroliths from animals other than domesticated dogs and cats found in the literature.

Analysis of 451,891 canine uroliths, feline uroliths, and feline urethral plugs from 1981 to 2007: perspectives from the Minnesota Urolith Center.

Urolithiasis is a general term referring to the causes and effects of stones anywhere in the urinary tract. Urolithiasis should not be viewed conceptually as a single disease with a single cause, but rather as a sequela of multiple interacting underlying abnormalities. Thus, the syndrome of urolithiasis may be defined as the occurrence of familial, congenital, or acquired pathophysiologic factors that, in combination, progressively increase the risk of precipitation of excretory metabolites in urine to form stones (ie, uroliths). The following epidemiologic discussion is based on quantitative analysis of 350,803 canine uroliths, 94,778 feline uroliths, and 6310 feline urethral plugs submitted to the Minnesota Urolith Center from 1981 to 2007.

Evaluation of the reproducibility and accuracy of pH-determining devices used to measure urine pH in dogs.

OBJECTIVE: To evaluate the reproducibility and accuracy of 4 portable pH meters, a reagent strip, and pH paper for measuring urine pH in dogs. DESIGN: Prospective masked randomized study. SAMPLE POPULATION: 201 free-catch urine samples from 114 hospitalized dogs. PROCEDURES: Urine samples were divided into 2-mL aliquots. Measurements of urine pH were obtained by use of a laboratory benchtop pH meter, 4 portable pH meters, a urine reagent strip, and pH paper. The pH of each aliquot was measured within 4 hours of collection by an evaluator unaware of the aliquot's origin. To assess reproducibility, the coefficient of variation for each pH measurement device was calculated. To determine which device was most accurate, the degree of agreement among the different devices was assessed in comparison with the benchtop pH meter, which was considered the reference method. RESULTS: 3 of the 4 portable pH meters had nearly perfect agreement with the reference method. The reagent strip and pH paper had moderate to poor agreement with the reference method. CONCLUSIONS AND CLINICAL RELEVANCE: Urine pH measurements should be made by use of a portable or benchtop pH meter when accurate measurements are crucial for diagnosis or treatment. Reagent strips and pH papers are useful in obtaining pH approximations but are not recommended when accurate measurements of urine pH are required.

A case-control study of the effects of nephrolithiasis in cats with chronic kidney disease.

OBJECTIVE: To determine whether nephrolithiasis was associated with an increase in mortality rate or in the rate of disease progression in cats with naturally occurring stage 2 (mild) or 3 (moderate) chronic kidney disease. DESIGN: Retrospective case-control study. ANIMALS: 14 cats with stage 2 (mild) or 3 (moderate) chronic kidney disease (7 with nephroliths and 7 without). PROCEDURES: All cats were evaluated every 3 months for up to 24 months. Possible associations between nephrolithiasis and clinicopathologic abnormalities, incidence of uremic crises, death secondary to renal causes, and death secondary to any cause were evaluated. RESULTS: There were no clinically important differences in biochemical, hematologic, or urinalysis variables between cats with and without nephroliths at baseline or after 12 and 24 months of monitoring. No associations were detected between nephrolithiasis and rate of disease progression, incidence of uremic crises, or death. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in cats with mild or moderate chronic kidney disease, nephrolithiasis was not associated with an increase in mortality rate or in the rate of disease progression. Findings support recommendations that cats with severe kidney disease and nephrolithiasis be managed without surgery.

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.

Clinical evaluation of dietary modification for treatment of spontaneous chronic kidney disease in cats.

Objective-To determine whether a renal diet modified in protein, phosphorus, sodium, and lipid content was superior to an adult maintenance diet in minimizing uremic episodes and mortality rate in cats with stage 2 or 3 chronic kidney disease (CKD). Design-Double-masked, randomized, controlled clinical trial. Animals-45 client-owned cats with spontaneous stage 2 or 3 CKD. Procedures-Cats were randomly assigned to an adult maintenance diet (n = 23 cats) or a renal diet (22) and evaluated trimonthly for up to 24 months. Efficacy of the renal diet, compared with the maintenance diet, in minimizing uremia, renal-related deaths, and all causes of death was evaluated. Results-Serum urea nitrogen concentrations were significantly lower and blood bicarbonate concentrations were significantly higher in the renal diet group at baseline and during the 12- and 24-month intervals. Significant differences were not detected in body weight; Hct; urine protein-to-creatinine ratio; and serum creatinine, potassium, calcium, and parathyroid hormone concentrations. A significantly greater percentage of cats fed the maintenance diet had uremic episodes (26%), compared with cats fed the renal diet (0%). A significant reduction in renal-related deaths but not all causes of death was detected in cats fed the renal diet. Conclusions and Clinical Relevance-The renal diet evaluated in this study was superior to an adult maintenance diet in minimizing uremic episodes and renalrelated deaths in cats with spontaneous stage 2 or 3 CKD.