Impact of hyperlipidaemia on intermediary metabolism, faecal microbial metabolites and urinary characteristics of lipoprotein lipase deficient vs. normal cats.

Findings in humans and rats indicate that hyperlipidaemia may be associated with enhanced endogenous oxalate (Ox) synthesis, which may be relevant for calcium oxalate (CaOx) urolith formation. Moreover, changes in lipid metabolism are proposed to negatively affect gut microbiota. This study aimed to investigate those potential interactions in hyperlipidaemic cats. Therefore, 10 normal control cats and seven lipoprotein lipase (LPL)-deficient cats were fed a low-fat diet for seven weeks. During the last week of the study, cats were housed in metabolic cages to collect urine and faeces. Blood was taken on the last day of the study. The LPL-deficient cats had significantly higher serum triglyceride concentrations than normal cats, while lactate dehydrogenase (LDH) activity was not different. Urinary relative supersaturation with CaOx, urinary Ox, calcium, and citrate excretions, and urine pH did not differ between groups. Lower faecal acetic, propionic and total short-chain fatty acid concentrations were observed in the LPL-deficient cats. In conclusion, hyperlipidaemia does not appear to be a specific risk factor for CaOx urolith formation in cats. In contrast to results in rats, hyperlipidaemia was not accompanied by elevated serum LDH activity. As LDH can synthesise Ox from glycolate or other precursors, this might be one possible explanation for the similar urinary parameters in the LPL-deficient and normal cats. Non-diet-induced hyperlipidaemia was not associated with marked changes in faecal microbial metabolites, suggesting no differences in the composition of the intestinal microbiota.

Evaluation of the Live Biotherapeutic Product, Asymptomatic Bacteriuria Escherichia coli 2-12, in Healthy Dogs and Dogs with Clinical Recurrent UTI.

BACKGROUND: Antimicrobial resistance is an emerging problem. HYPOTHESIS/OBJECTIVE: To investigate the safety and efficacy of a live biotherapeutic product, ASB E. coli 2-12 for UTI treatment. ANIMALS: Six healthy research dogs; nine client-owned dogs with recurrent UTI. METHODS: Prospective noncontrolled clinical trial. For safety data, research dogs were sedated, a urinary catheter was inserted into the bladder; 1010 CFU/mL of ASB E. coli 2-12 was instilled. Urine was cultured on days 1, 3, and 8 post-instillation and dogs were observed for lower urinary tract signs (LUTS). For client-owned dogs, ASB E. coli 2-12 was instilled similarly and urine cultures analyzed on days 1, 7, and 14 days postinstillation. RESULTS: No LUTS were noted in any of the 6 research dogs after ASB E. coli 2-12 infusion. Pulse field gel electrophoresis (PFGE) studies confirmed the bacterial strains isolated matched that ASB E. coli 2-12 strain. Four of the nine client-owned dogs had complete or nearly complete clinical cures by day 14. Of these four dogs, 3 also had microbiologic cures at day 14; one of these dogs had subclinical bacteriuria (in addition to ASB E. coli 2-12). Three of these four dogs had ASB E. coli 2-12 isolated from their urine at day 14. With the exception of mild, temporary, self-limiting, hyporexia in two dogs on the day of biotherapeutic administration, there were no major adverse effects. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest ASB E. coli 2-12 is safe and should be investigated in a larger controlled study evaluating clinical UTI in dogs.

Nanoparticle Tracking Analysis for the Enumeration and Characterization of Mineralo-Organic Nanoparticles in Feline Urine.

Urinary stone disease, particularly calcium oxalate, is common in both humans and cats. Calcifying nanoparticles (CNP) are spherical nanocrystallite material, and are composed of proteins (fetuin, albumin) and inorganic minerals. CNP are suggested to play a role in a wide array of pathologic mineralization syndromes including urolithiasis. We documented the development of a clinically relevant protocol to assess urinary CNP in 9 healthy cats consuming the same diet in a controlled environment using Nanoparticle Tracking Analysis (NTA®). NTA® is a novel method that allows for characterization of the CNP in an efficient, accurate method that can differentiate these particles from other urinary submicron particulates. The predominant nanoscale particles in feline urine are characteristic of CNP in terms of their size, their ability to spontaneously form under suitable conditions, and the presence of an outer layer that is rich in calcium and capable of binding to hydroxyapatite binders such as alendronate and osteopontin. The expansion of this particle population can be suppressed by the addition of citrate to urine samples. Further, compounds targeting exosomal surfaces do not label these particulates. As CNP have been associated with a number of significant urologic maladies, the method described herein may prove to be a useful adjunct in evaluating lithogenesis risk in mammals.

ACVIM Small Animal Consensus Recommendations on the Treatment and Prevention of Uroliths in Dogs and Cats.

In an age of advancing endoscopic and lithotripsy technologies, the management of urolithiasis poses a unique opportunity to advance compassionate veterinary care, not only for patients with urolithiasis but for those with other urinary diseases as well. The following are consensus-derived, research and experience-supported, patient-centered recommendations for the treatment and prevention of uroliths in dogs and cats utilizing contemporary strategies. Ultimately, we hope that these recommendations will serve as a foundation for ongoing and future clinical research and inspiration for innovative problem solving.

Urinary Neutrophil Gelatinase-associated Lipocalin as a Marker for Identification of Acute Kidney Injury and Recovery in Dogs with Gentamicin-induced Nephrotoxicity.

BACKGROUND: Acute kidney injury (AKI) is associated with high mortality rates in dogs, which may be a consequence of late recognition using traditional diagnostic tests. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein-induced during kidney injury that may identify AKI earlier than traditional tests. OBJECTIVES/HYPOTHESIS: To evaluate urinary NGAL (uNGAL) and uNGAL-to-urinary creatinine ratio (UNCR) as early markers of kidney injury and recovery in an AKI model in dogs. It was hypothesized that these markers would document AKI earlier than serum creatinine concentration. ANIMALS: Five purpose-bred dogs. METHODS: Prospective study. Acute kidney injury, defined as a > 50% increase in serum creatinine concentration above baseline, was induced in dogs by gentamicin administration (8-10 mg/kg SC q8h). Blood and urine collected for biochemical analyses and uNGAL and urinary creatinine concentrations, respectively, during AKI induction and recovery. RESULTS: Acute kidney injury was diagnosed significantly earlier based on a 7-fold increase in UNCR compared to a > 50% increase in serum creatinine concentration (day 8; range, 2-10 mg/dl vs day 16; range, 14-19 mg/dl; P = .009). During recovery, the initial decrease in UNCR preceded the decrease in serum creatinine concentration by a median of 2 days. The uNGAL changes paralleled UNCR changes, but the increase in uNGAL was triphasic; the initial peak occurred earlier than UNCR (median, day 11 versus median, day 19). CONCLUSIONS AND CLINICAL IMPORTANCE: The UNCR was early marker of gentamicin-induced AKI and its decrease documented onset of renal recovery. Additional studies are needed to validate this marker in dogs with naturally occurring renal injury.

Antimicrobial Susceptibility Patterns in Urinary Tract Infections in Dogs (2010-2013).

BACKGROUND: Urinary tract infections (UTIs) are common in dogs. The responsible bacterial populations have evolved with increasing resistance to many antimicrobials. OBJECTIVE: To characterize the antimicrobial susceptibility patterns of canine urinary tract isolates over a 51-month period. ANIMALS: One thousand six hundred and thirty-six bacterial isolates from 1,028 dogs. METHODS: Aerobic bacterial isolate growth and susceptibility data from urine cultures of dogs were identified, retrospectively. Medical records were reviewed to obtain signalment, comorbidities, and antimicrobial use in the previous 30 days. The UTIs were further categorized as uncomplicated, complicated, or pyelonephritis. RESULTS: Common bacterial isolates identified were Escherichia coli (52.5%), Staphylococcus spp. (13.6%), and Enterococcus spp. (13.3%). In vitro susceptibility among all isolates varied for commonly prescribed antimicrobials (amoxicillin [59%], amoxicillin/clavulanic acid [76%], cephalexin [66%], enrofloxacin [74%] and trimethoprim-sulfamethoxazole [86%]). For all antimicrobials tested (except aminoglycosides), in vitro susceptibility was higher in uncomplicated versus complicated infections (P < .05). Uncomplicated infection isolate susceptibility rates remained ≤90% for PO administered antimicrobials. Administration of amoxicillin, doxycycline, and enrofloxacin, but not amoxicillin/clavulanic acid in the previous 30 days was associated with resistance to that antimicrobial. Multidrug resistant isolates of E. coli and Staphylococcus spp. were more common in dogs with complicated than uncomplicated UTIs (36% versus 21%, P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: In vitro susceptibility was highly variable and no PO administered antimicrobial had >90% efficacy among isolates tested. Multidrug resistance was frequent among isolates tested suggesting that routine culture and susceptibility testing is indicated. Previously prescribed antimicrobials may affect empirical choices made pending susceptibility testing.

Evaluation of neutrophil gelatinase-associated lipocalin as a marker of kidney injury in dogs.

BACKGROUND: Acute kidney injury (AKI) is a common and often fatal disorder in dogs. HYPOTHESIS: Urine neutrophil gelatinase-associated lipocalin (NGAL)/creatinine ratio is a sensitive and specific biomarker of AKI in dogs. ANIMALS: Ninety-four dogs. METHODS: Prospective study. Dogs were classified as follows: (1) healthy dogs, (2) dogs with lower urinary tract disorders, (3) dogs with chronic kidney disease (CKD), (4) dogs with azotemic International Renal Interest Society (IRIS) AKI Grades II-V, and (5) dogs with IRIS AKI Grade I (nonazotemic). Urinary NGAL was quantitated in each dog using an ELISA assay and concentrations were expressed as a ratio to urinary creatinine concentration from the same specimen, and designated the urinary NGAL/creatinine ratio (UNCR). RESULTS: There was a significant difference in UNCR among the study groups (P < .001). Both the azotemic and nonazotemic AKI groups had higher UNCR when compared with all other groups (P < .001 for all pairs). There was a statistically significant difference in UNCR between dogs diagnosed with CKD compared with dogs with lower urinary tract diseases (P = .005) as well as between dogs with CKD and healthy dogs (P = .001). Receiver operator characteristics (ROC) analysis of UNCR as an indicator of azotemic and nonazotemic AKI had an area under the ROC curve of 0.94 and 0.96, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: NGAL/creatinine ratio is a sensitive and specific marker of AKI. It can be used to screen patients at risk for AKI and can be utilized to diagnose milder forms of AKI potentially earlier in the course of the disease.

Tumoral calcinosis form of hydroxyapatite deposition disease in related red-bellied short-necked turtles, Emydura subglobosa.

Ten of 12 red-bellied short-necked turtles from a single clutch presented at 9 months of age with multiple white to tan nodules on their feet. Histologically, the nodules were composed of large periarticular deposits of mineralized crystalline material that extended into the joint spaces of interphalangeal joints and was surrounded by granulomatous inflammation and fibrosis. Crystallographic analysis determined the material to be apatite (calcium phosphate hydroxide) consistent with the tumoral calcinosis form of hydroxyapatite deposition disease (HADD). HADD has previously been described in aquatic turtles and rarely lizards and must be differentiated from gout in reptiles. A cause for the tumoral calcinosis lesions in these turtles could not be determined; however, based on previous reports in this species, a species-specific predilection, in conjunction with unknown environmental factors, is suspected. The use of the terms HADD, pseudogout (calcium pyrophosphate crystal deposition disease), and calcinosis circumscripta has been inconsistent, creating confusion in the literature.

Evaluation of the efficacy and safety of high dose short duration enrofloxacin treatment regimen for uncomplicated urinary tract infections in dogs.

BACKGROUND: Uncomplicated urinary tract infections (UTI) in dogs usually are treated with antimicrobial drugs for 10-14 days. Shorter duration antimicrobial regimens have been evaluated in human patients. HYPOTHESIS: A high dose short duration (HDSD) enrofloxacin protocol administered to dogs with uncomplicated UTI will not be inferior to a 14-day treatment regimen with amoxicillin-clavulanic acid. ANIMALS: Client-owned adult, otherwise healthy dogs with aerobic bacterial urine culture yielding ≥ 10(3) CFU/mL of bacteria after cystocentesis. METHODS: Prospective, multicenter, controlled, randomized blinded clinical trial. Enrolled dogs were randomized to group 1 (enrofloxacin 18-20 mg/kg PO q24h for 3 days) or group 2 (amoxicillin-clavulanic acid 13.75-25 mg/kg PO q12h for 14 days). Urine cultures were obtained at days 0, 10, and 21. Microbiologic and clinical cure rates were evaluated 7 days after antimicrobial treatment was discontinued. Lower urinary tract signs and adverse events also were recorded. RESULTS: There were 35 dogs in group 1 and 33 in group 2. The microbiologic cure rate was 77.1 and 81.2% for groups 1 and 2, respectively. The clinical cure rate was 88.6 and 87.9% for groups 1 and 2, respectively. Cure rates between groups did not differ according to the selected margin of noninferiority. CONCLUSIONS AND CLINICAL IMPORTANCE: HDSD enrofloxacin treatment was not inferior to a conventional amoxicillin-clavulanic acid protocol for the treatment of uncomplicated bacterial UTI in dogs. Further research is warranted to determine if this protocol will positively impact owner compliance and decrease the emergence of antimicrobial resistance.

Holmium:YAG laser lithotripsy for urolithiasis in horses.

BACKGROUND: Laser lithotripsy has been used as an alternative to surgical removal of uroliths. OBJECTIVE: To describe the procedure and efficacy of laser lithotripsy for removal of lower urinary tract uroliths in horses. Additionally, the ultrastructure and the differences in mineralogy and microstructure from 1 successful and 1 unsuccessful laser lithotripsy case are described. ANIMALS: Six client-owned horses with 7 episodes of naturally occurring urocystoliths, urethroliths, or both. METHODS: Retrospective study of all horses treated between 2006 and 2008 by laser lithotripsy. All horses were sedated followed by laser lithotripsy. Quantitative urolith analysis was performed in all cases. Ultrastructure and microstructure analyses were performed on uroliths from 2 horses. RESULTS: Procedural success was achieved in 5 of 7 laser lithotripsy procedures. No complications occurred as a result of laser lithotripsy. One horse developed uroabdomen likely as a result of manual lithotrite disruption of the bladder after failure of laser lithotripsy. There were differences in microstructure between 1 urolith that was successfully fragmented by laser lithotripsy and 1 urolith that was resistant to laser fragmentation. CONCLUSIONS AND CLINICAL IMPORTANCE: Laser lithotripsy is an effective procedure for removal of some urocystoliths, urethroliths, or both in horses.

Frequency and risk factors for urinary tract infection in cats with diabetes mellitus.

BACKGROUND: Identification and control of infections are important in the management of diabetic cats. Urinary tract infections have not been well characterized in diabetic cats. This retrospective study was performed to review and characterize urinary tract infections in diabetic cats. HYPOTHESIS: Urinary tract infections are common in diabetic cats. ANIMALS: A review was made of the medical records of 141 diabetic cats that had had urine obtained for culture by antepubic cystocentesis and that had not been treated with antibiotics, undergone urinary tract catheterization or urinary tract surgery within 2 weeks of urine collection or had urethral obstruction at the time of urine collection. METHODS: A review of medical records. RESULTS: Urinary tract infection was identified in 18 of 141 diabetic cats. Escherichia coli was the most common isolate (67%). Female cats were at increased risk (prevalence odds ratios [POR], 3.7; 95% confidence interval [CI], 1.3 to 10.2; P = .013). Clinical signs of lower urinary tract disease and findings on urine sediment examination were good predictors of positive urine cultures. CONCLUSIONS AND CLINICAL IMPORTANCE: Urinary tract infections are common in diabetic cats regardless of status of diabetic control, suggesting routine monitoring with urine sediment exams or urine culture is warranted.