BACKGROUND:In people with chronic kidney disease (CKD), inadequate renal ammonia excretion contributes to metabolic acidosis and is associated with worse outcomes. However, the prognostic relevance of ammonia excretion in dogs with CKD remains unclear. HYPOTHESIS/OBJECTIVES:A reduced urine ammonia-to-creatinine ratio (UACR) would be associated with shorter survival and faster disease progression in dogs with stable CKD. ANIMALS:Fifty client-owned dogs with International Renal Interest Society (IRIS) stages II-IV CKD receiving a therapeutic renal diet. METHODS:Prospective, observational longitudinal study. Dogs were followed for up to 12 months or until death. Progressive CKD was defined as a > 25% increase in serum creatinine from baseline. Dogs were categorized based on UACR < 2.0 or ≥ 2.0. Associations with survival and CKD progression were assessed using Cox proportional hazards and Kaplan-Meier analyses. RESULTS:Most dogs were IRIS stage II (41/50, 82%). Dogs with UACR < 2.0 at enrollment had a significantly greater risk of death (HR 3.045; 95% CI, 1.372-7.102) and shorter median survival (189 vs 445 days, P = .008). Dogs with UACR < 2.0 also had a significantly shorter time to CKD progression (median 132 vs 445 days; P = .0002). In addition, UPC ratio < 1.0 was associated with a lower risk of death (HR 0.351; 95% CI, 0.142-0.879). CONCLUSIONS AND CLINICAL IMPORTANCE:Lower UACR (<2.0) was associated with higher case fatality and faster disease progression in dogs with azotemic CKD. Urine ammonia-to-creatinine ratio might be a useful biomarker for identifying dogs which could benefit from alkali therapy.

BACKGROUND:Inadequate ammonia excretion is thought to drive the development of metabolic acidosis in people with chronic kidney disease (CKD) and correlates with worse clinical outcomes, such as faster progression to end-stage kidney disease and increased case fatality. HYPOTHESIS/OBJECTIVES:To determine if urine ammonia-to-creatinine ratio (UACR) correlates with serum creatinine concentration as a renal function marker in healthy dogs and dogs with CKD and whether UACR is altered in the presence of CKD. ANIMALS:The study group comprised 46 healthy and 50 stable International Renal Interest Society (IRIS) Stages 2, 3, and 4 CKD dogs. METHODS:This was a prospective, single-time point study. Serum biochemistry variables were measured. Urinary ammonia and creatinine concentrations were measured and used to calculate UACR. Group comparisons were made with the Mann-Whitney test. Correlation between UACR and serum renal and electrolyte values was assessed using Spearman's correlation test. Relationships between UACR, renal variables, electrolytes, urine specific gravity, age, and body weight were explored with multiple linear regression. RESULTS:CKD dogs had lower UACR (median 2.2; range 0.9-10.5) than healthy dogs (median 7.1; range 0.7-40.0) (P < .001). UACR was inversely correlated with creatinine concentrations (P < .001, rs = -0.535). The relationship between UACR and creatinine persisted after controlling for age, body weight, electrolytes, renal functional variables, and urine specific gravity. CONCLUSIONS AND CLINICAL IMPORTANCE:These findings suggest that ammonia excretion is impaired in dogs with diminished renal function.

ABSTRACT Background Inadequate ammonia excretion is thought to drive the development of metabolic acidosis in people with CKD and to correlate with worse outcomes. Objectives To determine if urine ammonia‐to‐creatinine ratio (UACR) correlates with serum creatinine as a renal function marker in healthy cats and cats with CKD and whether UACR is related to the presence of CKD. Animals The study group comprised 74 healthy and 45 stable IRIS stage 2–4 CKD cats. Methods Prospective, single‐time point study. Serum biochemistry variables were measured. Urinary ammonia and creatinine concentrations were measured and used to calculate UACR. Group comparisons were made using the Mann–Whitney test. Correlation between UACR concentrations and serum renal and electrolyte values used Spearman's correlation test. Relationships between UACR, renal variables, electrolytes, urine specific gravity, age, and body weight were explored with multiple linear regression. Results Chronic kidney disease cats (median 4.2; range 0.6–9.2) had lower UACR than healthy cats (median 7.6; range 3.0–23.7; p < 0.01). UACR was inversely correlated with creatinine concentration (p < 0.01, rs = −0.545). The relationship between UACR and creatinine persisted after controlling for age, body weight, electrolytes, renal functional variables, and urine‐specific gravity. Conclusions and Clinical Importance These findings suggest that ammonia excretion is impaired with declining renal function.

Background: Lymphoma has been implicated as a possible cause of proteinuria in dogs. However, information about the potential importance of proteinuria in dogs with lymphoma is limited. Hypothesis: To determine if the presence of proteinuria at diagnosis was associated with median survival times in dogs with lymphoma and if lymphoma stage (I-V) or type (B vs T) were associated with the presence of proteinuria. Animals: Eighty-six client-owned dogs with a new diagnosis of lymphoma between 2008 and 2020. Methods: This was a retrospective cross-sectional study with dogs divided into proteinuric or nonproteinuric groups based on dipstick urine protein (protein >= 30 mg/dL classified as proteinuric) or a ratio of dipstick protein to urine specific gravity (ratio >= 1.5 classified as proteinuric). Dogs were excluded for: (1) treatment within 2 months with glucocorticoid, anti-neoplastic, or anti-proteinuric therapies, (2) diagnosed hypercortisolism or renal lymphoma, (3) active urine sediment, or (4) urine pH >8. Survival analysis utilized a Kaplan-Meier estimator and log-rank testing. Results: There was a significant difference in median survival between proteinuric and nonproteinuric dogs classified by urine dipstick (245 days [91, 399] vs 335 days [214, 456]; P = .03) or UP : USG (237 days [158, 306] vs 304 days [173, 434]; P = .03). No difference in prevalence of proteinuria was identified between stages (I-V) or types (B and T). Conclusions and Clinical Importance: Proteinuria appears to be negatively associated with survival time in dogs newly diagnosed with lymphoma.

BACKGROUND:Disruption of acid-base homeostasis can lead to many clinical problems. Ammonia excretion by the kidneys is critical to maintaining acid-base homeostasis through bicarbonate production. Measurement of ammonia excretion may help determine if the kidneys are properly functioning in maintaining acid-base balance. Reference intervals are essential tools for clinical decision-making but do not currently exist for urinary ammonia-to-creatinine ratio (UACR) in feline patients.OBJECTIVE:This study aimed to generate a reference interval (RI) for UACR in healthy adult cats.METHODS:The study used samples from client-owned adult healthy cats that presented to the University of Florida Primary Care and Dentistry service (n = 92). Physical examination, serum biochemistry, urinalysis, urine ammonia, and creatinine concentrations were measured. Cats were excluded if there were significant abnormalities in their urinalysis or biochemistry panel. The RI for UACR was calculated according to the recommendation of the American Society for Veterinary Clinical Pathology. The UACR was evaluated for correlation with serum bicarbonate, weight, age, and sex.RESULTS:The RI for UACR was 3.4-20.7 with 90% confidence intervals for the lower and upper limits of (3.0-3.7) and (16.0-23.7), respectively. No significant correlation with age, sex, or weight was found. There was no discernable relationship between serum bicarbonate and UACR.CONCLUSIONS:Establishing an RI for UACR in healthy adult cats will allow further studies to determine if changes in UACR are observed during specific disease states.

Abstract Background Ammonium excretion decreases as kidney function decreases in several species, including cats, and may have predictive or prognostic value in patients with chronic kidney disease (CKD). Urine ammonia measurement is not readily available in clinical practice, and urine anion gap (UAG) has been proposed as a surrogate test. Objectives Evaluate the correlation between urine ammonia‐to‐creatinine ratio (UACR) and UAG in healthy cats and those with CKD and determine if a significant difference exists between UAG of healthy cats and cats with CKD. Animals Urine samples collected from healthy client‐owned cats (n = 59) and those with stable CKD (n = 17). Methods Urine electrolyte concentrations were measured using a commercial chemistry analyzer and UAG was calculated as ([sodium] + [potassium]) − [chloride]. Urine ammonia and creatinine concentrations had been measured previously using commercially available enzymatic assays and used to calculate UACR. Spearman's rank correlation coefficient between UAG and UACR was calculated for both groups. The UAG values of healthy cats and cats with CKD were assessed using the Mann‐Whitney test (P < .05). Results The UAG was inversely correlated with UACR in healthy cats (P < .002, r0 = −0.40) but not in cats with CKD (P = .55; r0 = −0.15). A significant difference was found between UAG in healthy cats and those with CKD (P < .001). Conclusions and Clinical Importance The UAG calculation cannot be used as a substitute for UACR in cats. The clinical relevance of UAG differences between healthy cats and those with CKD remains unknown.

OBJECTIVE:To describe the therapeutic protocol used to normalize severe hypertriglyceridemia in a dog.CASE SUMMARY:A 7-month-old, 1.2-kg female Pomeranian presented with acute polyuria, polydipsia, and ocular discoloration. Diagnoses included diabetic ketosis, severe hypertriglyceridemia (>225 mmol/L [>20,000 mg/dl]), lipemia retinalis, and bilateral uveitis. The triglyceride concentration was near normal within 2 days of initiating treatment with fenofibrate, regular insulin constant rate infusion (CRI), manual therapeutic plasma exchange (TPE), and a low-fat diet. All clinical signs resolved. The dog has had no relapse of hypertriglyceridemia at the time of writing the manuscript, 6 months later, with continued treatment of diabetes mellitus.NEW OR UNIQUE INFORMATION PROVIDED:This is the first case report documenting the combination of fenofibrate, insulin CRI, and manual TPE for treatment of severe hyperlipidemia in a dog. Detailed protocols for manual TPE and a novel insulin CRI are provided. A discussion of multiple spurious biochemical and hematologic errors associated with the severe hypertriglyceridemia is also provided.

OBJECTIVEThis study served to compare the degree of adrenocortical suppression following a 2-week administration of loteprednol etabonate (LE) and prednisolone acetate (PA) ophthalmic drops.PROCEDURESIn this prospective double-masked triple-crossover study, 21 clinically healthy dogs were randomized to receive loteprednol etabonate ophthalmic suspension 0.5%, prednisolone acetate ophthalmic suspension 1%, or artificial tears (AT). Each group (LE, PA, and AT) received one drop in each eye every 12 h for 2 weeks, followed by a 3-week washout period between treatment blocks. ACTH stimulation tests were performed before and after each treatment block. Serum cortisol samples were drawn before and 60 min after administration of 1 μg/kg cosyntropin IV. Repeated-measurement ANOVA followed by a Tukey's multiple comparisons test (or a Friedman test followed by a Dunn's multiple comparisons test) were used to compare pre- and post-treatment cortisol values between each group. A p-value of ≤.05 was considered significant.RESULTSA total of 18 dogs completed the study. Prestimulation cortisol values were lower in the PA group compared to the LE (p = .0106), but not AT (p = .0589) groups, and post-stimulation cortisol values were lower in the PA group than either LE (p = .0005) or AT (p = .0002) groups. There was no significant difference detected in pre- or post-stimulation cortisol values after the treatment periods between LE and AT.CONCLUSIONSBased on the reduced suppression of cortisol values, LE caused significantly less hypothalamic-pituitary-adrenal axis suppression than PA. A topical steroid with minimal adrenocortical suppression, such as LE, may be favorable in patients where systemic glucocorticoid effects should be avoided.

Abstract Background Sampling from a peripheral intravenous catheter (PIVC) might be a more efficient and less traumatic collection of blood for serum biochemistry (SB) or CBC than direct venipuncture (DV). Agreement between results of samples obtained by these methods has not been evaluated in dogs. Objectives The primary objectives were to determine whether sampling from PIVC could be used in place of DV for dogs. We hypothesized DV and PIVC samples would have clinically equivalent SB and CBC results. Animals Sixty‐one client‐owned dogs were included in each study arm. Methods This was a partially randomized method‐comparison study. Paired DV and PIVC samples obtained within 1 to 2 minutes after, or approximately 24 hours after, placement of a PIVC in a cephalic vein were evaluated for agreement and bias using percentage difference plots (with a priori application of consensus total allowable error), Bland‐Altman analysis, Passing‐Bablok regression analysis, Wilcoxon signed rank test, and McNemar's test. Results There was statistically and clinically acceptable agreement and no bias between sampling methods for the majority of results. Analytes with the most frequent disagreement were aspartate aminotransferase, total bilirubin, potassium, bicarbonate, and leukocyte differential counts, as well as red blood cell count, hemoglobin, hematocrit, and packed cell volume in the hospitalized PIVC sampling group. Few observed differences would change clinical decision making. Conclusions and Clinical Importance PIVC sampling can provide generally acceptable SB and CBC results for most dogs, but clinicians should be aware of a few values for which disparate results might occasionally be obtained.

AbstractBackgroundAmmonia is produced and excreted by the kidney, contributing to systemic acid‐base homeostasis through the production of bicarbonate. Disorders of acid‐base balance can lead to many clinical problems and measuring ammonia excretion helps in determining if the kidneys are responding to acid‐base challenges appropriately. Reference intervals are integral to clinical decision‐making, and there is no current RI for the urine ammonia‐to‐creatinine ratio (UACR) in dogs.ObjectiveThis study aimed to generate an RI for the UACR in healthy adult dogs.MethodsThe study used adult, client‐owned dogs that were presented to the University of Florida Primary Care and Dentistry service (n = 60). Physical examinations were performed and serum chemistry and urinalysis samples were obtained. Urine ammonia and creatinine concentrations were determined. Dogs were excluded if there were significant abnormalities in either their urinalysis or serum chemistry results. The RI for the UACR was calculated according to the recommendation of the American Society for Veterinary Clinical Pathology. Data were evaluated for correlation with serum bicarbonate, weight, age, and sex.ResultsThe RIs for the UACR were 0.16‐23.69 with 90% confidence intervals for the lower and upper limits of (0.13‐1.17) and (20.50‐23.75), respectively. No significant impact of age, sex, or weight was found. There was no discernable relationship between serum bicarbonate and UACR.ConclusionsEstablishing an RI for UACR in healthy adult dogs will allow for further studies to determine if alterations are observed during specific disease states.

Viral mediated gene therapy has progressed after overcoming early failures, and gene therapy has now been approved for several conditions in Europe and the USA. Glycogen storage disease (GSD) type Ia, caused by a deficiency of glucose-6-phosphatase-α, has been viewed as an outstanding candidate for gene therapy. This follow-up report describes the long-term outcome for the naturally occurring GSD-Ia dogs treated with rAAV-GPE-hG6PC-mediated gene therapy.

BackgroundPreanalytic protein adsorption to polymer and glass container surfaces may decrease urine protein concentration measurements and urine protein: creatinine ratios (UPC).Hypothesis/ObjectivesUrine stored in PC or glass containers will have lower UPC than urine stored in HP containers. The specific objective was to determine whether clinically relevant differences in UPC would be detected after storage in glass, PC, or HP containers using common storage times and temperatures.AnimalsTwelve client‐owned dogs with proteinuria.MethodsProspective, nonmasked study, divided into 2 phases. The first phase was a pilot study involving multiple (n = 5) measurements at each storage condition using 24‐hours urine samples from 2 dogs with persistent renal proteinuria of different magnitude. The second phase used urine samples from 10 dogs with proteinuria of variable magnitude. Sample aliquots were stored in HP, PC, and glass containers at 24°C for 4 hours, 4°C for 12 hours, and −20°C for 72 hours. The UPC of each was measured after storage and compared with baseline.ResultsStatistically significant but clinically irrelevant differences were found in phase 1. In phase 2, storage conditions did not affect urinary protein or creatinine concentrations or UPC.Conclusions and Clinical ImportanceCollection and storage of canine urine samples in clean HP, PC, or glass containers at 24°C for 4 hours, 4°C for 12 hours, or −20°C for 72 hours is unlikely to result in clinically relevant decreases in measured UPC values.

An approximately 2-year-old female Doberman Pinscher was referred for the evaluation of bilateral, chronic proliferative conjunctivitis. Ophthalmic examination revealed bilateral thick, opaque pseudomembranes originating from the conjunctivae that prevented visualization of the cornea and interior structures of the eye. Histopathological findings of biopsies of the pseudomembranes were consistent with ligneous conjunctivitis. Serum plasminogen activity levels were within the normal range. Treatment with topical and systemic anti-inflammatory and immunosuppressive drugs did not improve the conjunctival lesions. The pseudomembranes were surgically excised, and the conjunctival surfaces were reconstructed with amniotic membrane. At final re-examination two years postsurgery, there was no evidence of recurrence of the pseudomembranes. To the authors' knowledge, this is the first reported case of the successful treatment of canine ligneous conjunctivitis with amniotic membrane transplantation.

CASE DESCRIPTION A 3-year-old spayed female Bengal cat was evaluated because of a history of bilateral pleural effusion and hydronephrosis of the right kidney. CLINICAL FINDINGS Cytologic analysis of a pleural fluid sample revealed characteristics of a pure transudate with a high percentage of lymphocytes. Results of fluid biochemical testing were not consistent with urine or chyle. Serum biochemical analysis and echocardiography yielded no evidence of hypoalbuminemia or high hydrostatic pressure secondary to cardiac disease. Abdominal ultrasonography revealed hydronephrosis of the right kidney and hydroureter of the right ureter. TREATMENT AND OUTCOME Exploratory laparotomy with nephrectomy of the right kidney was performed. At the time of surgery, there was no evidence of communication between the retroperitoneal space and thoracic cavity. No other treatments were performed. No evidence of pleural fluid accumulation was detected 1 week after surgery, and no recurrence of clinical signs associated with pleural effusion was observed for > 1 year after surgery. CLINICAL RELEVANCE Transudative, or nonchylous lymphatic, pleural effusion secondary to intra-abdominal disease, but independent of a low plasma protein concentration, is uncommon in veterinary medicine. This case emphasized that urinary tract obstruction should be considered as a differential diagnosis for cats with pleural effusion when more common disorders are not identified. Even without evidence of direct communication between the abnormal kidney or retroperitoneal space and the pleural space, removal of the hydronephrotic kidney appeared curative.

Background The urine protein:creatinine ratio (UPC) is used to quantify urine protein excretion and guide recommendations for monitoring and treatment of proteinuria. Hypothesis/Objectives Home urine samples will have lower UPCs than hospital samples. The objectives were to compare UPCs of samples collected in each setting and to determine whether environment of sample collection might affect staging, monitoring or treatment recommendations. Animals Twenty‐four client‐owned dogs. Methods Prospective, nonmasked study. Clients collected a urine sample from their dog at home and a second sample was collected at the hospital. Dogs receiving corticosteroids or angiotensin‐converting enzyme inhibitors were excluded, as were those with urine samples of inadequate volume, no protein on dipstick analysis, or active urine sediment. Samples were refrigerated after collection, dipstick and sediment evaluations were completed and each sample was frozen at −80°C within 12 hours. UPCs were performed on frozen samples within 2 months. Results From 81 paired samples, 57 were excluded. Of the remaining 24, 12/24 (50%) had higher hospital sample UPCs, 9/24 (38%) had identical UPCs, and 3/24 (12%) had lower hospital UPCs. The UPCs of hospital samples were higher than home samples for the total population (P = .005) and the subset with UPC > 0.5 (P = .001). Conclusions Setting and related circumstances of urine collection in dogs is associated with UPC differences; results are usually higher in hospital than in home samples. This difference has the potential to affect clinical interpretation.

A 3.1-kg (6.82-lb) 7-month-old sexually intact female Shih Tzu mix was evaluated because of an acute onset of vomiting and signs of abdominal pain when being picked up from the floor. Prior to evaluation, the owner observed 2 episodes of vomiting, with vomitus containing partially digested food and saliva. The patient did not have a previous history of dietary changes but was reported to occasionally chew the carpet. There was no previous history of gastrointestinal disease. The dog was current on vaccinations and had been dewormed twice. On physical examination, the patient was bright, alert, and responsive, with a heart rate of 125 beats/min, respiratory rate of 28 breaths/min, body temperature of 39.1°C (102.4°F), pink mucous membranes, capillary refill time < 2 seconds, and moderate signs of discomfort on palpation of the cranial aspect of the abdomen. Initial diagnostic evaluation including serum biochemical analysis and CBC revealed only minimal changes in a few variables that were consistent with the patient’s age and vomiting. Abdominal radiographs were obtained and revealed a moderately distended stomach containing homogenous soft tissue opaque material, 2 small (< 2-mm) mineral opacities, and diffusely fluidand gas-filled small intestines (including gas within the descending duodenum) with dimensions within reference ranges. Abdominal ultrasonography was performed (Figure 1).

Esophageal strictures are uncommon in cats with causes including medications, ingestion of caustic substances, or gastroesophageal reflux under anesthesia. Bougienage and balloon dilation are the main treatments for strictures but have variable success rates. This paper describes the novel use of a cutting balloon for dilation of a fibrous stricture in a cat that was previously refractory to treatment with traditional balloon dilation.

A severe increase in total bilirubin coincided with a decline in neurologic status to comatose in a 9 yr old spayed female mixed-breed dog being treated for immune-mediated hemolytic anemia. MRI of the brain was performed to investigate potential causes for the neurologic signs. MRI revealed bilaterally symmetrical hyperintensities within the caudate nuclei, globus pallidus, thalamus, deep cerebellar nuclei, and cortical gray matter on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, which coincided with areas of bilirubin deposition and neuronal necrosis (kernicterus) identified on necropsy examination. This is the second case report of an adult dog exhibiting kernicterus, and the first report to document MRI findings associated with that condition. Kernicterus is an uncommonly reported complication of hyperbilirubinemia in dogs, but is potentially underreported due to difficulties in recognizing subtle lesions and distinguishing kernicterus from other potential causes of neurologic abnormalities with readily available antemortem tests. MRI may be helpful in supporting the diagnosis of kernicterus.

A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.