Association of proteinuria at time of diagnosis with survival times in dogs with lymphoma.

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.

Effect of common storage temperatures and container types on urine protein : creatinine ratios in urine samples of proteinuric dogs.

BACKGROUND: Preanalytic protein adsorption to polymer and glass container surfaces may decrease urine protein concentration measurements and urine protein: creatinine ratios (UPC). HYPOTHESIS/OBJECTIVES: Urine 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. ANIMALS: Twelve client-owned dogs with proteinuria. METHODS: Prospective, 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. RESULTS: Statistically 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 IMPORTANCE: Collection 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.

Long-term safety and efficacy of AAV gene therapy in the canine model of glycogen storage disease type Ia.

BACKGROUND: 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. METHODS: A total of seven dogs were treated with rAAV-GPE-hG6PC-mediated gene therapy. The first four dogs were treated at birth, and three dogs were treated between 2 and 6 months of age to assess the efficacy and safety in animals with mature livers. Blood and urine samples, radiographic studies, histological evaluation, and biodistribution were assessed. RESULTS: Gene therapy improved survival in the GSD-Ia dogs. With treatment, the biochemical studies normalized for the duration of the study (up to 7 years). None of the rAAV-GPE-hG6PC-treated dogs had focal hepatic lesions or renal abnormalities. Dogs treated at birth required a second dose of rAAV after 2-4 months; gene therapy after hepatic maturation resulted in improved efficacy after a single dose. CONCLUSION: rAAV-GPE-hG6PC treatment in GSD-Ia dogs was found to be safe and efficacious. GSD-Ia is an attractive target for human gene therapy since it is a monogenic disorder with limited tissue involvement. Blood glucose and lactate monitoring can be used to assess effectiveness and as a biomarker of success. GSD-Ia can also serve as a model for other hepatic monogenic disorders.

Resolution of nonurine transudative pleural effusion in a cat after removal of a hydronephrotic kidney.

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.

Iron homeostasis and disorders in dogs and cats: a review.

Iron is an essential element for nearly all living organisms and disruption of iron homeostasis can lead to a number of clinical manifestations. Iron is used in the formation of both hemoglobin and myoglobin, as well as numerous enzyme systems of the body. Disorders of iron in the body include iron deficiency anemia, anemia of inflammatory disease, and iron overload. This article reviews normal iron metabolism, disease syndromes of iron imbalance, diagnostic testing, and treatment of either iron deficiency or excess. Recent advances in diagnosing iron deficiency using reticulocyte indices are reviewed.

Adeno-associated virus-mediated correction of a canine model of glycogen storage disease type Ia.

Glycogen storage disease type Ia (GSDIa; von Gierke disease; MIM 232200) is caused by a deficiency in glucose-6-phosphatase-alpha. Patients with GSDIa are unable to maintain glucose homeostasis and suffer from severe hypoglycemia, hepatomegaly, hyperlipidemia, hyperuricemia, and lactic acidosis. The canine model of GSDIa is naturally occurring and recapitulates almost all aspects of the human form of disease. We investigated the potential of recombinant adeno-associated virus (rAAV) vector-based therapy to treat the canine model of GSDIa. After delivery of a therapeutic rAAV2/8 vector to a 1-day-old GSDIa dog, improvement was noted as early as 2 weeks posttreatment. Correction was transient, however, and by 2 months posttreatment the rAAV2/8-treated dog could no longer sustain normal blood glucose levels after 1 hr of fasting. The same animal was then dosed with a therapeutic rAAV2/1 vector delivered via the portal vein. Two months after rAAV2/1 dosing, both blood glucose and lactate levels were normal at 4 hr postfasting. With more prolonged fasting, the dog still maintained near-normal glucose concentrations, but lactate levels were elevated by 9 hr, indicating that partial correction was achieved. Dietary glucose supplementation was discontinued starting 1 month after rAAV2/1 delivery and the dog continues to thrive with minimal laboratory abnormalities at 23 months of age (18 months after rAAV2/1 treatment). These results demonstrate that delivery of rAAV vectors can mediate significant correction of the GSDIa phenotype and that gene transfer may be a promising alternative therapy for this disease and other genetic diseases of the liver.

A retrospective study of the relationship between tracheal collapse and bronchiectasis in dogs.

Tracheal collapse is common in middle age toy and miniature breed dogs. Cartilaginous defects have been identified histologically and are considered a form of chondromalacia. In addition to tracheal cartilaginous changes, concurrent lower airway histologic changes indicative of inflammation have been noted in dogs with tracheal collapse and these changes may lead t o concurrent bronchiectasis. The purpose of this study was to investigate the prevalence of bronchiectasis in dogs with a previous radiographic diagnosis of tracheal collapse. The thoracic radiographs of 60 dogs with tracheal collapse were evaluated for evidence of concurrent bronchiectasis. Eighteen of 60 (30%) dogs had evidence of bronchiectasis, and all were cylindrical in morphology. The signalment of affected dogs was similar to that previously reported. The occurrence of bronchiectasis in this group of dogs with tracheal collapse (18 dogs) was six times higher (P < 0.05) than the expected prevalence within a random sample population (three dogs). The results of this study provide evidence of a link between tracheal collapse and bronchiectasis. A finding of bronchiectasis with tracheal collapse should encourage further evaluation for chronic lower airway disease in these patients.

Ocular manifestations of endocrine disease.

Small animal patients with endocrinopathies are at risk of developing many ophthalmic conditions resulting from endocrine hormone imbalances. Diabetic animals frequently develop cataracts but can also have numerous other ocular problems, including uveitis, keratopathy, retinopathy, and the effects of lipid derangements and systemic hypertension. Cushing's patients can develop complications from hyperlipidemia and hypertension and sometimes present with corneal disease. Acute blindness from sudden acquired retinal degeneration has been associated with disease of the pituitary-adrenal axis. Growth hormone disturbances can result in the secondary ocular effects of hypertension or of thyroid deficiency (e.g., corneal infiltrates, decreased tear production, neurologic dysfunction). Hyperthyroid animals can present with the ocular manifestations of systemic hypertension. Disorders of calcium homeostasis are unusual, typically manifesting as cataracts in hypocalcemic patients or as metastatic calcification of the ocular tissues.

Magnetic resonance imaging features of extradural hematomas associated with intervertebral disc herniation in a dog.

Myelography and magnetic resonance imaging (MRI) were performed on a 4-year-old neutered female Rottweiler with bilateral pelvic limb paresis. On the myelogram, there was extradural spinal cord compression at the level of the T11-12 intervertebral disc. Inadvertent placement of epidural contrast medium also allowed identification of a 1-cm circular filling defect in the epidural space dorsal to the compressed spinal cord. MRI showed partial loss of the nucleus pulposus signal of the T11-12 disc, a focal signal void within the vertebral canal at T11 compatible with a free disc fragment, and extradural masses compressing the spinal cord at T10-11 and T11-12. Hemorrhage within the masses was confirmed on T2*-weighted images. A mixture of hematoma and mineralized disc material was found at surgery, and there was no histopathologic evidence of neoplasia. In this article, the appearance on MRI of hemorrhage associated with intervertebral disc herniation is discussed.