Spontaneous painful disease in companion animals can facilitate the development of chronic pain therapies for humans.

OBJECTIVE: To outline the role that spontaneous osteoarthritis (OA) in companion animals can play in translational research and therapeutic pharmacological development. OUTLINE: Narrative review summarizing the opportunities and limitations of naturally occurring, spontaneous OA as models of human OA pain, with a focus on companion animal pets. The background leading to considering inserting spontaneous disease models in the translational paradigm is provided. The utility of this model is discussed in terms of outcome measures that have been validated as being related to pain, and in terms of the potential for target discovery is outlined. The limitations to using companion animal pets as models of human disease are discussed. CONCLUSIONS: Although many steps along the translational drug development pathway have been identified as needing improvement, spontaneous painful OA in companion animals offers translational potential. Such 'models' may better reflect the complex genetic, environmental, temporal and physiological influences present in humans and current data suggests the predictive validity of the models are good. The opportunity for target discovery exists but is, as yet, unproven.

Accuracy of non-operative identification of the sentinel lymph node using combined gamma and ultrasound scanning.

AIM: To assess how accurately the sentinel lymph node (SLN) can be identified percutaneously, using gamma probe and ultrasound technology. MATERIALS AND METHODS: Women with breast cancer, scheduled for wide local excision or mastectomy with SLN biopsy (SLNB), were included. Peri-areolar intradermal injection of technetium-99 nanocolloid was performed on the morning of surgery and 1-2 ml of blue dye was injected in the peri-areolar region once the patient was anaesthetized. Prior to surgery, a gamma probe was used over the skin to identify any hot spot that could represent a SLN. Ultrasound, guided by the hot spot, was then used to visualize potential SLNs and guide the insertion of a localizing wire. The accuracy in localizing the SLN by preoperative gamma-probe guided ultrasonography was assessed by comparison to SLNB. RESULTS: A SLN was correctly identified and marked using gamma-probe guided ultrasonography in 44 of 59 cases (75%; 95% CI: 63-86%). CONCLUSION: This study supports the case for investigating percutaneous gamma probe and ultrasound guided interventions in the axilla in women with breast cancer, as a potential alternative to surgical SLNB.

Can additional histopathological examination of ultrasound-guided axillary lymph node core biopsies improve preoperative diagnosis of primary breast cancer nodal metastasis?

AIM: To assess whether an additional histopathological examination of ultrasound-guided core biopsy (USCB)/fine-needle aspiration (FNA) of abnormal axillary lymph nodes (ALN) can improve the preoperative diagnosis of axillary nodal metastasis. MATERIALS AND METHODS: Women with suspected invasive breast cancer and abnormal axillary ultrasound (AUS), but negative USCB on standard histopathological assessment were included. From the core biopsies six additional levels were sectioned for haematoxylin and eosin examination, and two levels were sectioned for immunohistochemistry with AE1/3. The presence of metastatic disease was noted. RESULTS: The USCB of 102 patients were submitted for additional histopathological examination, of whom 58 had screen-detected lesions and 44 had symptomatic lesions. Eighty underwent axillary surgery for invasive carcinoma (n = 74) or for ductal carcinoma in situ (DCIS) requiring mastectomy (n = 6). Twelve patients were found to have nodal disease with a mean of two nodes involved. The additional histopathological assessment of the nodal USCBs revealed tumour not seen at the standard examination in only three cases, which consisted of isolated tumour cells (n = 2) and micrometastasis (n = 1). All three patients underwent subsequent axillary node clearance; however, no upgrade of axillary disease was found at final histopathology. CONCLUSION: Additional histopathological examination of USCBs of radiologically abnormal ALN does not improve the preoperative diagnosis of axillary nodal metastasis in primary breast cancer and may lead to unnecessary axillary clearance.

Evaluation of clinical and histopathologic prognostic factors for survival in canine osteosarcoma of the extracranial flat and irregular bones.

Osteosarcoma is the most common bone tumor in dogs. However, current literature focuses primarily on appendicular osteosarcoma. This study examined the prognostic value of histological and clinical factors in flat and irregular bone osteosarcomas and hypothesized that clinical factors would have a significant association with survival time while histological factors would not. All osteosarcoma biopsy samples of the vertebra, rib, sternum, scapula, or pelvis were reviewed while survival information and clinical data were obtained from medical records, veterinarians, and owners. Forty-six dogs were included in the analysis of histopathological variables and 27 dogs with complete clinical data were included in the analysis of clinical variables. In the histopathologic cox regression model, there was no significant association between any histologic feature of osteosarcoma, including grade, and survival time. In the clinical cox regression model, there was a significant association between the location of the tumor and survival time as well as between the percent elevation of alkaline phosphatase (ALP) above normal and survival time. Controlling for ALP elevation, dogs with osteosarcoma located in the scapula had a significantly greater hazard for death (2.8) compared to dogs with tumors in other locations. Controlling for tumor location, every 100% increase in ALP from normal increased the hazard for death by 1.7. For canine osteosarcomas of the flat and irregular bones, histopathological features, including grade do not appear to be rigorous predictors of survival. Clinical variables such as increased ALP levels and tumor location in the scapula were associated with decreased survival times.

Axillary lymph node core biopsy for breast cancer metastases -- how many needle passes are enough?

AIM: To determine the diagnostic yield of each of three core passes when sampling abnormal lymph nodes in patients presenting with breast cancer. MATERIALS AND METHODS: All patients suspected of having breast cancer had axillary ultrasound as part of initial assessment. Radiologically abnormal nodes (cortical thickness >2.3mm or round shape) were biopsied with three passes of a 22 mm throw 14 G core biopsy needle and sent for histopathology in separate numbered pots. Data were collected prospectively, and analysis performed on the data of 55 consecutive patients who had positive nodes on at least one core biopsy needle pass. RESULTS: Of 55 patients with a positive node on core biopsy, tumour was noted in all three cores taken in 39 (70.9%). Lymph node metastasis was detected in 45 (81.8%) first core biopsies. With the first two cores taken, positive results were detected in 53 of 55 cases (96.4%). In both cases where tumour was only found on a third core biopsy pass, no lymph node tissue was present in the first two biopsy passes. CONCLUSION: Two well-directed 14 G core biopsy samples from an abnormal axillary node are adequate for diagnosis of breast cancer metastasis.

Hourglass cell development in the soybean seed coat.

BACKGROUND AND AIMS: Hourglass cells (HGCs) are prominent cells in the soybean seed coat, and have potential use as 'phytofactories' to produce specific proteins of interest. Previous studies have shown that HGCs initiate differentiation at about 9 d post-anthesis (dpa), assuming their characteristic morphology by 18 dpa. This study aims to document the structural changes in HGCs during this critical period, and to relate these changes to the concurrent development of a specific soybean peroxidase (SBP) encoded by the Ep gene. METHODS: Pods were collected from plants at specific growth stages. Fresh material was processed for analysis of Ep peroxidase activity. Tissues were processed for scanning and transmission electron microscopy, as well as extracted for western blotting. A null variety lacking expression of Ep peroxidase was grown as a control. KEY RESULTS AND CONCLUSIONS: At 9 dpa, HGCs are typical undifferentiated plant cells, but from 12-18 dpa they undergo rapid changes in their internal and external structure. By 18 dpa, they have assumed the characteristic hourglass shape with thick cell walls, intercellular air spaces and large central vacuoles. By 45 dpa, all organelles in HGCs have been degraded. Additional observations indicate that plasmodesmata connect all cell types. SBP activity and SBP protein are detectable in the HGC before they are fully differentiated (approx. 18 dpa). In very early stages, SBP activity appears localized in a vacuole as previously predicted. These results increase our understanding of the structure and development of the HGC and will be valuable for future studies aimed at protein targeting to components of the HGC endomembrane systems.

Perceptions of quality of life and priorities of owners of cats with heart disease.

BACKGROUND: Owners' perceptions and priorities regarding quality of life (QoL) are important considerations given the unknown efficacy of many commonly administered medications, stress of hospital visits, difficulties providing home care, and personal choices including euthanasia. OBJECTIVE: To describe the relative importance of quality versus quantity of life to owners of cats with heart disease. ANIMALS: Two hundred and thirty-nine cats with heart disease. METHODS: Prospective questionnaire-based clinical study. Cat owners completed a questionnaire to identify important parameters when assessing their cat's QoL, the relative importance of quality versus quantity of life, and willingness to trade survival time for QoL. Variables associated with these parameters were evaluated with multivariate analyses. RESULTS: Appetite, owner interaction, sleep patterns, and litterbox habits were deemed important to QoL. Concern over pet suffering was significantly greater than concern over life expectancy. Ninety-three percent of owners were willing to trade survival time for good QoL; 57% of these were willing to trade up to 6 months. On multivariate analysis, the only factor significantly (P=.002) associated with willingness to trade 6 months was study site. Owner concern regarding stress of administering medications at home increased with number and frequency of medications. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicated that QoL is more important to owners of cats with heart disease than longevity. The various priorities and concerns of cat owners should be taken into account in order to provide optimal care.

A modern approach to noise induced hearing loss in military operations.

The symposium successfully brought together key military medical and personnel managers with civilian experts in hearing disorders and charities to help streamline our knowledge of the aetiology, investigation, prevention and management of NIHL. A requirement for seamless medical care for veterans with NIHL was recognised and collaborative work has commenced.

Recurrent herpes in the rabbit and man.

Herpesvirus was present in secretory glands and frequently in tears of rabbits with recurrent herpetic keratitis even in the absence of corneal lesions. In normal people, herpesvirus could be cultured from saliva and tears. Chronic virus multiplication in structures such as the lacrimal and salivary glands, rather than latency, may cause recurrent herpetic disease.

Measurement of chronic pain in companion animals: Discussions from the Pain in Animals Workshop (PAW) 2017.

In the face of increasing recognition and interest in treating chronic pain in companion animals, we struggle with a lack of therapeutic options. A significant barrier to the development of new therapeutics, or the critical evaluation of current therapies, is our inability to accurately measure chronic pain and its impact on companion animals. Over the last 20 years, much progress has been made in developing methods to measure chronic pain via subjective and objective methods - particularly in owner assessment tools and measurements of limb use and activity. Most work has been focused on chronic joint pain conditions, but there has been relatively little work in other areas of chronic pain, such as neuropathic and cancer pain. Although progress has been made, there is a considerable interest in improving our assessment of chronic pain, as evidenced by the multiple disciplines across industry, academia, and clinical practice from the veterinary and human medical fields that participated in the Pain in Animals Workshop held at the National Institutes of Health in 2017. This review is one product of that meeting and summarizes the current state of knowledge surrounding the measurement of chronic pain (musculoskeletal, cancer, neuropathic), and its impact, in cats and dogs.

Measurement of chronic pain in companion animals: Priorities for future research and development based on discussions from the Pain in Animals Workshop (PAW) 2017.

The estimation of long-standing pain in companion animals through the measurement of different dimensions impacted by pain is a fundamental requirement if pain management, and pain therapeutic development, are to advance. Although pain management in veterinary medicine has advanced considerably in the last 20 years, there is much critical work to do in the area of measurement of chronic pain. To date, most work has centered on musculoskeletal pain, and has been focused around the measurement of limb use and the development of owner-completed questionnaires, or clinical metrology instruments (CMI). Recent areas of research have extended to developing measures of activity, sensory function (quantitative sensory testing; nociceptive withdrawal reflexes), and quality of life (QoL). Across all these areas, more data on validity are needed, and studies should be extended to other painful disease states. By necessity, assessing measurement tools requires testing in field studies, which incur considerable time and expense. Facilitating these studies could be optimized with a collaborative (industry, academia and private practice) approach, and the utility of the information produced from all field studies would be enhanced by full and transparent reporting and data sharing, including data already generated by industry in the form of studies submitted to the regulatory authorities.

Differential regulation of four members of the ACC synthase gene family in plum.

The regulation of ACC synthase (ACS) genes was studied in early ('Early Golden') and late ('Shiro') Japanese plum cultivars (Prunus salicina L.) in order to determine the role of this gene family in fruit ripening. Of the four Ps-ACS cDNAs isolated, two (Ps-ACS1 and -3) showed differential expression between the two cultivars. Ps-ACS1 accumulated during fruit ripening of 'Early Golden' ('EG') and 'Shiro' ('SH') in ethylene-dependent and -independent manners, respectively. Ps-ACS3a transcripts accumulated throughout fruit development and during 'EG' fruit ripening. Ps-ACS3b was detected only during ripening of 'SH' fruit. Furthermore, Ps-ACS3a transcript accumulation was negatively regulated by ethylene, whereas Ps-ACS3b was positively induced by the hormone. In both cultivars, the expression of Ps-ACS4 and -5 is under positive and negative feedback control by ethylene, respectively. Genetic analyses of 'EG' and 'SH' cultivars demonstrated that 'EG' is homozygous for Ps-ACS3a whereas 'SH' is heterozygous for Ps-ACS3 (a/b). The role of ethylene-overproducer 1-like in delaying fruit ripening by interacting with Ps-ACS proteins was also studied. The effect of the plant hormones, auxin, gibberellin, and cytokinin, in regulating ethylene production by promoting the induction of the different Ps-ACS mRNAs in plum was investigated. A model is presented in which differences in Ps-ACS alleles and gene expression between early and late plums are critical in determining the ripening behaviour of the cultivars.

Meta-analysis of sentinel node biopsy in ductal carcinoma in situ of the breast.

BACKGROUND: The need for sentinel lymph node (SLN) biopsy in patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS) is debated. Advocates recommend such biopsy based on a high incidence of SLN involvement in some series. Opponents discourage SLN biopsy based on a perceived low incidence of nodal involvement in this setting. These contradictory arguments are generally based on small studies. The present study is a meta-analysis of the reported data on the incidence of SLN metastasis in patients with DCIS. METHODS: A search of electronic databases identified studies reporting the frequency of SLN metastases in DCIS. The random-effects method was used to combine data. RESULTS: Twenty-two published series were included in the meta-analysis. The estimate for the incidence of SLN metastases in patients with a preoperative diagnosis of DCIS was 7.4 (95 per cent confidence interval (c.i.) 6.2 to 8.9) per cent compared with 3.7 (95 per cent c.i. 2.8 to 4.8) per cent in patients with a definitive (postoperative) diagnosis of DCIS alone. This was a significant difference with an odds ratio of 2.11 (95 per cent c.i. 1.15 to 2.93). CONCLUSION: Patients with a preoperative diagnosis of DCIS should be considered for SLN biopsy.

Detection of viral bioagents using a shear horizontal surface acoustic wave biosensor.

Viruses are of high medical and biodefense concern and their detection at concentrations well below the threshold necessary to cause health hazards continues to be a challenge with respect to sensitivity, specificity, and selectivity. Ideally, assays for accurate and real time detection of viral agents would not necessitate any pre-processing of the analyte, which would make them applicable for example to bodily fluids (blood, sputum) and man-made as well as naturally occurring bodies of water (pools, rivers). We describe herein a robust biosensor that combines the sensitivity of surface acoustic waves (SAW) generated at a frequency of 325MHz with the specificity provided by antibodies for the detection of viral agents. A lithium tantalate-based SAW transducer with silicon dioxide waveguide sensor platform featuring three test and one reference delay lines was used to adsorb antibodies directed against either Coxsackie virus B4 or the category A bioagent Sin Nombre virus (SNV), a member of the genus Hantavirus, family Bunyaviridae, negative-stranded RNA viruses. Rapid detection (within seconds) of increasing concentrations of viral particles was linear over a range of order of magnitude for both viruses, although the sensor was approximately 5 x 10(5)-fold more sensitive for the detection of SNV. For both pathogens, the sensor's selectivity for its target was not compromised by the presence of confounding Herpes Simplex virus type 1. The biosensor was able to detect SNV at doses lower than the load of virus typically found in a human patient suffering from hantavirus cardiopulmonary syndrome (HCPS). Further, in a proof-of-principle real world application, the SAW biosensor was capable to selectively detect SNV agents in complex solutions, such as naturally occurring bodies of water (river, sewage effluent) without analyte pre-processing. This is the first study that reports on the detection of viral agents using an antibody-based SAW biosensor that has the potential to be used as a hand-held and self-contained device for rapid viral detection in the field.

Complication rate, outcome, and risk factors associated with surgical repair of fractures of the lateral aspect of the humeral condyle in dogs.

OBJECTIVE: To determine outcome, report complications, and risk factors for complications associated with the surgical treatment of fractures of the lateral aspect of the humeral condyle (FLHC) in dogs. STUDY DESIGN: Fifty dogs with FLHC that had been repaired surgically were included in this retrospective case series. METHODS: The medical records and radiographs from 50 dogs with FLHC from 1990--2006 were analyzed. RESULTS: The complication rate was 30%. For every 30-minute increase in surgical time the odds of a complication increased by 2.00 (95% CI: 1.06, 3.77). For every 10 degrees increase in the angle between the transcondylar screw and a line between the epicondyles viewed on a craniocaudal radiograph there was a 4.82 (95% CI: 1.23, 18.86) greater odds of an intracondylar fracture gap appearing on postoperative radiographs. When an intracondylar fracture gap was present after surgery there was a 25% long-term radiographic outcome failure rate, whereas there was a 0% radiographic failure rate in the dogs in which an intracondylar fracture gap was not present. In conclusion, transcondylar screw placement parallel to the epicondylar line should be attempted for the repair of FLHC. An increase in surgical time leads to an increase in postoperative complication rate. The presence of an intracondylar fracture gap may be associated with fracture failure. CLINICAL SIGNIFICANCE: Screw angulation predisposed to postoperative intracondylar fracture gap which in turn may be associated with higher fracture fixation failure rate. The dogs that had prolonged surgical times had an increased complication rate.

Cholangitis and Cholangiohepatitis in Dogs: A Descriptive Study of 54 Cases Based on Histopathologic Diagnosis (2004-2014).

BACKGROUND: Cholangitis in dogs appears to be more common than previously thought, but understanding of the disease remains incomplete. OBJECTIVE: To describe a population of dogs with cholangitis or cholangiohepatitis. ANIMALS: Fifty-four client-owned dogs with cholangitis or cholangiohepatitis. METHODS: Medical records of dogs with cholangitis or cholangiohepatitis confirmed by histopathology between January 2004 and December 2014 were identified using a computer-based search and retrospectively reviewed. RESULTS: Clinical signs included vomiting (72.2%), lethargy (70.4%), and inappetence (64.8%). Most dogs (49/50) had increased liver enzyme activities, hyperbilirubinemia (32/50), and hypercholesterolemia (24/43). Ultrasonographic abnormalities of the hepatobiliary system were seen in 84% of cases. On histopathology, 53 of 54 affected dogs had neutrophilic cholangitis (NC) or cholangiohepatitis, whereas 1 dog had lymphocytic cholangitis. Most cases (42/54) were chronic. Evidence of concurrent biliary disease (46.2%) and biliary tract obstruction (42.6%) was common. Seventeen of 36 biliary and 11 of 25 liver cultures were positive for bacterial growth; Escherichia coli and Enterococcus spp. were most common. Median patient survival was 671 days (95% confidence interval [CI]: 114-1,426). On Cox regression, dogs that did not have a cholecystectomy performed had a 2.1 greater hazard for death (P = 0.037; 95% CI: 1.0-4.3) compared to cholecystectomized dogs. Dogs >13 years old had a 5.0 greater hazard for death (P = 0.001; 95% CI: 1.9-13.2) compared to younger dogs. CONCLUSIONS AND CLINICAL SIGNIFICANCE: Chronic NC or cholangiohepatitis was most common. Cholecystitis and biliary tract obstruction often occurred in conjunction with cholangitis. Cholecystectomized dogs had decreased risk of death; thus, cholecystectomy may improve patient outcome.

Outcome following treatment of feline gastrointestinal mast cell tumours.

Prognosis of feline gastrointestinal mast cell tumours (FGIMCT), based on limited available literature, is described as guarded to poor, which may influence treatment recommendations and patient outcome. The purpose of this study is to describe the clinical findings, treatment response, and outcome of FGIMCT. Medical records of 31 cats diagnosed with and treated for FGIMCT were retrospectively reviewed. Data collected included signalment, method of diagnosis, tumour location (including metastatic sites), treatment type, cause of death and survival time. Mean age was 12.9 y. Diagnosis was made via cytology (n = 15), histopathology (n = 13) or both (n = 3). Metastatic sites included abdominal lymph node (n = 10), abdominal viscera (n = 4) and both (n = 2). Therapeutic approaches included chemotherapy alone (n = 15), surgery and chemotherapy (n = 7), glucocorticoid only (n = 6) and surgery and glucocorticoid (n = 3). Lomustine (n = 15) and chlorambucil (n = 12) were the most commonly used chemotherapy drugs. Overall median survival time was 531 d (95% confidence interval 334, 982). Gastrointestinal location, diagnosis of additional cancers, and treatment type did not significantly affect survival time. Cause of death was tumour-related or unknown (n = 12) and unrelated (n = 8) in the 20 cats dead at the time of analysis. The prognosis for cats with FGIMCT may be better than previously reported, with 26% of cats deceased from an unrelated cause. Surgical and medical treatments (including prednisolone alone) were both associated with prolonged survival times. Treatment other than prednisolone may not be necessary in some cats. Continued research into prognostic factors and most effective treatment strategies are needed.

Isolation and characterization of four ethylene signal transduction elements in plums (Prunus salicina L.).

Plums are climacteric fruits: their ripening is associated with a burst of ethylene production and respiration rate. Stone fruits, including plum, have a distinct pattern of growth and development, described as a double sigmoid pattern. In order to understand the developmental control of ethylene perception in plum, four ethylene perception and signal transduction components (EPSTCs) were characterized, including two ETR1-like proteins (Ps-ETR1 and Ps-ERS1), a CTR1-like protein, and an ethylene-responsive element-binding factor (ERF). Their regulation was studied throughout fruit development and ripening in early and late cultivars. Analysis of transcript levels revealed that only Ps-ERF1 and Ps-ERS1 accumulated immediately after fertilization. Increases in Ps-ETR1 and Ps-CTR1 transcript levels could not be detected before S3 of fruit development. Marked differences associated with the ripening behaviour of early ('Early Golden') and late ('Shiro') Japanese plum cultivars were observed. The early cultivar showed ripening patterns typical of climacteric fruits accompanied by sharp increases of the four transcript levels in an ethylene-dependent manner. However, the late cultivar exhibited a suppressed-climacteric pattern, with a slight increase in ethylene production related to ripening. The accumulation of the Ps-ETR1 (and not Ps-CTR1) mRNA in the late cultivar was ethylene independent. Ps-ERS1 mRNA was expressed at low, constant levels, while, Ps-ERF1 remained undetectable. The differences between the two plum cultivars in the date and rate of ripening in relation to the differences in the accumulation patterns of the four mRNAs are discussed.

Electrolyte solution structure and its effect on the properties of electric double layers with surface charge regulation.

The physical origin of charged interfaces involving electrolyte solutions is in the thermodynamic equilibrium between the surface reactive groups and certain dissolved ionic species in the bulk. This equilibrium is very strongly dependent on the precise local density of these species, also known as potential determining ions in the solution. The latter, however, is determined by the overall solution structure, which is dominated by the large number of solvent molecules relative to all solutes. Hence, the solvent contribution to the molecular structure is a crucial factor that determines the properties of electric double layers. Models that explicitly account for the solvent structure are often referred to as "civilized" as opposed to the "primitive" ones that consider the solvent as a structureless continuum. In the present paper, we demonstrate that for a physically correct description of charged interfaces that involve electrolyte solutions (electric double layers), the full solution structure needs to be taken into account in conjunction with the precise surface chemistry governed by the thermodynamic equilibrium. The analysis shows how the surface charge depends on various experimentally relevant parameters, many of which are outside the realm of simple electrostatics. We present results on the effects of solvent molecular dimensions, ionic solvation, surface chemistry, solvophilicity and solvophobicity.

The Use of Darbepoetin to Stimulate Erythropoiesis in the Treatment of Anemia of Chronic Kidney Disease in Dogs.

BACKGROUND: Darbepoetin alfa (darbepoetin) is an erythropoiesis-stimulating agent used for the treatment of anemia secondary to chronic kidney disease (CKD) in dogs, but reports describing response are lacking. HYPOTHESIS/OBJECTIVES: To evaluate the effectiveness of darbepoetin in dogs with anemia secondary to CKD, dosing protocols, and adverse events. ANIMALS: Thirty-three client-owned dogs with naturally occurring CKD, including 26 with comorbidities. METHODS: Multi-institutional retrospective study. RESULTS: The median starting dosage and highest dosage of darbepoetin administered were 0.5 and 0.8 µg/kg SC once weekly, respectively. Response to treatment was defined as achieving a packed cell volume (PCV) ≥30% or an increase in PCV ≥10%. Twenty-eight of 33 dogs (85%) achieved a PCV ≥30% and 22 of 33 (67%) dogs achieved an increase in PCV ≥10%. Median time to achieve a PCV ≥30% was 29 days. A higher starting dosage was associated with achieving an increase in PCV ≥10% (P = .01). No dog sustained a response at a dosing interval >q21d. Potential adverse events included increased blood pressure requiring treatment (n = 12), seizures (n = 5), vomiting (n = 3), diarrhea (n = 3), and possible pure red cell aplasia (PRCA) (n = 2). CONCLUSIONS AND CLINICAL IMPORTANCE: Darbepoetin, when combined with treatment of comorbidities, is an effective treatment for anemia secondary to CKD in dogs. A dosing interval >q21d was ineffective at maintaining a response to treatment. PRCA was a possible adverse event in 2 of 33 dogs (6%).