Alloimmune Conditions in the Neonatal Foal.

Alloimmune disorders occur in foals when pregnant mares produce antibodies against antigens on the foal's cells or tissues, and concentrate them within colostrum. Once foals nurse and absorb colostral antibodies, they can develop hematologic or cutaneous manifestations that can occur individually or in combination. These include neonatal isoerythrolysis, a hemolytic anemia directed against factors on the foal's erythrocytes, alloimmune thrombocytopenia when the antibodies are directed against platelet antigens, alloimmune neutropenia when they are directed against neutrophil antigens, and a combination of suspected alloimmune ulcerative dermatitis, neutropenia and thrombocytopenia. Foals can also develop neutrophilic dermatitis which is suspected to be alloimmune.

A nonsense variant in Rap Guanine Nucleotide Exchange Factor 5 (RAPGEF5) is associated with equine familial isolated hypoparathyroidism in Thoroughbred foals.

Idiopathic hypocalcemia in Thoroughbred (TB) foals causes tetany and seizures and is invariably fatal. Based upon the similarity of this disease with human familial hypoparathyroidism and occurrence only in the TB breed, we conducted a genetic investigation on two affected TB foals. Familial hypoparathyroidism was identified, and pedigree analysis suggested an autosomal recessive (AR) mode of inheritance. We performed whole-genome sequencing of the two foals, their unaffected dams and four unaffected, unrelated TB horses. Both homozygosity mapping and an association analysis were used to prioritize potential genetic variants. Of the 2,808 variants that significantly associated with the phenotype using an AR mode of inheritance (P<0.02) and located within a region of homozygosity, 1,507 (54%) were located in a 9.7 Mb region on chr4 (44.9-54.6 Mb). Within this region, a nonsense variant (RAPGEF5 c.2624C>A,p.Ser875*) was significantly associated with the hypoparathyroid phenotype (Pallelic = 0.008). Affected foals were homozygous for the variant, with two additional affected foals subsequently confirmed in 2019. Necropsies of all affected foals failed to identify any histologically normal parathyroid glands. Because the nonsense mutation in RAPGEF5 was near the C-terminal end of the protein, the impact on protein function was unclear. Therefore, we tested the variant in our Xenopus overexpression model and demonstrated RAPGEF5 loss-of-function. This RAPGEF5 variant represents the first genetic variant for hypoparathyroidism identified in any domestic animal species.

Effects of a 10% dimethyl sulfoxide solution on radiocarpal joint amikacin pharmacokinetics during intravenous regional limb perfusion in standing sedated horses.

OBJECTIVE: To determine the effect of a 10% dimethyl sulfoxide (DMSO) solution on the peak concentration (CMAX ) of amikacin in the radiocarpal joint (RCJ) during intravenous regional limb perfusion (IVRLP) compared with 0.9% NaCl. STUDY DESIGN: Randomized crossover study. ANIMALS: Seven healthy adult horses. METHODS: The horses underwent IVRLP with 2 g of amikacin sulfate diluted to 60 mL using a 10% DMSO or 0.9% NaCl solution. Synovial fluid was collected from the RCJ at 5, 10, 15, 20, 25, and 30 minutes after IVRLP. The wide rubber tourniquet placed on the antebrachium was removed after the 30 min sample. Amikacin concentrations were quantified by a fluorescence polarization immunoassay. The mean CMAX and time to peak concentration (TMAX ) of amikacin within the RCJ were determined. A one-sided paired t-test was used to determine the differences between treatments. The significance level was p < .05. RESULTS: The mean ± SD CMAX in the DMSO group was 1361.8 ± 593 µg/mL and in the 0.9% NaCl group it was 860 ± 481.6 µg/mL (p = .058). Mean TMAX using the 10% DMSO solution was 23 and 18 min using the 0.9% NaCl perfusate (p = .161). No adverse effects were associated with use of the 10% DMSO solution. CONCLUSION: Although there were higher mean peak synovial concentrations using the 10% DMSO solution no difference in synovial amikacin CMAX between perfusate type was detected (p = .058). CLINICAL SIGNIFICANCE: Use of a 10% DMSO solution in conjunction with amikacin during IVRLP is a feasible technique and does not negatively affect the synovial amikacin levels achieved. Further research is warranted to determine other effects of using DMSO during IVRLP.

Correction: Mutations in MITF and PAX3 Cause "Splashed White" and Other White Spotting Phenotypes in Horses.

[This corrects the article DOI: 10.1371/journal.pgen.1002653.].

Closure of a patent ductus arteriosus in a 2-week-old llama cria using an Amplatz canine duct occluder.

A two-week-old female llama cria was brought to the UC Davis Large Animal Hospital for evaluation of a cardiac murmur and suspected syncopal episodes. A grade IV/VI left basilar continuous murmur was present on cardiac auscultation. Echocardiography revealed a left-to-right shunting patent ductus arteriosus (PDA), mild left ventricular enlargement, scant pericardial effusion, and a suspected persistent left cranial vena cava. The PDA was successfully closed with an Amplatz canine duct occluder. Mild mitral regurgitation was present on echocardiography performed 7 d following PDA occlusion. No syncopal episodes were observed in hospital prior to or following PDA occlusion. At approximately 1 mo following PDA closure, a grade I/VI left apical systolic murmur was present and the cria's body condition was improved. Key clinical message: Patent ductus arteriosus closure is achievable in New World camelids using interventional cardiology which provides a minimally invasive treatment option for valuable or companion animals. Since interventional cardiac catheterization is commonly performed in small animal species, veterinary cardiologists are well-equipped to apply these skills to camelids.

Fermeture d'un canal artériel persistant chez un lama cria âgé de 2 semaines à l'aide d'un obturateur de conduit canin Amplatz. Une femelle lama cria âgée de deux semaines a été amenée à l'UC Davis Large Animal Hospital pour l'évaluation d'un souffle cardiaque et d'épisodes syncopaux suspectés. Un souffle continu basilaire gauche de grade IV/VI était présent à l'auscultation cardiaque. L'échocardiographie a révélé une persistance du canal artériel avec perméabilité de gauche à droite (PDA), une légère hypertrophie ventriculaire gauche, un léger épanchement péricardique et une suspicion de veine cave crâniale gauche persistante. Le PDA a été fermé avec succès avec un obturateur de conduit canin Amplatz. Une régurgitation mitrale légère était présente sur l'échocardiographie réalisée 7 jours après l'occlusion du PDA. Aucun épisode de syncope n'a été observé à l'hôpital avant ou après l'occlusion du PDA. Environ 1 mois après la fermeture du PDA, un souffle systolique apical gauche de grade I/VI était présent et l'état corporel du cria s'était amélioré.Message clinique clé :La fermeture brevetée du canal artériel est réalisable chez les camélidés du Nouveau Monde en utilisant la cardiologie interventionnelle qui offre une option de traitement peu invasive pour les animaux de valeur ou de compagnie. Étant donné que le cathétérisme cardiaque interventionnel est couramment pratiqué chez les petites espèces animales, les cardiologues vétérinaires sont bien équipés pour appliquer ces compétences aux camélidés.(Traduit par Dr Serge Messier).

Equine antimicrobial therapy: Current and past issues facing practitioners.

Equine antimicrobial therapy has advanced over time with the availability of increasing pharmacokinetic and pharmacodynamic studies in horses, allowing for greater evidence-based clinical decision-making. However, many challenges to optimal antimicrobial therapy remain and further research is needed to address these areas. There are a limited number of approved antimicrobials for use in horses, which creates a need for compounded preparations for clinicians. Extra-label drug use is commonplace in equine practice, which warrants continual education of veterinarians about policies and updates. Performance and competitive horses have their own unique concerns when it comes to antimicrobial use and drug testing. In keeping with the use of a broader range of antimicrobials over time, antimicrobial resistance is emerging as an important issue facing veterinary medicine, including equine practice. Another challenge is that of drug interactions and adverse drug events for which there are little scientific data available for horses, especially for critically important diseases such as Rhodococcus equi infection. Finally, much progress has been made in the availability of equine-specific antimicrobial susceptibility break points. These aid clinicians in interpreting culture and susceptibility results and antimicrobial selection. Even with these advances, continuing education and further research are needed in this area.

Bacterial meningitis after dental extraction in a 17-year-old horse.

Dental extractions in horses may result in bacteremia, which can lead to systemic complications. Bacterial meningitis following oral cheek tooth extractions in a 17-year-old Thoroughbred gelding is described in this report. The bacterial meningitis was confirmed by histopathology. The gelding was presented for evaluation of intermittent fever, loose feces, and mild colic signs which started 5 days after cheek tooth extraction. This case illustrates a rare complication associated with oral tooth extraction in a horse and highlights the unusual presenting features of meningitis. Key clinical message: Bacterial meningitis secondary to oral cheek tooth extraction should be considered as differential diagnosis; particularly in cases with the development of pyrexia a few days after the procedure.

Méningite bactérienne après extraction dentaire chez un cheval de 17 ans. Les extractions dentaires chez les chevaux peuvent entraîner une bactériémie, ce qui peut amener des complications systémiques. Un cas de méningite bactérienne à la suite d'extractions buccales de dents jugales chez un hongre pur-sang de 17 ans est décrite dans ce rapport. La méningite bactérienne a été confirmée par histopathologie. Le hongre a été présenté pour évaluation d'une fièvre intermittente, de selles molles et de signes de coliques légers qui ont commencé 5 jours après l'extraction de la dent jugale. Ce cas illustre une complication rare associée à l'extraction dentaire orale chez un cheval et met en évidence des caractéristiques inhabituelles de la méningite.Message clinique clé :La méningite bactérienne secondaire à l'extraction buccale des dents jugales doit être considérée comme un diagnostic différentiel, en particulier dans les cas de développement d'une pyrexie quelques jours après l'intervention.(Traduit par Dr Serge Messier).

Antimicrobial Selection for the Equine Practitioner.

Antimicrobial drugs play an important, often central, role in the therapeutic management of mature horses and foals with a variety of illnesses, including those requiring critical care. Antimicrobial use must be based on rational principles involving thorough patient evaluation and sound clinical judgment that indicate a high likelihood that the patient has a bacterial infection and that antimicrobials are indicated to promote recovery. The aim of antimicrobial treatment is to inflict an insult on infecting bacteria sufficient to kill the organism or render it susceptible to inactivation by natural host defenses or the local microenvironment without adversely affecting the patient.

A De Novo MITF Deletion Explains a Novel Splashed White Phenotype in an American Paint Horse.

Splashed white is a coat color pattern in horses characterized by extensive white patterning on the legs, belly, and face often accompanied by blue eyes and deafness. Three mutations in microphthalmia-associated transcription factor (MITF) and two mutations in Paired Box 3 (PAX3) have been identified that explain splashed white patterns (SW1-SW5). An American Paint Horse stallion with a splashed white phenotype and blue eyes, whose parents were not white patterned, was negative for the 5 known splashed white variants and other known white spotting alleles. This novel splashed white phenotype (SW6) was hypothesized to be caused by a de novo mutation in MITF or PAX3. Analysis of whole-genome sequencing using the EquCab3.0 reference genome for comparison identified an 8.7 kb deletion in MITF on ECA16 (NC_009159.3:g.21551060-21559770del). The deletion encompassed part of intron 7 through the 3' UTR of exon 9 of MITF, including the helix-loop-helix DNA-binding domain (ENSECAT00000006375.3). This variant is predicted to truncate protein and impair binding to DNA. Sanger sequencing confirmed the stallion was heterozygous for the MITF deletion. No single nucleotide polymorphisms (SNPs) or structural variants were identified in PAX3 or any of the other candidate genes that were unique to the stallion or predicted to affect protein function. Genotyping five of the stallion's splashed white offspring, including one all white foal, found that they were also heterozygous for the deletion. Given the role of MITF in producing white pattern phenotypes, and the predicted deleterious effect of this mutation, this 8.7 kb deletion is the likely causal variant for SW6.

Pharmacokinetics of maropitant citrate after oral administration of multiple doses in adult horses.

The neurokinin-1 (NK-1) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood in horses, and clinical use of NK-1 receptor antagonists has not been reported. This study aimed to determine the pharmacokinetics and safety of maropitant after administration of multiple doses. We hypothesized that maropitant concentrations would be similar at steady state to those reported in dogs, with minimal adverse effects. Maropitant was administered at 4 mg/kg orally, once daily for 5 days in seven adult horses. Serial plasma maropitant concentrations were measured by liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic parameters were determined. The maximum, minimum, and average concentrations of maropitant achieved at steady state were 375.5 ± 200, 16.8 ± 7.7, and 73.5 ± 45.1 ng/ml, respectively. The terminal elimination half-life was 11.6 ± 1.4 hr, and the accumulation index was 1.3 ± 0.07. Heart rate decreased between Day 1 and Day 5 (p = .005), with three horses having heart rates of 20 beats per minute and atrioventricular block on Day 5. Pharmacokinetics of repeated maropitant administration suggests the drug could be considered for use in healthy horses. Further investigation on the clinical relevancy of its cardiac effects is warranted.

Resolution of neurologic signs presumed to be associated with hyperammonemia in 2 endurance horses.

This case report describes 2 endurance horses with non-hepatic hyperammonemia. The animals were competing in a 160-km endurance competition in extreme heat conditions and were presented for obtundation. One of the horses also had evidence of blindness. The blood ammonia concentration was elevated (196 µmol/L and 249 µmol/L) and both horses improved following treatment with intravenous fluids and supportive care. These are the first documented cases of clinical signs presumed to be associated with hyperammonemia in endurance horses. Despite the severity of the clinical presentation, both horses made a full recovery. Key clinical message: Non-hepatic hyperammonemia should be considered as a potential cause of blindness and obtundation in competing endurance horses. Horses appear to respond well to treatment with intravenous fluids.

Fin des signes neurologiques présumés être associés avec de l'hyperammoniémie chez deux chevaux d'endurance. Le présent rapport de cas décrit la situation de deux chevaux d'endurance avec une hyperammoniémie non-hépatique. Les animaux compétitionnaient dans une course d'endurance de 160 km dans des conditions de chaleur extrême et furent présentés pour confusion. Un des chevaux avait également des évidences de cécité. Les concentrations d'ammoniaque sanguin étaient élevées (196 µmol/L et 249 µmol/L) et les deux chevaux s'améliorèrent à la suite du traitement avec des fluides intraveineux et des soins de support. Ces cas représentent les premiers cas documentés de signes cliniques présumés être associés avec de l'hyperammoniémie chez des chevaux d'endurance. Malgré la sévérité de la présentation clinique, les deux chevaux ont récupéré complètement.Message clinique clé :L'hyperammoniémie non-hépatique devrait être considérée comme une cause potentielle de cécité et de confusion chez des chevaux d'endurance en compétition. Les chevaux semblent bien répondre à un traitement avec des fluides intraveineux.(Traduit par Dr Serge Messier).

Pharmacokinetics of single doses of maropitant citrate in adult horses.

The neurokinin-1 (NK) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood and likely under-recognized in horses. Use of NK-1 receptor antagonists in horses has not been reported. The purpose of this study was to determine the pharmacokinetic profile of maropitant in seven adult horses after single intravenous (IV; 1 mg/kg) and intragastric (IG; 2 mg/kg) doses. A randomized, crossover design was performed. Serial blood samples were collected after dosing; maropitant concentrations were measured using LC-MS/MS. Pharmacokinetic parameters were determined using noncompartmental analysis. The mean plasma maropitant concentration 3 min after IV administration was 800 ± 140 ng/ml, elimination half-life was 10.37 ± 2.07 h, and volume of distribution was 6.54 ± 1.84 L/kg. The maximum concentration following IG administration was 80 ± 40 ng/ml, and elimination half-life was 9.64 ± 1.27 hr. Oral bioavailability was variable at 13.3 ± 5.3%. Maropitant concentrations achieved after IG administration were comparable to those in small animals. Concentrations after IV administration were lower than in dogs and cats. Elimination half-life was longer than in dogs and shorter than in cats. This study is the basis for further investigations into using maropitant in horses.

Pharmacokinetics of chloramphenicol base in horses and comparison to compounded formulations.

Chloramphenicol is commonly used in horses; however, there are no studies evaluating the pharmacokinetics of veterinary canine-approved tablets. Studies using different formulations and earlier analytical techniques led to concerns over low bioavailability in horses. Safety concerns about human health have led many veterinarians to prescribe compounded formulations that are already in suspension or paste form. The objective of this study was to evaluate the pharmacokinetics of approved chloramphenicol tablets in horses, along with compounded preparations. The hypothesis was that chloramphenicol has low absorption and a short half-life in horses leading to low serum concentrations and that compounded preparations have lower relative bioavailability. Seven horses were administered chloramphenicol tablets (50 mg/kg orally). In a crossover design, they were administered two compounded preparations to compare all three formulations at the same dose (50 mg/kg). Cmax was 5.25 ± 4.07 µg/ml at 4.89 hr, 4.96 ± 3.31 µg/ml at 4.14 hr, and 3.84 ± 2.96 µg/ml at 4.39 hr for the tablets, paste, and suspension, respectively. Elimination half-life was 2.65 ± 0.75, 3.47 ± 1.47, and 4.36 ± 4.54 hr for tablets, paste, and suspension, respectively. The AUC0→∞ was 17.93 ± 7.69, 16.25 ± 1.85, and 14.00 ± 5.47 hr*µg/ml for the tablets, compounded paste, and compounded suspension, respectively. Relative bioavailability of compounded suspension and paste was 78.1% and 90.6%. Cmax after administration of all formulations did not reach the recommended MIC target of 8 µg/ml set by the Clinical Laboratory Standards Institute (CLSI) for most bacteria. Multidose studies are warranted, but the low serum concentrations suggest that bacteria with MIC values lower than CLSI recommendations should be targeted in adult horses.

Comparison of corneal degeneration and calcific band keratopathy from 2000 to 2013 in 69 horses.

OBJECTIVE: To compare signalment, presentation, treatment, and outcome in horses diagnosed with corneal degeneration (CD) or calcific band keratopathy (CBK) at a referral hospital. ANIMALS STUDIED: Sixty-nine horses (87 eyes) diagnosed with either CD or CBK. PROCEDURES: Medical records of horses diagnosed with CD or CBK at the University of California-Davis Veterinary Medical Teaching Hospital (UCD-VMTH) between 2000 and 2013 were reviewed. Signalment, concurrent ophthalmic diagnoses, previous therapies, diagnostic tests, systemic diagnoses, treatment, follow-up, and outcomes were compared between horses diagnosed with CD or CBK. Age, breed, and gender were compared between the CD/CBK and UCD-VMTH populations. RESULTS: Thirty-three horses (42 eyes) and 36 horses (45 eyes) were diagnosed with CD and CBK, respectively. Horses with CD or CBK were significantly older (P < 0.001) than the UCD-VMTH population with a median age of 16 or 18 years, respectively. Appaloosas were significantly overrepresented in the CD/CBK population (33%) in comparison with the UCD-VMTH population (1.8%, P < 0.001). Equine recurrent uveitis was concurrently diagnosed in 67% and 84% of horses with CD or CBK, respectively. Pituitary pars intermedia dysfunction (PPID) was diagnosed significantly less often in horses with CD vs. CBK (P = 0.03). Chemical chelation with ethylenediaminetetraacetic acid was performed significantly less frequently in horses diagnosed with CD (7.1%) vs. CBK (31.1% of eyes) (P = 0.012). CONCLUSIONS: Despite some differences, equine CD and CBK are relatively similar conditions and may represent a continuum of disease severity. Horses with PPID should be monitored closely for corneal disease including CBK.

Antimicrobial Pharmacology for the Neonatal Foal.

Neonatal foals are at high risk of developing sepsis, which can be life-threatening. Early antimicrobial use is a critical component of the treatment of sepsis. Because the neonatal foal has unique pharmacologic physiology, antimicrobial choice and dosing are often different than in adult horses. Broad-spectrum, bactericidal, and intravenous antimicrobials should be considered first-line therapy for septic foals. A combination of aminoglycoside and beta-lactam antimicrobial or third-generation cephalosporin is an excellent empirical first choice for treating septic foals, until culture and susceptibility results are available. Renal function should be monitored carefully in foals being treated with aminoglycosides.

MEDICAL MANAGEMENT OF RECURRENT EOSINOPHILIC GRANULOMA IN TWO BLACK RHINOCEROS (DICEROS BICORNIS).

Recurrent eosinophilic granuloma (EG) in two captive eastern black rhinoceros ( Diceros bicornis michaeli) was effectively managed with glucocorticoids and antihistamines. The first case was a female and the second case was a male. The animals were housed at separate institutions and initially presented with hemorrhagic oral lesions. Multifocal lesions occurred in the second case. Multiple biopsies were taken from each animal, all of which were consistent with EG. Each animal was anesthetized multiple times for surgical treatment but experienced frequent recurrence. Due to lack of response to therapy and the risks and adverse events associated with repeated anesthesia, medical treatment was initiated in both cases using a tapering dose of oral dexamethasone. The lesions dramatically improved, but would recur frequently after treatment. Hydroxyzine, an oral antihistamine, greatly reduced the incidence and severity of the lesions. Medical management with glucocorticoids and antihistamines minimized stressful anesthetic events in both cases and contributed to the successful management of this recurrent disease. The exact pathogenesis of EG in black rhinoceros remains unknown but response to antihistamines suggests an allergic etiology.

Mutations in MITF and PAX3 cause "splashed white" and other white spotting phenotypes in horses.

During fetal development neural-crest-derived melanoblasts migrate across the entire body surface and differentiate into melanocytes, the pigment-producing cells. Alterations in this precisely regulated process can lead to white spotting patterns. White spotting patterns in horses are a complex trait with a large phenotypic variance ranging from minimal white markings up to completely white horses. The "splashed white" pattern is primarily characterized by an extremely large blaze, often accompanied by extended white markings at the distal limbs and blue eyes. Some, but not all, splashed white horses are deaf. We analyzed a Quarter Horse family segregating for the splashed white coat color. Genome-wide linkage analysis in 31 horses gave a positive LOD score of 1.6 in a region on chromosome 6 containing the PAX3 gene. However, the linkage data were not in agreement with a monogenic inheritance of a single fully penetrant mutation. We sequenced the PAX3 gene and identified a missense mutation in some, but not all, splashed white Quarter Horses. Genome-wide association analysis indicated a potential second signal near MITF. We therefore sequenced the MITF gene and found a 10 bp insertion in the melanocyte-specific promoter. The MITF promoter variant was present in some splashed white Quarter Horses from the studied family, but also in splashed white horses from other horse breeds. Finally, we identified two additional non-synonymous mutations in the MITF gene in unrelated horses with white spotting phenotypes. Thus, several independent mutations in MITF and PAX3 together with known variants in the EDNRB and KIT genes explain a large proportion of horses with the more extreme white spotting phenotypes.

Acquired multiple acyl-CoA dehydrogenase deficiency and marked selenium deficiency causing severe rhabdomyolysis in a horse.

This report describes a case of severe rhabdomyolysis in a pregnant mare associated with histopathologic and biochemical features of both selenium deficiency and acquired multiple acyl-CoA dehydrogenase deficiency (MADD) due to seasonal pasture myopathy (SPM). This case highlights the importance of assessing plasma selenium levels in horses with clinical signs of pasture myopathy as this deficiency may be a contributing or exacerbating factor.

Déficience multiple acquise de déshydrogénase acyl-CoA et carence en sélénium marquée causant une rhabdomyolyse grave chez un cheval. Ce rapport décrit le cas d'une rhabdomyolyse grave chez une jument gravide associée à des caractéristiques histopathologiques et biochimiques de la carence en sélénium et d'une carence multiple acquise de déhydrogénase acyl-CoA (MADD) causées par la myopathie saisonnière des pâturages (SPM). Ce cas souligne l'importance d'évaluer les niveaux de sélénium dans le plasma des chevaux manifestant des signes cliniques de myopathie du pâturage car cette carence peut être un facteur contributif ou aggravant.(Traduit par Isabelle Vallières).

Imaging diagnosis-aortic aneurysm and ureteral obstruction secondary to umbilical artery abscessation in a 5-week-old foal.

A 5-week-old foal was evaluated for fever and hematuria of 3 days duration. Cystoscopy localized the blood to be originating from the left ureter. Abdominal ultrasonography revealed left hydronephrosis, hydroureter, and omphaloarteritis of the left umbilical artery with abscess formation that communicated with an arterial structure. Computed tomography (CT) revealed a large aortic aneurysm within the center of the abscess. An exploratory celiotomy was performed and the infection was nonresectable. The prognosis for life was grave; therefore the colt was euthanized. Necropsy findings confirmed the antemortem diagnosis. Ultrasound and CT imaging in this case provided an accurate antemortem diagnosis.

Retrospective evaluation of acute kidney injury in horses treated with nonnitrogenous bisphosphonates (2013-2020): 8 cases.

OBJECTIVE: To describe a population of horses with acute kidney injury (AKI) following administration of bisphosphonates including clinical signs, clinicopathologic data, treatment, and outcome. DESIGN: Retrospective study from August 2013 to July 2020. SETTING: Veterinary university teaching hospital. ANIMALS: Eight adult horses with AKI following administration of nonnitrogenous bisphosphonates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five horses received intramuscular clodronate (5/8; 62.5%) and 3 horses received intravenous tiludronate (3/8; 37.5%). Six horses (6/8; 75%) received concurrent nonsteroidal anti-inflammatory drugs. The most common initial presenting complaint was poor appetite (6/8; 75%), followed by abnormal urination (2/8; 25%). At the time of initial evaluation, the mean serum or plasma creatinine was 451.72 ± 190.06 µmol/L (5.11 ± 2.15 mg/dL) and BUN was 18.84 ± 8.85 mmol/L (52.75 ± 24.77 mg/dL). Five horses (5/6; 83.3%) had either an increased number of red blood cells (n = 4) or hemoprotein (n = 1) in the urine. All horses were treated with IV isotonic, balanced crystalloids either as a bolus, continuous rate infusion, or a combination of the 2. Seven horses (7/8; 87.5%) survived the initial episode of AKI and 1 horse (1/8; 12.5%) was euthanized. Of the 7 surviving horses, 2 horses (2/7; 28.5%) went on to develop chronic renal dysfunction. Warmblood breeds were overrepresented in the AKI group (P = 0.008; odds ratio: 11.5, 95% confidence interval: 1.8-72.1), when compared to horses that received bisphosphonates during the study period and did not develop AKI. CONCLUSIONS: Bisphosphonate administration, with or without concurrent nonsteroidal anti-inflammatory drugs, can be associated with AKI in horses. Serum creatinine should be monitored prior to and following bisphosphonate treatment to minimize this risk. Further evaluation of renal function is warranted in horses that develop clinical signs of poor appetite, lethargy, or altered urination in the days following bisphosphonate treatment.