Clustering analysis of lipoprotein profiles to identify subtypes of hypertriglyceridemia in Miniature Schnauzers.

BACKGROUND: Hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, predisposing them to life-threatening diseases. Varied responses to management strategies suggest the possibility of multiple subtypes. HYPOTHESIS/OBJECTIVE: To identify and characterize HTG subtypes in Miniature Schnauzers through cluster analysis of lipoprotein profiles. We hypothesize that multiple phenotypes of primary HTG exist in this breed. ANIMALS: Twenty Miniature Schnauzers with normal serum triglyceride concentration (NTG), 25 with primary HTG, and 5 with secondary HTG. METHODS: Cross-sectional study using archived samples. Lipoprotein profiles, generated using continuous lipoprotein density profiling, were clustered with hierarchical cluster analysis. Clinical data (age, sex, body condition score, and dietary fat content) was compared between clusters. RESULTS: Six clusters were identified. Dogs with primary HTG were dispersed among 4 clusters. One cluster showed the highest intensities for triglyceride-rich lipoprotein (TRL) and low-density lipoprotein (LDL) fractions and also included 4 dogs with secondary HTG. Two clusters had moderately high TRL fraction intensities and low-to-intermediate LDL intensities. The fourth cluster had high LDL but variable TRL fraction intensities with equal numbers of NTG and mild HTG dogs. The final 2 clusters comprised only NTG dogs with low TRL intensities and low-to-intermediate LDL intensities. The clusters did not appear to be driven by differences in the clinical data. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study support a spectrum of lipoprotein phenotypes within Miniature Schnauzers that cannot be predicted by triglyceride concentration alone. Lipoprotein profiling might be useful to determine if subtypes have different origins, clinical consequences, and response to treatment.

Sequence Analysis of Six Candidate Genes in Miniature Schnauzers with Primary Hypertriglyceridemia.

Miniature Schnauzers are predisposed to primary hypertriglyceridemia (HTG). In this study, we performed whole genome sequencing (WGS) of eight Miniature Schnauzers with primary HTG and screened for risk variants in six HTG candidate genes: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE. Variants were filtered to identify those present in ≥2 Miniature Schnauzers with primary HTG and uncommon (<10% allele frequency) in a WGS variant database including 613 dogs from 61 other breeds. Three variants passed filtering: an APOE TATA box deletion, an LMF1 intronic SNP, and a GPIHBP1 missense variant. The APOE and GPIHBP1 variants were genotyped in a cohort of 108 Miniature Schnauzers, including 68 with primary HTG and 40 controls. A multivariable regression model, including age and sex, did not identify an effect of APOE (estimate = 0.18, std. error = 0.14; p = 0.20) or GPIHBP1 genotypes (estimate = -0.26, std. error = 0.42; p = 0.54) on triglyceride concentration. In conclusion, we did not identify a monogenic cause for primary HTG in Miniature Schnauzers in the six genes evaluated. However, if HTG in Miniature Schnauzers is a complex disease resulting from the cumulative effects of multiple variants and environment, the identified variants cannot be ruled out as contributing factors.

Lipoprotein profiles in Miniature Schnauzer dogs with idiopathic hypertriglyceridemia and hypercortisolism.

Miniature Schnauzer dogs (MSs) are predisposed to both idiopathic hypertriglyceridemia (iHTG) and hypercortisolism (HCort). To our knowledge, the lipoprotein profiles of MSs with iHTG have not been compared to those with HCort. We analyzed cholesterol and triglyceride concentrations and lipoprotein fractions in 4 groups of MSs: normotriglyceridemia (NTG) without concurrent disease (Healthy-NTG), HCort and NTG (HCort-NTG), HCort and HTG (HCort-HTG), and iHTG. Lipoprotein fractions were assessed by lipoprotein electrophoresis and compared between groups. Fifty-one plasma samples were analyzed. Twenty-five dogs had NTG (16 Healthy-NTG, 9 HCort-NTG) and 26 dogs had HTG (7 iHTG, 19 HCort-HTG). Dogs with iHTG or HCort-HTG had significantly higher cholesterol concentrations than Healthy-NTG dogs. Dogs with HCort-HTG had higher cholesterol than HCort-NTG dogs. There was a significantly higher low-density lipoprotein (LDL) percentage in iHTG and HCort-HTG dogs than HCort-NTG dogs. HCort-HTG dogs also had lower high-density lipoproteins (HDL) than HCort-NTG dogs. It was not possible to readily distinguish MSs with iHTG from MSs with HCort-HTG or Healthy-NTG using lipoprotein electrophoresis fractions. The diagnosis of iHTG remains a diagnosis by exclusion.

Hypertriglyceridemia in equines with refractory hyperinsulinemia treated with SGLT2 inhibitors.

Background: Sodium-Glucose CoTransporter-2 (SGLT2) inhibitors, the -flozin group of drugs, which block glucose reuptake in the renal proximal tubule, are being increasingly used off-label to treat horses with refractory hyperinsulinemia. After 2 years of use by animals in our group, a horse on canagliflozin was incidentally noted to be hyperlipemic. Case Description: We have been following a cohort of equines (n = 20) treated with SGLT2 inhibitors due to refractory hyperinsulinemia. The animals are owned by members of the Equine Cushing's and Insulin Resistance Group and treated by their attending veterinarians. The index case was a 23 years old gelding with a 2 years history of recurring laminitis that began canagliflozin therapy to control hyperinsulinemia which was no longer responsive to metformin. Between 6 and 10 weeks post start of therapy, significant weight loss was noticed. Two days later he was hospitalized with colic symptoms and hyperlipemia but was bright, alert, and eating well throughout. Canagliflozin was discontinued and triglycerides returned to normal reference values within 10 days. A subsequent study of 19 other horses on SGLT2 inhibitors revealed varying degrees of hypertriglyceridemia, all asymptomatic. Conclusion: While this class of drugs holds great promise for cases of refractory hyperinsulinemia and laminitis that do not respond to diet or metformin therapy, hypertriglyceridemia is a potential side effect. In our experience, animals remained asymptomatic and eating well. Further study of hypertriglyceridemia in horses on SGLT2 inhibitors and the possible mitigating effect of diet is indicated. To our knowledge, this is the first report of hypertriglyceridemia with canagliflozin treatment in equines.

Successful multimodal treatment of extreme hypertriglyceridemia in a juvenile diabetic dog.

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.

Therapy for feline secondary hypertriglyceridemia with fenofibrate.

OBJECTIVES: The aim of this study was to assess the short-term safety and efficacy of fenofibrate in controlling secondary hypertriglyceridemia in cats. METHODS: This was a prospective cohort study. Seventeen adult cats with hypertriglyceridemia (serum triglycerides [TG] >160 mg/dl) were enrolled. Cats received a median dose of 5 mg/kg (range 3.2-6) fenofibrate (q24h PO) for 1 month. Serum TG, total cholesterol (TC), creatine kinase and liver enzymes (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase) were evaluated before (t0) and after 1 month (t1) of fenofibrate treatment. RESULTS: The causes of secondary hypertriglyceridemia were diabetes mellitus (DM; 29.4%), obesity (29.4%), hyperadrenocorticism (HAC) and DM (11.7%), HAC without DM (5.9%), hypersomatotropism (HST) and DM (5.9%), hypothyroidism (5.9%), long-term treatment with glucocorticoids (5.9%) and chylothorax (5.9%). Serum TG (t0 median 920 mg/dl [range 237-1780]; t1 median 51 mg/dl [range 21-1001]; P = 0.0002) and TC (t0 median 278 mg/dl [range 103-502]; t1 median 156 mg/dl [range 66-244]; P = 0.0001) concentrations showed a significant decrease after 1 month of fenofibrate treatment. Fifteen cats normalized their TG concentration at t1 (88.2%). Of the eight cats that were hypercholesterolemic at t0, six (75%) normalized their TC concentrations at t1. One of 17 cats (5.9 %) presented with diarrhea; the remaining 16 did not show any adverse effects. CONCLUSIONS AND RELEVANCE: DM and obesity are the most common endocrine causes of secondary hyperlipidemia, although it can also be found in cats with HAC, HST or hypothyroidism. This study suggests that fenofibrate treatment was associated with reduction and normalization of TG and TC concentrations in cats with moderate and severe hypertriglyceridemia, regardless of the cause of secondary hypertriglyceridemia. Further work should focus on controlled studies with a greater number of cases.

Associations among serum insulin, calprotectin, and C-reactive protein concentrations in Miniature Schnauzers with idiopathic hyperlipidemia before and after feeding an ultra-low-fat diet.

BACKGROUND: Miniature Schnauzers (MS) commonly have idiopathic hypertriglyceridemia (HTGL), which is associated with insulin resistance (IR) and a subclinical inflammatory phenotype. OBJECTIVES: Determine the association between indicators of IR and inflammatory biomarkers in MS with and without HTGL and identify how indicators of IR are affected by dietary intervention in MS with HTGL. ANIMALS: Seventy MS with HTGL and 79 MS without HTGL. In addition, 15 MS with HTGL were placed on a low-fat diet. METHODS: Serum concentrations of triglycerides, cholesterol, calprotectin, insulin, and glucose were compared between groups. RESULTS: Serum glucose and calprotectin concentrations (shown to be higher in MS with HTGL than in MS without HTGL) were inversely correlated (ρ = -.28; P < .001). After dietary intervention, median serum insulin concentrations were 8.1 mU/L compared to 20.8 mU/L before dietary intervention (P = .06). Dogs with complete resolution of HTGL after dietary intervention (5 dogs) had significantly lower serum insulin concentrations compared to baseline (P = .03). CONCLUSION AND CLINICAL IMPORTANCE: The subclinical inflammatory phenotype in MS with HTGL appears to be associated with IR. Resolution of HTGL by dietary intervention is associated with a decrease in serum insulin concentrations. The implication of the increase in serum calprotectin concentrations after resolution of HTGL warrants further study.

Fenofibrate treatment for severe hypertriglyceridemia in dogs.

Lipid disorders are relatively common in dogs. Hyperlipidemia can be primary or secondary to other diseases. In humans, fenofibrate is used to control hypertriglyceridemia. In dogs, there are no studies evaluating fenofibrate in hypertriglyceridemia. The aim of the study was to evaluate the safety and efficacy of fenofibrate to control severe hypertriglyceridemia in dogs. A total of 124 dogs (n = 124) with severe hypertriglyceridemia (>300 mg/dL, 3.39 mmol/L) were randomly distributed in the fenofibrate group (n = 64) and the diet group (n = 60). Dogs of the fenofibrate group were treated with fenofibrate (10 mg/Kg) once daily. Dogs of the diet group were treated with low-fat diet (10%). Serum triglycerides (TGs), total cholesterol (TC), liver enzymes, and creatine kinase concentrations were evaluated, before and after 1 mo of medical or dietary treatment. Triglyceride concentrations were reduced with fenofibrate (P < 0.001), and 85.93% of the dogs normalized their levels. Triglyceride concentrations also decreased with low-fat diet (P < 0.001), but only 26.6% of the dogs normalized their levels. Triglyceride concentrations were reduced with fenofibrate (P < 0.01) and with low-fat diet (P < 0.01). Of the cases with hypercholesterolemia, 53.7% and 50% of the dogs normalized their TC concentrations, with fenofibrate and diet, respectively. No significant adverse effects were observed (3% showed diarrhea). Fenofibrate was safe and effective in reducing and normalizing TG concentrations in dogs with severe hypertriglyceridemia, regardless of the cause of hyperlipidemia. The low-fat diet was effective in reducing, but not normalizing, TG concentrations. Fenofibrate and low-fat diet were effective in reducing TC concentrations. This is the first study evaluating fibrates in dogs with severe hypertriglyceridemia and comparing results with a low-fat diet.

Sequence analysis of the coding regions of the apolipoprotein C2 (APOC2) gene in Miniature Schnauzers with idiopathic hypertriglyceridemia.

It has been hypothesized that idiopathic hypertriglyceridemia in Miniature Schnauzers is hereditary, but the gene responsible has yet to be identified. The objective of this study was to determine if there were coding variants in the apolipoprotein C2 (APOC2) gene in Miniature Schnauzers with idiopathic hypertriglyceridemia. Blood samples from 12 Miniature Schnauzers with idiopathic hypertriglyceridemia were analyzed. Genomic DNA was extracted from whole blood, and the three coding exons of APOC2 were amplified by PCR. The PCR amplicons were sequenced and analyzed for variants relative to the canine reference genome (CanFam3.1 assembly). A second objective was to determine the extent of variation in coding exons of APOC2 in a large and diverse canine population using the Dog Biomedical Variant Database Consortium variant catalog, comprised of whole genome sequencing variant calls from 582 dogs of 126 breeds and eight wolves. There were no variants detected in the coding exons of APOC2 for any of the 12 Miniature Schnauzers with idiopathic hypertriglyceridemia. Variants in the coding exons of APOC2 were also rare in the Dog Biomedical Variant Database Consortium variant catalog; a single synonymous variant was identified in a heterozygous state in a Tibetan Mastiff. Thus, we concluded that coding variants in APOC2 are unlikely to be a major cause of idiopathic hypertriglyceridemia in North American Miniature Schnauzers and furthermore, that such coding variants are rare in the canine population.

Effect of a low-fat diet on serum triglyceride and cholesterol concentrations and lipoprotein profiles in Miniature Schnauzers with hypertriglyceridemia.

BACKGROUND: Hypertriglyceridemia is common in Miniature Schnauzer (MS). Dietary management of hypertriglyceridemia is important, but no studies are available. HYPOTHESIS/OBJECTIVES: To evaluate the effect of a commercially available low-fat diet on serum triglyceride and cholesterol concentrations and lipoprotein profiles in MS with hypertriglyceridemia. ANIMALS: Sixteen MS with hypertriglyceridemia and 28 MS without hypertriglyceridemia. METHODS: Prospective clinical trial. Four blood samples (1-2 months before and 1 day before diet change and 2 and 3 months after the dogs were fed the low-fat diet) were collected from the MS with hypertriglyceridemia. RESULTS: Serum triglyceride concentrations for the 2 samples after the diet change (median of sample 3 = 177 mg/dL; range, 48-498; median of sample 4 = 168 mg/dL; range, 77-745) were significantly lower than the 2 samples before the diet change (median of sample 1 = 480 mg/dL; range, 181-1320; median of sample 2 = 493 mg/dL; range, 114-1395; P < .001). Serum cholesterol concentrations for the 2 samples after the diet change (mean for sample 3 = 257 mg/dL, SD = 82.2; mean for sample 4 = 178 mg/dL, SD = 87.4) were also significantly lower than the 2 samples before the diet change (mean for sample 1 = 381 mg/dL, SD = 146.1; mean for sample 2 = 380 mg/dL, SD = 134.7; P < .001). Before the diet change, 15/16 (94%) of hyperlipidemic MS were classified as hyperlipidemic based on their lipoprotein profiles alone. After the diet change, significantly fewer MS (7/16; 44%; odds ratio = 19.3; 95% CI = 2.0-184.0; P = .006) were classified as hyperlipidemic based on lipoprotein profile analysis. CONCLUSIONS AND CLINICAL IMPORTANCE: The study diet was effective in reducing serum triglyceride and cholesterol concentrations and correcting lipoprotein profiles in MS with hypertriglyceridemia.

Effects of marked hypertriglyceridemia and lipid clearance techniques on canine biochemistry testing.

Triglyceride concentrations in dogs with hyperlipidemic disorders can exceed concentrations used by assay manufacturers for interference testing. High-speed centrifugation or the polar solvent LipoClear reduce triglyceride concentrations, but efficacy requires evaluation in veterinary species. We determined the effect of marked hypertriglyceridemia on canine biochemistry testing; assessed the ability of high-speed centrifugation or LipoClear to correct lipemic interferences; and determined if LipoClear introduces inaccuracy into biochemistry assays. Fifteen pooled canine serum samples were aliquoted and spiked with equal volumes of water or Intralipid [triglyceride concentration 33.9 mmol/L (3,000 mg/dL)]. Intralipid aliquots underwent lipid removal by high-speed centrifugation or LipoClear treatment, and a water-spiked aliquot underwent LipoClear treatment. Biochemistry panels were performed using a Vitros 4600 chemistry analyzer. Results were compared by paired t-test or Wilcoxon test. Total observed errors were considered clinically acceptable if below veterinary allowable total error (TEa) guidelines. Statistically significant (p ≤ 0.05) interferences were introduced by Intralipid for 15 of 15 analytes. Median observed error exceeded TEa for potassium and enzymatic carbon dioxide, neither of which were identified by the manufacturer as susceptible to lipemic interference. After centrifugation, median observed error exceeded TEa for potassium and chloride. LipoClear treatment resulted in median errors that exceeded TEa for total protein, chloride, and phosphorus. Given that severe lipemia can occur in dogs with primary or secondary hyperlipidemia, veterinary laboratories should perform their own interference testing at triglyceride concentrations relevant to their patient population and provide this information to clinicians to ensure optimal case management.

Evaluation of Hypertriglyceridemia as a Mediator Between Endocrine Diseases and Pancreatitis in Dogs.

The role of hypertriglyceridemia (HTG) secondary to endocrine diseases in the occurrence of pancreatitis in dogs has not been fully investigated. The objective of the present study was to evaluate HTG as a mediator between endocrine diseases and pancreatitis in dogs. The study design was a retrospective case-control study. Medical records of dogs newly diagnosed with acutely presenting pancreatitis between 2012 and 2014 were reviewed for the presence or absence of hyperadrenocorticism (HAC), diabetes mellitus (DM), and hypothyroidism. A matched case-control analysis was performed, and the association between endocrine diseases and pancreatitis was evaluated using multiple logistic regression analysis. In dogs with pancreatitis, the odds of HAC (P < .001) and DM (P < .001) were 4.5 and 12.4 times that of dogs without pancreatitis, respectively. HTG significantly mediated the association between DM and pancreatitis but not between HAC and pancreatitis. Additional studies will be necessary to confirm these findings and to further elucidate the associations between endocrine diseases and pancreatitis.

Hypercholesterolemia and hypertriglyceridemia as biochemical markers of disease in companion rabbits.

BACKGROUND: Inflammation has important effects on lipid metabolism, but the relationship between hyperlipidemia, inflammation, and disease remains unknown in rabbits. While rabbits are sensitive to dietary hypercholesterolemia, the etiology of hyperlipidemia when fed non-atherogenic diets is uncertain. OBJECTIVES: This study aimed to determine the association between hypercholesterolemia and patient characteristics, diseases, and select CBC and biochemistry analytes in rabbits, and to measure plasma lipoprotein lipid fractions in rabbits with inflammatory and other diseases. METHODS: Complete blood count and plasma biochemistry data, including total cholesterol concentrations, were evaluated in 531 companion rabbits. Lipoprotein cholesterol fractions (non-high-density lipoprotein cholesterol [non-HDLc] and high-density lipoprotein [HDLc]) and triglycerides were measured using a colorimetric enzymatic assay in archived plasma from a subset of 267 rabbits. Rabbits were categorized by age, sex, spay/neuter status, breed, diet status (fed atherogenic dietary components or not), the organ system affected by disease, and the pathologic process. RESULTS: Cholesterol was associated with fibrinogen (P = 0.01), globulins (P < 0.01), and heterophil (P < 0.01) concentrations. Adjusting for diet, rabbits with severe infection or sepsis (odds ratio [OR] = 13.25, 95% CI = 5.83-30.12), renal failure (OR = 14.42, 95% CI = 5.69-36.54), and hepatopathy (OR = 8.55, 95% CI = 3.55-20.62) had increased risks of hypercholesterolemia. Increased non-HDLc and triglyceride concentrations were also associated with these three disease states (P < 0.05). CONCLUSIONS: Hyperlipidemia is associated with biochemical and CBC markers of inflammation, and with severe infection or sepsis, renal failure, and hepatopathy. Independent of diet, increased cholesterol, non-HDLc, and triglycerides are indicators of disease in companion rabbits.

Hypertriglyceridemia and transient corneal lipidosis in a cat following intravenous lipid therapy for permethrin toxicosis.

An 8-year-old male neutered domestic shorthair cat developed corneal lipidosis and marked hypertriglyceridemia approximately 36 hours after intravenous lipid therapy (IVLT) for the treatment of permethrin toxicosis. The cat's ocular changes resolved approximately 72 hours after IVLT without treatment. This study reports a rare complication of IVLT.

Hypertriglycéridémie et lipidose cornéenne transitoire chez un chat après une lipidothérapie intraveineuse pour une toxicose à la perméthrine. Un chat commun mâle stérilisé âgé de 8 ans a développé une lipidose cornéenne et une hypertriglycéridémie marquée environ 36 heures après une lipidothérapie intraveineuse (LTI) pour le traitement de la toxicose à la perméthrine. Les changements oculaires du chat se sont résorbés sans traitement environ 72 heures près la LTI. Cette étude signale une complication rare de la LTI.(Traduit par Isabelle Vallières).

Clinical Consequences of Hypertriglyceridemia-Associated Proteinuria in Miniature Schnauzers.

BACKGROUND: Primary hypertriglyceridemia is a common condition in older Miniature Schnauzers that recently has been associated with proteinuria and underlying glomerular pathology, particularly glomerular lipid thromboemboli. Consequences of glomerular disease can include hypertension, thromboembolic disease, and cardiac disease. The incidence of these sequelae in Miniature Schnauzers with hypertriglyceridemia-associated proteinuria (HTGP) is unknown. OBJECTIVE: To investigate prevalence of hypertension, decreased antithrombin III activity, and cardiac disease in Miniature Schnauzers with and without HTGP. ANIMALS: Thirty-two Miniature Schnauzers ≥7 years old. METHODS: Prospective case-control study. Data collected from dogs included a CBC, biochemistry panel, urinalysis, urine protein-to-creatinine ratio, urine cortisol-to-creatinine ratio, serum total thyroxine concentration, fasting serum triglyceride concentration, indirect blood pressure, antithrombin III activity, and serum cardiac troponin I concentration. Results from dogs with HTGP (serum triglyceride concentration ≥ 100 mg/dL and urine protein-to-creatinine ratio >0.5) were statistically compared to normotriglyceridemic, nonproteinuric dogs. RESULTS: Eighteen of the 32 dogs (56%) had primary hypertriglyceridemia. Of those dogs, 8 of 18 had proteinuria. None of the HTGP dogs were azotemic or hypoalbuminemic. Serum albumin concentration, alkaline phosphatase activity, and cholesterol concentration were significantly increased in dogs with HGTP compared to those without HGTP. No increased risk of hypertension, decreased antithrombin III activity, or cardiac disease was noted. Limited data from 8 dogs with HTGP showed no development of hypoalbuminemia or azotemia over a median follow-up period of 18 months. CONCLUSIONS AND CLINICAL IMPORTANCE: Geriatric Miniature Schnauzers with HGTP may have a good prognosis overall, and are not typically azotemic or hypoalbuminemic.

Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs.

Miniature Schnauzer dogs are predisposed to idiopathic hypertriglyerceridemia, which increases risk for diseases such as pancreatitis and gallbladder mucocele. Recently, elevated triglyceride concentrations have been associated with proteinuria in this breed, although it is difficult to determine which abnormality is primary. Retrospective review of renal tissue from 27 proteinuric Miniature Schnauzers revealed that 20 dogs had ultrastructural evidence of osmophilic globules consistent with lipid in glomerular tufts. Seven of these dogs had lipid thromboemboli in glomerular capillary loops that distorted their shape and compressed circulating erythrocytes. Triglyceride concentrations were reported in 6 of these 7 dogs, and all were hypertriglyceridemic. In addition, glomerular lipidosis (defined as accumulation of foam cells within peripheral capillary loops) was identified in a single dog. The remaining 12 dogs had smaller amounts of lipid that could only be identified ultrastructurally. Neither signalment data nor clinicopathologic parameters (serum albumin, serum creatinine, urine protein-to-creatinine ratio, and blood pressure) differed among the various types of lipid lesions. During the time course of this study, all dogs diagnosed with glomerular lipid thromboemboli were Miniature Schnauzers, underscoring the importance of recognizing these clear spaces within capillary loops as lipid.

Validation of the Accutrend Plus point-of-care triglyceride analyzer in horses, ponies, and donkeys.

OBJECTIVE: To assess the accuracy and reliability of a point-of-care (POC) triglyceride analyzer and to establish reference intervals for blood ([TRIG]POC/WB ) and plasma triglyceride concentrations ([TRIG]POC/PL ) in horses, ponies, and donkeys. DESIGN: Prospective study. SETTING: University teaching hospital. ANIMALS: 120 adult healthy equids (78 horses and ponies, 42 donkeys) and 79 equids suffering from hypertriglyceridemia (73 horses and ponies, 6 donkeys). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: [TRIG]POC/WB and [TRIG]POC/PL were measured using a POC analyzer and plasma triglyceride concentrations were measured using a standard laboratory assay ([TRIG]LAB/PL ). Reference intervals were determined. Test accuracy was assessed by Bland-Altman comparison of POC measurements with standard laboratory measurements and by evaluating linearity of dilutional series. Test reliability was assessed by repeated serial measurements. [TRIG]POC/WB and [TRIG]POC/PL were below the analytic range of the POC assay (<0.8 mmol/L [<70 mg/dL]) in healthy horses and ponies, whereas the reference intervals were 0.82-3.14 mmol/L (73-278 mg/dL) and 0.87-3.02 mmol/L (77-267 mg/dL), respectively, in donkeys. The POC analyzer systematically overestimated triglyceride concentrations when compared to a standard laboratory assay. The difference between [TRIG]POC/WB and [TRIG]POC/PL was small and clinically negligible. The coefficient of variation of repeated measures performed on the POC analyzer was below 10% for [TRIG]POC/WB and [TRIG]POC/PL , both in horses and donkeys and at all concentration ranges. CONCLUSIONS: The POC analyzer allows accurate and reliable measurement of [TRIG]POC/WB and [TRIG]POC/PL in horses, ponies, and donkeys in clinical settings. Assay-specific reference intervals should be determined for diagnosis and clinical monitoring of hypertriglyceridemia in equids.

Proteinuria and lipoprotein lipase activity in Miniature Schnauzer dogs with and without hypertriglyceridemia.

Spontaneous hyperlipidemia in rats causes glomerular disease. Idiopathic hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, but its relationship with proteinuria is unknown. Decreased activity of major lipid metabolism enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), may play a role in the cyclic relationship between hyperlipidemia and proteinuria. These enzymes have also not been previously investigated in Miniature Schnauzers. The aims of this study were to determine the relationship between HTG and proteinuria in Miniature Schnauzers and to measure LPL and HL activities in a subset of dogs. Fifty-seven Miniature Schnauzers were recruited (34 with and 23 without HTG). Fasting serum triglyceride concentrations and urine protein-to-creatinine ratios (UPC) were measured in all dogs, and LPL and HL activities were determined in 17 dogs (8 with and 9 without HTG). There was a strong positive correlation between triglyceride concentration and UPC (r = 0.77-0.83, P < 0.001). Proteinuria (UPC ≥ 0.5) was present in 60% of dogs with HTG and absent from all dogs without HTG (P < 0.001). Proteinuric dogs were not azotemic or hypoalbuminemic. Dogs with HTG had a 65% reduction in LPL activity relative to dogs without HTG (P < 0.001); HL activity did not differ. Proteinuria occurs with HTG in Miniature Schnauzers and could be due to lipid-induced glomerular injury. Reduced LPL activity may contribute to the severity of HTG, but further assay validation is required.

Mucopolysaccharidosis type VI in a juvenile miniature schnauzer dog with concurrent hypertriglyceridemia, necrotizing pancreatitis, and diabetic ketoacidosis.

A 7-month-old, neutered male miniature schnauzer dog with a history of cryptorchidism and umbilical hernia was referred for diabetic ketoacidosis. Clinical evaluation revealed stunted growth, skeletal abnormalities, hypertriglyceridemia, diabetic ketoacidosis, and acute necrotizing pancreatitis. Further testing was diagnostic for mucopolysaccharidosis type VI causing the stunted growth and skeletal deformities, but no connection between mucopolysaccharidosis type VI, hypertriglyceridemia, and pancreatic diseases was found.

Mucopolysaccharidose de type VI chez un jeune chien Schnauzer miniature atteint d'hypertriglycéridémie, de pancréatite nécrosante et d'acidocétose diabétique concomitantes. Un chien Schnauzer miniature castré âgé de 7 mois avec une anamnèse de cryptorchidie et d'hernie ombilicale a été référé pour une acidocétose diabétique. L'évaluation clinique a révélé une croissance arrêtée, des anomalies squelettiques, l'hypertriglycéridemie, l'acidocétose diabétique et une pancréatite nécrosante aiguë. Des tests supplémentaires ont permis de diagnostiquer une mucopolysaccharidose de type VI causant une croissance arrêtée et des difformités squelettiques, mais aucun lien avec la mucopolysaccharidose de type VI, l'hypertriglycéridémie et les maladies pancréatiques n'a été trouvé.(Traduit par Isabelle Vallières).