Cat Friendly Practice improves feline visits, resulting in increased laboratory testing and increased diagnosis of certain common feline conditions.

OBJECTIVES: Cat Friendly Practices (CFPs) were compared with non-CFP control practices to determine whether CFPs had an increased proportion of clinical visits, number of visits per cat per year and inclusion of diagnostic testing. To measure diagnostic testing behavior, the numbers and types of tests analyzed and clinically relevant findings were compared. METHODS: In a retrospective analysis comparing CFPs and non-CFPs, clinic financial data and associated diagnostic tests from a commercial laboratory for 2018 and 2021 were analyzed. Data were stratified based on visit type and included revenue per visit type, revenue per patient, the number of visits per year and the proportion of visits that included diagnostic testing. Analyses of clinical findings for June 2021 to June 2022 examined clinical findings associated with biochemistry, complete blood count, urinalysis and thyroid testing categories at diagnostic patient visits, the proportion of clinical visits in which each finding was observed, the volume of testing categories as a proportion of clinical visits, and the proportion of diagnostic visits with one, two, three or four testing categories. RESULTS: The average revenue per feline visit and visits that included diagnostic testing were higher at CFPs. There was no difference in the proportion of wellness visits; however, CFPs had higher mean visits per year per patient. CFPs performed diagnostic testing at 12% more clinical visits, and had higher annual revenue per feline patient for all visits and for visits including diagnostic testing. CFPs had higher odds of patients having >1 visit that included bloodwork or urinalysis. They were more likely to include all four testing categories and less likely to include only one category at a diagnostic visit. CFPs identified a higher number of cats with clinical findings. CONCLUSIONS AND RELEVANCE: CFPs exhibited unique diagnostic testing behavior by performing more diagnostic tests more frequently and identifying a higher number of cats with abnormal findings.

Adult chicken hens (Gallus gallus) have measurable circulating plasma symmetric dimethylarginine via liquid chromatography-tandem mass spectrometry.

OBJECTIVE: To investigate whether chickens (Gallus gallus) have measurable plasma symmetric dimethylarginine (SDMA) and to establish the diagnostic utility of the commercially available immunoassay (IA) for measurement of SDMA. ANIMALS: 245 chicken hens. METHODS: Blood samples were assessed for renal-focused biochemistry analytes. Plasma SDMA was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS/MS) and a high-throughput IA. A Passing-Bablok regression was used to compare the results of IA to LC-MS/MS/MS and reference intervals SDMA values were calculated. RESULTS: The reference interval for plasma SDMA measured by LC-MS/MS/MS is 5.58 to 10.62 µg/dL (range of values, 5 to 15 µg/dL). The concentration of SDMA measured by IA ranged from 1 to 12 µg/dL with a median of 7 µg/dL. Concentrations measured by SDMA-IA demonstrated a low correlation to the SDMA LC-MS/MS reference method. A Passing-Bablok linear regression analysis had a slope of 1.67 (95% CI, 1.35 to 2.14), an intercept of -5.76 (95% CI, -9.90 to -3.35), and a Kendall τ correlation of 0.39. CLINICAL RELEVANCE: SDMA circulates in chicken plasma and should be investigated as a potential renal biomarker in future studies. Because SDMA-IA exhibits a low correlation to the reference method (LC-MS/MS) future assessments of SDMA in chickens should utilize LC-MS/MS assays and compare them to the reference interval created here.

Evaluation of renal values during treatment for heartworm disease in 27 client-owned dogs.

BACKGROUND: Canine heartworm disease (CHD) caused by Dirofilaria immitis remains a common preventable disease with increasing incidence in some parts of the USA. The treatment guidelines of the American Heartworm Society (AHS) currently recommend monthly macrocyclic lactone administration, 28 days of doxycycline given orally every 12 h and three injections of melarsomine dihydrochloride (1 injection on day 2 of treatment followed 30 days later by 2 injections 24 h apart). Minocycline has also been utilized when doxycycline is unavailable. The systemic effects of CHD, which particularly impact cardiac and renal function, have been described, with infected dogs often experiencing renal damage characterized by an increase in serum concentrations of renal biomarkers. Although the AHS treatment protocol for CHD has been shown to be safe and effective in most cases, the potential for complications remains. No study as of yet has evaluated changes in symmetric dimethylarginine (SDMA), a sensitive marker of renal function, during treatment for CHD. The purpose of the present study was to evaluate renal function in dogs by measuring serum creatinine and SDMA concentrations during the adulticide treatment period. METHODS: Serum creatinine and SDMA concentrations were measured in 27 client-owned dogs affected by CHD at the following time points: prior to starting doxycycline or minocycline therapy (baseline), during doxycycline or minocycline therapy (interim), at the time of the first dose of melarsomine (first dose), at the time of the second dose of melarsomine (second dose) and at the dog's follow-up visit after treatment, occurring between 1 and 6 months after completion of therapy (post-treatment). Concentrations of creatinine and SDMA were compared between time points using a mixed effects linear model. RESULTS: Mean SDMA concentrations following the second dose of melarsomine were significantly lower (-1.80 ug/dL, t-test, df = 99.067, t = -2.694, P-Value = 0.00829) than baseline concentrations. There were no other statistically significant differences in the concentration of either biomarker between the baseline and the other time points in CHD dogs undergoing treatment. CONCLUSIONS: The results suggest that the current AHS protocol may not have a substantial impact on renal function.

The association between symmetric dimethylarginine concentrations and various neoplasms in dogs and cats.

Following the introduction of the symmetric dimethylarginine (SDMA) immunoassay, cases were reported where the SDMA concentration was markedly increased above the reference interval (RI) with neither concurrent increases in serum creatinine (Cr) concentrations nor clinical signs of kidney disease. Many of these animals were also concurrently diagnosed with cancer, most commonly lymphoma. The purpose of the study was to evaluate the association of increased SDMA in dogs and cats with lymphoma and other cancers as compared with age- and breed-matched non-tumour controls. In this retrospective case-control study, serum chemistry results from 1804 tumour cases, and age- and breed-matched non-tumour control animals were used. Matched-pair odds ratios between animals diagnosed with neoplasms and non-tumour controls for dichotomized SDMA values were determined by tumour type. SDMA concentrations were significantly higher in dogs and cats with lymphoma (p < .0001) compared with non-tumour controls. The odds ratio for increased SDMA concentrations in dogs with lymphoma was 10.0 (95% CI, 5.98-16.72) and for cats with lymphoma was 3.04 (95% CI 1.95-4.73). A significant number of canine and feline lymphoma cases had an increased SDMA concentration not associated with an increased Cr concentration (p < .001). Canine and feline lymphoma patients have an increased odds of having a SDMA concentration above the RI at diagnosis. Further characterization and evaluation of dogs and cats with lymphoma is required to help understand the mechanism(s) and the clinical significance of these alterations.

Evaluation of renal injury and function biomarkers, including symmetric dimethylarginine (SDMA), in the rat passive Heymann nephritis (PHN) model.

Symmetric dimethylarginine (SDMA) is a serum biomarker of excretory renal function which consistently correlates with glomerular filtration rate (GFR) across multiple species including rats, dogs, and humans. In human and veterinary clinical settings SDMA demonstrates enhanced sensitivity for detection of declining renal function as compared to other serum biomarkers, but application in preclinical study designs thus far has been limited. The purpose of this study was to determine the performance of serum SDMA in a rat passive Heyman nephritis model of glomerulopathy. In addition to SDMA other biomarkers of excretory renal function were measured including serum creatinine (sCr), blood urea nitrogen (BUN), and cystatin C along with creatinine clearance. Urinary renal biomarkers including microalbumin (µALB), clusterin (CLU), cystatin C, kidney injury marker-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin (OPN) were also measured. PHN was induced using commercial sheep anti-Fx1A serum. Tissue, serum, and urine were collected from groups of control and anti-Fx1A-treated animals for biomarker evaluation, hematology, urinalysis, serum biochemistry, and histologic examination of kidney. Over the course of a 28-day study, concentrations of the urinary biomarkers µALB, CLU, cystatin C, NGAL, KIM-1 and the serum biomarker cystatin C increased significantly in anti-Fx1A-treated rats as compared to controls but no significant increase in serum SDMA, sCr, BUN, or creatinine clearance were noted in anti-Fx1A-treated rats. Given lack of direct GFR measurement or significant change in the renal function biomarkers sCr, BUN, and creatinine clearance, it is unclear if GFR differed significantly between control and anti-Fx1A-treated rats in this study, though urinary biomarkers and histopathologic findings supported renal injury in anti-Fx1A-treated rats over the time course investigated. This study is among the first to investigate serum SDMA in a rat model relevant to preclinical safety assessment and serves to inform future experimental designs and biomarker selection when evaluation of glomerular injury is of priority.

Evaluation of Renal Biomarkers, Including Symmetric Dimethylarginine, following Gentamicin-Induced Proximal Tubular Injury in the Rat.

Symmetric dimethylarginine (SDMA) is an excretory renal function biomarker shown to correlate well with glomerular filtration rate in dogs, cats, humans, and rats. The objectives of this study were to determine utility of serum SDMA as a renal biomarker in a rat model of gentamicin-induced renal injury and to provide validation of a commercially available SDMA immunoassay for rat serum. Rats were randomly assigned to one of three dose levels of gentamicin (20, 50, or 100 mg/kg) or a vehicle control group and dosed once daily by subcutaneous injection for either four or ten days. Serum and urine renal biomarker evaluation, including serum SDMA, hematologic and serum biochemical analysis, urinalysis, and histologic examination of kidney, were performed. Before biologic validation, analytic validation of the SDMA immunoassay for rat serum was performed, including assessment of assay accuracy, precision, analytical sensitivity, linearity, analyte stability, and interference testing. Among markers of excretory renal function, SDMA and serum creatinine increased earliest and at the lowest gentamicin concentrations and were significantly increased in both the 50- and 100- mg/kg dose levels in the four- and ten-dose treatment groups compared with controls. Time- and dose-dependent increases were noted for all urinary biomarkers investigated in this study, with microalbumin being most responsive and osteopontin least responsive for detection of gentamicin-induced injury across dose levels and schedules investigated. The SDMA immunoassay met all set quality requirements assessed in analytical validation. This study is the first to investigate performance of serum SDMA compared with other excretory renal function markers in a rat gentamicin acute toxicity model. In this study, serum SDMA was an earlier biomarker for detection of gentamicin-induced toxicity than serum cystatin C, BUN, and creatinine clearance. The SDMA immunoassay provides a reliable commercially available assay for future renal investigations in rat models.

Serum Symmetric Dimethylarginine Concentration in Greyhound Pups and Adults.

Greyhounds have developed numerous physiologic and hematologic adaptations specific to the breed. Adult Greyhounds have significantly higher serum creatinine (sCr) concentrations than non-Greyhound dogs; this is primarily attributed to their large muscle mass. Adult Greyhounds also have significantly higher symmetric dimethylarginine (SDMA) concentrations than non-Greyhound dogs. In this study we evaluated serum SDMA and sCr concentrations in 48 Greyhound pups from 11 litters, with no exposure to racing, in order to determine if the higher SDMA or sCr concentration in adults is a breed-related trait or is associated with extra-physiological causes (e.g., racing environment, drug administration, etc.). The distribution of SDMA concentration for all the pups (mean: 0.70 µmol/L; 95% CI: 0.70-0.74 µmol/L) was not statistically different from that found in a group of 183 adult Greyhounds; whereas, distribution of sCr concentration in the pups (mean: 76.9 µmol/L; 95% CI: 70.7-83.1 µmol/L) was significantly different than that observed in adult Greyhounds, suggesting that the 2 samples were drawn from different populations. This study provides evidence to support that the higher serum SDMA concentration in Greyhounds is a breed-related trait.

Risk of Development of Chronic Kidney Disease After Exposure to Borrelia burgdorferi and Anaplasma spp.

Lyme disease is a multi-faceted illness caused by infection due to Borrelia burgdorferi. Acute kidney damage secondary to Lyme disease is well described but less so as a chronic event. The role of Anaplasma spp. and secondary kidney dysfunction is not known. A retrospective cohort study was performed to determine if dogs within a defined Lyme disease and anaplasmosis region with B. burgdorferi or Anaplasma spp. antibodies had an increased risk of chronic kidney disease (CKD). Patient exposure was defined as having a B. burgdorferi or Anaplasma spp. antibody positive result recorded at any point in the available patient history. CKD was defined as concurrent increased symmetric dimethylarginine and creatinine (Cr) for a minimum of 25 days with inappropriate urine specific gravity (USG). Patients were matched using propensity scoring to control for age, region, and breed. Contingency tables were used to compare dogs seropositive and not seropositive to B. burgdorferi and Anaplasma spp. and CKD outcome. For each comparison that was performed, statistical significance was defined by a P-value of <.025. The risk ratio of CKD for patients exposed to B. burgdorferi and Anaplasma spp. were found to be 1.43 (95% confidence interval [CI, 1.27, 1.61], P < .0001) and 1.04, (95% CI [0.87, 1.24], P = .6485), respectively. Results suggest in this cohort no increased risk for developing CKD when exposed to Anaplasma spp. but a significant increase in risk for developing CKD with exposure to B. burgdorferi.

Association Between Exposure to Ehrlichia spp. and Risk of Developing Chronic Kidney Disease in Dogs.

Ehrlichiosis is a common vector-borne disease caused by Ehrlichia spp. This retrospective matched cohort study was performed to determine if dogs with Ehrlichia spp. antibodies had an increased incidence of chronic kidney disease (CKD). Exposure to Ehrlichia spp. was defined as having an Ehrlichia spp. antibody-positive result recorded at any point in their available patient history. The outcome of CKD was defined as concurrent increased symmetric dimethylarginine (>14 µg/dL) and creatinine (>1.5 mg/dL) for a minimum of 25 days with inappropriate urine specific gravity (<1.030). Patients were matched using propensity score matching to control for age, geography, and breed. A total of 22,440 patients and controls in E canis-endemic regions of the United States were used in this analysis. Contingency tables were used to compare dogs with and without exposure to Ehrlichia spp.-infected ticks and CKD outcome. The relative risk of CKD for patients exposed to ticks carrying Ehrlichia spp. was found to be 2.12 (95% confidence interval [1.35-3.15], p < 0.0006). This study identified that testing positive for Ehrlichia spp. antibodies in E canis-endemic regions is associated with higher incidence of CKD in dogs.

Comparative performance of IDEXX SDMA Test and the DLD SDMA ELISA for the measurement of SDMA in canine and feline serum.

Kidney disease is common in companion animals, and traditionally diagnosed with serum creatinine concentration (sCr), blood urea nitrogen, and abnormal urinalysis findings. Symmetric dimethylarginine (SDMA) is a novel kidney biomarker that reflects glomerular filtration rate, increasing earlier than sCr with acute kidney injury and chronic kidney disease. This prospective study compared accuracy and precision of two commercial SDMA assays, the IDEXX SDMA Test and the DLD SDMA ELISA, relative to the established reference method, liquid chromatography/mass spectrometry (LC-MS). Thirty canine and 30 feline pooled serum samples were used to evaluate accuracy compared to LC-MS. Pooled canine samples with a low SDMA concentration and pooled feline samples with a high SDMA concentration were used to evaluate precision. Using a best fit linear model, the IDEXX SDMA Test resulted in a slope of 1.06 and an intercept of 0.34, with R2 = 0.99, and the DLD SDMA ELISA resulted in a slope of 0.37 and an intercept of 11.33, with R2 = 0.27, when compared to LC-MS. Estimated bias over a clinically relevant range for SDMA (10-45 µg/dL) was 1-2 µg/dL for the IDEXX SDMA Test, while DLD SDMA ELISA showed considerable bias, 5-8 µg/dL. Day-to-day precision analysis of the low SDMA concentration samples showed 7.7% total coefficient of variation (CV) for the IDEXX SDMA Test and 31.1% for the DLD SDMA ELISA. For the high SDMA concentration samples, total CV was 2.3% for the IDEXX SDMA Test and 28.2% for the DLD SDMA ELISA. In this study the IDEXX SDMA Test was more accurate and more precise in macroscopically normal serum than the DLD SDMA ELISA when compared to the reference method of LC-MS. The IDEXX SDMA Test is more suitable for clinical use in the diagnosis and monitoring of kidney disease in dogs and cats.