Evaluation of Predictors of the Development of Azotemia in Cats

Background: Chronic kidney disease (CKD) is a common condition in geriatric cats. Diagnosis is based on the development of persistent azotemia with inadequate urine concentrating ability. Biomarkers are sought for early identification.
Hypothesis: Clinical variables, urine concentrating ability, proteinuria, and N -acetyl-β- d -glucosaminidase (NAG) index will be predictive of cats at risk of developing azotemia within 12 months.
Animals: Client-owned nonazotemic geriatric (≥9 years) cats.
Methods: Prospective longitudinal cohort study monitoring a population of healthy nonazotemic geriatric cats every 6 months until development of azotemia, death, or the study end point (September 30, 2007). Multivariable logistic regression analysis was used to assess baseline clinical, biochemical, and urinalysis variables, urine protein to creatinine ratio (UP/C), urine albumin to creatinine (UA/C) ratio, and urinary NAG index as predictors of development of azotemia.
Results: One hundred and eighteen cats were recruited with a median age of 13 years. Ninety-five cats (80.5%) had been followed or reached the study end point by 12 months of which 30.5% (29/95) developed azotemia. Age, systolic blood pressure, plasma creatinine concentration, urine specific gravity, UP/C, UA/C, and NAG index were significantly associated with development of azotemia in the univariable analysis ( P ≤ .05). However, in the multivariable analysis, only plasma creatinine concentration with either UP/C (Model 1) or UA/C (Model 2) remained significant.
Conclusions and Clinical Importance: This study demonstrates a high incidence of azotemia in a population of previously healthy geriatric cats. Proteinuria at presentation was significantly associated with development of azotemia although causal association cannot be inferred. Evaluation of NAG index offered no additional benefit.     

Comparison of Efficacy of Long‐term Oral Treatment with Telmisartan and Benazepril in Cats with Chronic Kidney Disease

Background

The efficacy and benefits of telmisartan in cats with chronic kidney disease (CKD) have not previously been reported.

Hypothesis

Long‐term treatment of cats with CKD using telmisartan decreases urine protein‐to‐creatinine ratio (UP/C) similar to benazepril.

Animals

Two‐hundred and twenty‐four client‐owned adult cats with CKD.

Methods

Prospective, multicenter, controlled, randomized, parallel group, blinded clinical trial with noninferiority design. Cats were allocated in a 1 : 1 ratio to either telmisartan (1 mg/kg; n = 112) or benazepril (0.5–1.0 mg/kg; n = 112) PO q24 h. The primary endpoint was prospectively defined as the change in proteinuria (benazepril:telmisartan) based on a log transformed weighted average of UP/C change from baseline (AUC 0→t/t) as a percentage compared using a confidence interval (CI) approach. Changes of UP/C from baseline were assessed on all study days and corrected for multiple comparisons.

Results

Telmisartan proved noninferior to benazepril in controlling proteinuria (CI, −0.035 to 0.268). At Day 180, UP/C compared to baseline in the telmisartan group was significantly lower (−0.05 ± 0.31; P = .016), whereas in the benazepril group the change (−0.02 ± 0.48) was not statistically significant (P = .136). Similar results were obtained at all assessment points with significant decrease in UP/C occurring with telmisartan but not benazepril.

Conclusion and Clinical Importance

Both telmisartan and benazepril were well tolerated and safe. Telmisartan proved to be noninferior to benazepril and significantly decreased proteinuria relative to baseline at all assessment points whereas benazepril did not.     

Differential Rotation and Dynamics of the Solar Interior

Splitting of the sun's global oscillation frequencies by large-scale flows can be used to investigate how rotation varies with radius and latitude within the solar interior. The nearly uninterrupted observations by the Global Oscillation Network Group (GONG) yield oscillation power spectra with high duty cycles and high signal-to-noise ratios. Frequency splittings derived from GONG observations confirm that the variation of rotation rate with latitude seen at the surface carries through much of the convection zone, at the base of which is an adjustment layer leading to latitudinally independent rotation at greater depths. A distinctive shear layer just below the surface is discernible at low to mid-latitudes.     

Characterization of Transgenic Pigs That Express Human Decay Accelerating Factor and Cell Membrane‐tethered Human Tissue Factor Pathway Inhibitor

The expression of human complement regulatory proteins (hCRP; hDAF, hCD59, and hMCP) in pig tissues has been suggested as one of strategies to overcome the hyperacute rejection (HAR) in pig‐to‐human transplantation. Expression of human tissue factor pathway inhibitor (hTFPI) in porcine endothelial cells has been suggested as a remedy to overcome microvascular thrombosis. To investigate the effects of these combined transgenes, we established transformed pig cells expressing human decay accelerating factor (hDAF) under the control of enhancer promoter (5′LTR‐PCMVIE), and the fusion protein (hTFPI/hCD4) consisting of the functional domains (K1 and K2) of hTFPI and membrane‐tethering domains (D3 and D4) of hCD4 under the control of PCMVIE. Transgenic pigs were generated with the transformed porcine cells through somatic cell nuclear transfer (SCNT) technology. Analysis of quantitative PCR and real‐time quantitative RT‐PCR showed that four copies of hDAF were integrated and 391 copies of hDAF mRNA expressed in the cells of the transgenic pig. The enhancing activity of 5′LTR was approximately 2 fold compared to CMVIE promoter only. The cell viability test showed that more than 80% of ear cells were viable in the presence of 50% human serum. The chromogenic substrate assay and immunocytochemical staining with tail cells showed that the TFPI activity of fusion protein was observed on the cell membrane. The membrane localization of hDAF and hTFPI proteins was observed by immunocytochemical staining, and the expression of transgenes in heart and liver tissues was also confirmed by immunohistochemistry.     

Changes in Systolic Blood Pressure over Time in Healthy Cats and Cats with Chronic Kidney Disease

Background

Hypertension is a common problem in older cats, most often associated with chronic kidney disease (CKD). Cross‐sectional studies have suggested that blood pressure in cats increases with age.

Hypothesis/Objectives

To determine whether blood pressure in cats increases with age and whether this occurs independently of the presence of CKD. To investigate risk factors for developing hypertension.

Animals/Subjects

Two hundred and sixty‐five cats with CKD and 133 healthy cats ≥9 years were retrospectively identified.

Methods

Four groups were created according to status at initial evaluation (CKD or healthy) and blood pressure at the last included visit (normotensive [NT] or developed hypertension [DH]): Healthy‐NT, Healthy‐DH, CKD‐NT and CKD‐DH. Systolic blood pressure (SBP) over time slopes were compared with 0 and between groups. Risk factors for the development of hypertension were investigated, and associations of biochemical and clinical variables with SBP were examined.

Results

Cats that were hypertensive at CKD diagnosis (n = 105) were not included in further analyses. Twenty‐seven cats with CKD and 9 healthy cats developed hypertension ≥3 months after diagnosis of CKD or their first visit. Systolic blood pressure significantly increased with age in all cats (P < .001). Healthy cats were at less risk than cats with CKD to become hypertensive (hazard ratio 0.2, P < .001), with creatinine being an independent risk factor for the development of hypertension.

Conclusions and Clinical Importance

The high prevalence of hypertension in azotemic cats in this study shows the importance of monitoring of SBP in elderly cats, and in particular in cats with CKD.     

Ca2+ Cascade and Meiotic Resumption of the Caprine Primary Oocyte

In this study, we investigated the fluctuations of concentration of intracytoplasmic free Ca(2+) during in vitro maturation of caprine primary oocytes and its role in meiotic resumption. Oocytes that were extracted from caprine ovaries were cultured and allowed to mature in vitro to determine their developmental stages including germinal vesicle (GV), germinal vesicle breakdown (GVBD), metaphase of the first meiotic division (MI) and metaphase of the second meiotic division (MII). Intracytoplasmic free Ca(2+) turnovers of caprine oocytes at these different developmental stages were measured using the calcium fluorescent probe Fura-2/AM (C(44)H(47)N(3)O(24)) to investigate the dynamics of cytosolic free Ca(2+) during in vitro maturation of oocytes and the role of Ca(2+) in inducing the initiation of meiotic resumption of oocytes. Moreover, the oocytes were cultured in Ca(2+) culture medium and Ca(2+)-free culture medium to examine the effect of extracellular Ca(2+) on the oocyte maturation. The results indicated that Ca(2+) concentrations at GV, GVBD, MI and MII stages were 78.06, 147.41, 126.97 and 97.73 nmol/l, respectively, and that 86.30% of oocytes remained at the GV stage and no oocyte developed to MII in Ca(2+)-free culture medium, and 1.1% of oocytes stayed at the GV stage and 83.5% of oocytes developed to MII in Ca(2+) culture medium. These results suggest that the occurrence of GVBD and cell cycle progression to MI and MII stages are closely related to Ca(2+), and that extracellular Ca(2+) performs a specific function for the initiation of meiotic resumption in caprine oocytes.     

Cardiorespiratory,sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone,morphine or tramadol in dogs

ObjectiveTo evaluate the cardiorespiratory, sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone, morphine or tramadol in dogs.Study designExperimental, blinded, randomized, crossover study.AnimalsSix mixed breed dogs (two males and four females) weighing 10 ± 4 kg.MethodsThe animals were randomly divided into four treatments: D (10 μg kg^?1 of dexmedetomidine), DM (dexmedetomidine 10 μg kg^?1 and methadone 0.5 mg kg^?1); DMO (dexmedetomidine 10 μg kg^?1 and morphine 0.5 mg kg^?1), and DT (dexmedetomidine 10 μg kg^?1 and tramadol 2 mg kg^?1). The combinations were administered intramuscularly in all treatments. The variables evaluated were heart rate (HR), respiratory rate (f_R), rectal temperature (RT), systolic arterial pressure (SAP), sedation scale and pedal withdrawal reflex. These variables were measured at T0 (immediately before the administration of the protocol) and every 15 minutes thereafter until T105.ResultsA decrease in HR and f_R occurred in all the treatments compared with T0, but no significant difference was observed between the treatments. The RT decreased from T45 onward in all the treatments. The SAP did not show a difference between the treatments, but in the DT treatment, the SAP was lower at T30 and T45 compared with T0. The D treatment had lower scores of sedation at T15 to T75 compared with the other treatments, and the DMO and DM treatments showed higher scores at T60 and T75 compared with DT.Conclusions and clinical relevanceThe treatments with morphine and methadone added to the dexmedetomidine showed higher sedation scores than the control treatment and the treatment with tramadol added to the dexmedetomidine showed no relevant differences in any of the variables evaluated in the study.