Relationship of glomerular filtration rate based on serum iodixanol clearance to IRIS staging in cats with chronic kidney disease

We examined the correlation between the glomerular filtration rate (GFR) estimated from an equation based on the serum iodixanol clearance technique and International Renal Interest Society (IRIS) stages of chronic kidney disease (CKD) in cats. The equation included the injection dose, sampling time, serum concentration and estimated volume of distribution (Vd) of the isotonic, nonionic, contrast medium iodixanol as a test tracer. The percent changes in the median basal GFR values calculated from the equation in CKD cats resembled those of IRIS stages 1–3. These data validate the association between the GFR derived from the simplified equation and IRIS stages based on the serum creatinine concentration in cats with CKD. They describe the GFR ranges determined using single-sample iodixanol clearance for healthy cats and cats with various IRIS stages of CKD.     

Assessment of glomerular filtration rate with dynamic computed tomography in normal Beagle dogs

The objective of our study was to determine individual and global glomerular filtration rates (GFRs) using dynamic renal computed tomography (CT) in Beagle dogs. Twenty-four healthy Beagle dogs were included in the experiment. Anesthesia was induced in all dogs by using propofol and isoflurane prior to CT examination. A single slice of the kidney was sequentially scanned after a bolus intravenous injection of contrast material (iohexol, 1 mL/kg, 300 mgI/mL). Time attenuation curves were created and contrast clearance per unit volume was calculated using a Patlak plot analysis. The CT-GFR was then determined based on the conversion of contrast clearance per unit volume to contrast clearance per body weight. At the renal hilum, CT-GFR values per unit renal volume (mL/min/mL) of the right and left kidneys were 0.69 ± 0.04 and 0.57 ± 0.05, respectively. No significant differences were found between the weight-adjusted CT-GFRs in either kidney at the same renal hilum (p = 0.747). The average global GFR was 4.21 ± 0.25 mL/min/kg and the whole kidney GFR was 33.43 ± 9.20 mL/min. CT-GFR techniques could be a practical way to separately measure GFR in each kidney for clinical and research purposes.     

Serum cystatin C concentration can be used to evaluate glomerular filtration rate in small dogs

Serum cystatin C levels (CysC) are used in human medicine to document progressive kidney failure. Although CysC are not thought to be useful for the diagnosis of kidney dysfunction in dogs, there has been no specific consideration of body weight as a confounding issue. The aim of this study was to assess that the utility of CysC for the diagnosis of decreased glomerular filtration rate (GFR) in smaller vs. larger dogs. In clinically healthy dogs, serum creatinine (Cre) and CysC correlate directly with body weight; we found that dogs weighing <20 kg had significantly lower CysC than those weighing ≥20 kg (0.27 ± 0.07 vs. 0.34 ± 0.05 mg/l, respectively, P<0.001). In dogs weighing <20 kg, CysC had superior diagnostic accuracy for the detection of mildly decreased plasma iohexol clearance (PCio) (<1.8 ml/min/kg) compared with Cre (sensitivity 100% vs. 80.9% and specificity 100% vs. 85.7%); this was not true for dogs weighing ≥20 kg. Additionally, using a cut-off PCio of <1.8 ml/min/kg, the area under receiver-operating characteristics curve (AUC) of CysC was significantly higher than that of Cre in dogs weighing <20 kg (P<0.05); this was not true for dogs weighing ≥20 kg (P=0.695). In conclusion, CysC is a useful marker for the detection of a mild decreasing GFR compared with Cre in dogs weighing <20 kg.     

Glomerular filtration rate estimated by 3-sample plasma clearance of iohexol in 118 healthy dogs

BACKGROUND: Glomerular filtration rate (GFR) decreases in the aging human kidney, but limited data exist in dogs. HYPOTHESIS: There is an effect of age and body size on estimated GFR in healthy dogs. ANIMALS: One hundred and eighteen healthy dogs of various breeds, ages, and body weights presenting to 3 referral centers. METHODS: GFR was estimated in clinically healthy dogs between 1 and 14 years of age. GFR was estimated from the plasma clearance of iohexol, by a compartmental model and an empirical correction formula, normalized to body weight in kilograms or liters of extracellular fluid volume (ECFV). For data analysis, dogs were divided into body weight quartiles 1.8-12.4, 13.2-25.5, 25.7-31.6, and 32.0-70.3 kg. RESULTS: In the complete data set, there was no trend toward lower estimated GFR/kg or GFR/ECFV with increasing age. GFR decreased with age in dogs in the smallest weight quartile only. A significant negative linear relationship was detected between body weight and estimated GFR/kg and GFR/ECFV. Reference ranges in different weight quartiles were 1.54-4.25, 1.29-3.50, 0.95-3.36, and 1.12-3.39 mL/min/kg, respectively. Standardization to ECFV rather than kilogram body weight did not produce substantial changes in the relationships between GFR estimates and age or weight. CONCLUSIONS AND CLINICAL IMPORTANCE: Interpretation of GFR results for early diagnosis of renal failure should take into account the weight and the age of the patient for small dogs.     

Glomerular filtration rate in dogs with leishmaniasis and chronic kidney disease

BACKGROUND: Glomerular filtration rate (GFR) measurement is an indicator of kidney function. However, its usefulness in dogs at early stages of spontaneous chronic kidney disease (CKD) of glomerular origin, where routine laboratory techniques are not sufficiently sensitive, remains unproved. HYPOTHESIS: That GFR is reduced in proteinuric nonazotemic or mildly azotemic dogs with CKD secondary to leishmaniasis. ANIMALS: Twenty-six dogs with CKD secondary to leishmaniasis and 10 healthy dogs (control group). METHODS: CBC, serum biochemistry, and urinalysis (microalbuminuria and urine protein/creatinine ratio [UPC]) were performed in all dogs. GFR was calculated by measuring exogenous creatinine clearance. Based on degree of proteinuria and serum creatinine concentration (SCr), dogs were classified as group A (control; n = 10): UPC < 0.2, SCr < 1.4 mg/dL; group B (n = 8): UPC, 0.2-0.5, SCr < 1.4 mg/dL; group C (n = 10): UPC > 0.5, SCr < 1.4 mg/dL; group D (n = 5): SCr, 1.4-2 mg/dL; group E (n = 3): SCr > 2 mg/dL. Results: GFR (mL/kg/min) was 3.9 +/- 0.29, 4.4 +/- 0.74, 4.5 +/- 1.44, 2.8 +/- 0.97, and 1.5 +/- 0.43 for groups A, B, C, D, and E, respectively. Eleven dogs (1 from group B, 3 from group C, 4 from group D, and all 3 dogs from group E) had an abnormally low GFR. Four dogs from group B and 5 dogs from group C had a GFR above the upper reference range (>4.5 mL/min/kg). CONCLUSION AND CLINICAL RELEVANCE: Some proteinuric nonazotemic or mildly azotemic dogs with leishmaniasis have low GFR, but glomerular hyperfiltration occurs in other dogs.     

Estimation of glomerular filtration rate in healthy cats using single-slice dynamic CT and Patlak plot analysis

Commonly used clinical indicators of renal disease are either insensitive to early dysfunction or have delayed results. Decreased glomerular filtration rate (GFR) indicates renal dysfunction before there is a loss of 50% of functional nephrons. Most tests evaluate global rather than individual kidney function. Dynamic computed tomography (CT) and Patlak plot analysis allows for individual GFR to be tested. Our objectives were to establish a procedure and provide reference values for determination of global GFR in 10 healthy cats using dynamic CT (CTGFR). This method of GFR determination was compared against serum iohexol clearance (SIC). A single CT slice centered on both kidneys and the aorta was acquired every fifth second during and after a bolus injection of iohexol (240 mgI/ml; 300 mgI/kg) for 115 s. Using data from this dynamic acquisition, Patlak plots were obtained, GFR was calculated, and results were compared to global GFR determined by iohexol clearance. The average global CTGFR estimate was 1.84 ml/min x kg (SD = 0.43; range = [1.22, 2.45]). The average global GFR measured using SIC was 2.45 ml/min x kg (SD = 0.58; range = [1.72, 3.69]). GFR measurements estimated by both dynamic CT and SIC were positively associated (estimated Spearman rank correlation coefficient = 0.72; P = 0.0234). The CTGFR method consistently underestimated GFR with a bias of -0.62 (SE = 0.1307) when compared to SIC (P = 0.0011). In healthy cats, CTGFR was capable of determining individual kidney function and appears clinically promising.     

IOHEXOL PLASMA CLEARANCE IN HEALTHY DOGS AND CATS

Iohexol plasma clearance as a measure of glomerular filtration was determined in 31 dogs and 19 cats after an intravenous (i.v.) bolus injection. All animals were healthy and privately owned. Serial blood samples were taken before and up to 4 h after tracer injection. Iohexol plasma concentration was determined using X-ray fluorescence. A plasma tracer elimination curve was generated and clearance was calculated by dividing the injected dose by the area under the curve estimated using a two-compartment pharmacological model. Clearance was normalized to body weight (BW), body surface area (BSA), and extracellular fluid volume (ECFV). Mean, SD, and coefficient of variation of plasma clearance, before and after normalization, were calculated. Linear regression analyses were performed between body size and normalized plasma clearances. No significant linear relation was found between BSA and clearance normalized to BSA in dogs, and between BSA, BW, ECFV and clearance normalized to BSA, BW, and ECFV in cats. The optimal method for normalization of iohexol plasma clearance in dogs was by using BSA. In cats, all three methods tested were considered satisfactory. Normalization to BSA appears to be superior to normalization to BW and ECFV in dogs, and can be recommended for clinical use.     

Symmetric Dimethylarginine Assay Validation,Stability, and Evaluation as a Marker for the Early Detection of Chronic Kidney Disease in Dogs

Background

Symmetric dimethylarginine (SDMA) is a small molecule formed by methylation of arginine, and released into blood during protein degradation. SDMA is primarily eliminated by renal excretion and is a promising endogenous marker of glomerular filtration rate (GFR).

Objectives

To validate an assay for SDMA measurement, determine stability of SDMA in blood, and compare SDMA with serum creatinine concentration (sCr) and GFR for early detection of decreasing kidney function in dogs with chronic kidney disease (CKD).

Animals

Eight male dogs affected with X‐linked hereditary nephropathy and 4 unaffected male littermates.

Methods

Prospective study validating SDMA measurement using liquid chromatography‐mass spectrometry, assessing stability of SDMA in serum and plasma, and serially determining sCr, SDMA, and GFR (using iohexol clearance) in dogs during progression from preclinical disease to end‐stage renal failure. Correlations were determined using linear regression. Timepoints at which sCr, SDMA, and GFR identified decreased renal function were compared using defined cutoffs, trending in an individual dog, and comparison with unaffected littermates.

Results

Symmetric dimethylarginine was highly stable in serum and plasma, and the assay demonstrated excellent analytical performance. In unaffected dogs, SDMA remained unchanged whereas in affected dogs, SDMA increased during disease progression, correlating strongly with an increase in sCr (r = 0.95) and decrease in GFR (r = −0.95). Although trending improved sCr''s sensitivity, SDMA identified, on average, <20% decrease in GFR, which was earlier than sCr using any comparison method.

Conclusions and Clinical Importance

Symmetric dimethylarginine is useful for both early identification and monitoring of decreased renal function in dogs with CKD.     

Effects of AI protocol and time interval from onset of estrus to AI on conception rate in Japanese Black cows

Two different artificial insemination (AI) protocols were investigated to determine the effect of the time interval from the onset of estrus (as detected by a pedometer) to the AI on the conception rate in Japanese Black cows. Seventy‐three cows were divided into two groups that received AI either after the induction of synchronized ovulation (synchronized AI group; n = 26) or at the time of observed estrus (control AI group; n = 47). Each group was further divided into two subgroups, which were artificially inseminated either 0–12 h (early AI group; n = 21) or 12–24 h (late AI group; n = 52) after the onset of estrus. There was no significant difference in the conception rate between the synchronized AI and control AI groups. The AI protocol and the detection of estrus using a threshold of counted steps (as measured by a pedometer) in this study could be effective for planned reproduction management without the observation of standing estrus in Japanese Black cows.     

The pharmacokinetics of thiamphenicol in lactating cows

The pharmacokinetics of thiamphenicol were studied after intravenous and intramuscular administration of 25 mg/kg body weight in lactating cows. Distribution (t _1/2) and elimination (t _1/2) half-lives of 6.10±1.39 min and 1.60±0.30 h, respectively, were obtained after intravenous administration. The body clearance was 3.9±0.077 ml/kg per min and the apparent volume of distribution was 1220.79±256.67 ml/kg. The rate at which thiamphenicol appeared in the milk, as indicated by the penetration half-life (t _1/2P) (serum to quarters), was found to be 36.89±11.14 min. The equivalent elimination half-life (t _1/2E) (quarters to serum) from the milk was 3.62±1.06 h and the peak thiamphenicol concentration in the milk was 23.09±3.42 µg/ml at 2.5±0.32 h.After intramuscular injection, the elimination half-life was 2.2±0.40 h, the absorption half-life was 4.02±1.72 min and the peak concentration in the serum was 30.90±5.24 µg/ml at 23±8.4 min. The bioavailability after intramuscular administration approached 100%. The penetration half-life was 50.59±6.87 min, the elimination half-life was 5.91±4.97 h and the mean peak concentration in the milk was 17.37±2.20 µg/ml at 3.4±0.22 h.Abbreviations AUC area under the concentration-time curve - CAP chloramphenicol - C _max peak concentration - IM intramuscular - IV intravenous - TAP thiamphenicol - t _1/2 distribution half-life - t _1/2 elimination half-life - V _c volume of central compartment - V _d volume of distribution     

Alterations in biochemical profiles and reproduction performance in postpartum dairy cows with metritis

The aim of the present study was to evaluate the biochemical profile and reproductive performance in postpartum dairy cows with clinical metritis. The research was carried out using performed on 213 pluriparous lactating cows from two dairy herds in southeast Brazil. Dairy cows were assigned into a group of healthy cows (n = 147) and cows with metritis (n = 66). Blood samples to assess serum albumin, cholesterol, fibrinogen, calcium, gamma-glutammyltransferase (GGT), aspartate aminotransferase (AST) and β-hydroxybutyrate (BHBA) concentrations were performed on day 8 ± 2 postpartum. Metritic cows had lower (p < .05) serum albumin, cholesterol and calcium concentration, and higher (p < .05) GGT and AST activity, and BHBA and fibrinogen concentrations when compared to the healthy group. The calving-to-conception interval and services per pregnancy were higher in metritic cows (p < .01) than in healthy cows and the conception rate at first service was lower in metric group (p < .01). Variable importance in projection plots demonstrated that cholesterol was the main discriminator between metritic and healthy cows. Our results indicated alterations in the biochemical profile and impaired reproduction performance in metritic cows.     

日粮中添加藜麦秸秆对奶牛生产性能和血清生化指标的影响

为研究日粮中添加藜麦秸秆对奶牛生产性能和血清生化指标的影响,试验根据胎次相同,产犊时间、体重、产奶量相近的原则,选择16头中国荷斯坦奶牛作为试验牛。采用单因子随机试验设计,随机分为4组,每组4头牛,分别饲喂4种不同比例藜麦秸秆的全混合日粮(TMR)。藜麦秸秆的干物质(DM)添加比例分别为0%(Ⅰ组),5%(Ⅱ组),10%(Ⅲ组),15%(Ⅳ组)。预试期10d,正式期60d。结果表明:试验Ⅱ、Ⅲ组的产奶量、4%标准乳产量显著高于试验Ⅰ组(P<0.05),试验Ⅱ、Ⅲ组的产奶量分别比试验Ⅰ组高6.58%和6.87%,试验Ⅱ、Ⅲ组的4%标准乳分别比试验Ⅰ组高5.37%和10.61%;试验Ⅰ、Ⅱ、Ⅲ、Ⅳ组的乳脂率、乳糖率、乳蛋白率和乳总固形物差异均不显著(P>0.05);试验Ⅰ、Ⅱ、Ⅲ组和Ⅳ组的粗蛋白质(CP)、中性洗涤纤维(NDF)、酸性洗涤纤维(ADF)的表观消化率差异不显著(P>0.05);试验Ⅰ、Ⅱ、Ⅲ、Ⅳ组葡萄糖、甘油三酯、高密度脂蛋白、低密度脂蛋白、尿素氮、总蛋白、白蛋白、球蛋白、谷丙转氨酶、谷草转氨酶和碱性磷酸酶差异均不显著(P>0.05)。综上所述,奶牛日粮中添加藜麦秸秆能提高其产奶量,对血清生化指标无不利影响。     

Pharmacokinetics of metoclopramide in calves with renal dysfunction

To clarify the effect of renal dysfunction on pharmacokinetics of the prokinetic agent metoclopramide (MCP), we administered intravenously 0.4 mg/kg MCP to healthy calves and calves subjected to right kidney vessel ligation (ligation) without or with a subsequent left nephrectomy (ligation plus removal). Plasma MCP concentration, glomerular filtration rate (GFR) and plasma prolactin level were measured by liquid chromatography-tandem mass spectrometry, simplified equation using iodixanol and enzyme-linked immunosorbent assay, respectively. Only in calves with ligation plus removal, plasma MCP concentrations were increased significantly 6, 8 and 12 hr after injection, showing that a negative correlation was observed between the plasma MCP concentrations and GFR value. A tendency to increase in plasma PRL concentration was noted also in these calves. In conclusions, plasma MCP concentrations depend on the GFR mode in calves, and its critical GFR value was estimated.     

Use of a three-blood-sample plasma clearance technique to measure GFR in horses

Measurement of renal function in horses poses a particular challenge because plasma creatinine is influenced by muscle mass which is highly developed and variable between individuals, while conventional clearance methods involve potentially daunting problems, particularly urine collection and bladder washout. This paper provides data which enable technetium-diethyleneaminopentacetic acid (Tc-DTPA) clearance to be used to calculate glomerular filtration rate (GFR)/extracellular fluid volume (ECFV) as an expression of GFR in horses, as previously validated in humans, dogs and calves. Apart from being arguably a more physiological expression of GFR than using derivatives of body weight, the use of GFR/ECFV eliminates a source of delay and error, namely measurement of the injected dose, and offers the convenience of requiring only three blood samples. It therefore has advantages for both research and clinical applications.