Estimation of glomerular filtration rate in calves using the contrast medium iodixanol

To develop a simple procedure for estimating glomerular filtration rate (GFR) in calves, a three-sample method using iodixanol was first compared to that using the standard agent inulin. Iodixanol and inulin were co-administered intravenously to calves at 40 mg I/kg and 40 mg/kg, respectively, and blood was collected 30, 60, 120, and 180 min later. Serum iodixanol and inulin concentrations were separately determined by high performance liquid chromatography and colorimetry. Serum urea nitrogen (UN) and creatinine concentrations were also measured. GFR estimated by iodixanol was consistent with that using inulin in clinically healthy calves. Based on GFR estimations in healthy calves and those renal-loaded with iodixanol, it was found that the serum creatinine concentrations became elevated when GFR decreased to 60% of the reference value. In contrast, serum UN concentrations fluctuated widely, presumably due to extra-renal factors. When GFR was estimated using the three-sample method and compared with the single-blood-sample method, 62/69 (90%) of samples tested were within the agreement plots. The results demonstrated that the single-blood-sample method using iodixanol may be useful in monitoring GFR in calves.     

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.     

A Single‐Blood‐Sample Method Using Inulin for Estimating Feline Glomerular Filtration Rate

Background

Application of a multisample method using inulin to estimate glomerular filtration rate (GFR) in cats is cumbersome.

Objectives

To establish a simplified procedure to estimate GFR in cats, a single‐blood‐sample method using inulin was compared with a conventional 3‐sample method.

Animals

Nine cats including 6 clinically healthy cats and 3 cats with spontaneous chronic kidney disease.

Methods

Retrospective study. Inulin was administered as an intravenous bolus at 50 mg/kg to cats, and blood was collected at 60, 90, and 120 minutes later for the 3‐sample method. Serum inulin concentrations were colorimetrically determined by an autoanalyzer method. The GFR in the single‐blood‐sample method was calculated from the dose injected, serum concentration, sampling time, and estimated volume of distribution on the basis of the data of the 3‐sample method.

Results

An excellent correlation was observed (r = 0.99, P = .0001) between GFR values estimated by the single‐blood‐sample and 3‐sample methods.

Conclusions and Clinical Importance

The single‐blood‐sample method using inulin provides a practicable and ethical alternative for estimating glomerular filtration rate in cats.     

Serum clearance of iodixanol for estimating glomerular filtration rate in calves

To evaluate serum clearance of iodixanol, applicable to the estimation of glomerular filtration rate (GFR), clinically healthy and experimentally-induced nephropathy calves were prepared. Iodixanol was administered intravenously at 40 mg I/kg, and blood was withdrawn 60, 120, and 180 min later. Serum iodixanol concentration was determined by high-performance liquid chromatography. No statistical difference in GFR was noted between strains (Holstein vs. Japanese Black) or sexes, and the α(2)-adrenergic agonist xylazine increased GFR. In calves subjected to right renal vessel ligation, followed by a left nephrectomy, a marked reduction in GFR was observed with renal ischemic changes. These results suggest that the GFR estimation by serum iodixanol clearance is a ready-to-use tool in calf research and practice owing to the ease of monitoring serial renal function.     

Single-injection inulin clearance for routine measurement of glomerular filtration rate in cats

Glomerular filtration rate (GFR) was determined in 53 cats using an inulin single-injection method. Thirty healthy young adult cats were used to establish normal values. The procedure was also used in 23 cats that were either older than 10 years or had borderline serum creatinine levels. The total clearance was calculated from the decay of the serum inulin concentration after injection of 3000 mg/m(2)body surface area using a two-compartment model. Concomitant inulin and iohexol clearance in nine cats showed excellent correlation between the two methods. Calculated normal values for GFR in 30 healthy cats were 35.9-58.5 (median 46.0) ml/min/m(2)or 2.07-3.69 (median 2.72) ml/min/kg. A few cats with normal creatinine or blood urea nitrogen levels were detected as having reduced GFR and therefore being in a state of early renal dysfunction. The study indicates that single-injection inulin clearance is a valuable tool for routine GFR measurement in cats. An "inulin excretion test" using only one blood sample 3h after the administration of 3000 mg/m(2)body surface area could prove an attractive alternative for the assessment of renal function in daily practice.     

Evaluation of plasma clearance of inulin in clinically normal and partially nephrectomized cats

OBJECTIVE: To evaluate accuracy of measuring plasma clearance of inulin as an alternative renal function test for estimation of glomerular filtration rate (GFR) in cats. ANIMALS: 10 cats, first studied with intact kidneys and subsequently studied following partial nephrectomy. PROCEDURE: Clearance studies were performed in 10 clinically normal cats; those same cats then underwent partial nephrectomy, and clearance studies were performed again. Plasma concentration of inulin was determined after administration at 50 mg/kg of body weight to cats while renally intact and 45 mg/kg after the partial nephrectomy. Plasma clearance of inulin (PCin) was determined by dividing the dose by the area under the plasma inulin concentration versus time curve. Results for PCin were compared with values obtained simultaneously for urinary clearance of exogenously administered creatinine (Ccr), a widely accepted method for measurement of GFR in cats with intact kidneys and cats with reduced renal mass. RESULTS: Results of PCin were strongly correlated (r2 = 0.912, P < 0.001) with Ccr. Repeatability of determination of PCin was similar to that of Ccr. Sensitivity and specificity of PCin were superior and equivalent to that of Ccr, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Determination of PCin provides a reliable estimate of GFR in cats and is a promising alternative to determining Ccr in cats.     

Effects of administration of fluids and diuretics on glomerular filtration rate, renal blood flow, and urine output in healthy awake cats

OBJECTIVES: To determine effects of commonly used diuretic treatments on glomerular filtration rate (GFR), renal blood flow (RBF), and urine output (UO) and compare 2 methods of GFR measurement in healthy awake cats. ANIMALS: 8 healthy cats. PROCEDURE: In a randomized crossover design, cats were randomly allocated to 4 groups: control; IV administration of fluids; IV administration of fluids and mannitol; and IV administration of fluids, dopamine, and furosemide. Inulin and para-aminohippuric acid were used for determination of plasma clearance for GFR and RBF, respectively. Plasma clearance of technetium-Tc-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) was also used for GFR determination. RESULTS: Furosemide-dopamine induced the largest UO, compared with other groups. Both mannitol and fluid therapy increased RBF, compared with the control group. Mannitol, and not fluid therapy, increased RBF, compared with furosemide-dopamine. There were significant differences in GFR values calculated from 99mTc-DTPA and inulin clearances between the 2 groups. In all groups, use of 99mTc-DTPA caused underestimation of GFR, compared with use of inulin. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy awake cats, administration of furosemide-dopamine did not increase GFR or RBF despite increased UO. Fluid therapy and fluid therapy plus mannitol improved RBF. Determination of GFR by use of 99mTc-DTPA cannot always be substituted for inulin clearance when accurate measurement is required.     

Glomerular filtration rate in cows estimated by a prediction formula

To testify the relevance of Jacobsson's equation for estimating bovine glomerular filtration rate (GFR), we prepared an integrated formula based on its equation using clinically healthy dairy (n = 99) and beef (n = 63) cows, and cows with reduced renal function (n = 15). The isotonic, nonionic, contrast medium iodixanol was utilized as a test tracer. The GFR values estimated from the integrated formula were well consistent with those from the standard multisample method in each cow strain, and the Holstein equation prepared by a single blood sample in Holstein dairy cows. The basal reference GFR value in healthy dairy cows was significantly higher than that in healthy beef cows, presumably due to a breed difference or physiological state difference. It is concluded that the validity for the application of Jacobsson's equation to estimate bovine GFR is proven and it can be used in bovine practices.     

Colorimetric assay for the quantification of serum iodixanol concentration and its application on estimation of glomerular filtration rate in cattle

A colorimetric assay used to quantify the non-ionic contrast medium iodixanol in sera was validated and compared with high-performance liquid chromatography. The application of this assay to estimate glomerular filtration rates (GFR) in cattle was examined. Serum iodixanol was de-iodinated by alkaline hydrolysis and the amount of released iodine was subsequently determined using a ceric arsenite method. There was a close correlation between the two methods using identical specimens. In clinically healthy cattle with different body weights, the reference value (166.3-178.8 mL/min/m(2)) based on body surface area was fairly stable as compared with that (2.13-3.63 mL/min/kg) based on body weight. Based on GFR data in healthy and renal-impaired cattle, when the GFR decreased to more than 60% of the reference value, serum urea nitrogen and creatinine concentrations increased. The colorimetric assay is a simple method for the estimation of GFR in cattle and requires no expensive equipment.     

Effects of methimazole on renal function in cats with hyperthyroidism

The purpose of this study was to investigate the effects of methimazole on renal function in cats with hyperthyroidism. Twelve cats with naturally occurring hyperthyroidism and 10 clinically normal (i.e., control) cats were included in this study. All cats initially were evaluated with a history, physical examination, complete blood count, serum biochemistry profile, basal serum total thyroxine concentration, complete urinalysis, and urine bacterial culture. Glomerular filtration rate (GFR) was estimated by a plasma iohexol clearance (PIC) test. After initial evaluation, hyperthyroid cats were treated with methimazole until euthyroidism was achieved. Both groups of cats were then reevaluated by repeating the initial tests four to six weeks later. The mean (+/-standard deviation) pretreatment estimated GFR for the hyperthyroid cats was significantly higher (3.83+/-1.82 ml/kg per min) than that of the control cats (1.83+/-0.56 ml/kg per min). Control of the hyperthyroidism resulted in a significantly decreased mean GFR of 2.02+/-0.81 ml/kg per minute when compared to pretreatment values. In the hyperthyroid group, the mean increases in serum urea nitrogen (SUN) and creatinine concentrations and the mean decrease in the urine specific gravity after treatment were not statistically significant when compared to pretreatment values. Two of the 12 hyperthyroid cats developed abnormally high serum creatinine concentrations following treatment. These results provide evidence that cats with hyperthyroidism have increased GFR compared to normal cats, and that treatment of feline hyperthyroidism with methimazole results in decreased GFR.     

Quantitative renal scintigraphic determination of the glomerular filtration rate in cats with normal and abnormal kidney function, using 99mTc-diethylenetriaminepentaacetic acid.

The nuclear imaging technique known as quantitative renal scintigraphy was validated as a means to assess the kidney function of cats. Renal function tests were performed in 6 healthy cats and 3 cats with clinical manifestations of kidney failure. In addition, the nephrotoxic drugs, gentamicin sulfate, or amphotericin B were used in an attempt to induce renal failure in 4 cats. Using linear regression analysis, equations were derived to estimate the glomerular filtration rate (GFR) on the basis of the renal percent uptake of 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). One-way ANOVA and Student's t test were used to evaluate treatment effects on clearances of inulin and creatinine, percent uptake of 99mTc-DTPA, and serum creatinine concentrations. The results show that the percent uptake of 99mTc-DTPA by the kidneys correlated well with the GFR obtained through the clearance of inulin. Thus, it was concluded that quantitative renal scintigraphy, using 99mTc-DTPA as a marker of kidney function, is an adequate technique to estimate the kidney function of healthy cats and cats with functional renal impairment. The best estimate of the GFR of cats, using the percentage dose of 99mTc-DTPA, was obtained on the 1- to 3-minute postinjection interval of the marker, using data that was background-subtracted, but not corrected for tissue absorption of gamma rays or binding of 99mTc-DTPA to plasma proteins. There was no significant difference in the mean inulin clearance, creatinine clearance, or percent uptake of 99mTc-DTPA between the 3 treatment groups of this study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Optimum conditions for serum clearance of iodixanol,applicable to the estimation of glomerular filtration rate in horses

To estimate the glomerular filtration rate (GFR) in horses, an optimum dose of the nonionic contrast medium iodixanol as a tracer was assessed with blood-sample times. Iodixanol was administered intravenously at 10–40 mg I/kg to geldings and mares, and blood was collected 30, 60, 90, 120, 150, and 180 min later. Serum iodixanol concentration was determined by high-performance liquid chromatography (HPLC), and serum urea nitrogen (UN) and creatinine concentrations were also measured. The combination of 20 mg I/kg iodixanol and sampling times of 60, 90, and 120 min after injection was considered to be appropriate for practical use. In clinically healthy horses, the reference values were determined to be 1.90 ± 0.03 ml/min/kg (150.8 ± 2.94 ml/min/m²), consistent with historical data using different tracers. The result suggests that serum clearance of iodixanol is a ready-to-use tool for a screening of alterations in the equine GFR, although it is necessary to perform a more longitudinal study using horses with a variety of renal functions.     

A single sample method for evaluating 51chromium-ethylene diaminic tetraacetic acid clearance in normal and hyperthyroid cats.

BACKGROUND: Chronic kidney failure is frequently seen in middle-aged and elderly cats. 51Chromium-ethylene diaminic tetraacetic acid (51Cr-EDTA) clearance and single blood sample (SBS) method are used in several species to estimate the glomerular filtration rate (GFR). HYPOTHESIS: The hypothesis of this study was that 51Cr-EDTA clearance could be determined using an SBS method in normal and hyperthyroid cats. ANIMALS: Forty-six cats were included in this study, with an average age of 9.5 years. Of these cats, 27 had hyperthyroidism; 19 were healthy. METHODS: After IV injection of 51Cr-EDTA (average dose: 4.25 MBq), 7 blood samples were obtained between 5 and 240 minutes. Reference clearance was calculated in mL/min and mL/min/kg body weight, using a 2-compartment model. Optimal time for clearance measurement with SBS was then determined by systematically comparing each individual plasma concentration to the reference multisample clearance. RESULTS: The average reference plasma clearance of 51Cr-EDTA for all cats was 14.9 mL/min (3.7 mL/min/kg). The clearance in hyperthyroid cats averaged 16.4 mL/min (4.3 mL/min/kg) and in normal cats averaged 10.3 mL/min (2.4 mL/min/kg). The optimal time for the SBS was 48 minutes after injection of tracer 51Cr-EDTA (R2= 0.9414), giving the following converting equation: clearance = (0.0066 x DV48 minutes) - 0.9277 (in mL/min). CONCLUSIONS AND CLINICAL IMPORTANCE: In this study, the single sample 51Cr-EDTA clearance method was used to estimate the global GFR in cats. The method identified differences in clearance between normal and hyperthyroid cats. The optimal time for an SBS was 48 minutes.     

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.     

Single-injection method for evaluation of renal function with 14C-inulin and 3H-tetraethylammonium bromide in dogs and cats

A double-isotope single-injection method without urine collection for the estimation of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in dogs and cats was evaluated. The GFR was determined, using 14C-inulin and ERPF was determined, using [3H]tetraethylammonium bromide. Using a modified single exponential, 1-compartment mathematical model, the renal clearance of these solutes was estimated with a plasma radioactivity disappearance curve constructed from samples collected over a 150-minute time period. In 25 dogs, GFR, ERPF, and filtration fraction were 3.55 +/- 0.14 ml/kg/min, 10.51 +/- 0.72 ml/kg/min, and 0.34 +/- 0.02, respectively. In 25 cats, GFR, ERPF, and filtration fraction were 3.24 +/- 0.14 ml/kg/min, 8.14 +/- 0.53 ml/kg/min, and 0.39 +/- 0.02, respectively. This time-efficient and reliable method, using beta-emitting isotopes, yielded renal functional values well within the normal ranges reported by a variety of other isotopic and nonisotopic procedures. The advantages of the present procedure over previous double-isotope single-injection methods include the use of less costly, lower energy-using, and less penetrating beta emittors, as well as a shortened blood sampling schedule.     

Estimating glomerular filtration rate in healthy dogs using inulin without urine collection

The goals of this study were to determine if the glomerular filtration rate (GFR) in dogs could be estimated by plasma inulin clearance and/or infusion inulin clearance analyses without urine collection, and to compare these results with GFR values obtained by urinary inulin clearance analysis. The dogs included in this study were healthy 20 beagles. Inulin clearance values were obtained by urinary inulin clearance, infusion inulin clearance, and plasma inulin clearance techniques. Urinary inulin clearance was 4.09±0.52 ml min(-1) kg(-1) (body weight); infusion inulin clearance, 4.01±0.49 ml min(-1) kg(-1); and plasma inulin clearance, 4.14±0.66 ml min(-1) kg(-1). The urinary inulin clearance was strongly correlated with infusion inulin clearance and weakly correlated with plasma inulin clearance. The GFR for dogs can be estimated by infusion and plasma inulin clearance analyses by blood sampling alone, without urine collection.     

COMPARISON BETWEEN THE SCINTIGRAPHIC UPTAKE AND PLASMA CLEARANCE OF 99mTc-DIETHYLENETRIAMINEPENTACETIC ACID (DTPA) FOR THE EVALUATION OF THE GLOMERULAR FILTRATION RATE IN DOGS

The scintigraphically measured percentage dose uptake of ^99mTc-DTPA by the kidneys and the plasma clearance of ^99mTc-DTPA have been reported to correlate well with inulin clearance. These two parameters were evaluated in seven dogs with known or suspected naturally occurring renal disease and compared to simultaneously measured renal inulin clearance. Correlation between inulin clearance and the ^99mTc-DTPA plasma clearance was better ( p =.0016) than the correlation between the percentage DTPA uptake by the kidney. It was concluded that measurement of ^99mTc-DTPA plasma clearance is a more accurate method to estimate global glomerular filtration rate (GFR) than the percentage kidney uptake.     

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.     

Comparison of standard and radionuclide methods for measurement of glomerular filtration rate and effective renal blood flow in female horses.

Comparison of standard and radionuclide methods for measuring glomerular filtration rate (GFR) and effective renal blood flow (ERBF) was performed in 8 healthy female horses. Inulin and p-aminohippurate solutions were administered IV as a bolus, followed by sustained administration. Urine and plasma inulin and p-aminohippurate concentrations and urine volume were measured. Glomerular filtration rate and ERBF were calculated on the basis of these measurements. Glomerular filtration rate and ERBF were measured on the basis of plasma clearance of the radiopharmaceuticals, 99mTc-labeled diethylene-triaminepentaacetic acid (99mTc-DTPA) and [131I]-o-iodohippuric acid (131I-OIH), respectively. Mean +/- SEM GFR, using inulin, was 1.83 +/- 0.21 ml/min/kg of body weight. Mean GFR, using 99mTc-DTPA was 1.79 +/- 0.18 ml/min/kg. Mean ERBF, using p-aminohippurate, was 15.13 +/- 1.28 ml/min/kg. Mean ERBF, using 131I-OIH, was 18.42 +/- 1.57 ml/min/kg. Analysis of variance indicated no significant difference between mean values for GFR and ERBF. Radionuclide measurement of GFR and ERBF compared well with standard methods and is an alternative technique to the cumbersome standard methods for determination of GFR and ERBF in horses.     

A Single Sample Method for Evaluating 51Chromium-Ethylene Diaminic Tetraacetic Acid Clearance in Normal and Hyperthyroid Cats

Background: Chronic kidney failure is frequently seen in middle-aged and elderly cats. ⁵¹Chromium-ethylene diaminic tetraacetic acid (⁵¹Cr-EDTA) clearance and single blood sample (SBS) method are used in several species to estimate the glomerular filtration rate (GFR).
Hypothesis: The hypothesis of this study was that ⁵¹Cr-EDTA clearance could be determined using an SBS method in normal and hyperthyroid cats.
Animals: Forty-six cats were included in this study, with an average age of 9.5 years. Of these cats, 27 had hyperthyroidism; 19 were healthy.
Methods: After IV injection of ⁵¹Cr-EDTA (average dose: 4.25 MBq), 7 blood samples were obtained between 5 and 240 minutes. Reference clearance was calculated in mL/min and mL/min/kg body weight, using a 2-compartment model. Optimal time for clearance measurement with SBS was then determined by systematically comparing each individual plasma concentration to the reference multisample clearance.
Results: The average reference plasma clearance of ⁵¹Cr-EDTA for all cats was 14.9 mL/min (3.7 mL/min/kg). The clearance in hyperthyroid cats averaged 16.4 mL/min (4.3 mL/min/kg) and in normal cats averaged 10.3 mL/min (2.4 mL/min/kg).
The optimal time for the SBS was 48 minutes after injection of tracer ⁵¹Cr-EDTA ( R ²= 0.9414), giving the following converting equation: clearance = (0.0066 × DV_{48 minutes}) – 0.9277 (in mL/min).
Conclusions and Clinical Importance: In this study, the single sample ⁵¹Cr-EDTA clearance method was used to estimate the global GFR in cats. The method identified differences in clearance between normal and hyperthyroid cats. The optimal time for an SBS was 48 minutes.