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 Iodixanol was administered intravenously at 40 mg I/kg, and blood was withdrawn 60, 120, and 180 min later.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.     

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.     

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.     

Simplified procedure for the estimation of glomerular filtration rate following intravenous administration of iodixanol in cats

Objective-To compare the use of a single-sample method involving IV administration of iodixanol with a multisample method involving inulin for the estimation of glomerular filtration rate (GFR) in cats. Animals-24 cats, including 15 healthy cats and 9 cats with naturally occurring renal diseases. Procedures-Each cat was coadministered iodixanol (a nonionic contrast medium; dose providing 40 mg of I/kg) and inulin (50 mg/kg), IV, and blood samples were collected 60, 90, and 120 minutes later. Serum iodixanol and inulin concentrations were determined by means of high-performance liquid chromatography and colorimetry, respectively. Serum urea nitrogen and creatinine concentrations were also measured. Results-Analysis of the data from healthy cats and cats with naturally occurring renal diseases revealed an excellent correlation between GFR values estimated by the multisample and single-sample methods with iodixanol. Likewise, GFR values estimated from the single-sample method with iodixanol were closely correlated with those calculated from the multisample method with inulin. Conclusions and Clinical Relevance-For estimation of GFR in cats, use of a single-sample method with iodixanol, instead of a multisample procedure, may be an expedient tool in both clinical and research settings because of its benefits to patient well-being as a result of reduced stress associated with blood sample collection.     

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.     

The relationship between some plasma clearance methods for estimation of glomerular filtration rate in dogs with pyometra

The purpose of the present study was to compare different pharmacokinetic models for estimation of glomerular filtration rate (GFR) in 50 dogs with pyometra. GFR was estimated by plasma clearance (CLplasma) of iohexol by four 1-compartment methods (CL1c), a 2-compartment method (CL2c), and the trapezoidal method (CLtr). Regression analysis was performed to establish correction formulas for prediction of CLtr from the CL1c values and to find optimal times of sampling. Standardization of clearance values to body weight (kg), body surface area (m2) and extracellular fluid volume (ECFV) was compared by ranking of values. CLtr and CL2c values were similar, whereas CL1c overestimated CLtr. CLtr could be predicted from 2 samples at 2 and 3 hours after injection, using the formula CLtr = 4.52 + 0.84CL1c - 0.00080(CL1c)2 (R2 = .97). Similar relationships were found when sampling at 2 and 4 hours or at 2, 3 and 4 hours after injection, whereas predictions from the 3- and 4-hour estimates were not optimal (R2 = .79). The 2-sample methods for calculating GFR/ECFV generally produced unreliable predictions of the complete curve GFR/ECFV values. For some dogs, the choice of standardization procedure substantially changed the apparent level of renal function relative to other dogs in the study. We conclude that by applying an appropriate correction formula, GFR may be estimated using 2 blood samples at 2 and 3, or 2 and 4 hours after injection of iohexol when renal function is normal or moderately reduced. The method of standardizing the analysis with respect to body size may influence interpretation of the results substantially.     

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.     

Use of plasma clearance of iohexol for estimating glomerular filtration rate in cats

OBJECTIVE: To determine whether plasma clearance of iohexol (PCio) can be used to estimate glomerular filtration rate (GFR) in cats. ANIMALS: 4 renal-intact and 6 partially nephrectomized adult cats. PROCEDURE: Plasma clearance of iohexol was determined after IV administration of iohexol; plasma concentrations of iodine were measured by use of a colorimetric assay. Results for PCio were compared with simultaneously obtained values for urinary clearance of creatinine (CCr). RESULTS: The colorimetric assay used to measure plasma iodine concentrations was extremely precise. Results of PCio for all cats, renal-intact cats, and partially nephrectomized cats were closely associated with results of CCr. Mean difference between CCr and PCio determined for all cats was 0.95 ml/min/kg, which was < 30% of mean CCr for renal-intact cats. Coefficients of variance for PCio (5%) and CCr (8%) in renal-intact cats were similar. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma clearance of iohexol determined by use of a simple colorimetric assay provided an estimation of GFR in cats that was not significantly different from that provided by CCr. Moreover, PCio more reliably estimates renal function than BUN and plasma creatinine concentrations. Because determination of PCio is less labor intensive and invasive, compared with CCr, it may be easier to perform in a clinical setting.     

Evaluation of iohexol clearance used to estimate glomerular filtration rate in clinically normal foals

OBJECTIVE: To determine whether pharmacokinetic analysis of data derived from a single i.v. dose of iohexol could be used to predict creatinine clearance and evaluate simplified methods for predicting serum clearance of iohexol with data derived from 2 or 3 blood samples in clinically normal foals. ANIMALS: 10 healthy foals. PROCEDURE: Serum disposition of iohexol and exogenous creatinine clearance was determined simultaneously in each foal (5 males and 5 females). A 3-compartment model of iohexol serum disposition was selected via standard methods. Iohexol clearance calculated from the model was compared with creatinine clearance. Separate limited-sample models were created with various combinations of sample times from the terminal slope of the plasma versus time profile for iohexol. Correction factors were determined for the limited-sample models, and iohexol clearance calculated via each method was compared with exogenous creatinine clearance by use of method comparison techniques. RESULTS: Mean exogenous creatinine clearance was 2.17 mL/min/kg. The disposition of iohexol was best described by a 3-compartment open model. Mean clearance value for iohexol was 2.15 mL/min/kg and was not significantly different from mean creatinine clearance. A method for predicting serum iohexol clearance based on a 2-sample protocol (3- and 4-hour samples) was developed. CONCLUSIONS AND CLINICAL RELEVANCE: Iohexol clearance can be used to predict exogenous creatinine clearance and can be determined from 2 blood samples taken after i.v. injection of iohexol. Appropriate correction factors for adult horses and horses with abnormal glomerular filtration rate need to be determined.     

Assessment of glomerular filtration rate in normal dog: analysis of the 51Cr-EDTA clearance and its relation to several endogenous parameters of glomerular filtration

In 34 normal dogs the 51Cr-EDTA plasma clearance (C) according to the single injection technique was determined. The biexponential plasma disappearance curves were analysed according to a two compartment model. The results were compared with the plasma levels of creatinine and urea and with the endogenous creatinine clearance. In particular the dependence on body-weight (W) (range 8 to 57 kg) was established for several parameters. The dependence of C (ml per minute) on W (kg) could be described with both a linear function (C = 10 + 2.5 W) and a power function (C = 4.2 W0.88). The total distribution volume was equivalent to 19.6 per cent of W (range 12.1 to 33.5 per cent) whereas the rate constant lambda 0 (mean value 0.020 per minute, range 0.0115 to 0.0266 per minute) characterising the renal excretion did not depend on W. Good reproducibility (r = 0.92) of the C values was found in a test involving 13 dogs.     

Evaluation of a single injection of 99mTc-labeled diethylenetriaminepentaacetic acid for measuring glomerular filtration rate in horses.

Glomerular filtration rate (GFR) was measured in 12 clinically normal horses, using the standard inulin clearance method, and values were compared with values for 2 methods, using a single rapid IV injection of 99mTc-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). The first 99mTc-DTPA method used a 2-compartment model to calculate GFR blood clearance of the tracer. The second method used sequential digital gamma camera images of the kidneys to determine fractional accumulation of the total dose of the tracer in the kidneys (percentage of injected dose, gamma camera) from 0 to 10 minutes after radionuclide administration. Linear correlation among the 3 methods was determined. Mean (+/- SD) GFR, using the inulin clearance method, was 154.67 +/- 42.28 ml/min/100 kg of body weight. Mean GFR, using the 2-compartment blood clearance curve, was 146.92 +/- 27.49 ml/min/100 kg. Mean GFR, using percentage of injected dose (gamma camera method) was 154.7 +/- 22.00 ml/min/100 kg. The percentage of injected dose (gamma camera method) did not correlate significantly to the inulin clearance results. However, a significant (r = 0.666, P less than 0.018) correlation was observed between the inulin method and the 99mTc-DTPA blood clearance method. Significant (P less than 0.0001) difference also was observed in the split function of the equine kidneys, with GFR of the right kidney contributing 60.1 +/- 9.12% of the total function, as determined by 99mTc-DTPA gamma camera imaging. Because the 99mTc-DTPA blood clearance method does not require urine collection, it may be a more practical procedure to measure GFR in the horse.     

Exogenous creatinine clearance as a measure of glomerular filtration rate in dogs with reduced renal mass

Renal mass was surgically reduced in 78 dogs by uninephrectomy or by combined renal infarction and uninephrectomy. Renal clearance of inulin and renal clearance of exogenous creatinine were determined simultaneously, and the creatinine to inulin clearance (C/I) ratio was calculated. Clearance procedures were performed 2 to 3 months after reduction of renal mass, and were repeated at intervals thereafter. Overall, the C/I ratio was 1.008 +/- 0.007 for 192 determinations, with a highly significant correlation (R2 = 0.994, P less than 0.0001) between creatinine clearance and inulin clearance. There was no significant effect of gender of dogs, time after partial renal ablation, or dietary protein intake on C/I ratios. Degree of renal ablation did not affect C/I ratios. The results indicated that exogenous creatinine clearance is a valid measure of glomerular filtration rate in both male and female dogs with reduced renal mass.     

Measurement of glomerular filtration rate, renal plasma flow, and endogenous creatinine clearance in cheetahs (Acinonyx jubatus jubatus).

Glomerular filtration rate (GFR), renal plasma flow (RPF), and the endogenous creatinine clearance (CCr) rate were determined in 13 captive cheetahs, Acinonyx jubatus jubatus (seven females and six males, 1.5-7.5 yr of age, x = 5.02 yr), during general anesthesia with Telazol and isoflurane by measuring the urinary clearances of inulin, para-aminohipppuric acid, and endogenous creatinine, respectively. Methods to determine GFR, RPF, and endogenous CCr in captive cheetahs were evaluated, and the relationship between GFR and CCr for this species was determined. The GFR and the RPF were stable during the procedure, with mean values of 1.59+/-0.17 ml/min/kg body weight and 5.12+/-1.15 ml/min/kg body weight, respectively. Although the mean value for CCr (1.47+/-0.20 ml/min/kg body weight) was significantly less than the corresponding value for GFR, the mean difference (0.11+/-0.02 ml/min/kg weight) between the two measurements was slight, and the values were highly correlated (R2 = 0.928; P < 0.0001). The measurement of CCr in cheetahs should provide a reliable estimate of GFR, facilitating the early detection of renal disease in this species.     

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.     

Measurement of glomerular filtration rate via urinary clearance of inulin and plasma clearance of technetium Tc 99m pentetate and exogenous creatinine in dogs

OBJECTIVE: To compare glomerular filtration rate (GFR) measured via urinary clearance of inulin (UCI) with plasma clearance of technetium Tc 99m pentetate (99mTc-pentetate) and creatinine in dogs. ANIMALS: 6 healthy Beagles and 18 Beagles with reduced renal function. PROCEDURE: 13 blood samples were obtained between 5 and 600 minutes after i.v. bolus injections of (99m)Tc-pentetate and creatinine. Plasma clearance of (99m)Tc-pentetate was computed on the basis of 1, 2, or 13 samples, and plasma clearance of creatinine was computed on the basis of 2, 5, or 13 samples. During plasma clearance procedures, constant i.v. infusion of carboxyl carbon 14 inulin was begun and UCI was determined in urine collected from 90 to 120, 120 to 180, and 180 to 240 minutes. Clearance procedures were repeated in 12 dogs to evaluate reproducibility of results. RESULTS: Significant association between UCI and plasma clearance was determined via all methods. However, plasma clearances were moderately to markedly different from UCI, depending on test substance, GFR, and sample numbers used for plasma clearance computations. Comparisons were particularly discordant when some methods of limiting samples were used to define plasma clearance. CONCLUSIONS AND CLINICAL RELEVANCE: Values derived from plasma clearance methods for (99m)Tc-pentetate and creatinine were not interchangeable with UCI results, which raises questions about their reliability as clinical research tools for measurement of GFR. Plasma clearance methods that are relative indices of renal function should not be interpreted as accurate measures of GFR without validation.