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At least 163 records · Page 9Linked to original sources
PubMed1997

A method for accurate measurement of GFR in conscious, spontaneously voiding rats.

Renal function measurement by clearance methods relies on accurately timed urine collection. In small experimental animals, renal function measurement is usually performed under anesthesia and/or with the application of bladder catheters to ensure accurate urine collection. To avoid both anesthesia and the need for bladder catheters we developed a method to measure glomerular filtration rate (GFR) in spontaneously voiding conscious rats. GFR was measured as the urinary clearance of constantly infused 125I-iothalamate. To correct for incomplete bladder emptying urinary clearance of 125I-iothalamate was multiplied by the ratio of plasma and urinary clearance of simultaneously infused 131I-hippuran, a correction method that has been previously validated in humans. Reproducibility of the technique was evaluated by analysis of the results of four consecutive clearance periods during the day (intra-assay variation) in a group of 17 rats and of two consecutive clearance periods on two or three separate days in a group of 20 rats (inter-assay variation), all with normal renal function. Application of the correction method reduced the intra-assay coefficient of variation (mean +/- SD) from 37.4 +/- 14.3 to 5.4 +/- 2.3% (P < 0.05). The mean inter-assay coefficient of variation fell slightly from 23.4 +/- 10.3 to 11.0 +/- 7.2% (P < 0.10). In rats with moderately impaired renal function (N = 8) the intra-assay variation fell from 27.9 +/- 20.7 to 2.7 +/- 1.6% (P < 0.05). Our data show that this correction method is a useful technique to assess renal function in conscious, spontaneously voiding rats.

Animals↗
PubMed1995

Optimising glomerular filtration rate and effective renal plasma flow measurements using a simple pharmacokinetic model.

We applied an open one compartment pharmacokinetic model for the determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) based on a rapid intravenous loading dose followed by a constant infusion of 125I-iothalamate and 131I-orthoiodohippurate in order to ensure constant plasma levels of the two clearance markers. The loading dose was based on the assumption that the volume of distribution of the two markers equals the extracellular volume (25% of the body weight). The infusion rate as calculated after the clearance of thalamate was estimated from body weight, age, sex and serum creatinine using Cockcrofts formula. The clearance of hippurate was assumed to be four times that of thalamate. We studied the reliability of this model in 212 patients with insulin dependent diabetes mellitus (IDDM; n = 74), nephrotic syndrome (NS; n = 18) and heart (HTX; n = 69) or kidney (KTX; n = 51) transplants. A steady state concentration was obtained in all patient groups, even when GFR was markedly depressed. In patients with diabetes, we observed more variance between plasma and urinary clearances of thalamate, which could be due to inaccuracies in urine sampling. In these patients, GFR should be measured using a method that is not dependent on urine collection. Also, the estimation of GFR by means of Cockcrofts equation seems to underestimate GFR in diabetic subjects.

Glomerular Filtration Rate↗
PubMed1994

Acute effects of increasing doses of nicorandil on renal function in man.

The effects of nicorandil, a nicotinamide derived vasodilator combining nitrate and potassium channel opener actions, on kidney function have not been determined. This study investigated changes in renal blood flow and glomerular filtration rate as estimated using simultaneous 131I-iodohippurate and 125I-iothalamate plasma clearances. Forty-two healthy subjects in sodium balance received placebo and 2.5 mg (n = 8), 5 mg (n = 9), 10 mg (n = 8), 20 mg (n = 8) or 30 mg (n = 9) nicorandil orally. Peak nicorandil plasma concentrations occurred in the first hour. Nicorandil produced dose related decreases in blood pressure with maximum reductions (mean +/- standard error of the mean) after 30 mg of -6 +/- 1 mmHg systolic and -8 +/- 2 mmHg diastolic. Renal blood flow averaged 655 +/- 28 ml/minute/1.73 m2 after placebo. Renal blood flow changed 10 +/- 11% after 2.5 mg, -6 +/- 8% after 5 mg, -12 +/- 11% after 10 mg, -11 +/- 5% after 20 mg, and 8 +/- 6% after 30 mg, however, these changes did not reach statistical significance. Glomerular filtration rate averaged 113 +/- 3 ml/minute/1.73 m2 and was unaltered after nicorandil. Nicorandil had no effect on filtration fraction but fractional excretion of sodium tended to decrease with dose. These dose-related effects of nicorandil are consistent with other mixed vasodilators. At therapeutic doses, renal perfusion and function are preserved despite reductions in systemic blood pressure by nicorandil.

Adolescent↗
PubMed1996

Precision of glomerular filtration rate determinations for long-term slope calculations is improved by simultaneous infusion of 125I-iothalamate and 131I-hippuran.

In studies on the progression of chronic renal failure the measurement of GFR must be very reliable. Sequential determination of GFR using the renal clearances of exogenous tracers such as inulin or iothalamate is the most accepted method. However, because of inaccuracies in urine collection, intratest variation, and thus intertest variation, of these clearances is considerable. This has a negative impact on the precision of long-term slope estimations. A previously described method of GFR determination on the basis of simultaneous infusion of 131I-hippuran and 125I-iothalamate corrects for inaccurate urine collection. To study whether this correction method improves the precision of the GFR slope measurement, this study analyzed longitudinal GFR data obtained in 71 patients with renal disease during a follow-up of 84 to 180 wk (477 renal function studies). All GFR were calculated by using both the standard renal clearance method and the correction method. The intratest and intertest coefficient of variation was significantly smaller for the correction method compared with the standard method (1.93 +/- 0.20 versus 8.48 +/- 1.66% P < 0.0005; and 2.88 +/- 0.32 versus 5.12 +/- 0.66%, P < 0.005, respectively). As a result, the precision of the GFR slope estimation was significantly better with the correction method compared with the standard method (error of the slope, 1.63 +/- 1.09 versus 2.35 +/- 2.36 mL/min per yr, P < 0.01). This improvement in precision of the slope by using the correction method reduces the necessary sample size needed to detect a GFR slope difference between interventions to about 30% of that needed when using the standard method. It is concluded that the precision of GFR measurements is improved by using correction for inaccurate urine collection with concomitant 131I-hippuran clearance.

Disease Progression↗
PubMed2000

Simultaneous technetium-99 MAG(3), iodine-131-orthoiodohippurate and iodine-125 iothalamate clearance and biodistribution after bolus injection in rats.

A bolus injection multiple blood sampling method was developed for the simultaneous measurement of blood and plasma clearance of three radiopharmaceuticals in rats. Technetium-99m mercaptoacetyltriglycine ([(99m)Tc]MAG(3)) and iodine-131-orthoiodohippurate ([(131)I]OIH) were used as makers of effective renal blood flow (ERBF), and iodine-125 iothalamate ([(125)I]IOT) was used as a marker of glomerular filtration rate (GFR). These methods can be easily performed in rats without arterial catheterization. Tissue biodistribution was studied in four groups of rats subjected to the following: group A, renal pedicle isolation (sham-operated); group B, ligature of one kidney pedicle; group C, ligature of both renal pedicles; and group D, ligature of both kidney pedicles and the bile duct. Renal clearance of [(99m)Tc]MAG(3) was greater than [(131)I]OIH and both agents were cleared faster than ([(125)I]-IOT). Either of the two markers of ERBF may be used in experimental studies, but it should be borne in mind that these are relative measurements of kidney performance. [(99m)Tc]MAG(3) and [(125)I]-IOT showed bile excretion in healthy rats, so they cannot completely fulfill the requirements for use as markers of ERBF. When renal function was impaired experimentally, [(99m)Tc]MAG(3) and [(125)I]-IOT were excreted in bile and [(131)I]OIH was secreted in the intestine. Thus, while the markers of ERBF and GFR may be reliable under normal physiological conditions, they may give progressively more erroneous values as renal function deteriorates.

Animals↗
PubMed1999

Clearance and renal extraction of technetium-99m-L,L-ethylenedicysteine, I-131-ortho-iodohippurate and I-125-iothalamate in pigs.

99mTc-L,L-ethylenedicysteine (99mTc-EC) has been proposed as a 99mTc-labelled alternative to radio-iodinated ortho-iodohippurate (OIH) for renal imaging and evaluation of renal function. The kinetics of this new renal function agent were studied by a single-injection plasma clearance technique in pigs. 99mTc-EC, 131I-OIH and 125I-iothalamate were injected and the plasma concentration of the three tracers was followed for 240 min. Renal, hepatic and total plasma clearance were calculated. There was no difference between the renal plasma clearance of 99mTc-EC and 131I-OIH (175 +/- 9 versus 178 +/- 8 ml min-1, P = 0.43), whereas the difference between the total plasma clearance of 99mTc-EC and 131I-OIH was highly significant (268 +/- 16 versus 185 +/- 9 ml min-1, P = 0.0001). 99mTc-EC had a significant hepatic clearance of 83 +/- 10 ml min-1 whereas the hepatic clearance of 131I-OIH was negligible. Renal plasma extraction of both 99mTc-EC and 131I-OIH decreased significantly between 2 and 240 min post-injection from 0.85 to 0.45% for 99mTc-EC and from 0.93 to 0.57% for 131I-OIH. Red blood cell binding of 99mTc-EC and 131I-OIH was 6.1% and 20%, respectively. The protein binding of 99mTc-EC and 131I-OIH was 32% for both tracers. We conclude that 99mTc-EC is not a suitable tracer for measuring renal function by the single-injection plasma clearance technique in pigs. This is due to a decreasing renal extraction and a significant hepatic clearance.

Animals↗
PubMed1995

Extended measurement of glomerular filtration rate and effective renal plasma flow in ambulatory patients.

We describe a standardized clearance method over 5 h (one hour equilibration followed by eight consecutive 30 min clearance periods [period 2-9]) for the estimation of GFR (iothalamate I125) and ERPF (hippuran I131) during water diuresis in ambulatory and exercising patients. Four groups were examined. In group I (normal controls, n = 15) there were no significant changes in GFR, ERPF and FF (P > 0.10) during repeated clearance periods (mean of period 2-5 versus period 6-9). The reproducibility of the method was studied at a mean interval of 3.7 weeks in a group of patients with stable reduction of GFR (group II, n = 7). The values for GFR, ERPF, FF and RVR did not change significantly in this group, and correlated significantly between repeated studies (r = 0.81 to r = 0.99). In group III (untreated hypertensive patients with reduced GFR, n = 13) there was a time dependent 7.2% decrease in GFR (P < 0.05), significantly different from group I (P < 0.02), a 10.0% decrease in ERPF (P < 0.01) and no significant change in FF (P = 0.08) when the mean of period 2-5 was compared with the mean of period 6-9. In healthy controls (group IV, n = 8) light sustained bicycle exercise (25 W) induced a 7.1% decline in GFR (P < 0.01), 17.4% decline in ERPF (P < 0.001) and a 13.6% increase in FF (P < 0.001). We conclude that ambulatory measurements of GFR and RPF can be carried out over a period of 5 h with satisfactory precision and repeatability. Ambulatory hypertensive patients with moderately reduced GFR showed the same degree of time dependent downward drift of GFR and ERPF without exercise as was seen in healthy individuals during light exercise. Accordingly, in these groups single clearance periods imply a risk for under or overestimation of renal function, and time controls are necessary during clearance studies.

Adult↗
PubMedDate not supplied

Pharmacokinetic aspects of measurement of glomerular filtration rate in the dog: a review.

Glomerular filtration rate (GFR) is estimated by means of clearance, defined as the volume of plasma that has been cleared of a particular substance per unit time. Glomerular filtration rate may be estimated by measuring the renal clearance of a filtration marker using data from both urine and plasma or by plasma clearance using only plasma data. Several alternative pharmacokinetic models are used for the calculation of clearance using various filtration markers with slightly different pharmacokinetic properties. The purpose of this article is to discuss how the choice of marker and pharmacokinetic model may influence estimated GFR values and to elucidate commonly used methods and reported GFR values in the dog.

Animals↗