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PubMed1988

Effects of altered physiologic states on clearance and biodistribution of technetium-99m MAG3, iodine-131 OIH, and iodine-125 iothalamate.

Technetium-99m mercaptoacetyltriglycine [( 99mTc]MAG3) is a new renal radiopharmaceutical with biologic properties similar to iodine-131 orthoiodohippuric acid [( 131I]OIH). MAG3 may be used as a replacement for [131I]OIH and/or [99mTc]DTPA. For this reason, we compared the effects of several potential adverse clinical conditions on the clearance and biodistribution of MAG3, OIH and a GFR marker. To simulate renal failure, five mice underwent bilateral renal pedical ligation. Twenty-four hours after surgery they were injected with MAG3 and OIH and killed 2 hr postinjection. Compared to sham operated controls, liver activity for MAG3 and OIH increased from 0.2% to 14.1% and 0.1% to 13.9%, respectively, while intestinal activity increased from 1.3% to 8.9% for MAG3 and 0.2% to 7.7% for OIH. Constant infusion studies were performed in rats to evaluate the effects of increased plasma organic acid levels, mannitol diuresis, dehydration, and acid/base imbalance on the clearance of OIH, MAG3, and [125I]iothalamate. No differences were noted between the OIH and MAG3 clearances following diuresis and dehydration and the differences involving acid/base imbalance were minimal. Dehydration depressed the clearance of [125I]iothalamate more than that of OIH or MAG3. Para-aminohippurate (PAH) infusion inhibited the clearance of MAG3 more than OIH supporting proximal tubular transport for MAG3; PAH had no effect on [125I]iothalamate. In summary HPLC purified MAG3 behaved similarly to OIH under adverse physiologic conditions and the data continue to support the use of MAG3 as a potential clinical substitute for OIH.

Acid-Base Imbalance↗
PubMed1979

A clinical trial of a new low osmolality contrast medium. Sodium and meglumine ioxaglate (Hexabrix) compared with meglumine iothalamate (Conray) for carotid arteriography.

The discomfort of cerebral arteriography is due mainly to the osmolality of the contrast medium injection. A new low osmolality contrast medium--Hexabrix (32% iodine)--sodium and meglumine salts of ioxaglic acid was compared with Conray 280 (28% iodine)--meglumine iothalamate for carotid arteriography in 33 conscious patients. 30 patients preferred the ioxaglate solution which caused significantly less sensation of heat. Three patients could not distinguish between the two media. No patient preferred iothalamate. Ioxaglic acid is a newly synthesized mono-acid dimer. Its salts produce the same osmolality as non-ionics (e.g. metrizamide), and one third of the osmolality of currently used mono-valent salts (e.g. meglumine iothalamate) in solutions of the same iodine content. Low osmolality contrast media have significant clinical advantages and will probably become the media of choice for arteriography and venography.

Adult↗
PubMed2003

A comparison of prediction equations for estimating glomerular filtration rate in adults without kidney disease.

The ability of the Modification of Renal Disease (MDRD) equation to predict GFR when compared with multiple other prediction equations in healthy subjects without known kidney disease was analyzed. Between May 1995 and December 2001, a total of 117 healthy individuals underwent (125)I-iothalamate or (99m)Tc-diethylenetriamine-pentaacetic acid (DTPA) renal studies as part of a routine kidney donor evaluation at either Brigham and Women's Hospital or Boston Children's Hospital. On chart review, 100 individuals had sufficient data for analysis. The MDRD 1, MDRD 2 (simplified MDRD equation), Cockcroft-Gault (CG), Cockcroft-Gault corrected for GFR (CG-GFR), and other equations were tested. The median absolute difference in ml/min per 1.73 m(2) between calculated and measured GFR was 28.7 for MDRD 1, 18.5 for MDRD 2, 33.1 for CG, and 28.6 for CG-GFR in the (125)I-iothalamate group and was 31.1 for MDRD 1, 38.2 for MDRD 2, 22.0 for CG, and 31.1 for CG-GFR in the (99m)Tc-DTPA group. Bias was -0.5, -3.3, 25.6, and 5.0 for MDRD 1, MDRD 2, CG, and CG-GFR, respectively, in subjects who received (125)I-iothalamate and -33.2, -36.5, 6.0, and -15.0 for MDRD 1, MDRD 2, CG, and CG-GFR, respectively, in those who received (99m)Tc-DTPA studies. Precision testing, as measured by linear regression, yielded R(2) values of 0.04 for CG, 0.05 for CG-GFR, 0.15 for MDRD 1, and 0.14 for MDRD in those who underwent (125)I-iothalamate studies and 0.18 for CG, 0.21 for CG-GFR, 0.40 for MDRD 1, and 0.38 for MDRD 2 for those who underwent (99m)Tc-DTPA studies. The MDRD equations were more accurate within 30 and 50% of the measured GFR compared with the CG and CG-GFR equations. When compared with the CG equation, the MDRD equations are more precise and more accurate for predicting GFR in healthy adults. The MDRD equations, however, consistently underestimate GFR, whereas the CG equations consistently overestimate measured GFR in people with normal renal function. In potential kidney donors, prediction equations may not be sufficient for estimating GFR; radioisotope studies may be needed for a better assessment of GFR. Further studies are needed to derive and assess GFR prediction equations in people with normal or mildly impaired renal function.

Adolescent↗
PubMed1990

Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study.

Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-diethylenetriamine-pentaacetic acid (DTPA), 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.

Creatinine↗
PubMed1978

Nonimmunologic complement activation in normal human serum induced by radiographic contrast media.

Two different radiographic contrast media (RCM), iothalamate and iodipamide, induced the activation of several complement (C) components in normal, genetically C2-deficient and agammaglobulinemic human sera in vitro. This activation was dose dependent and demonstrable by a reduction in whole C as well as C4, C2, C3, and C5 hemolytic activities. C6, C8, and C9 hemolytic activities were unaffected. Concommitant with the loss of C3 hemolytic activity was the appearance of C3 proteolytic cleavage products that were identified by immunoelectrophoresis. Both the loss of C3 hemolytic activity and the production of C3 fragments occurred in the presence of 10 mM EDTA, indicating RCM-induced C3 cleavage occurred without participation of the multicomponent C3/C5 convertases of either the classical or alternative C pathways. Furthermore, loss of C3 hemolytic activity was not due to the direct alteration of the C3 molecule by RCM because purified C3 was unaffected upon incubation with RCM at a concentration that induced 80% reduction in the C3 hemolytic activity in normal human serum. Serum samples obtained from 40 patients, before and 30 min after undergoing i.v. pyelography, revealed no significant change in total hemolytic C activity; 34 patients received sodium and methylglucamine diatrizoate and six received sodium iothalamate. Hemolytic C3 levels were also determined for the six patients before and 30 min after administration of sodium iothalamate and no significant change in activity was detectable.

Agammaglobulinemia↗
PubMedDate not supplied

Treatment of sudden deafness with sodium salts of triiodobenzoic acid derivatives.

Twenty-two patients with a complaint of sudden deafness were treated with one of the other of two radiopaque contrast media, 9 received daily doses of sodium iothalamate, and 13 were treated similarly with methylglucamine and sodium iodamide. Four of the first group and eight of the second demonstrated either an effective partial or a complete recovery of hearing function. Those failing to respond were generally classified completely deaf at admission and report nausea, vomiting, or vertigo at onset of sudden deafness. Treatment with sodium salts of triiodobenzoic acid derivatives, i.e., sodium iothalamate and methylglucamine and sodium iodamide, is judged to be effective in selected cases of sudden deafness.

Adolescent↗
PubMed1992

[A renal function analysis using computed tomography. CT clearance versus 131I-hippuran clearance].

The CT clearance in a number of urological patients (39 patients, 25 with normal renal function) was studied by means of an "area under curve" (AUC) method, using a region of interest. 31 patients were given meglumine ioxithalamate and 8 patients Iopamidol as a contrast medium. Both for total and partial function there was highly significant correlation with isotope clearance with good reproducibility. The difference in the pharmacokinetics of the contrast media affected the absolute clearance values.

Contrast Media↗
PubMedDate not supplied

The determination of commonly used iodinated contrast media in postmortem samples using HPLC and TLC.

A rapid micro method is described for the determination of diatrizoic, iothalamic, ioxaglic, and iopanoic acids in postmortem liver and blood. The compounds were extracted with methanol and analyzed by high performance liquid chromatography using a C18 column. The mobile phase consisted of methanol:PIC A with ultraviolet detection at 232 and 242 nm. Recoveries of about 85% were obtained. A thin layer chromatographic system is described which separates the four compounds. The spots were hydrolyzed and sprayed with a diazonium coupling reagent to produce colored spots with sensitivities of 0.02 to 0.1 micrograms. Postmortem levels are given for two deaths involving diatrizoic acid.

Chromatography, High Pressure Liquid↗
PubMed1990

Monitoring renal function in children with urological abnormalities.

In clinical practice glomerular filtration rate routinely is estimated by measuring serum creatinine and using the Schwartz formula for calculating an estimate of creatinine clearance or using the Gates formula for calculating the clearance of diethylenetriaminepentaacetic acid based on the uptake during radionuclide imaging. We compared these methods to the plasma clearance of iothalamate during extended constant infusion. All 3 tests were performed in 14 boys and 5 girls 9 months to 16 years old with urological abnormalities and moderate renal insufficiency. Using iothalamate as the reference, calculated creatinine clearance overestimated glomerular filtration rate by more than 20% in 12 of the 19 patients (63%). Diethylenetriaminepentaacetic acid uptake grossly overestimated glomerular filtration rate; in only 3 instances was the estimate within 20%. The accuracy of both formulas was better in older patients and in those with more normal renal function. We conclude that the Gates formula for measuring glomerular filtration rate is grossly inaccurate in children with diminished renal function and the Schwartz formula, although better, has a poor level of predictability.

Adolescent↗
PubMed1980

In vitro effects of radiographic contrast media on the complement system.

The effect of several radiographic contrast media on the complement system in vitro was examined using quantitative crossed immunoelectrophoresis. Diatrizoate, iothalamate, metrizoate, and methiodal did not cause electrophoretic conversion of C3 or properdin factor B. In fact, the small degree of spontaneous conversion occurring when serum is incubated in polypropylene tubes was inhibited by these contrast media or by hypertonic sodium chloride. Metrizamide caused enhanced conversion of C3 and factor B that was only partially inhibited by ethylene glycol tetracetic acid (EGTA) but completely inhibited by ethylenediaminetetraacetic acid (EDTA). Iodipamide caused a unique electrophoretic alteration of C3 that was not affected by EDTA or several other inhibitors and that was not identical with the usual products of C3 activation. Iodipamide in very low concentrations inhibited complement activation through the classical pathway.

Citrates↗
PubMed1983

The glomerular filtration rate in unrestrained rabbits determined by means of an implanted telemetrical device.

An implanted radio-telemetrical device, which consists of a Geiger-Müller detector, a high voltage supply and a FM transmitter, incapsulated in araldite (weight 130 g) was used to measure the body disappearance rate of 125I-iothalamate following a single i.v. bolus in unrestrained and undisturbed rabbits. The disappearance curve is practically monoexponential from 10 to 60 minutes after administration of the indicator and the disappearance rate constant (Ke) is closely correlated to the "final slope" of the plasma disappearance curve of 125I-iothalamate (kp) r=0.99). A linear correlation was also found between Ke and GFR measured simultaneously by constant infusion clearance technique, using an indicator not detected by the Geiger-Müller detector (51Cr-EDTA) (r=0.98). The ratios between the renal clearances of 125I-iothalamate, 51Cr-EDTA and inulin were determined by constant infusion clearance technique in a separate series of experiments since no data were available in the present literature. The results show that GFR can be determined by means of the telemetrical method and in a series of experiments in undisturbed rabbits GFR was found to be on average 4.7 ml . min-1 . kg-1 (expressed as inulin clearance). Using the same technique in lightly pentobarbital anesthetized rabbits GFR was on average 3.5 ml . min-1 . kg-1.

Animals↗
PubMedDate not supplied

Dyke Award. Evaluation of contrast-enhanced MR imaging in a brain-abscess model.

An alpha-streptococcus brain abscess was produced in five dogs and studied with magnetic resonance (MR) imaging (0.5 T) and computed tomography (CT). Non-contrast- and contrast-enhanced CT scans were obtained using gadolinium diethylenetriamine-pentaacetic acid (Gd DTPA) for MR imaging and meglumine iothalamate for CT scanning. Each animal was evaluated in the early and later cerebritis stages of abscess evolution. On MR, the area of cerebritis enhanced after administration of Gd DTPA in a manner similar to that observed with contrast-enhanced CT. However, contrast enhancement was greater on the MR examination. Early lesions in two animals were detected only with contrast-enhanced MR imaging. This experience suggests that intravenously administered agents such as Gd DTPA should increase the diagnostic potential of MR imaging in neurologic diseases, especially those altering the blood-brain barrier.

Animals↗
PubMed1997

Faster and easier radiochemical purity testing for [125I]sodium iothalamate.

A previous method for determination of the radiochemical purity (RCP) value of [125I]sodium iothalamate uses two paper strips and solvents (total developing time is approximately 2.5 h). To simplify and shorten the RCP testing procedure, our laboratory has developed a single-strip chromatography method that not only distributes free 125I and [125I]sodium iothalamate to different relative front (Rf) locations, but is also faster and easier to perform. RCP of [125I]sodium iothalamate was determined with the use of a 10-cm instant thin-layer chromatography strip impregnated with polysilicic acid gel (ITLC-SA) as the solid phase, and a mobile phase of 2-butanol:acetic acid:water (140:2.5:70, v/v). By using autoradiography and counting the strip segments in a gamma counter, our results indicated that free 125I migrated to Rf = 0.89-1.00 while the [125I]sodium iothalamate moved to Rf = 0.44-0.67. The total developing time for the single-strip ITLC-SA system was approximately 1 h.

Autoradiography↗
PubMed1988

Contrast media and glomerular filtration: dose dependence of clearance for three agents.

Determination of plasma clearance of contrast agents has been advocated as a means to assess glomerular filtration rate. To evaluate the feasibility of different agents for this purpose, we have compared, in healthy volunteers, the dose dependence of plasma clearance for three contrast media (iohexol, a nonionic agent, and iothalamate and metrizoate, which are ionic substances), with special emphasis on the lower dose range (2-20 mL corresponding to 0.9-12.9 g, depending on dose and agent). Iohexol and iothalamate were cleared at constant rates, irrespective of given dose, whereas metrizoate clearance increased significantly at lower doses. In general, the clearances or iothalamate and metrizoate were, respectively, moderately and markedly higher than that of iohexol. The clearance of different doses of metrizoate (2 mL versus a radiographic dose of 40 mL or more) was also compared with the clearance of [51Cr]EDTA in two groups of patients with reduced renal function. When compared with [51Cr]EDTA in patients with renal dysfunction, metrizoate was cleared significantly faster after a 2-mL dose, whereas clearances were identical when the metrizoate dose was 40 mL or more. These findings indicate that tubular secretion plays an active role in the elimination of metrizoate. The pharmacokinetic properties of iohexol, in combination with its low toxicity, make it a suitable agent for determination of glomerular filtration rate in clinical practice.

Adult↗
PubMed2000

Evolution of incipient nephropathy in type 2 diabetes mellitus.

BACKGROUND: We examined the course of glomerular injury in 12 Pima Indians with long-standing (>8 years) type 2 diabetes mellitus, normal serum creatinine, and microalbuminuria. They were compared with a group of 10 Pima Indians in Arizona with new-onset (<5 years) type 2 diabetes, normal renal function, and normoalbuminuria (<30 mg albumin/g creatinine on random urine specimens). METHODS: A combination of physiological and morphological techniques was used to evaluate glomerular function and structure serially on two occasions separated by a 48-month interval. Clearances of iothalamate and p-aminohippuric acid were used to determine glomerular filtration rate (GFR) and renal plasma flow, respectively. Afferent oncotic pressure was determined by membrane osmometry. The single nephron ultrafiltration coefficient (Kf) was determined by morphometric analysis of glomeruli and mathematical modeling. RESULTS: The urinary albumin-to-creatinine ratio (median + range) increased from 84 (28 to 415) to 260 (31 to 2232) mg/g between the two examinations (P = 0.01), and 6 of 12 patients advanced from incipient (ratio = 30 to 299 mg/g) to overt nephropathy (>/=300 mg/g). A 17% decline in GFR between the two examinations from 186 +/- 41 to 155 +/- 50 mL/min (mean +/- SD; P = 0.06) was accompanied by a 17% decline in renal plasma flow (P = 0.003) and a 6% increase in plasma oncotic pressure (P = 0.02). Computed glomerular hydraulic permeability was depressed by 13% below control values at both examinations, a result of a widened basement membrane and a reduction in frequency of epithelial filtration slits. The filtration surface area declined significantly, however, from 6.96 +/- 2.53 to 5.51 +/- 1.62 x 105 mm2 (P = 0.01), a change that was accompanied by a significant decline in the number of mesangial cells (P = 0.001), endothelial cells (P = 0.038), and podocytes (P = 0.0005). These changes lowered single nephron Kf by 20% from 16.5 +/- 6.0 to 13.2 +/- 3.6 nL/(minutes + mm Hg) between the two examinations (P = 0.02). Multiple linear regression analysis revealed that among the determinants of GFR, only the change in single nephron Kf was related to the corresponding change in GFR. CONCLUSION: We conclude that a reduction in Kf is the major determinant of a decline in GFR from an elevated toward a normal range as nephropathy in type 2 diabetes advances from an incipient to an overt stage.

Adult↗
PubMed1996

Renal effects of captopril, indomethacin and nifedipine in nephrotic patients after an oral protein load.

BACKGROUND: In this study we investigated whether the increase in proteinuria induced by an oral protein load may be prevented by the angiotensin-converting enzyme inhibitor (ACEI) captopril in patients with nephrotic syndrome, and whether the effects of captopril on renal haemodynamics and/or glomerular selectivity are comparable to those obtained with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin and the calcium-channel blocker (CaCB) nifedipine. METHODS: Twelve subjects underwent the following treatments: (1) low-protein meal (0.2 g protein/kg body wt), (2) high-protein meal (1.3 g protein/kg body wt), (3) high-protein meal plus oral captopril (50 mg), (4) high-protein meal plus oral nifedipine (10 mg), (5) high-protein meal plus oral indomethacin (50 mg). Urine and blood samples were obtained after meals and tested for total protein, immunoglobulin G and albumin. GFR and renal plasma flow (RPF) were calculated from iothalamate and p-aminohippuric acid clearances respectively. RESULTS: Mean arterial pressure decreased significantly after both captopril (-4%, P = 0.001) and nifedipine (-5%, P = 0.0019). Compared with the low-protein meal, mean values of GFR and RPF increased significantly after the high-protein meal alone (+21%, P = 0.0002; +10%, P = 0.0491 respectively), and after captopril (+18%, P = 0.0025; +24%, P = 0.0034 respectively) or nifedipine administration (+30%, P = 0.0001; +21%, P = 0.0036 respectively), whereas they remained unchanged after the high-protein meal plus indomethacin administration. FF did not change significantly under the five experimental conditions. The increase in urinary protein excretion induced by the meat load (total protein +18%, P = 0.0102; albumin +26%, P = 0.0316; IgG +28%, P = 0.0203) was entirely blocked by both captopril and indomethacin, whereas it was further increased by nifedipine administration. CONCLUSIONS: Both captopril and indomethacin, but not nifedipine, are able to prevent the increase in urinary protein excretion rate following a meat meal. The antiproteinuric effect of captopril is comparable to that of indomethacin, but the renal haemodynamic changes induced by these drugs differ considerably, because the filtration capacity and the renal functional reserve were preserved by captopril and decreased by indomethacin. The reduction in systemic blood pressure following administration of both captopril and nifedipine does not account for changes in proteinuria, since, with a similar degree of blood pressure lowering, urinary protein excretion is reduced by captopril and increased by nifedipine.

Adolescent↗