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PubMed1999

How to assess glomerular function and damage in humans.

In human subjects, the assessment of renal function and of its changes by interventions is limited to the measurement of glomerular filtration rate (GFR), renal blood flow and the estimation of proteinuria. In humans, GFR can be determined exactly by measuring the clearance of an ideal filtration marker, such as inulin. The classic method of measuring inulin clearance in humans includes constant intravenous infusion of the compound and timed collections of urine. In order to avoid the need for timed urine collections, a number of alternative procedures have been devised. All these methods only use determinations of inulin in plasma or serum. From these, the total body inulin clearance is obtained using pharmacokinetic calculations. In order to measure total body clearance, usually called plasma clearance, inulin is either given as a constant intravenous infusion or as a bolus infusion. Both procedures overestimate GFR because of incomplete distribution of inulin during the study periods. The error may be minimized by using model-independent pharmacokinetic calculations. Unlike inulin, creatinine is not a perfect filtration marker. This is because the substance is not only eliminated by glomerular filtration but also by tubular secretion. The extent of tubular creatinine secretion is not constant in various individuals. Serum creatinine concentration is a commonly used measure of renal function in clinical practice. This parameter is determined both by the renal elimination and by the production of the compound. Differences in creatinine production among subjects and over time in a single individual may occur because of changes in muscle mass. Radioisotopic filtration markers can easily and accurately be measured in plasma and serum. Using this method, the plasma concentration-time curve of these compounds can easily be studied after intravenous bolus injection. From the plasma concentration-time curves obtained, the total body clearance (plasma clearance) of the substances can be calculated using pharmacokinetic models. Most frequently, 125l-iothalamate, 99mTc-diethylenethiaminepenta-acetic acid and 51Cr-ethylenediaminetetra-acetic acid are used for the estimation of GFR in humans. The total body clearance of all these filtration markers overestimates GFR. The error induced by this phenomenon is particularly relevant at low levels of GFR. In recent years, iohexol has been used as a filtration marker. The substance can be measured in plasma, serum and urine using high-performance liquid chromatography. So far, good agreement has been shown for GFR determined by the classic inulin clearance and by the iohexol plasma clearance. Screening for proteinuria is commonly performed using reagent test strips. Quantitative measurements of marker proteins can be used to estimate the extent and the site of damage in the nephron. These measurements may be used to estimate the progression of renal disease and the response to therapeutic interventions. Of particular interest is the degree of albuminuria which indicates nephropathy in diabetic patients and end-organ damage in patients with hypertension.

Humans↗
PubMed1984

Iothalamate stimulates hydroperoxide formation by soybean lipoxygenase.

Sodium iothalamate produced a dose dependent increase in basal oxygen consumption when soybean lipoxygenase was incubated with arachidonic acid in 0.1M borate buffer pH 9.0. The increase in oxygen consumption was associated with an increase in absorbance at 234 nm indicating an increased conjugated diene formation. The stimulation of 02 consumption was demonstrated to be due to an increase in 1500H arachidonic formation. The increase in 1500H arachidonate formation could be blocked by mannitol which is an inhibitor of the lipoxygenase enzyme. N-methyl glucamine (meglumine) which is added to some preparations of iothalamate, was also able to suppress the increase in hydroperoxide formation in a dose dependent fashion.

Chromatography, High Pressure Liquid↗
PubMed1984

Comparative study of glomerular filtration rate with diverse labelled agents.

Clearances of 113mIn-EDTA, or 99mTc -DTPA or 131I-iothalamate were compared with 3H-inulin simultaneously in rabbits or dogs. The classical plateau method was explored followed by a second slope in some instances or by the single shot procedure in others. A two-compartmental mathematical model was always employed to compare and calculate. The study suggests that the diverse agents tested are handled following similar homeostatic trends and values, although the intervening membranes may act upon them individually with diffusion rates that may vary in relation to each substance, in particular at a given time interval.

Animals↗
PubMed1997

Measurement of glomerular filtration rate.

Glomerular filtration rate (GFR) is the standard measure of renal function and is critical for the diagnosis and management of renal diseases. Rigorous assessment of GFR requires the measurement of renal clearance of an exogenous marker that is freely filtered by the kidney, and that does not undergo metabolism, tubular secretion or absorption, such as inulin. While its clearance provides the most accurate method of measuring GFR, it is not suitable for routine clinical practice. Labeled compounds as alternative filtration markers, including 125I-iothalamate and 99mTc-diethylenetriaminepenta-acetic acid (DTPA), provide accurate and precise GFR measurements, but their use may be limited for safety reasons. To avoid exposing patients to radiation, investigators have proposed clearance procedures using minute doses of non-radioactive contrast agents, including iothalamate (ionic) and iohexol (non-ionic). This approach provides similar accuracy to inulin clearance. The most important limitation of all renal clearance methods is that urine is collected by spontaneous voiding, stimulated by water loading, and thus subject to errors due to incomplete emptying of the bladder. Thus, plasma clearance of a suitable exogenous marker (51Cr-EDTA, 125I-iothalamate, iohexol) has been suggested for measuring renal function, in which the elimination rate of the tracer after a single intravenous injection is evaluated. Plasma clearance of these markers estimated by multiple blood samples provides more precise information, but repeated sampling makes this method cumbersome. To overcome this drawback, abbreviated kinetic profiles have been proposed to predict GFR from the plasma disappearance curve (elimination phase). On analyzing the data with a simplified method that uses a one-compartment model (six blood samples only in the elimination phase), corrected with the Bröchner-Mortensen formula, an excellent correlation was found with inulin clearance. This method is currently employed for measuring GFR in multicenter clinical trials.

Animals↗
PubMed2002

Evaluation of renal function in transplant patients on tacrolimus therapy.

Glomerular filtration rate (GFR), as measured by 24-hour creatinine clearance and clearance of iothalamate, and effective renal plasma flow (ERPF), as measured by the clearance of para-aminohippuric acid (PAH), were evaluated at 2 weeks, 1 month, and 3 months after transplantation in 8 renal transplant patients and at 1 month and 1 year after transplantation in 9 liver transplant patients receiving tacrolimus (Prograf) therapy. In renal transplant patients, there was a significant increase in GFR after transplantation. There was no change in GFR at 1 and 3 months as compared to 2 weeks after transplantation, while ERPF (ml/min/1.73 m2) was lower (p < 0.05) at 3 months (212+/-42) compared to 1 month (306+/-118) after transplantation. In liver transplant patients, GFR and ERPF were below normal despite normal serum creatinine concentrations, but there was no difference in GFR or ERPF at 1 month and 1 year after transplantation. Although below normal, renal function was well preserved in transplant patients while receiving chronic tacrolimus therapy over the study period. Dosage alterations ofrenally eliminated drugs may be required for drugs with a narrow therapeutic index.

Adult↗
PubMed1996

Plasma clearance rate of 51Cr-EDTA provides a precise and convenient technique for measurement of glomerular filtration rate in diabetic humans.

It has not yet been fully clarified whether the plasma or renal clearance approach is the most reliable to investigate GFR in humans. The study presented here aimed to compare plasma decay with renal clearance of 51Cr-EDTA in 27 diabetic patients with patterns of renal function broadly dispersed in a wide range of values. Moreover, the comparison was also performed with renal clearance of nonlabeled iothalamate in a subgroup of 17 patients. A biexponential function was found to fulfill statistical and heuristic criteria for the modeling analysis of plasma 51Cr-EDTA decay with 19 samples after bolus intravenous 51Cr-EDTA injection. Individual GFR values from 51Cr-EDTA plasma clearance highly correlated with those from renal clearance (r2 = 0.977, P < 0.0001), but resulted on average about 2.5 mL.min-1.1.73 m-2 higher (66.8 +/- 6.5 mL.min-1.1.73 m-2 (mean +/- SE) versus 64.3 +/- 6.4, P < 0.02). This difference remained relatively constant from patients with normal renal function to those with impaired renal function, suggesting that the plasma clearance is slightly less accurate than renal clearance approach because of a constant extrarenal clearance rate. In the subgroup studied, a similar difference was found between GFR values from 51Cr-EDTA plasma clearance (84.7 +/- 7.3) and renal clearance of iothalamate (82.8 +/- 7.3), although not statistically significant (P = 0.4). Individual GFR values well correlated (r2 = 0.913, P < 0.0001). The precision and reproducibility of the experimental approaches were assessed by comparing three coefficients of variation: (1) CVb of the bolus injection, because of measurement errors; (2) CVc of the continuous infusion, which additionally includes errors of urine volume measurement and physiological variability in the same day; and (3) CVr of repeated measurements by using bolus injection, which also accounts for physiological variability in different days. CVc of iothalamate and 51Cr-EDTA infusions were 7.5 +/- 1.9% and 7.4 +/- 1.2% respectively. CVb and CVr of bolus injection of 51Cr-EDTA were 2.6 +/- 0.3% and 3.5 +/- 0.8% respectively. CVb and CVr of bolus injection of 51Cr-EDTA, but not CVc of iothalamate and 51Cr-EDTA infusions were twofold to tenfold lower than the percent yearly change reported in IDDM and NIDDM patients. More particularly, CVr was significantly less than CVc. In order to make the test less cumbersome, a reduced sampling schedule with seven samples was designed and validated. GFR measured with seven samples was 66.1 +/- 6.4 (P = 0.1 when compared with the full 19-sample schedule) with a CVb of 3.5 +/- 0.5%. This seven-sample protocol was not different from that obtained with the previously described simplified method of Brøchner-Mortensen (63.9 +/- 6.8, P = 0.16), yet yielding a statistically more accurate estimate (coefficient of variation for Brøchner-Mortensen method = 12.1 +/- 2.9, P = 0.004). Moreover, only bolus injection, along with modeling analysis of plasma clearance rate, allows the accurate measurement of the extracellular fluid volume, an important parameter in diabetic patients. It was concluded that the reduced seven-plasma sample protocol is able to detect as small as 4 to 5% changes per year in a single patient. Moreover, it provides precise and accurate estimate of GFR in diabetic patients with hyperfiltration, who are postulated to be at higher risk to develop renal damage.

Chromium Radioisotopes↗
PubMed2001

Protein binding of 99Tcm-DTPA compared with other GFR tracers.

99Tcm-Diethylenetriaminepentaacetic acid (99Tcm-DTPA) has been postulated to be more bound to plasma proteins than are other radiopharmaceuticals used for measurement of glomerular filtration rate (GFR). The results of protein binding experiments are, however, highly related to methodology. The aim of the present study was to compare the protein binding of the 99Tcm-DTPA preparation we use in our daily routine with that of the other five 99Tcm-DTPA preparations available and with other GFR tracers by using the same ultrafiltration method. Protein binding was studied in vitro after incubation in donor plasma and in vivo after single injection in patients. A correction for the uneven distribution of ultrafiltrable ions ('Donnan effect') was included. Quality control of six 99Tcm-DTPA preparations performed with thin layer chromatography showed a high labelling efficiency (96.2-99.9%). The in vitro protein binding ranged from 9.25% to 11.12%. The in vitro protein binding of 99Tcm-DTPA was not significantly different from that of 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) and 125I-iothalamate (10.99% vs 12.15%, and 9.55%). There was no difference in the in vivo protein binding of 99Tcm-DTPA 5 and 40 min after injection (13.28% vs 12.58%), and there was no difference in the protein binding of 99Tcm-DTPA and 51Cr-EDTA (12.93% vs 12.54%). In conclusion, in vitro and in vivo protein binding of 99Tcm-DTPA was 10-13%. The protein binding was not different from the binding of 51Cr-EDTA and 125I-iothalamate.

Algorithms↗
PubMed1975

Measurement of residual glomerular filtration rate in the patient receiving repetitive hemodialysis.

The objective of the current study was to determine the best index of residual glomerular filtration rate (GFR) by comparing simultaneously measured clearances of inulin, 125I-iothalamate, endogenous creatinine, urea and 169ytterbium diethylenetriaminepentaacetic acid (169YB-DTPA) in patients receiving repetitive hemodialysis. In patients with GFR less than 5 ml/min but greater than 1 ml/min, 125I-iothalamate clearance showed the best correlation with inulin clearance. However, creatinine clearance correlated better with inulin clearance than urea clearance and as well as urea + creatinine/2. In the patients with measured GFR less than 1 ml/min, the correlation of 125I-iothalamate, creatinine, urea and urea + creatinine/two clearances with inulin clearance was satisfactory. Similarly, satisfactory correlations were obtained when the relationships were examined across the entire range of measured clearances less than 5 ml/min. A simple, practical method is descriged for the accurate serial measurement of residual GFR in patients receiving repetitive dialysis.

Female↗
PubMed2000

Is a mixture of gadolinium and iodinated contrast material safe during MR arthrography?

OBJECTIVE: This study was designed to determine whether a mixture of iodinated contrast material and gadopentetate dimeglumine used during MR arthrography yields free gadolinium ion, a systemically toxic metal. MATERIALS AND METHODS: Mixtures of commercially available nonionic and ionic iodinated contrast agent, gadopentetate dimeglumine, lidocaine, and epinephrine were analyzed using a spectrophotometric titration with a gadolinium ion titrant and methyl thymol blue indicator. RESULTS: We found no significant dissociation of gadolinium ion when gadopentetate dimeglumine was mixed with iodinated contrast agents, lidocaine, or epinephrine in any of the dilutions tested. CONCLUSION: Gadopentetate dimeglumine and iodinated contrast material can be mixed before MR imaging without any release of free gadolinium and are therefore safe for confirming the intraarticular placement of contrast material before MR arthrography.

Arthrography↗
PubMed1991

Comparison of a single-injection technique and inulin clearance for determining glomerular filtration rate in the sheep.

Glomerular filtration rate (GFR) was assessed over a 2 h period by the clearance of inulin (Cin) and in the subsequent 2 h period by a single-injection technique using radiolabelled sodium iothalamate (Ciot) or chromium-EDTA (CEDTA). Regression analysis yielded a significant correlation (P less than 0.05) between the standard clearance technique and the single-injection method, with the relationship Ciot = -10.67 + 1.25Cin with a significant correlation coefficient of r = 0.71 (P less than 0.02). There was better agreement between clearance values of inulin measured on successive days than between values determined by the single-injection technique on successive days. Cin remains the method of choice in sheep.

Animals↗
PubMedDate not supplied

Renal arteriography. The choice of contrast material.

Angiographers responding to a questionnaire disagreed on the agent of choice for selective renal arteriography. Opinion differed regarding the advantages of sodium versus meglumine salts, diatrizoate versus iothalamate, and 50-60 percent concentration agents versus those in the 70-76 percent range. Although an increasing number of angiographers are using more concentrated agents for renal arteriography, there is little information available to indicate their safety for this purpose. Dog experiments were done to see whether Renografin 76 percent (R-76), at a reasonable dose, caused more severe changes than the lower concentration agents. The studies failed to demonstrate significant differences between R-76 and the less concentrated agents indicating that R-76 can be used for selective renal arteriography if the additional iodine is deemed necessary. Factors affecting nephrotoxicity of contrast media in patients with normal and abnormal kidneys are discussed.

Aminohippuric Acids↗
PubMed1985

Mechanism of renal concentration of technetium-99m glucoheptonate.

Seventy female Sprague-Dawley rats were studied to determine the mechanism of tubular localization and the effects of commonly encountered changes in hydration and acid-base balance on renal uptake and urinary excretion of technetium-99m glucoheptonate ([99mTc]GHA). The in-vivo protein binding and protein-free plasma clearance of [99mTc]GHA also were quantitated. Twenty additional rats were studied to determine the effects of PAH competition and probenecid blockade on renal uptake of [99mTc]dimercaptosuccinic acid (DMSA) in comparison with their effects on [99mTc]GHA localization. Kidney uptake of [99mTc]GHA averaged 11.17 +/- 0.49 (s.e.)% of the injected dose in control animals. This varied slightly among groups but was significantly reduced by probenecid blockade and para-aminohippuric acid (PAH) competition to 4.08 +/- 0.55 (p less than 0.005) and 2.39 +/- 0.14 (p less than 0.005), respectively. Technetium-99m DMSA was not affected in its renal accumulation by these maneuvers. The total plasma clearance of [99mTc]GHA was lower than iodine-125(125I)iothalamate but the clearance of the protein free supernate was higher, raising a possibility of some tubular secretion. Acidification of the urine which has been shown to reduce [99mTc]DMSA uptake appeared to have no effect on [99mTc]GHA. Hepatic uptake was minimal in all groups averaging less than 1% injected dose. These data demonstrate that renal accumulation of [99mTc]GHA is blocked by probenecid and PAH suggesting that it is actively concentrated in the proximal tubule by enzyme systems similar to those involved in PAH and hippuran transport. It appears that [99mTc]GHA uptake measures a different aspect of kidney function than [99mTc]DMSA.

Acid-Base Imbalance↗
PubMed1992

Crystal and molecular structure of the doubly unsaturated dehydropeptide Ac-delta Phe-Ala-delta Phe-NH-Me.

The dehydropeptide Ac-delta Phe-L-Ala-delta Phe-NH-Me, containing two dehydro-phenylalanine (delta Phe) residues, crystallizes from methanol/water in space group P2(1)2(1)2(1), with a = 12.508 (2), b = 12.746 (1) and c = 15.465 (9). In the crystalline state, the peptide chain assumes a right-handed 3(10)-helical conformation stabilized by two intramolecular hydrogen bonds, between the N-terminal acetyl group and the NH of delta Phe3, and between the CO of delta Phe1 and the NH of the C-terminal methylamide group, respectively. The two consecutive 10-membered rings formed by the hydrogen bonds have torsion angles quite close to the standard values for type III beta-bends. delta Phe1 is located in the (i + 1) position of the first beta-bend, while delta Phe2 is located in the (i + 2) position of the other beta-bend. In the crystal, the molecules are linked head to tail by intermolecular hydrogen bonds to form long helical chains. The axes of the helices are parallel to the c axis, but neighboring helices run in antiparallel directions. This crystal packing is similar to the packing motifs frequently observed in Aib-containing peptides.

Amino Acid Sequence↗
PubMed1998

Cervical spinal cord injury during cerebral angiography with MRI confirmation: case report.

We report the first case of MRI-documented cervical spinal cord injury during cerebral angiography. A 54-year-old woman underwent an angiogram for subarachnoid hemorrhage. Her head was secured in a plastic head-holder. At the end of the procedure, she was found to have a left hemiparesis. MRI revealed high signal in the cervical spinal cord. The etiology may have been mechanical due to patient positioning, or toxic, from contrast medium injection in the vessels feeding the spinal cord, or a combination of both.

Cerebral Angiography↗
PubMed1983

Eosinophilia caused by iodinated radiographic contrast media.

Statistically significant eosinophilia was noted in the peripheral blood of a group of 108 patients 48 h after the administration of iodinated radiographic contrast medium (RCM). The duration of eosinophilia was approximately 6 days. Eosinophilia had no accompanying clinical symptoms except for two cases where urticaria appeared. The incidence of eosinophilia was irrespective of dosage or type of RCM. Possible mechanisms responsible for eosinophilia have been considered. Since eosinophilias of other aetiologies are common, it is of practical importance to distinguish these from RCM-induced eosinophilias.

Contrast Media↗
PubMed1987

A comparison of the incidence of cardiac arrhythmias produced by two intravenous contrast media in coronary artery disease.

The incidence of cardiac arrhythmias in patients with coronary artery disease receiving intravenous contrast medium has been studied and comparison made between a conventional ionic medium (meglumine iothalamate) and a low osmolar medium (sodium meglumine ioxaglate). Occasional ventricular and atrial ectopics were frequently observed both before and during administration of the contrast medium and were regarded as insignificant. Significant arrhythmias occurred in five cases. Three of these however, were in the presence of acute myocardial ischaemia or recent infarction. There was no significant difference in the incidence of arrhythmias between the two contrast media. These results show that, in the absence of acute myocardial ischaemia, the incidence of life threatening arrhythmias in patients with proven coronary artery disease receiving intravenous contrast media is much lower than previously suspected.

Arrhythmias, Cardiac↗
PubMed1989

A comparative study to evaluate the role of intra-articular adrenaline in double-contrast knee arthrography.

The addition of adrenaline to meglumine iothalamate (Conray 280) in double-contrast knee arthrography significantly improves meniscal coating, in both immediate and delayed films, when compared with iothalamate alone. The quality of coating is comparable to that with sodium meglumine ioxaglate (Hexabrix 320) without adrenaline. The addition of adrenaline to ioxaglate produces no significant improvement in arthrographic quality in either immediate or delayed films. The use of iothalamate with adrenaline is less expensive than ioxaglate alone, but this financial advantage has to be balanced against the significantly greater pain associated with the use of intra-articular adrenaline.

Adolescent↗

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