Determining 'true' glomerular filtration rate in healthy adults using infusion of inulin and comparing it with values obtained using other clearance techniques or prediction equations.

OBJECTIVE: To determine 'true' glomerular filtration rate (GFR) in healthy adults as renal clearance following infusion of inulin, and compare that result with those obtained using other markers and clearance techniques and with estimations of GFR using creatinine-based prediction equations. MATERIAL AND METHODS: Twenty healthy volunteers (11 females) with a median age of 27 years (range 19-36 years) received bolus doses of inulin and iohexol i.v. and 16 blood samples were taken after injection. Then, inulin and iohexol were infused to give stable plasma concentrations and blood and urine samples were collected. Residual bladder volume was estimated using ultrasound scanning. Plasma and urine concentrations of inulin and iohexol were determined using chromatography and resorcinol methods, respectively. Different methods of GFR determination were compared as well as four formulae for GFR estimation based on serum creatinine. RESULTS: 'True' GFR, i.e. renal clearance of inulin during its infusion, was a median of 117 ml/min/1.73 m2 (inter-quartile range 106-129 ml/min/1.73 m2). Similar values of GFR were obtained with renal clearance of iohexol during its infusion and also with plasma (body) clearance of inulin or iohexol following bolus injections and using 16 or five plasma samples. Endogenous creatinine clearance was higher (p<0.001) than true GFR (median 23 ml/min/1.73 m2). Plasma clearance of iohexol and inulin based on their concentrations in four blood samples underestimated their renal clearance considerably. All four creatinine-based formulae markedly underestimated renal inulin clearance. CONCLUSIONS: Plasma and renal clearance of iohexol and inulin were similar in healthy adults. Underestimation of GFR was noted when plasma clearance of iohexol and inulin was based on four but not five or more blood samples. Some prediction equations underestimate true GFR to such an extent that caution must be taken when using them to evaluate normal or high GFR values.

Contact allergy to gold in patients with gold-plated intracoronary stents.

An increasingly common and effective method for the treatment of atherosclerotic disease in the coronary arteries is percutaneous transluminal coronary angioplasty (PTCA) and stenting. The stents are made of different metals. An increased rate of restenosis when using gold-plated stents has been shown. Contact allergy to gold is common in many countries. Recently, a study has shown an increased rate of contact allergy to nickel among patients with restenosis and a nickel-containing stent. The aims of our study were to investigate whether there was an increased rate of contact allergy to gold among patients with gold-plated stents and if this increased the risk of restenosis. 22 patients who had received a gold-plated stent were patch tested. An age- and sex-matched population of 88 patients, previously patch tested because of a suspected contact dermatitis, served as controls. In the stent group, 10/22 (45.5%) had a contact allergy to gold, in the control group 18/88 (20.5%); the difference is statistically significant (P = 0.04). There was no significant difference regarding frequency of restenosis. Our study indicates that there is a risk of sensitizing the patient when implanting a gold-plated stent. Further studies are needed to confirm these results and to evaluate whether there is an increased risk of restenosis.

Biliary and total extrarenal clearance of inulin and iohexol in pigs. A source of error when determining gfr as body clearance.

Biliary clearance, total extrarenal clearance, body and renal clearance of inulin and iohexol were determined in 11 normal and 11 nephrectomized pigs. The biliary clearance of inulin, calculated as biliary excretion divided by the plasma concentration, was 0.04 and 0.01 ml min(-1) 10 kg(-1) and of iohexol 0.21 and 0.1 ml min(-1) 10 kg(-1), in normal, respectively, nephrectomized pigs (p < 0.05). The extrarenal clearance of inulin, calculated as body minus renal clearance, was 2.7 and 0.7 ml min(-1) 10 kg(-1) and of iohexol 3.7 and 0.7 ml min(-1) 10 kg(-1) in normal, respectively, nephrectomized pigs (p < 0.05). Some hours after injection of the markers their plasma concentrations were much higher in the nephrectomized pigs. This higher plasma concentration was not matched by an equally higher biliary excretion and therefore biliary clearance decreased. The smaller total extrarenal clearance in nephrectomized pigs, i.e. the overestimation of GFR when calculated as body clearance, indicates that this source of error decreases with decreasing renal function.

Use of spiral CT and the contrast medium iohexol to determine in one session aortorenal morphology and the relative glomerular filtration rate of each kidney.

The aim of this study was to determine the relative glomerular filtration rate (GFR), i.e. the GFR of each kidney in percent of total GFR, by spiral CT. In 41 patients, who were part of a follow-up program after endoluminal stent grafting of aortic aneurysm, spiral CT with the contrast medium iohexol was used to evaluate the morphology of the aorta and kidneys. The opportunity was taken to utilize the already injected iohexol to determine the relative GFR with an extra CT sequence. In each patient two determinations were made, 6 or 12 months apart. The amount of a GFR marker accumulating in Bowman's space, tubuli, and renal pelvis within 2-3 min after i.v. injection, before any marker had left the kidney via the ureter, was defined as proportional to the GFR of that kidney. The renal accumulation of iohexol was obtained by spiral CT using 10-mm collimation and a table speed of 10 mm/s (pitch ratio 1:1) from the upper to the lower poles. The correlation coefficient between the relative GFR of each kidney determined at the first and second examination was excellent (r=0.99) with a median (range) difference of 1% (0-6%) of total GFR. The radiation dose calculated as the mean absorbed dose to the kidneys was 50 mGy and the effective dose 5 mSv. The morphology of aorta and kidneys and the relative GFR of each kidney can be determined in one session with spiral CT using iohexol as both angiographic contrast medium and as a GFR marker. It is also possible to take some plasma samples in the same session to determine iohexol concentration to calculate the body clearance of iohexol (or take plasma and urine samples to calculate the renal clearance of iohexol).

Clinically suspected pulmonary embolism: is it safe to withhold anticoagulation after a negative spiral CT?

The goal of this study was 3-month clinical outcome in nonanticoagulated patients with clinically suspected acute pulmonary embolism (PE) following a negative spiral CT. During a 6-month period 305 patients underwent spiral CT, of whom only 8 also had a lung scintigraphy. In patients with a final CT report read as not positive for acute PE, all hospital records and answers to a patient questionnaire were analyzed for episodes of venous thrombembolism (VTE). Acute PE was diagnosed at spiral CT in 61 patients (20%). Twenty-six of the remaining 244 patients were excluded from further analysis because of (a) long-term anticoagulation due to symptomatic acute deep venous thrombosis (n = 5), clinically diagnosed acute PE (n = 2), chronic recurrent VTE (n = 4), and cardiac disorders (n = 5); and (b) a normal perfusion scintigram (n = 4) or a negative pulmonary arteriogram (n = 6). Three patients were lost to follow-up. Among the remaining 215 patients only 10 had undergone a negative lower extremity venous study. Sixteen patients (7%) died during the follow-up period, 6 of whom underwent autopsy. Venous thrombembolism was diagnosed in three of the 215 patients (1.4%, 95% confidence limits: 0.5-4.0%), one causing the patient's death. Two patients had advanced thoracic malignancies and the third severe chronic obstructive pulmonary disease (84 years old). A negative spiral CT may be able to exclude clinically significant acute PE with the same accuracy as a normal lung scintigraphy or a negative pulmonary arteriography.

Assessing residual renal function and efficiency of hemodialysis--an application for urographic contrast media.

BACKGROUND: In patients on hemodialysis with end-stage renal disease there is an increasing interest in measuring both residual renal function (RRF) and quantity and quality of dialysis because insufficient dialysis gives higher mortality. For that purpose we have measured clearances of two urographic iodine (I) contrast media (CM) with different molecular masses (iohexol 821 u and iodixanol 1, 550 u). These CM are filtered through glomeruli and dialysis membranes and have higher molecular masses than urea and creatinine and might represent the dialyzability of the hypothetic uremic toxins with a molecular mass of 300-5,000 u. METHODS: Thirteen patients (8 of them were anuric) immediately after hemodialysis received 15 ml iohexol (300 mg I/ml i.v.) and 2 weeks later in the same way 15 ml iodixanol (320 mg I/ml). Nine other patients (2 anuric) received CM after only one dialysis; 8 got iohexol and 1 got iodixanol. After the CM injections the iodine concentrations were measured with X-ray fluorescence in blood and, when available, urine during the following 2 days including both the start and end of the next dialysis. Eighteen patients after two dialysis sessions, 2 weeks apart, received 10 ml iohexol i.v., and a single blood sample was taken at the start of the next dialysis 2 days later to determine RRF alone. RESULTS: In the 10 anuric patients the extrarenal clearances (mean +/- SD) were 2.5 +/- 1.1 and 2.7 +/- 1.1 ml/min/1.73 m(2) for iohexol and iodixanol, respectively. In patients with RRF good correlations were demonstrated between body clearance, based on two blood samples, and renal clearance of CM. Good correlations (r(2) = 0.853 for iohexol, r(2) = 0.933 for iodixanol) were noted between two-sample and single-sample body clearances. Repeated single sample iohexol clearances gave a coefficient of variation of 15%. During dialysis the clearances of iohexol and iodixanol were, respectively, 69 +/- 16 and 58 +/- 11 ml/min/1.73 m(2) when calculated from a single-pool model (hemodialysis clearance of CM from plasma). A median increase (rebound) of CM concentrations in plasma 45 min dialysis was 8% for iodixanol and 18% for iohexol. When the CM concentration 45 min after dialysis was used, the clearance values were by 8-10% lower and represented the hemodialysis clearance of CM from the extracellular compartments. The dialysis eliminations of iohexol and iodixanol were similar to that of urea, measured as percentage reduction of serum levels during dialysis. CONCLUSIONS: A single injection of CM at the end of dialysis followed by a single blood sample at the start of the next dialysis gives total body clearance, i.e., an estimation of the RRF. An additional blood sample at the end of the next dialysis gives dialysis efficiency.

Does post-angiographic hemodialysis reduce the risk of contrast-medium nephropathy?

OBJECTIVE: Several strategies have been employed to reduce the incidence of nephrotoxicity in connection with the administration of urographic contrast media. We present the results of a randomized study to explore the effect of a single hemodialysis treatment immediately after an angiographic examination. MATERIAL AND METHODS: The patients studied had moderately reduced renal function. Seventeen of the 32 patients had diabetic nephropathy and 15 had other renal diseases. They were randomly selected to undergo either hemodialysis or standard treatment following the angiographic examination. The glomerular filtration rate (GFR) was determined the day before and 1 week after administration of the contrast medium. All patients were hydrated and received oral calcium-channel blocking treatment before angiography. RESULTS: Hemodialysis lowered the level of contrast medium in plasma by approximately 80%. In spite of this no significant difference in renal iohexol clearance was noted between groups treated and not treated with hemodialysis. CONCLUSIONS: The risk of a marked and sustained reduction in renal function after administration of an iodine contrast medium is low with modern angiographic techniques. Hemodialysis reduces levels of contrast media in plasma but does not reduce the incidence of contrast-medium-induced nephrotoxicity in the GFR range from 10 to 25 ml/min.

Clearance of iohexol, 51Cr-EDTA and endogenous creatinine for determination of glomerular filtration rate in pigs with reduced renal function: a comparison between different clearance techniques.

In order to simplify and/or improve determination of glomerular filtration rate (GFR) the clearances of iohexol, 51Cr-EDTA and endogenous creatinine were simultaneously determined with different techniques in 21 anesthetized landrace pigs. Their GFR had been reduced to about 1/3 or less of normal GFR. After an intravenous bolus of the GFR markers, their plasma concentration curves were followed for 6 hours with 16 plasma samples. A bladder catheter collected urine during six 60-min periods. The plasma clearance was calculated by dividing "dose of marker" with "area under the plasma concentration curve" (AUC) from the time of injection to infinity using a one- (Clprovisional) and a three-compartment (ClAUC-3comp) model. The renal clearance of iohexol and 51Cr-EDTA was calculated by dividing the amount of marker excreted in the urine in a period by AUC in the same period. The AUC was for iohexol and 51Cr-EDTA determined by integrating the total area in the period (Clren adv)-our reference method representing the "true" GFR and for creatinine determined by using the arithmetic mean of the plasma concentration of the marker at the start and at the end of the urine collection period (Clren simple). Renal clearance of creatinine was significantly lower than renal clearance of iohexol (p = 0.0019) and 51Cr-EDTA (p = 0.0001). There were no significant differences between the renal clearances (Clren adv) of iohexol and 51Cr-EDTA or between their plasma clearances (ClAUC-3comp). For iohexol the median overestimation of the "true" GFR with Clprovisional was higher when "early" plasma samples (30-120 min) were used (4.5 ml min-1 10 kg-1) than when late samples (180-360 min) were used (1.9 ml min-1 10 kg-1). Subtraction of the median extrarenal clearance (known from a study of nephrectomized pigs) from the plasma clearances (ClAUC-3comp) of iohexol and 51Cr-EDTA in pigs with reduced renal function decreased the median overestimation of the "true" GFR from 1.9 to 1.0 ml min-1 10 kg-1 with iohexol and from 1.7 to 0.9 ml min-1 10 kg-1 with 51Cr-EDTA. The plasma clearance technique may be improved in pigs with reduced GFR by (i) including a "late" plasma sample in three- and one-compartment models, which tends to increase the AUC; (ii) introducing a correction formula by normalizing the GFR values of the one-compartment model to those of the three-compartment model, thereby compensating for the rapid early changes in plasma concentration of marker after the bolus injection of the marker; or (iii) subtracting a median (or mean) extrarenal clearance of the marker in pigs from the plasma clearance [according to (i) or (ii)]. The plasma clearance one-compartment technique may be improved in pigs with various levels of GFR values by normalizing the plasma clearance values to the renal clearance values, thereby compensating for both the early changes in plasma concentration of marker and the extrarenal clearance of marker.

The effect of endovascular aortic stents placed across the renal arteries.

OBJECTIVES: To investigate renal artery patency and renal function after deployment of aortic stents covering the orifices of renal arteries. DESIGN: Prospective open animal study. SETTING: Department of Experimental Surgery at a university hospital. MATERIALS: Twenty-three pigs were used. METHODS: Ten pigs were observed for 1 h after graft-anchoring aortic stents, Gianturco (5) and Palmaz (5), were placed so that the stents covered the renal arterial orifices. In 13 pigs, Gianturco (6) and Palmaz (7) stents without grafts were placed over the renal arteries and left in situ for 7 days. Renal function and blood flow were measured by renograms, iohexol clearance and ultrasonic blood flow meter and patency was verified by angiograms. The kidneys were microscopically examined for signs of ischaemia and microemboli. RESULTS: One renal artery covered by a graft-anchoring Gianturco stent occluded. The remaining renal arteries remained patent without any significant decrease in renal blood flow after stent deployment. Normal renal function and histology was maintained. CONCLUSIONS: Aortic stents placed at the level of the renal arteries do not affect renal blood flow within 1 week in this experimental model. This may prove valuable in endovascular treatment of aortic aneurysms and in other procedures involving stents.

Clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and creatinine for determining the glomerular filtration rate in pigs with normal renal function: comparison of different clearance techniques.

RATIONALE AND OBJECTIVES: We wanted to improve determination of the glomerular filtration rate (GFR) with plasma clearance techniques because the alternative-renal clearance techniques-may involve inaccurate urine sampling or risk of urinary tract infection when bladder catheterization becomes necessary. Therefore, we compared the renal and plasma clearances of iohexol and chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), as well as endogenous creatinine clearance, in 19 normal pigs using different techniques. METHODS: After an intravenous bolus injection of the GFR markers, 16 plasma samples were used to plot the marker concentrations versus time for 4.5 hr. Urine was collected during nine 30-min periods. Plasma clearance was calculated by dividing the dose of marker with the area under the plasma concentration curve (AUC) from the time of injection to infinity using one-compartment (ClAUC-slope) and three-compartment (ClAUC-3comp) models. The renal clearance was calculated by dividing the amount of marker excreted in the urine in a period with the AUC in the same period. This AUC was determined by integrating the total area in the period (Clren adv)--our reference method representing the "true" GFR--or by using the arithmetic mean of the plasma concentrations of the marker at the beginning and end of the urine collection period (Clren simple). Creatinine clearance was determined according to Clren simple. RESULTS: Renal clearances of iohexol and 51Cr-EDTA were significantly higher than creatinine clearance (P = .0002). There was no significant difference between the renal clearances of iohexol and 51Cr-EDTA or between their plasma clearances. The two mathematical methods of calculating the renal clearance of iohexol were highly correlated (rs = .99), as were the two methods of calculating its plasma clearance (rs = .95). Because of the extrarenal clearance of the markers, the plasma clearance methods for iohexol and 51Cr-EDTA always overestimated the true GFR. ClAUC-3comp was the method closest to the true GFR. For iohexol, the median overestimation of the GFR was higher with ClAUC-slope when early plasma samples (30-120 min) after injection of the marker were used (5.5 ml.min-1.10 kg-1) than when late samples (180-270 min) were used (4.0 ml.min-1.10 kg-1). After subtracting the median extrarenal clearances of iohexol and 51Cr-EDTA (previously determined in nephrectomized pigs) from their plasma clearances (ClAUC-3comp), the median overestimation of the true GFR was reduced from 2.0 to 1.1 ml.min-1.10 kg-1 with iohexol and from 2.1 to 1.3 ml.min-1.10 kg-1 with 51Cr-EDTA. CONCLUSION: GFR determination with plasma clearance techniques can be improved in three- and one-compartment models by taking late plasma samples and by subtracting the extrarenal plasma clearance of the species. One-compartment models can be improved by determining a correction formula in the species for the early parts of the decay curve of the plasma concentration of the marker.

Iohexol clearance for GFR-determination in renal failure--single or multiple plasma sampling?

The present study examined the agreement between single and multiple sample plasma clearance of iohexol, a non-ionic contrast agent, in renal failure. Sixty-five patients with varying degree of renal insufficiency received 10 ml iohexol (300 mg I/ml) i.v. and plasma samples were collected four times during the following 3-24 h. Plasma-iodine concentrations were determined by X-ray fluorescence. Predicted creatinine clearance was used to choose one of the samples for determination of single sample clearance. A single plasma specimen collected at 4 h for GFR above 50 ml/min, at 7 h for GFR between 20 and 50 ml/min, and at 24 h for GFR below 20 ml/min gave values in good agreement with those based on a four sample slope clearance. No sign of nephrotoxicity was noted after administration of the contrast agent. It is concluded that single sample plasma clearance after single injection of iohexol gives a good estimate of GFR in renal failure and is advantageous in clinical practice.

Extrarenal plasma clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and inulin in anephric pigs.

RATIONALE AND OBJECTIVES: To improve the measurement of the glomerular filtration rate (GFR), we determined the extrarenal plasma clearance of the GFR markers iohexol, chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), and inulin using 11 anephric pigs. METHODS: After an intravenous (i.v.) bolus injection of the markers, the decay curves of their plasma concentrations were monitored for 29 hr by 16 plasma samples. The area under the curve (AUC; concentration of marker versus time) was calculated according to one- and three-compartment kinetics. The extrarenal clearance was calculated by dividing the dose of marker by the AUC. RESULTS: In the three-compartment model, the median of the extrarenal clearances of iohexol, 51Cr-EDTA, and inulin were 0.87 ml.min-1.10 kg-1 (range = 0.62-1.26 ml.min-1.10 kg-1), 0.79 ml.min-1.10 kg-1 (range = 0.61-1.04 ml.min-1.10 kg-1), and 0.83 ml.min-1.10 kg-1 (range = 0.65-1.17 ml.min-1.10 kg-1). The extrarenal clearance of 51Cr-EDTA was slightly lower than that of iohexol and inulin when measured with the three-compartment model (p = .015). There was no statistically significant difference between the two models of kinetics in calculating clearance of the same marker. CONCLUSION: Our results indicate that subtracting the median values of the extrarenal clearance of the markers from the total plasma clearance will provide GFR values closer to the "true" GFR. This technique might prove useful in GFR calculations in patients with a very low GFR (e.g., residual GFR in patients on dialysis).

Determination of the relative glomerular filtration rate of each kidney in man. Comparison between iohexol CT and 99mTc-DTPA scintigraphy.

Iohexol and 99mTc-DTPA were used in 43 patients to determine the relative glomerular filtration rate (GFR), i.e., the GFR of each kidney in percent of total GFR. The amount of any GFR marker accumulating in Bowman's space, tubuli and renal pelvis within a few minutes after i.v. injection, before any marker had left the kidney via the ureter, was defined as proportional to the GFR of that kidney. The renal accumulation of iohexol was determined by CT using 10 slices of 8-mm thickness 1 to 4 minutes after injection. The renal accumulation of 99mTc-DTPA was determined with a gamma camera within 2 minutes after injection. The correlation coefficient between the two methods was 0.98. Due to the higher radiation dose from CT than from 99mTc-DTPA injection, relative GFR determination with CT should be performed when there is also a diagnostic need to reveal morphology.

The use of iohexol clearance to determine GFR in patients with severe chronic renal failure--a comparison between different clearance techniques.

UNLABELLED: The nonionic low-osmolar contrast medium iohexol was used as marker of glomerular filtration rate (GFR) in 53 patients with stable renal function (group I: n = 32, group II: n = 21). All the patients had clearance values < or = 30 ml.min-1.1.73 m-2 body surface; 40 patients < 20 ml.min-1.1.73 m-2 body surface. Simultaneous determinations of renal clearance and plasma clearance, both as slope clearance and single sample clearance, were performed after intravenous injection of 10 ml iohexol 300 mg iodine/ml. In groups I and II plasma was sampled early (around 3 hours) and late (up to 24 hours) after the injection. In group I urine was collected during four 40-minute periods and in group II during one 3-hour period and in group II the residual urine was estimated by ultrasound. Plasma and urine iodine concentrations were analyzed with X-ray fluorescence technique (Reanalyzer PRX90, Provalid AB, Sweden). In group II S-creatinine and tubular function test were followed to detect any signs of nephrotoxicity. In 6 anuric patients (group III) 10 ml iohexol 300 mg I/ml was injected to assess its extrarenal clearance. In groups I and II the slope clearance correlated excellently with the single sample clearance (r = 0.99) when a late plasma sample was used in both techniques. In group II, where residual urine was estimated by ultrasound, renal clearance correlated better with slope clearance than in group I (r = 0.94 vs r = 0.89). There were no signs of nephrotoxicity in the parameters noted. In group III, extrarenal plasma clearance of iohexol did not exceed 2 ml.min-1.1.73 m-2. CONCLUSION: GFR < 20 ml/min can accurately and safely be determined as renal clearance or plasma clearance of iohexol after an intravenous dose of 10 ml 300 mg I/ml. Plasma clearance techniques, which have the practical clinical advantage of no urine sampling, do at low GFR require a late plasma sample taken, for instance, 24 hours after injection of iohexol, irrespective of whether slope technique or single sample technique or one-compartment or poly-compartment models are used.

CT of a parathyroid lipoadenoma. Case report.

A 54-year-old woman with primary hyperparathyroidism underwent parathyroid exploration following negative ultrasonography, CT and 99Tc-201Tl scintigraphy. A 2 x 1.5 x 1-cm large mass dorsal to the midportion of the left thyroid lobe was extirpated and a hyperfunctional lipoadenoma containing 70% or more of fatty tissue was verified microscopically. Retrospective evaluation of CT revealed a well demarcated lipomatous mass with a homogeneous density similar to that of subcutaneous fat corresponding to the surgical finding.