Effects of lysine infusion on the renal metabolism of aprotinin (Trasylol) in man

1992 ◽  
Vol 83 (3) ◽  
pp. 295-299 ◽  
Author(s):  
R. Rustom ◽  
P. Maltby ◽  
J. S. Grime ◽  
H. R. Stockdale ◽  
M. Critchley ◽  
...  

1. Aprotinin (Trasylol) is a cationic 6500 Da polypeptide that inhibits proteolytic enzymes, and when labelled with 99mTc it is a reproducible marker for the renal tubular turnover of small filtered proteins in man. Lysine potently inhibits tubular peptide uptake, and may thus depress the uptake and metabolism of aprotinin. This was investigated in 14 glomerulonephritic patients with normal renal function and variable proteinuria and in one healthy subject. 2. 99mTc-labelled aprotinin was given intravenously alone, and again 3 days later, immediately after the intravenous administration of 3–6 g of lysine, followed by an infusion over 1 h of 0.3–1.9 g of lysine/kg in individual patients. Activity over kidneys and in urine was measured over 24 h and chromatography was used to separate the undegraded peptide from free isotope. 3. At the low dosage of lysine (< 0.8 g/kg) given to six patients, kidney activity (representing tubular uptake) was unchanged, but early urine samples contained some undegraded aprotinin. Urinary excretion of free isotope, representing tubular metabolism, fell from 1.6 ± 0.2% of dose/h with no lysine to 0.9 ± 0.1% of dose/h in the 24 h after lysine, suggesting suppression of tubular aprotinin degradation. Corrected fractional degradation was calculated from the mean urinary excretion of free isotope over a given interval, determined by chromatography, divided by the mean cumulative kidney counts over this same interval, and this also fell after lysine from 0.06 ± 0.006 to 0.03 ± 0.006 h−1 (P<0.005) between 3.75 and 24 h. 4. By contrast, in nine subjects given more lysine (> 0.8 g/kg) tubular uptake fell and urine contained more undegraded aprotinin at all times. However, the corrected urinary excretion of free isotope (determined by chromatography) was unchanged and, paradoxically, fractional degradation rose from 0.06 + 0.01 to 0.10 ± 0.01% of dose/h (P<0.025) between 3.75 and 24 h. 5. Thus, lysine seemed to have a biphasic effect, inhibiting tubular peptide degradation at the low dosage, but depressing uptake into the tubular cell at the high dosage. This, in turn, might relieve intra cellular proteolytic enzymes from autoinhibition by aprotinin and result in a paradoxical restoration of tubular metabolism.

Blood ◽  
1966 ◽  
Vol 28 (5) ◽  
pp. 708-725 ◽  
Author(s):  
DAVID A. SEARS ◽  
PEARL R. ANDERSON ◽  
ARTHUR L. FOY ◽  
HAROLD L. WILLIAMS ◽  
WILLIAM H. CROSBY

Abstract Quantitative and qualitative studies of urinary iron excretion were performed in 12 patients with hemolytic disease and in one normal subject given an intravenous infusion of hemoglobin. In 9 patients with significant intravascular hemolysis, increased urinary excretion of nonhemoglobin iron was observed with amounts as high as 10.75 mg. pen 24 hours. In 7 of 8 patients in whom fractions of the urinary iron were studied, the majority of the iron was in the sediment (hemosiderin). Ferritin was demonstrated in the urine by immunologic and electrophoretic technics and accounted for a significant percentage of iron excreted. In several patients, day-night variations in hemolysis were associated with parallel fluctuations in iron excretion. The results were analyzed in relation to current concepts of glomerular clearance and renal tubular metabolism of hemoglobin. The significance to body iron balance of the massive "iron diuresis" occurring in some of these patients was discussed.


1993 ◽  
Vol 85 (6) ◽  
pp. 733-736 ◽  
Author(s):  
R. Rustom ◽  
J. S. Grime ◽  
P. Maltby ◽  
H. R. Stockdale ◽  
M. J. Jackson ◽  
...  

1. The new method developed to measure renal tubular degradation of small filtered proteins in patients with normal renal function, using radio-labelled aprotinin (Trasylol) (R. Rustom, J. S. Grime, P. Maltby, H. R. Stockdale, M. Critchley, J. M. Bone. Clin Sci 1992; 83, 289–94), was evaluated in patients with chronic renal failure. 2. Aprotinin was labelled with either 99mTc (40 MBq) or 131I (0.1 MBq), and injected intravenously in nine patients, with different renal pathologies. 51Cr-EDTA clearance (corrected for height and weight) was 40 + 5.4 (range 11.2-81) ml min−1 1.73 m−2. Activity in plasma and urine was measured over 24–48 h, and chromatography on Sephadex-G-25-M was used to separate labelled aprotinin from free 99mTcO4− or 131I−. Renal uptake was measured for 99mTc-labelled aprotinin only. 3. The volume of distribution was 20.2 + 2.3 litres. Chromatography showed all plasma activity as undegraded aprotinin, and urine activity only as the free labels (99mTcO4− or 131I−). 4. As in patients with normal renal function, activity in the kidney appeared promptly, with 5.7 + 2.5% of the dose detected even at 5 min. Activity rose rapidly to 9.4 + 1.6% of dose after 1.5 h, then more slowly to 15.0 + 0.5% of dose at 4.5 h, and even more slowly thereafter, reaching 24.1 + 2.8% of dose at 24 h. Extra-renal uptake was again insignificant, and both 99mTcO4− and 131I− appeared promptly in the urine, with similar and uniform rates of excretion over 24 h. 5. Both tubular uptake at 24 h and the rate of tubular metabolism over 24 h were lower than in the patients with normal renal function studied previously, but only the rate of tubular metabolism was directly related to the glomerular filtration rate (r = 0.75, P <0.02). 6. Correction for the reduced glomerular filtration rate yielded values for both tubular uptake (0.67 + 0.14 versus 0.32 + 0.03% of dose/ml of glomerular filtration rate, P <0.005), and tubular metabolism (0.033 + 0.07 versus 0.015 + 0.001% of dose h−1 ml−1 of glomerular filtration rate, P <0.005) that were higher by comparison with those for patients with normal renal function studied previously. 7. Fractional renal degradation of 99mTc-aprotinin (in h−1), derived from the mean rate of urinary excretion of the free isotope over a given interval, divided by the mean cumulative kidney uptake over the same interval, also fell steeply early, and then more slowly to 0.07 + 0.01 h−1 at 14.25 h (between 4.5 and 24 h). 8. It is concluded that the method described previously is also suitable in patients with chronic renal failure, allowing further research into renal disease progression.


1989 ◽  
Vol 82 (3) ◽  
pp. 139-141 ◽  
Author(s):  
M Labib ◽  
M Abdel-Kader ◽  
L Ranganath ◽  
S Martin ◽  
V Marks

Despite the well known effects of chronic alcohol abuse on the gastrointestinal, cardiovascular, nervous and endocrine systems, little information is available on its effect on renal function. To assess renal function we measured urinary excretion of albumin, α1 microglobulin and retinol binding protein in 30 chronic alcoholic patients. Our data shows that 40% of chronic alcoholic patients have impaired renal tubular function.


1978 ◽  
Vol 76 (3) ◽  
pp. 411-415 ◽  
Author(s):  
J. J. LEGROS

The mean rate of excretion of neurophysins in the urine of 16 patients with kidney disease but without tubular dysfunction was 0·48 ± 0·14 (s.e.m.) ng/min, whereas the rate in 16 patients with tubular dysfunction was 3·64 ± 1·56 ng/min (significantly different; 2P < 0·01). In the whole group of 32 patients there was a relationship (r = 0·57) between the rate of excretion of neurophysins in the urine and the clearance of lysozyme. The increased rate of urinary excretion of neurophysins observed in some patients with kidney disease therefore appears to be related to a disorder of renal tubular function. It is shown that the raised levels of neurophysins observed in the serum of some patients with kidney disease are not attributable to a decrease in the urinary clearance of neurophysins.


1981 ◽  
Vol 46 (3) ◽  
pp. 487-493 ◽  
Author(s):  
H. W. Symonds ◽  
Denise L. Mather ◽  
M. J. Vagg

1. The excretion of 75Se and stable Se in bile and urine was measured in four steers during 6 h after intravenous injections of 75Se as either selenite or selenate containing either 5 or 5000 μg carrier Se.2. When 5000 μg Se were given, the rate of urinary excretion and plasma clearance of 75Se was similar for both salts. Approximately 23% was excreted in urine and plasma clearance was triexponential, the mean half-life (t½) of the successive components, α, β and γ, being 2·3, 15·2 and 465 min respectively. The amount of 75Se excreted in bile was small; 1·94% of the 75SeO32− and 0·86% of the 75SeO42− dose.3. When 5 μg Se were given the plasma clearance of 75Se was initially biexponential but the entry of 75Se-labelled protein from the liver caused an increase in plasma radioactivity after 30–40 min. The effect was most marked after 5 μg 75SeO32− when plasma 75Se radioactivity returned to 60% of the activity present at 2 min. Values for t½ of the two components of clearance for 75SeO32− and 75SeO42− were respectively α 2·6 and 2·5 min, and β 15·9 and 36·6 min. Similar amounts of 75Se appeared in bile (0·2% of the dose) after injections of either salt but much less 75Se was excreted in urine after 75SeO32− (6%) than after 75SeO42− (37%).4. At low dosage rates (5 μg) Se is more readily incorporated into tissues from SeO32− than from SeO42−.


1987 ◽  
Vol 73 (5) ◽  
pp. 487-491 ◽  
Author(s):  
Eugenia Damiani ◽  
Maria Teresa Cattaneo ◽  
Cristina Sessa ◽  
Emanuele Zucca ◽  
Franco Cavalli ◽  
...  

Urinary excretion of N-acetyl-beta-glucosaminidase (NAG) is an early marker of nephrotoxicity. NAG activity was assayed by the fluorimetric method of Leaback and Walker in 17 patients treated (22 courses) with carboplatin (CBDCA, 220–550 mg/m2) before infusion and 24, 48, 72 and 96 h after. Increased excretion of NAG, a sensitive index of renal tubular damage, was observed following 10 of the 22 courses. A transient increase in plasma creatinine and/or abnormal proteinuria was observed in 6 cases. Impaired renal function prior to therapv seems to be a predisposing factor to the nephrotoxicity.


2001 ◽  
Vol 40 (04) ◽  
pp. 107-110 ◽  
Author(s):  
B. Roßmüller ◽  
S. Alalp ◽  
S. Fischer ◽  
S. Dresel ◽  
K. Hahn ◽  
...  

SummaryFor assessment of differential renal function (PF) by means of static renal scintigraphy with Tc-99m-dimer-captosuccinic acid (DMSA) the calculation of the geometric mean of counts from the anterior and posterior view is recommended. Aim of this retrospective study was to find out, if the anterior view is necessary to receive an accurate differential renal function by calculating the geometric mean compared to calculating PF using the counts of the posterior view only. Methods: 164 DMSA-scans of 151 children (86 f, 65 m) aged 16 d to 16 a (4.7 ± 3.9 a) were reviewed. The scans were performed using a dual head gamma camera (Picker Prism 2000 XP, low energy ultra high resolution collimator, matrix 256 x 256,300 kcts/view, Zoom: 1.6-2.0). Background corrected values from both kidneys anterior and posterior were obtained. Using region of interest technique PF was calculated using the counts of the dorsal view and compared with the calculated geometric mean [SQR(Ctsdors x Ctsventr]. Results: The differential function of the right kidney was significantly less when compared to the calculation of the geometric mean (p<0.01). The mean difference between the PFgeom and the PFdors was 1.5 ± 1.4%. A difference > 5% (5.0-9.5%) was obtained in only 6/164 scans (3.7%). Three of 6 patients presented with an underestimated PFdors due to dystopic kidneys on the left side in 2 patients and on the right side in one patient. The other 3 patients with a difference >5% did not show any renal abnormality. Conclusion: The calculation of the PF from the posterior view only will give an underestimated value of the right kidney compared to the calculation of the geometric mean. This effect is not relevant for the calculation of the differntial renal function in orthotopic kidneys, so that in these cases the anterior view is not necesssary. However, geometric mean calculation to obtain reliable values for differential renal function should be applied in cases with an obvious anatomical abnormality.


1966 ◽  
Vol 53 (2) ◽  
pp. 177-188 ◽  
Author(s):  
P. Lund-Johansen ◽  
T. Thorsen ◽  
K. F. Støa

ABSTRACT A comparison has been made between (A), a relatively simple method for the measurement of aldosterone secretion rate, based on paper chromatography and direct densitometry of the aldosterone spot and (B) a more elaborate isotope derivative method. The mean secretion rate in 9 normal subjects was 112 ± 26 μg per 24 hours (method A) and 135 ± 35 μg per 24 hours (method B). The »secretion rate« in one adrenalectomized subject after the intravenous injection of 250 μg of aldosterone was 230 μg per 24 hours (method A) and 294 μg per 24 hours (method B). There was no significant difference in the mean values, and correlation between the two methods was good (r = 0.80). It is concluded that the densitometric method is suitable for clinical purposes as well as research, being more rapid and less expensive than the isotope derivative method. Method A also measures the urinary excretion of the aldosterone 3-oxo-conjugate, which is of interest in many pathological conditions. The densitometric method is obviously the less sensitive and a prerequisite for its use is an aldosterone secretion of 20—30 μg per 24 hours. Lower values are, however, rare in adults.


1974 ◽  
Vol 75 (4) ◽  
pp. 647-652 ◽  
Author(s):  
G. Rannevik ◽  
J. Thorell

ABSTRACT Eight amenorrhoeic women were given 100 μg synthetic LRH (Hoechst) iv and im, respectively, at an interval of 2 weeks. Four of the women received the iv injection first and four the im injection. The urinary excretion of oestrogens and pregnanediol was low and unaltered throughout the test weeks. The effects of LRH were compared by serial measurements of the plasma LH and FSH during 8 h. The initial response of LH for up to 25 min and that of FSH for up to 60 min were equal whether LRH was given iv or im. The difference appeared later. Four hours after the injection the mean increase of LH to iv injection was 0.5 ng/ml (N. S.), while that to im injection was 1.9 ng/ml (P < 0.01). The corresponding values for FSH were 1.3 (P < 0.05) and 3.2 (P < 0.001). The effect of LRH administration im was thus found to be larger and more prolonged.


1974 ◽  
Vol 75 (1) ◽  
pp. 50-63 ◽  
Author(s):  
Kristian F. Hanssen

ABSTRACT Twenty newly diagnosed, but as yet untreated patients of both sexes with classical juvenile diabetes were investigated by determining the mean plasma immunoreactive growth hormone (IRHGH) and urinary IRHGH for a 24 hour period before and during initial insulin treatment. The plasma IRHGH was significantly higher (0.05 > P > 0.01) before than during initial insulin treatment. During initial insulin treatment, the mean plasma IRHGH was significantly higher (0.01 > P > 0.001) than in a control group. The urinary IRHGH was significantly higher (0.01 > P > 0.001) before than during insulin treatment. The increased urinary IRHGH observed before insulin treatment is thought to be partly due to a defective renal tubular reabsorption of growth hormone. No significant correlation was found between the mean blood sugar and plasma or urinary IRHGH either before or during insulin treatment.


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