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Continuous Infusion Urography in Unilateral Hydronephrosis
Vol. 114, September Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1975 by The Williams & Wilkins Co.
CONTINUOUS INFUSION UROGRAPHY IN UNILATERAL HYDRONEPHROSIS KURT G. NABER, HORST KUNI
AND
PAUL 0. MADSEN*
From the Departments of Urology and Nuclear Medicine, University of Marburg, Germany, and the Section of Urology, Veterans Administration Hospital and the Department of Surgery, University of Wisconsin School of Medicine, A1adison, Wisconsin
ABSTRACT
In cases of unilateral
the urine concentration of contrast on the remaining renal function, the rate of turnover in the obstructed renal and the function of the contralateral Contrast medium for a single injection or a short infusion time is excreted by the normal contralateral kidney, without allowing high enough plasma levels long enough for sufficient urine concentrations in the hydronephrotic kidney. This excretion rate can be compensated for continuous infusion urography for several hours with large doses of contrast medium (up to 1,250 ml. 30 per cent This method was theoretically computerized, tested in animal experiments and clinically used in 11 patients. It can improve the diagnostic possibilities of excretory urography, especially in cases of unilateral obstruction, and can minimize the need for retrograde pyelography with its known complications. for example diatrizoate,
Drip infusim1 urography with high dosage contrast medium and delayed pictures has improved the diagnostic possibilities, particularly in cases of renal impairment and/or obstructed urine flow. Even in patients with complete post-renal anuria the upper urinary tract sometimes can be visualized sufficiently. 1-• This phenomenon can be explained by the continuation of some renal function, even following total ureteral obstruction. Urine that is produced enters the renal pelvis and is reabsorbed by pyelolymphatic and pyelovenous pathways. 5 • 6 The concentration of a clearance substance in the renal pelvis, for example of contrast medium, depends ' on the remaining renal function, the rate of turnover in the renal pelvis, the volume of the renal pelvis and the plasma concentration. On the other hand, the plasma level depends on the dose administered and mainly on the function of the contralateral kidney. Since the urine concentration of purely glomerularly filtered substances-and this applies to diatrizoate and iothalamate, both substances used for excretory urography (IVP) 7 • 8 -is proportional to the plasma concentration, a high plasma concentration would be most effective. However, this is limited by adverse reactions like nausea and vomiting. Therefore, we investigated whether the results could also be improved by continuous infusion of a contrast medium. With this procedure the Accepted for publication December 20, 1974. Read at annual meeting of American Urological Association, St. Louis, Missouri, May 19-23, 1974. * for reprints: Veterans Administration HosOverlook Terrace, IVIadison) Vh.sconsin 53705.
peak plasma concentration does not have to be increased even when a high total dose is administered. In case of obstructed urine flow the rate of turnover in the renal becomes an important additional factor. The actual urine concentration in the renal pelvis that is reached (as a fraction of the theoretically possible final concentration at a certain plasma level) depends on the duration of this plasma concentration. At a turnover rate of 1 per cent or 0.1 per cent of the total volume per minute, for example 50 per cent of the final concentration at a certain plasma concentration will be reached at 70 and 700 minutes, respectively, and 95 per cent at 5 and 50 hours, respectively. In cases of unilateral hydronephrosis the contrast medium is rapidly excreted by the contralateral kidney and a continuous infusion is necessary to maintain a sufficient plasma concentration for a certain length of time. EXPERIMENTAL STUDIES
In a preliminary experimental trial in 3 dogs we performed IVP during a period of 26 days after ureteral occlusion on 1 side. After 14 days the site of obstruction could not be visualized a dose of 100 ml. 30 per cent diatrizoate, a dose corresponding to a usual drip infusion urngraphy. However, 24 days after ureteral obstruction an x-ray taken 7 hours after infusion of 750 ml. contrast medium during a period of 4 hours showed the of ligation of the upper ureter (fig. 1). The volume of the renal pelvis measured at autopsy was 220 ml. In a fourth dog with unilateral ligation of the -;,Jreter for 4 n1onths v-1e even found a 1;veak
338
NABER, KUNI AND MADSEN
positive outlining of the hydronephrotic sac 5 hours after infusion of 1,250 ml. contrast medium during a period of 6 hours. In previous experimental studies in dogs we have determined the volume and the turnover of urine in the renal pelvis in acute and chronic hydronephrosis. •. 9 These parameters were determined by the distribution space and disappearance rate of ••mTc pertechnetate injected into the renal pelvis. From these data the urine flow was calculated. The glomerular filtration rate (GFR) was simultaneously determined by the clearance of 1251-iothalamate being continuously infused. It was remarkable that despite largely differing turnover rates, the urine flows in acute and chronic hydronephrosis were found to be in the same range, between 0.05 to 0.1 ml. per minute. THEORETICAL CONSIDERATION
Using these and other experimental data 10- 12 we calculated on an analogue computer (Telefunken RAT 700) the course of urine concentration in the obstructed renal pelvis in acute and chronic hydronephrosis after single injection with and without subsequent continuous infusion for a certain length of time, and investigated the dependence on the rate of turnover in the occluded renal pelvis and on the function of the contralateral kidney. For these calculations we used a 2-compartment model for the extracellular space with S, representing the rapidly miscible and 8 2 , which is twice as large as 8 1 , representing the slowly miscible compartment (fig. 2). The renal pelvis of the occluded and freely draining kidney is represented by S 3 and S 4, respectively. The intercompartmental clearance is represented by p,. 2 and p,. • and p 1. 4 indicate the GFRs of the occluded and normal draining
kidney, respectively. The Ps., is the urine flow of the occluded kidney, which is totally reabsorbed, and p4.0 is the flow of the freely draining kidney. Figure 3 shows the conditions in acute hydronephrosis. After a single intravenous injection of a given dose there is the typical biphasic exponential decrease of the plasma concentration (P), if a 2-compartment model is used, and the corresponding concentration course in the slowly miscible extracellular compartment (E). The urine of the freely draining kidney (N) has its maximum concentration at approximately 5 minutes after injection, followed by a rapid decrease. The urine concentration in the occluded renal pelvis does not reach maximum until 80 minutes after injection but is exceeding the maximum concentration of the normal kidney. It can be concluded that the usual dose sufficient for a normally functioning kidney can also be used in acute hydronephrosis if delayed x-ray pictures are taken. Figure 4 shows the conditions in an example of chronic hydronephrosis. The upper part shows the plasma concentration after a single injection of a given dose and after additional infusion of 2 doses per hour. The lower part shows the corresponding urine concentrations in the occluded renal pelvis with a GFR of only 0.32 ml. per minute but at variable urine flows. Assuming a flow of 0.05 ml. per minute 2 ½ hours after the infusion was terminated the maximum urine concentration is reached. It can be demonstrated that by a 4-hour infusion the peak urine concentration is increased approximately 8 times as compared to a single dose injection in this example. In addition, if the volume increase of the occluded renal pelvis as compared to the freely draining kidney is also taken into account, a 2.4 times higher density of
Fm. 1. Urogram of unilateral hydronephrosis in dog following ligation of upper ureter 24 days earlier. Seven hours after infusion of 750 ml. 30 per cent diatrizoate for 4 hours, site of obstruction could be visualized.
CONTINUOUS INFUSION UROGRAPHY IN UNILATERAL HYDRONEPHROSIS
339
and slowly (S 2 ) miscible kidneys. Pm·n represents
Fm. 2. Four-compartment compartments of extracellular flovvs between various .-,,m,,m·trr,Pn
,ll.cute. Hydronei:ihrosis ( 3 h)
Ext race I I ular Compartments S1 1783 ml S2 3566 m!
I ntercomparlmenlal Clearance 170 ml/min
2
3
h
Renai Peives:
S3 S4
L,
ml.
3 m!
GFR. ?1,3
V1A
5.7
ml/min
~0.0 mi/min
Urine Flows:
's'3,1
'?4,0
0.06 ml/ min 3.00 ml/ min
FIG. 3. Relative concentrations of diatrizoate calculated by analogue computer in acute hydronephrosis after single intravenous injection in plasma (P), in slowly miscible compartment of extracellular space (E), in renal pe!ves of freely draining (N) and totally obstructed (H) kidneys.
' contrast medium can be expected at the same 1 urine concentration (a spheric shape of the renal pelvis is assumed). a density of the occluded renal pelvis 2 112 hours after termination of the infusion corresponds to the density of a normally functioning 25 minutes after injection of a single dose. In most cases this should be sufficient for diagnostic purposes. The dependence on the urine turnover rate shows that under otherwise identical conditions the increase of urine turnover is followed an earlier but lower maximum urine concentration. Note the low urine concentration after a line). The influence of che fonction of the contralateral is sh 0~1i/n in l[J· 5.
of a given dose only a 2-hour infusion of 1 dose per hour was assumed. If no contralateral kidney is present a concentration 8 times higher in the occluded renal can be reached as compared to the situation when a contralateral kidney with a GFR of 60 ml. per minute is present. The dotted line shows the plasma and urine concentrations after a single n,,Pr,,rn,n of 1 dose of contrast medium with a GFR of the contralateral kidney of 60 ml. per minute. CLINICAL APPLICATION
340
NABER, KUNI AND MADSEN
Chron. Hydronephrosis ( 6 d)
10
Dog# 51 Flow 93,1 (ml/min)
0.5
0.025
1.6
0.05
Extracellular Compartments 1783 ml 51 3566 ml 52 lntercompartmental Clearance 170 ml/min lj> 1,2 Renal Pelves:
53 54
0.8
0.1
2
3
4
0.2 0.025 0.2
6
8
h
39 ml 3 ml
GFR:
~1.3 ?1.4
0.32 ml/min 60.00 ml/min
Urine Flows:
'? 3,1 ?4,0
variable 1.9 ml/min
Fm. 4. Relative concentrations of diatrizoate in plasma and urine calculated by analogue computer in example of chronic hydronephrosis (ureter ligation 6 days before) after single intravenous injection of given dose of contrast medium with (heavy lines) and without (thin lines) subsequent infusion of 2 doses per hour for 4 hours. Urine turnover in obstructed renal pelvis varied from 0.025 to 0.2 ml. per minute, resulting in earlier but lower urine peak concentration at high turnover rates. GFR
'? 1.4
(ml/min)
0
15 30 60 1.6
Chron. Hydronephrosis ( 6 d) Dog# 51 Extracellular Compartments 1783 ml 51 3566 ml 52 lntercompartmental Clearance 170 ml/min ' lj> 1,2 Renal Pelves:
Urine(H)
53 54
0
39 ml 3 ml
GFR:
0.8
~1.3 15
?1,4
0 32 ml/min variable
Urine Flows:
30 60 8
'? 3,1 !' 4,0
0.05 ml/min 1.9 ml/min
Fm. 5. Same example of chronic hydronephrosis as in figure 4 but with infusion of only 1 dose per hour for 2 hours assumed. Under otherwise unchanged conditions GFR of contralateral kidney varied from O to 60 ml. per minute, resulting in lower plasma and urine concentrations in obstructed renal pelvis. Dotted line shows plasma and urine concentrations after single injection of 1 dose with GFR of contralateral kidney of 60 ml. per minute.
infusion urography. Initially, 250 ml. 30 per cent diatrizoate was injected and this was followed by a constant infusion during a period of 2 to 4 hours of 250 ml. contrast medium per hour. Only delayed x-ray pictures were taken. Positive urograms could be obtained in 10 patients 5 to 24 hours after the beginning of the infusion (see table). In 1 patient (P. W.) there was a non-functioning kidney, also proved by scintillation camera study. Only in 2 patients (W. C. and 0. H.) was there a transient rise in serum creatinine and this returned to normal the following day (see table). In 1 patient (G. E.) the infusion had to be discontinued after 3 hours because of vomiting.
CASE REPORTS
Case 1. F. E., a 71-year-old man, underwent usual drip infusion urography but the site of obstruction could not be demonstrated (fig. 6, A). After intravenous injection of 250 ml. 30 per cent diatrizoate followed by continuous infusion for 4 hours, a total of 1,000 ml., the site of obstruction in the right upper ureter could be seen (fig. 6, B). A retrograde pyelogram confirmed this (fig. 6, C) and a uric acid stone was removed. Case 2. B. M., a 55-year-old woman, had a ureterovaginal fistula 5 months following abdominal total hysterectomy. The distal ureter could not be visualized sufficiently by usual drip infusion
CONTINUOUS INFUSION UROGRAPHY IN UNILATERAL HYDRONEPHROSIS
urography with 250 ml. 30 per cent diatrizoate (fig. 7, A). However, after infusion of 750 ml. contrast medium for 3 hours the site of obstruction could be localized in the perivesical area (fig. 7, B). DISCUSSION
The new tri-iodinated contrast media used in urography have a low toxicity 2 • 13- 15 and make the intravenous administration of large amounts ble. This fact could be confirmed in our series of 11 patients who received a mean of 1,000 ml. 30 per cent diatrizoate (a mixture of sodium and Continuous infusion urography with 30 per cent diatrizoate in 11 patients with unilateral obstniction
Pt.
Cause of Obstruction
DG
Bladder Ca Calculus Prostatic Ca Calculus Bladder Ca Prostatic Ca Bladder Ca Calculus Calculus Stenosis of ureteropelvic junction Ureterovaginal fistula
FE WC
GE PW SW
PF OH
TH WW
BM
Con- DuraPosi- Serum Creatinine trast tion tive Meof Uro- Before After dium Infu- gram Used sion (hrs.) Infusion Infusion (mg.%) (mg.%) (ml.) (hrs.) 1.000 1,250 1,250 1,000 1,250 1,000 1,000 1,000 750 750
4.0 4.5 4.5 3.0 4.5 3.0 3.0
750
22 16 16 12 -
3.0
24 12 12
2.0 2.0
6 12
3.0
5
1.3
1.4
-
-
1.2 (2.2) 1.3 1.1 1.6 1.6 1.2 1.0 1.1 2.2 (3.0) 2.1 1.4 1.6 1.1
I
1.1
1.1
meglumine-diatrizoate in the rate of 40 to 18 and containing 168 mg. per ml. iodine). Two transient rises of 1.0 and 0.8 mg. per cent in serum creatinine and 2 decreases of 0.5 and 0.4 mg. per cent were observed. Since drip infusion urography is in routine clinical use the frequency of retrograde pyelography has been reduced already. The possible complications of N>h,"n·q pyelography in addition to its inconvenience and cost to the patient the search for methods that might be able to reduce the need for this further. The results, the theoretical considerations and the clinical have demonstrated that continuous infusion the accuracy of IVP in unilateral obstructive uropathy. Since method is only indicated when the diagnostic results of usual drip infusion urography are not sufficient and further x-ray examinations, that is retrograde pyelography, should be considered, the 2 or 3 additional x-ray pictures needed for continuous infusion do not represent significant additional radiation exposure. After the infusion of contrast medium has been discontinued the first x-ray picture should be taken within 2 to 4 hours, the second and third within 6 to 8 and 12 to 16 hours, respectively, depending on the function of the contralateral kidney and the urine turnover in case of complete or incomplete hydronephrosis. Because of the gradual urine concentration change in the obstructed renal pelvis and ureter, a time for x-ray exposure can be chosen within a few hours
F1G. 6. Case 1. A, usual drip infusion urography (250 ml. 30 per cent d.iatrizoate) 4 hours following infusion does not demonstrate obstruction. B, continuous infusion urography. that is rapid infusion of 250 ml. 30 cent diatrizoate followed by infusion of 250 ml. per hour for 4 hours, 17 hours following infusion demonstrates (arrow). C, retrograde urography.
342
NABER, KUNI AND MADSEN
antimicrobial agents that are rapidly cleared from the bloodstream. REFERENCES
FIG. 7. Case 2. A, usual drip infusion urography with 250 ml. 30 per cent diatrizoate does not demonstrate obstruction. B, continuous infusion urography with 750 ml. 30 per cent diatrizoate for 3 hours demonstrates obstruction (arrow). around the expected peak concentration without essential loss of quality. Combining the principle of this technique with usual drip infusion urography we occasionally use a modified method. If the conventional urogram with x-ray pictures taken at 15, 30 and 60 minutes post-injection shows a unilateral hydronephrosis, but it becomes unlikely that the point of obstruction will be clarified on further delayed pictures, we inject an additional 250 ml. 30 per cent diatrizoate followed by continuous infusion for 1 or 2 hours at an infusion rate of 250 ml. per hour with 3 x-ray pictures taken in the usual manner (2 to 4 hours, 6 to 8 hours and 12 to 16 hours). The costs for the additional amount of contrast medium, the time involved and the only minimal side effects should make up for the expenses of retrograde pyelography with its known morbidity. In case of a so-called non-functioning kidney in the usual urogram a renogram or camera scintiscan should be performed first. Continuous infusion urography may be tried only if some function can be demonstrated but otherwise no positive result can be expected. This principle outlined in the example of a diagnostic procedure may also be of importance for therapeutic considerations, for example in the treatment of infection in an obstructed kidney with
1. Berdon, W. E., Levitt, S. B., Baker, D. H., Becker, J. A. and Uson, A. C.: Hydronephrosis in infants and children-value of high dosage excretory urography in predicting renal salvageability. Amer. J. Roentgen., 109: 380, 1970. 2. Ensor, R. D., Anderson, E. E. and Robinson, R. R.: Drip infusion urography in patients with renal disease. J. Urol., 103: 267, 1970. 3. Schwartz, W. B., Hurwit, A. and Ettinger, A.: Intravenous urography in the patient with renal insufficiency. New Engl. J. Med., 269: 277, 1963. 4. Voegeli, E. and Fuchs, W. A.: Die Urographie bei Niereninsuffizienz. Act. Urol., 1: 101, 1970. 5. Naber, K. G. and Madsen, P. 0.: Der Resorptionsmodus von Staffen verschiedener Molekulgrosse aus dem total verschlossenen Nierenbecken. Experimentelle Studie am Hund. Urol. Int., 28: 256, 1973. 6. Naber, K. G. and Madsen, P. 0.: Renal function during acute total ureteral occlusion and the role of tne lymphatics: an experimental study in dogs. J. Urol., 109: 330, 1973. 7. Schlungbaum, W.: Distribution, excretion and absorption of renal I-131-labelled roentgen contrast medium. Fortschr. Roentgenstr., 96: 795, 1962. 8. Sigman, E. M., Elwood, C., Reagan, M. E., Morris, A. M. and Catanzaro, A.: The renal clearance of I1' 1 labelled sodium iothalamate in man. Invest. Urol., 2: 432, 1965. 9. Naber, K. G. and Madsen, P. 0.: Renal function in chronic hydronephrosis with and without infection and the role of the lymphatics. An experimental study in dogs. Urol. Res., 2: 1, 1974. 10. Sapirstein, L. A., Herrold, M. R., Janakis, M. and Ogden, E.: Validity of values for glomerular filtration rate and extra-cellular fluid obtained from plasma concentration-time decay curves after single injections of mannitol in the dog. Amer. J. Physiol., 171: 487, 1952. 11. Streicher, H-J., Kuni, H., Graul, E. H., Domarus, H., von and Graf zu Solms-Laubach, E. L.: Nieren- und Leberuntersuchungen nach venoser renoportaler Anastomose beim Hund. Bruns Beitr. Clin. Chir., 216: 659, 1968. 12. Kuni, H. and Graul, E. H.: Method of clearance determinations with 51 Cr-EDTA during decreasing blood concentrations. Atompraxis, 13: 375, 1967. 13. Baltzer, G., Kuni, H., Dombrowski, H., Kothe, E., Dolle, W. and Graul, E. H.: Investigations on renal function during and after intravenous administration of contrast media. Urol. Nephrol., 1: 129, 1969. 14. Bahlmann, J. and Gollnisch, H. J.: Nierenfunktion nach Infusionspyelographie. Klin. Wochenschr., 51: 275, 1973. 15. Gup, A. K., Fischman, J. L., Aldridge, G. and Schlegel, J. U.: The effect of drip infusion pyelography on renal function. Amer. J. Roentgen., 98: 102, 1966.
THE JOURNAL OF UROLOGY
Copyright© 1975 by The Williams & Wilkins Co.
CONTINUOUS INFUSION UROGRAPHY IN UNILATERAL HYDRONEPHROSIS KURT G. NABER, HORST KUNI
AND
PAUL 0. MADSEN*
From the Departments of Urology and Nuclear Medicine, University of Marburg, Germany, and the Section of Urology, Veterans Administration Hospital and the Department of Surgery, University of Wisconsin School of Medicine, A1adison, Wisconsin
ABSTRACT
In cases of unilateral
the urine concentration of contrast on the remaining renal function, the rate of turnover in the obstructed renal and the function of the contralateral Contrast medium for a single injection or a short infusion time is excreted by the normal contralateral kidney, without allowing high enough plasma levels long enough for sufficient urine concentrations in the hydronephrotic kidney. This excretion rate can be compensated for continuous infusion urography for several hours with large doses of contrast medium (up to 1,250 ml. 30 per cent This method was theoretically computerized, tested in animal experiments and clinically used in 11 patients. It can improve the diagnostic possibilities of excretory urography, especially in cases of unilateral obstruction, and can minimize the need for retrograde pyelography with its known complications. for example diatrizoate,
Drip infusim1 urography with high dosage contrast medium and delayed pictures has improved the diagnostic possibilities, particularly in cases of renal impairment and/or obstructed urine flow. Even in patients with complete post-renal anuria the upper urinary tract sometimes can be visualized sufficiently. 1-• This phenomenon can be explained by the continuation of some renal function, even following total ureteral obstruction. Urine that is produced enters the renal pelvis and is reabsorbed by pyelolymphatic and pyelovenous pathways. 5 • 6 The concentration of a clearance substance in the renal pelvis, for example of contrast medium, depends ' on the remaining renal function, the rate of turnover in the renal pelvis, the volume of the renal pelvis and the plasma concentration. On the other hand, the plasma level depends on the dose administered and mainly on the function of the contralateral kidney. Since the urine concentration of purely glomerularly filtered substances-and this applies to diatrizoate and iothalamate, both substances used for excretory urography (IVP) 7 • 8 -is proportional to the plasma concentration, a high plasma concentration would be most effective. However, this is limited by adverse reactions like nausea and vomiting. Therefore, we investigated whether the results could also be improved by continuous infusion of a contrast medium. With this procedure the Accepted for publication December 20, 1974. Read at annual meeting of American Urological Association, St. Louis, Missouri, May 19-23, 1974. * for reprints: Veterans Administration HosOverlook Terrace, IVIadison) Vh.sconsin 53705.
peak plasma concentration does not have to be increased even when a high total dose is administered. In case of obstructed urine flow the rate of turnover in the renal becomes an important additional factor. The actual urine concentration in the renal pelvis that is reached (as a fraction of the theoretically possible final concentration at a certain plasma level) depends on the duration of this plasma concentration. At a turnover rate of 1 per cent or 0.1 per cent of the total volume per minute, for example 50 per cent of the final concentration at a certain plasma concentration will be reached at 70 and 700 minutes, respectively, and 95 per cent at 5 and 50 hours, respectively. In cases of unilateral hydronephrosis the contrast medium is rapidly excreted by the contralateral kidney and a continuous infusion is necessary to maintain a sufficient plasma concentration for a certain length of time. EXPERIMENTAL STUDIES
In a preliminary experimental trial in 3 dogs we performed IVP during a period of 26 days after ureteral occlusion on 1 side. After 14 days the site of obstruction could not be visualized a dose of 100 ml. 30 per cent diatrizoate, a dose corresponding to a usual drip infusion urngraphy. However, 24 days after ureteral obstruction an x-ray taken 7 hours after infusion of 750 ml. contrast medium during a period of 4 hours showed the of ligation of the upper ureter (fig. 1). The volume of the renal pelvis measured at autopsy was 220 ml. In a fourth dog with unilateral ligation of the -;,Jreter for 4 n1onths v-1e even found a 1;veak
338
NABER, KUNI AND MADSEN
positive outlining of the hydronephrotic sac 5 hours after infusion of 1,250 ml. contrast medium during a period of 6 hours. In previous experimental studies in dogs we have determined the volume and the turnover of urine in the renal pelvis in acute and chronic hydronephrosis. •. 9 These parameters were determined by the distribution space and disappearance rate of ••mTc pertechnetate injected into the renal pelvis. From these data the urine flow was calculated. The glomerular filtration rate (GFR) was simultaneously determined by the clearance of 1251-iothalamate being continuously infused. It was remarkable that despite largely differing turnover rates, the urine flows in acute and chronic hydronephrosis were found to be in the same range, between 0.05 to 0.1 ml. per minute. THEORETICAL CONSIDERATION
Using these and other experimental data 10- 12 we calculated on an analogue computer (Telefunken RAT 700) the course of urine concentration in the obstructed renal pelvis in acute and chronic hydronephrosis after single injection with and without subsequent continuous infusion for a certain length of time, and investigated the dependence on the rate of turnover in the occluded renal pelvis and on the function of the contralateral kidney. For these calculations we used a 2-compartment model for the extracellular space with S, representing the rapidly miscible and 8 2 , which is twice as large as 8 1 , representing the slowly miscible compartment (fig. 2). The renal pelvis of the occluded and freely draining kidney is represented by S 3 and S 4, respectively. The intercompartmental clearance is represented by p,. 2 and p,. • and p 1. 4 indicate the GFRs of the occluded and normal draining
kidney, respectively. The Ps., is the urine flow of the occluded kidney, which is totally reabsorbed, and p4.0 is the flow of the freely draining kidney. Figure 3 shows the conditions in acute hydronephrosis. After a single intravenous injection of a given dose there is the typical biphasic exponential decrease of the plasma concentration (P), if a 2-compartment model is used, and the corresponding concentration course in the slowly miscible extracellular compartment (E). The urine of the freely draining kidney (N) has its maximum concentration at approximately 5 minutes after injection, followed by a rapid decrease. The urine concentration in the occluded renal pelvis does not reach maximum until 80 minutes after injection but is exceeding the maximum concentration of the normal kidney. It can be concluded that the usual dose sufficient for a normally functioning kidney can also be used in acute hydronephrosis if delayed x-ray pictures are taken. Figure 4 shows the conditions in an example of chronic hydronephrosis. The upper part shows the plasma concentration after a single injection of a given dose and after additional infusion of 2 doses per hour. The lower part shows the corresponding urine concentrations in the occluded renal pelvis with a GFR of only 0.32 ml. per minute but at variable urine flows. Assuming a flow of 0.05 ml. per minute 2 ½ hours after the infusion was terminated the maximum urine concentration is reached. It can be demonstrated that by a 4-hour infusion the peak urine concentration is increased approximately 8 times as compared to a single dose injection in this example. In addition, if the volume increase of the occluded renal pelvis as compared to the freely draining kidney is also taken into account, a 2.4 times higher density of
Fm. 1. Urogram of unilateral hydronephrosis in dog following ligation of upper ureter 24 days earlier. Seven hours after infusion of 750 ml. 30 per cent diatrizoate for 4 hours, site of obstruction could be visualized.
CONTINUOUS INFUSION UROGRAPHY IN UNILATERAL HYDRONEPHROSIS
339
and slowly (S 2 ) miscible kidneys. Pm·n represents
Fm. 2. Four-compartment compartments of extracellular flovvs between various .-,,m,,m·trr,Pn
,ll.cute. Hydronei:ihrosis ( 3 h)
Ext race I I ular Compartments S1 1783 ml S2 3566 m!
I ntercomparlmenlal Clearance 170 ml/min
2
3
h
Renai Peives:
S3 S4
L,
ml.
3 m!
GFR. ?1,3
V1A
5.7
ml/min
~0.0 mi/min
Urine Flows:
's'3,1
'?4,0
0.06 ml/ min 3.00 ml/ min
FIG. 3. Relative concentrations of diatrizoate calculated by analogue computer in acute hydronephrosis after single intravenous injection in plasma (P), in slowly miscible compartment of extracellular space (E), in renal pe!ves of freely draining (N) and totally obstructed (H) kidneys.
' contrast medium can be expected at the same 1 urine concentration (a spheric shape of the renal pelvis is assumed). a density of the occluded renal pelvis 2 112 hours after termination of the infusion corresponds to the density of a normally functioning 25 minutes after injection of a single dose. In most cases this should be sufficient for diagnostic purposes. The dependence on the urine turnover rate shows that under otherwise identical conditions the increase of urine turnover is followed an earlier but lower maximum urine concentration. Note the low urine concentration after a line). The influence of che fonction of the contralateral is sh 0~1i/n in l[J· 5.
of a given dose only a 2-hour infusion of 1 dose per hour was assumed. If no contralateral kidney is present a concentration 8 times higher in the occluded renal can be reached as compared to the situation when a contralateral kidney with a GFR of 60 ml. per minute is present. The dotted line shows the plasma and urine concentrations after a single n,,Pr,,rn,n of 1 dose of contrast medium with a GFR of the contralateral kidney of 60 ml. per minute. CLINICAL APPLICATION
340
NABER, KUNI AND MADSEN
Chron. Hydronephrosis ( 6 d)
10
Dog# 51 Flow 93,1 (ml/min)
0.5
0.025
1.6
0.05
Extracellular Compartments 1783 ml 51 3566 ml 52 lntercompartmental Clearance 170 ml/min lj> 1,2 Renal Pelves:
53 54
0.8
0.1
2
3
4
0.2 0.025 0.2
6
8
h
39 ml 3 ml
GFR:
~1.3 ?1.4
0.32 ml/min 60.00 ml/min
Urine Flows:
'? 3,1 ?4,0
variable 1.9 ml/min
Fm. 4. Relative concentrations of diatrizoate in plasma and urine calculated by analogue computer in example of chronic hydronephrosis (ureter ligation 6 days before) after single intravenous injection of given dose of contrast medium with (heavy lines) and without (thin lines) subsequent infusion of 2 doses per hour for 4 hours. Urine turnover in obstructed renal pelvis varied from 0.025 to 0.2 ml. per minute, resulting in earlier but lower urine peak concentration at high turnover rates. GFR
'? 1.4
(ml/min)
0
15 30 60 1.6
Chron. Hydronephrosis ( 6 d) Dog# 51 Extracellular Compartments 1783 ml 51 3566 ml 52 lntercompartmental Clearance 170 ml/min ' lj> 1,2 Renal Pelves:
Urine(H)
53 54
0
39 ml 3 ml
GFR:
0.8
~1.3 15
?1,4
0 32 ml/min variable
Urine Flows:
30 60 8
'? 3,1 !' 4,0
0.05 ml/min 1.9 ml/min
Fm. 5. Same example of chronic hydronephrosis as in figure 4 but with infusion of only 1 dose per hour for 2 hours assumed. Under otherwise unchanged conditions GFR of contralateral kidney varied from O to 60 ml. per minute, resulting in lower plasma and urine concentrations in obstructed renal pelvis. Dotted line shows plasma and urine concentrations after single injection of 1 dose with GFR of contralateral kidney of 60 ml. per minute.
infusion urography. Initially, 250 ml. 30 per cent diatrizoate was injected and this was followed by a constant infusion during a period of 2 to 4 hours of 250 ml. contrast medium per hour. Only delayed x-ray pictures were taken. Positive urograms could be obtained in 10 patients 5 to 24 hours after the beginning of the infusion (see table). In 1 patient (P. W.) there was a non-functioning kidney, also proved by scintillation camera study. Only in 2 patients (W. C. and 0. H.) was there a transient rise in serum creatinine and this returned to normal the following day (see table). In 1 patient (G. E.) the infusion had to be discontinued after 3 hours because of vomiting.
CASE REPORTS
Case 1. F. E., a 71-year-old man, underwent usual drip infusion urography but the site of obstruction could not be demonstrated (fig. 6, A). After intravenous injection of 250 ml. 30 per cent diatrizoate followed by continuous infusion for 4 hours, a total of 1,000 ml., the site of obstruction in the right upper ureter could be seen (fig. 6, B). A retrograde pyelogram confirmed this (fig. 6, C) and a uric acid stone was removed. Case 2. B. M., a 55-year-old woman, had a ureterovaginal fistula 5 months following abdominal total hysterectomy. The distal ureter could not be visualized sufficiently by usual drip infusion
CONTINUOUS INFUSION UROGRAPHY IN UNILATERAL HYDRONEPHROSIS
urography with 250 ml. 30 per cent diatrizoate (fig. 7, A). However, after infusion of 750 ml. contrast medium for 3 hours the site of obstruction could be localized in the perivesical area (fig. 7, B). DISCUSSION
The new tri-iodinated contrast media used in urography have a low toxicity 2 • 13- 15 and make the intravenous administration of large amounts ble. This fact could be confirmed in our series of 11 patients who received a mean of 1,000 ml. 30 per cent diatrizoate (a mixture of sodium and Continuous infusion urography with 30 per cent diatrizoate in 11 patients with unilateral obstniction
Pt.
Cause of Obstruction
DG
Bladder Ca Calculus Prostatic Ca Calculus Bladder Ca Prostatic Ca Bladder Ca Calculus Calculus Stenosis of ureteropelvic junction Ureterovaginal fistula
FE WC
GE PW SW
PF OH
TH WW
BM
Con- DuraPosi- Serum Creatinine trast tion tive Meof Uro- Before After dium Infu- gram Used sion (hrs.) Infusion Infusion (mg.%) (mg.%) (ml.) (hrs.) 1.000 1,250 1,250 1,000 1,250 1,000 1,000 1,000 750 750
4.0 4.5 4.5 3.0 4.5 3.0 3.0
750
22 16 16 12 -
3.0
24 12 12
2.0 2.0
6 12
3.0
5
1.3
1.4
-
-
1.2 (2.2) 1.3 1.1 1.6 1.6 1.2 1.0 1.1 2.2 (3.0) 2.1 1.4 1.6 1.1
I
1.1
1.1
meglumine-diatrizoate in the rate of 40 to 18 and containing 168 mg. per ml. iodine). Two transient rises of 1.0 and 0.8 mg. per cent in serum creatinine and 2 decreases of 0.5 and 0.4 mg. per cent were observed. Since drip infusion urography is in routine clinical use the frequency of retrograde pyelography has been reduced already. The possible complications of N>h,"n·q pyelography in addition to its inconvenience and cost to the patient the search for methods that might be able to reduce the need for this further. The results, the theoretical considerations and the clinical have demonstrated that continuous infusion the accuracy of IVP in unilateral obstructive uropathy. Since method is only indicated when the diagnostic results of usual drip infusion urography are not sufficient and further x-ray examinations, that is retrograde pyelography, should be considered, the 2 or 3 additional x-ray pictures needed for continuous infusion do not represent significant additional radiation exposure. After the infusion of contrast medium has been discontinued the first x-ray picture should be taken within 2 to 4 hours, the second and third within 6 to 8 and 12 to 16 hours, respectively, depending on the function of the contralateral kidney and the urine turnover in case of complete or incomplete hydronephrosis. Because of the gradual urine concentration change in the obstructed renal pelvis and ureter, a time for x-ray exposure can be chosen within a few hours
F1G. 6. Case 1. A, usual drip infusion urography (250 ml. 30 per cent d.iatrizoate) 4 hours following infusion does not demonstrate obstruction. B, continuous infusion urography. that is rapid infusion of 250 ml. 30 cent diatrizoate followed by infusion of 250 ml. per hour for 4 hours, 17 hours following infusion demonstrates (arrow). C, retrograde urography.
342
NABER, KUNI AND MADSEN
antimicrobial agents that are rapidly cleared from the bloodstream. REFERENCES
FIG. 7. Case 2. A, usual drip infusion urography with 250 ml. 30 per cent diatrizoate does not demonstrate obstruction. B, continuous infusion urography with 750 ml. 30 per cent diatrizoate for 3 hours demonstrates obstruction (arrow). around the expected peak concentration without essential loss of quality. Combining the principle of this technique with usual drip infusion urography we occasionally use a modified method. If the conventional urogram with x-ray pictures taken at 15, 30 and 60 minutes post-injection shows a unilateral hydronephrosis, but it becomes unlikely that the point of obstruction will be clarified on further delayed pictures, we inject an additional 250 ml. 30 per cent diatrizoate followed by continuous infusion for 1 or 2 hours at an infusion rate of 250 ml. per hour with 3 x-ray pictures taken in the usual manner (2 to 4 hours, 6 to 8 hours and 12 to 16 hours). The costs for the additional amount of contrast medium, the time involved and the only minimal side effects should make up for the expenses of retrograde pyelography with its known morbidity. In case of a so-called non-functioning kidney in the usual urogram a renogram or camera scintiscan should be performed first. Continuous infusion urography may be tried only if some function can be demonstrated but otherwise no positive result can be expected. This principle outlined in the example of a diagnostic procedure may also be of importance for therapeutic considerations, for example in the treatment of infection in an obstructed kidney with
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