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Evaluation of Renal Function by Excretory Urography
0022-534 7/80/1244-0437$02.00/0 Vol. 124, October
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1980 by The Williams & Wilkins Co.
Review Article EVALUATION OF RENAL FUNCTION BY EXCRETORY OROGRAPHY MARC P. BANNER
AND
HOWARD M. POLLACK
From the Department of Radiology, University of Pennsylvania School of Medicine and Hospital, Philadelphia, Pennsylvania
subclinical dose levels but this is negligible compared to glomerular filtration at clinical dose levels. The concentration of diatrizoate in the glomerular filtrate is the same as it is in plasma. In the proximal tubule isosmotic reabsorption of sodium and water increases diatrizoate concentration 5 to 10 times. Although proximal tubular reabsorption is independent of the state of hydration facultative reabsorption in the distal tubule and collecting duct allows urinary diatrizoate concentrations of 30 to 50 times the plasma value in the presence of antidiuretic hormone. 10 Fluid deprivation before an IVP, by increasing circulating antidiuretic hormone, produces higher urine diatrizoate concentrations9 and, thence, better pyelograms.11 In a discussion of the relationship between the density of contrast medium seen on the radiograph and renal function it is convenient to consider renal parenchymal opacification-the nephrogram-separately from caliceal or pelvic opacificationthe pyelogram.
The capacity of the kidney to excrete circulating organic iodinated compounds in concentrations sufficiently high to render the urine radiopaque provides the basis for excretory urography (IVP). When renal function is normal or only moderately decreased collecting system opacification ordinarily is excellent. On the other hand, when renal function is appreciably impaired visualization of the collecting system on the involved side or sides after a standard dose of contrast medium characteristically is poor or non-existent. Based on these observations the IVP has been recommended as a test of renal function. 1- 3 Unfortunately, however, the physiological determinants underlying renal contrast visualization fail to support the validity of this extrapolation and, moreover, reliance upon it may lead to potentially serious errors in interpretation. Although the excretion of contrast medium used for an IVP is a physiological process that depends, in the broad sense, on the functional status of the kidney, the present day IVP is not a reliable test for either the presence or severity of renal functional impairment. 4- 7 In the past, when contrast media contained less iodine per molecule than do current agents and dosages were limited by fear of toxicity pyelograms were produced whose density was relatively proportional to renal function. However, modem contrast media contain more iodine atoms per molecule than do older agents and are of exceedingly low toxicity. Therefore, they often are used in relatively large amounts and may be so highly concentrated in the blood that even kidneys with significantly decreased function may excrete enough contrast medium to produce diagnostic, if not excellent pyelograms. 6• 8 To appreciate why renal function and an IVP cannot always be equated an understanding of the physiological basis of an IVP is necessary.
NORMAL NEPHROGRAPHIC DENSITY
NORMAL IVP
The currently used urographic agents are hypertonic, water soluble salts derived from an iodinated benzoic acid precursor. Diatrizoate, the anion of sodium diatrizoate and methylglucamine diatrizoate, can be considered the prototype agent. Identical considerations apply to iothalamate, an isomer of diatrizoate and the anion of methylglucamine iothalamate. This agent also is in widespread use for the IVP. After rapid intravenous injection diatrizoate is diluted immediately in the circulating plasma volume and begins to diffuse into the extravascular space, while simultaneously undergoing filtration by the kidneys. Equilibration between the intravascular and extravascular compartment concentrations occurs approximately 10 minutes after injection. The plasma level of diatrizoate at this time is a direct function of the injected dose and body size. As urinary excretion proceeds the plasma diatrizoate level decreases, resulting in re-entry of diatrizoate from the extravascular to the intravascular compartment. 9 Although earlier, now obsolete contrast agents were secreted by the renal tubules present day agents are excreted almost entirely by glomerular filtration and are not reabsorbed. 8 • 9 A small amount of tubular secretion can be demonstrated at 437
Rapid injection of a bolus of contrast medium produces maximum plasma iodine concentration and a faint total-body opacification in which vascular organs (such as the liver, spleen and intestines) become slightly opaque even though they do not excrete the contrast agent. A radiograph of the kidneys approximately 15 seconds after such an injection, as the bolus clears the renal artery on its first circulation, demonstrates a profound nephrogram. The intensity of this purely vascular nephrogram is dependent on renal blood flow and not on the functional status of the renal parenchyma per se. Differential corticomedullary opacification often is present, similar to that seen with renal arteriography. As the vascular component of this nephrogram peaks and then fades a homogeneous tubular or excretory nephrogram follows. This nephrogram is largely a manifestation of contrast material in the proximal tubular lumina and, as such, it depends on the filtered load-the product of the glomerular filtration rate and plasma diatrizoate concentration. Being related to glomerular filtration rate this tubular nephrogram is dependent on renal function. However, it ordinarily is independent of the state of hydration. 12 In normal subjects the nephrogram attains its maximal density by the end of the bolus injection of contrast medium and remains dense for approximately 2 minutes, at which time contrast molecules begin to reach the calices. The nephrogram then fades gradually as the pyelogram develops. At this time patients with a normal glomerular filtration rate may show dense opacification of the papillae related to high concentrations of contrast medium in the collecting tubules, which,is a normal phenomenon and is not to be confused with pathological causes of increased papillary density, such as tubular ectasia or. papillary necrosis. NORMAL PYELOGRAPHIC DENSITY
Pyelographic density is determined mainly by the amount of contrast material in the calices and pelvis at a given time. It is dependent on the concentration of contrast medium in the
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urine and on the volume of urine in the collecting system, that is the total number of iodine atoms in the pathway of the x-ray beam. 13 Either sodium or methylglucamine is used as the cation for the contrast molecules. Since methylglucamine is not reabsorbed it produces a more pronounced osmotic diuresis than does the sodium salt. The result is a greater urinary iodine concentration with the latter but better pyelocaliceal distension with the former. IVPs made with the 2 different cations are remarkably similar in day-to-day practice, 14- 16 although clinical studies have suggested a slight superiority with the sodium salt, 17 especially when abdominal ureteral compression is applied. As noted previously dehydration before an IVP improves pyelographic quality. The technique of a drip infusion IVP, in which a large dose of contrast material is combined with an equal volume of distilled water or glucose and then infused into the patient in several minutes, has achieved considerable popularity since its introduction by Schencker in 1964. 18 Although large doses of contrast material had been used sporadically for an IVP before then it was probably the novelty and convenience of adminis-tration of the drip infusion technique that stimulated a general tendency to use larger doses. No urographic advantage is gained when a large dose of contrast material is given by infusion rather than by bolus injection. 19
contrast medium indicates a high probability of some degree of renal compromise. The finding of such a persistent nephrogram may suggest renal failure induced by contrast medium earlier than the diagnosis is possible clinically. 22 With regard to the filtered load of contrast medium any evaluation of nephrographic density alterations must begin with a knowledge of the amount of contrast medium administered and its delivery time (bolus versus drip). Diminished filtration states can then be considered. These include patients with decreased cardiac output and poor renal perfusion, and those with hypotension, either on the basis of trauma or consequent to a vasovagal response to the injection of urographic contrast material. Reduced cortical blood flow delays and diminishes the early vascular nephrogram; the decreased glomerular filtration rate has the same effect upon the tubular nephrogram. However, as the latter develops it eventually exceeds the density of the normal nephrogram. The time sequence of the paradoxically dense nephrogram in hypotension is similar to that of the obstructive nephrogram. They have in common a
ABNORMAL !VP
Abnormal nephrographic density. Alterations in either axis of the nephrographic time-density relationship are significant. Conditions that delay the arrival of contrast medium at the glomerulus (diminished renal blood flow) and those that prolong its transit time within the tubule (obstruction, acute tubular necrosis and renal vein thrombosis) are examples of time alterations. Changes in either component of the filtered load (plasma contrast concentration or glomerular filtration rate) alter radiographic density. Diminished renal blood flow will be considered primarily in a separate section on the hypertensive IVP. Of the conditions that prolong the transit of contrast material in the tubules obstruction serves as a prototype to illustrate nephrographic alterations. In the immediate post-obstructive period renal blood flow and glomerular filtration rate remain nearly normal and urographic contrast medium freely enters the nephron. Movement of intratubular urine is slowed by the obstruction, permitting increased water reabsorption. This, plus concomitant tubular distension, allows a continuous input of contrast medium into the tubules at a rate far exceeding the ability of urine to be discharged into the renal pelvis. With an acute increase in intrapelvic pressure urine can leak also through small ruptures at the caliceal fornices into the renal sinus and be reabsorbed by renal lymphatics, decreasing intrapelvic pressure and further facilitating glomerular filtration. 20 The time-density curve of the obstructive nephrogram depends on the balance between the rates at which contrast material enters the nephron and leaves the collecting ducts. With acute severe obstruction inflow exceeds outflow, the kidney becomes swollen and large, and the nephrogram becomes progressively denser over a period of hours (fig. 1). However, with chronic obstruction renal blood flow decreases, 21 so that eventually the glomerular filtration rate may not be adequate to deliver sufficient contrast medium to enable the tubules to opacify significantly. Under these circumstances and especially in the presence of a normal contralateral kidney a poor nephrogram will result. Generally speaking, the intensity of the nephrogram is roughly proportional to the remaining integrity of the kidney. Abnormally dense nephrograms may be seen in a variety of conditions, including acute obstruction, hypotension, renal vein thrombosis and acute renal failure (fig. 2). Recent observations suggest that an abnormally persistent nephrogram after the use of iodinated
FIG. 1. Obstructive nephrogram: 4-hour IVP shows persistently dense nephrogram in enlarged right kidney and delayed faint visualization of mildly dilated pyelocaliceal system and proximal ureter (arrowheads) down to obstructing ureteral calculus at L3-IA interspace (curved arrow).
Fm. 2. Acute renal failure secondary to myoglobinuric nephropathy. Bilateral persistently dense nephrograms noted on 24-hour IVP. Presumably, precipitation of myoglobin in renal tubules prevented contrast medium from reaching calices or pelves with resultant absent pyelograms. Note vicarious excretion of contrast medium with subsequent gallbladder visualization (GB). Contrast medium also may be excreted vicariously by intestinal tract.
IVP EVALUATION OF RENAL FUNCTION
markedly slowed rate of flow along the nephron. Maximal tubular reabsorption of sodium and water leaves large amounts of contrast medium in the tubules and, hence, the eventual increased radiopacity of this type of nephrogram (fig. 3).23 A sometimes dramatic consequence of hypotension is an acute reduction in kidney size because of diminished renal blood flow and intratubular volume. Such changes in kidney size may occur quite rapidly and are reversed when blood pressure is restored. Increased blood pressure also clears the nephrogram and fills the calices. 24 Abnormal pyelographic density. Abnormal pyelographic density may be seen with either normal or abnormal renal
FIG. 3. IVP during hypotension, performed for nephrolithiasis. A, 2minute uro-tomogram shows prompt and symmetric nephrograms. Shortly thereafter patient had hypotension and bradycardia and was treated intravenously with 2.5 mg. atropine. B, radiograph at 10 minutes while blood pressure was returning to normal still shows persistent nephrograms and no caliceal filling. Note 3 opaque stones in left kidney (arrowheads). Normally, collecting system should be well filled and densely opaque by this time. C, subsequent radiograph after blood pressure and pulse returned to normal demonstrates good filling of collecting systems. Calculi in left lower pole calices are seen again.
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function. In the presence of normal kidneys it may be caused by any of the diminished filtration states that alter the nephrogram. However, unlike the nephrogram, the pyelogram is sensitive to changes in hydration. Administration of fluids before an IVP may lessen pyelographic density significantly (fig. 4). 13 Diuretics and the presence of diabetes insipidus also can impair pyelographic visualization. 13 The inability to standardize and control the degree of patient dehydration, as exemplified by the marked variation in urine osmolality in normal patients after an overnight fast, is 1 factor that makes the IVP an unsatisfactory test of renal function. 8 Unless doses are standardized on a volume-for-weight basis renal function of any one patient cannot be compared to that of another. Such strict standardization is not used customarily, since the IVP is performed primarily for the delineation of morphology and not function. It is, thus, more advantageous to use large quantities of contrast material rather than the small doses necessary to detect deviations in renal function. Most patients receive a standard dose of 75 or 100 cc contrast medium, which is large enough to obscure reductions in renal function of ~50 per cent. 25 The evaluation of radiographic density is a subjective phenomenon varying from one observer to another. Therefore, it cannot be quantitated accurately. Attempts to do so are further complicated by the superimposition of intestinal gas, fecal material and soft tissue densities, variations in radiographic techniques and, finally, the varying geometries of the renal collecting systems. It is clearly apparent, then, that judging renal function on the basis of pyelocaliceal density is a precarious undertaking. Even radiography of voided urine specimens, as advocated by some, 25 does not materially improve the reliability of the estimate. In patients with obstructive uropathy the dilutional effect of large volumes of urine on the excreted contrast medium must also be taken into consideration. Excellent pyelographic density in the face of renal disease represents another pitfall in the attempt to equate urographic appearance with renal function. This is best exemplified by the unilateral severely contracted kidney, which still exhibits excellent nephrographic and pyelographic density as long as the opposite kidney retains good function. Ellis and associates showed that a unilaterally diseased kidney with a glomerular filtration rate <10 ml. per minute may concentrate adequately because it does not excrete the load of water and solute that would be necessary were both kidneys diseased similarly. 26 In this setting the superimposition of significant nephron loss in the normal kidney results in failure of concentration by the original abnormal side. Thus, the adequacy of contrast visualization in the unilaterally diseased kidney cannot be accepted per se as a quantitative estimate of its true functional state. Certainly, any attempts to predict the potential life-sustaining capability of an abnormal kidney based solely on radiographic impressions of pyelographic density are ill-advised at best and catastrophic at worst (fig. 5). Other causes of unilateral (or bilateral) renal non-visualization on an IVP include 1) virtually complete destruction of the nephron population of the involved kidney, 2) total or high grade occlusion of the renal artery, 3) high grade to total obstruction of urine flow and 4) high rates of solute and water excretion by the involved organ, such as may occur occasionally after relief of urinary tract obstruction. A kidney that fails to excrete contrast material, especially if its ureter is obstructed suddenly, may be a kidney that is actively filtering urine and will revert to an entirely normal appearance after removal of the obstruction. This is true even if the contralateral kidney has undergone compensatory hypertrophy. 27 Return of useful renal function has been observed after ureteral obstruction and renal non-visualization of up to 150 days. 28 The inability of the IVP to ascertain whether nonvisualization is related to reversible or irreversible functional impairment points out the imprecision of designating a kidney
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reflux or from faulty neuromuscular development of the ureter. Uncomplicated urinary tract infection may cause ureteral dilatation through the inhibitory effect of endotoxin on ureteral smooth muscle, and hormonal effect on smooth muscle tone is thought to cause, at least in part, "pregnancy dilatation" of the urinary tract. 31 Conversely, the absence of dilated calices does not always exclude obstruction, as in patients with intermittent hydronephrosis who have no apparent difficulty when urine flow rate is low or moderate but under the stress of diuresis have typical radiological findings and, often, flank pain. The fact that the IVP does not, strictly speaking, depict the urinary tract in its average physiological state is sometimes overlooked. All contrast agents are, by nature of their hyperosmolarity, diuretics of varying potency, capable of causing a temporary dilatation of the readily distensible calices, pelves and ureters. Large doses of contrast medium, especially when administered with added fluid as in an infusion IVP, may even produce a transient hydronephrotic pattern. 18 Acute distension of the bladder with its well known inhibitory effect on ureteral emptying also may have a role in the development of this phenomenon. 32• 33 Finally, abdominal ureteral compression, when effectively applied, temporarily obstructs the upper urinary tract. HYPERTENSIVE IVP
Although, as we have seen, an IVP is more a morphologic than a functional study attempts to modify it have been made
Fm. 4. Effect of hydration on pyelographic density. A, IO-minute IVP shows normal nephrograms out markedly diminished pyelographic density. Careful questioning disclosed that patient had ingested 2 cups of coffee just before study. B, repeat study next day after overnight dehydration with same amount of contrast medium injected as in part A. Note excellent pyelographic density. In absence of urinary tract obstruction intravenous administration of diuretic immediately after study in part B would produce picture similar to part A within 10 to 15 minutes.
as non-functioning rather than non-visualizing. A non-visualizing kidney on an IVP may demonstrate iodine excretion by computed tomography, since that imaging modality is much more sensitive than the IVP in detecting low concentrations of iodine. 29 Regarding obstructive uropathy mention should be made of an interesting and not entirely explained observation. In acute upper urinary tract obstruction, especially when produced by a ureteral calculus, an initial IVP may demonstrate only a dense nephrogram or faint pyelocaliceal visualization on delayed films. However, a repeat IVP several days later often shows a normal nephrogram and more prompt pyelogram even though the calculus has not changed its position (fig. 6). We believe 2 possible explanations are available: 1) initial ureteral edema at the site of the lodged calculus may partially subside, lessening the degree of obstruction, and 2) although still speculative continued upper tract obstruction may allow for the establishment of an increasing number of pyelosinus and pyelolymphatic communications. By lowering intrapelvic pressure these communications would permit filtered urine and contrast medium to exit the collecting system despite the presence of the obstructing stone. The practical implication of these facts is obvious. No decision to either remove or retain a kidney should be based solely on its appearance on an IVP. Urinary tract dilatation cannot always be equated with obstruction. The mega-urinary tract of primary diabetes insipidus develops in the absence of an anatomic obstruction.30 Dilatation is accounted for by the adaptation of the urinary tract to the large volume of urine continually excreted. Hydroureter and hydronephrosis also may result from primary vesicoureteral
Fm. 5. Pyelographic density in unilateral renal disease. A, IVP shows normal right kidney and shrunken left kidney containing ring calcifications in upper and lower pole calices from old renal tuberculosis. Note contrast excretion into clubbed mid pole calices (c). Narrowed renal pelvis and normal proximal ureter (dots) are of comparable density to right collecting system. B, 6 months later right distal ureter became obstructed by bladder tumor. IVP now shows enlarged right kidney with faint visualization of dilated collecting system (dots). Previously diseased left kidney cannot handle increased solute and water load secondary to obstructed right kidney and fails to concentrate contrast material. Calcified calices in small left kidney now readily apparent (compare to part A). Subsequent IVP after relief of rightsided obstruction virtually identical to part A.
IVP EVALUATION OF RENAL FUNCTION
Fm. 6. IVP during acute obstructive uropathy. A, faint visualization of mildly dilated right renal collecting system and ureter noted at time of acute right renal colic. Note obstructing stone in distal right ureter (arrow). B, 3 days later calculus has not moved (arrow) and degree of dilatation is comparable. However, pyelographic visualization is much improved and comparable to normal left side. Note standing column of contrast material in right ureter down to unchanged calculus.
so as to generate reliably selected physiologic data. The rapid sequence or hypertensive IVP represents such an effort. 34 In these studies films are taken at I-minute intervals for the first 5 minutes after contrast injection in an attempt to compare appearance time and density of contrast medium in the parenchyma and the collecting systems of both kidneys. It is hoped that the decreased glomerular filtration rate accompanying renal ischemia may reflect itself as a diminished nephrogram and a delayed pyelogram of decreased density. However, the sensitivity of this radiographic split-function test is considerably lessened by the inconsistency with which diminution in renal blood flow produces detectable nephrographic and pyelographic derangements. Difficulties are produced by the relative insensitivity of radiographic techniques in detecting small differences in iodine concentration, by differences in collecting system geometry between the 2 kidneys and by the contrast-induced diuresis that further obscures differences in urine iodine concentration. Amplatz attempted to take advantage of this latter effect by pointing out that a kidney affected with renal artery stenosis should reabsorb a greater percentage of its filtered water than normal. 35 By further increasing diuresis through the use of urea given at the conclusion of the IVP he demonstrated that the ischemic kidney retains more contrast material in its collecting system (paradoxical hyperconcentration) after the urea washout than does the contralateral kidney. However, this modification has not increased the accuracy of a hypertensive IVP significantly and generally is considered too impractical for general use. Another variation of a hypertensive IVP (vasodilated IVP) is based on the observations that 1) kidneys enlarge in response to diuretics and 2) a kidney with renal artery stenosis enlarges less than one with a normal renal artery. The test is performed by measuring changes in renal size during the IVP after intravenous injection of ethacrynic acid or furosemide. An increase in area of ~5 to 10 per cent is considered normal, while lesser
increases are suggestive of renal ischemia. 36 Although a vasodilated IVP has the advantages of a quantitative study and, theoretically, could detect bilateral renal artery stenosis, recent reports have shown a high incidence of falsely positive and indeterminant results in hypertensive patients without renal artery stenosis. 37 Although 83 per cent of the patients with unilateral renoprival hypertension have a positive hypertensive IVP 17 per cent do not and 10 per cent of the patients with essential hypertension have a falsely positive study. 38 A high percentage of patients with bilateral or segmental arterial stenosis show false results, pointing out the shortcomings of the IVP in the diagnosis of renovascular hypertension. In many centers it is no longer used as a screening procedure for this disease. IVP IN RENAL FAILURE
Although azotemia may be caused by pre-renal factors that diminish renal blood flow or by post-renal urinary tract obstruction the majority of patients with chronic uremia have some form of intrinsic renal disease. The common pathological alteration in this group of patients is loss of nephrons, which results in a depressed glomerular filtration rate. Although the remaining nephrons are normal or even functionally hypertrophied (intact nephron hypothesis) it is characteristic of uremia that urine cannot be concentrated normally. 39 These alterations impair all of the IVP determinants of nephrographic and pyelographic density except one-the plasma iodine concentration. Hence, to compensate for the expectedly poor IVP in the patient with renal failure the injected dose of contrast medium must be increased to increase the plasma iodine concentration and the filtered load. It is important to anticipate the presence ofrenal failure in patients being referred for an IVP. The results of laboratory studies should, therefore, be available before the IVP to determine the dose of contrast medium for the patient. Blood urea nitrogen and creatinine values are helpful if they
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are elevated. However, the glomerular filtration rate may be as low as 25 per cent of normal, while the creatinine and blood urea values remain within the normal range, as typified by the elderly man with prostatic disease and senile renal atrophy. 11 For this reason, it is recommended that, all other things being equal, elderly patients should empirically receive higher doses of contrast material than are normally used for younger patients. Despite predictably suboptimal visualization valuable information can be obtained from an IVP in most cases, despite marked diminution in renal function or severe oliguria. 12 There are no absolute limits of laboratory values above which an IVP should not be performed, since valuable information has been obtained in patients with a blood urea nitrogen as high as 200 mg./100 dl. and creatinine clearance values <10 dl. per minute. 40 Realistically speaking, however, there is little point in pursuing an IVP in most patients with advanced renal failure for several reasons. First, the clinical information most often required, that is the presence or absence of obstruction, can be obtained safely and accurately by ultrasonography. Second, there is a small but apparently real risk of aggravating preexisting renal disease through the use of contrast medium. It must be kept in mind that the blood urea nitrogen may be elevated for reasons unrelated to renal functional impairment. The use of large doses of contrast material in conjunction with tomography almost always yields a nephrogram that allows estimation of renal size and contour. 6• 40 The appearance of a nephrogram indicates that some glomerular filtration exists. 13 Collecting system visualization ranges from trace to poor but is sufficient in most cases to diagnose or exclude obstruction (fig. 7) .12• 40• 41 Pyelographic density in patients with uremia resulting from urinary tract obstruction usually is far greater than that seen with intrinsic renal disease causing a similar degree of uremia because 1) there are likely to be more functioning nephrons than in intrinsic disease, leading to a larger filtered load, 2) the slow flow down the tubules will allow better reabsorption of water and sodium than with polyuric renal failure and 3) the distended pyelocaliceal system provides a greater depth of contrast medium than usual. 42 Matalon and Eisinger showed that the IVP could be improved if the uremic patient underwent vigorous dialysis before the examination. 43 By lowering the blood urea concentration os-
motic diuresis is diminished and the concentration of urine solutes (including contrast material) is increased. An added advantage to dialysis before an IVP is that the patient will be improved clinically and will tolerate the study better. Although Matalon and Eisinger were able to opacify the urinary tract of patients in whom an IVP with the same technique had been unsuccessful previously the results of other observers are less striking despite comparable reductions in blood urea and creatinine levels. 41 • 44• 45 General experience has been that collecting system visualization before dialysis may be enhanced slightly after dialysis. Dialysis usually does not permit visualization of a collecting system not visualized before dialysis nor does it impair visualization of a system seen before dialysis. Fluid deprivation before an IVP will not enhance urinary contrast medium concentration in patients with renal insufficiency and, in fact, may actually be dangerous. 42 Ultrasonography represents an alternative method of imaging the urinary tract of patients in uremia. The desired information about renal size and contour, the presence or absence of parenchymal cystic disease, and the state of the renal pelvis and calices (obstructed or not) can be more easily and rapidly obtained with ultrasound than with an IVP. The tremendous advantage of ultrasonography is its lack of dependence upon renal function. Hence, an efficacious initial evaluation of the urinary tract in the uremic patient need consist only of an abdominal plain film to detect opaque urinary tract calculi and a renal ultrasonogram to differentiate medical from surgical renal disease. An IVP usually can be circumvented. In view of the apparent deleterious effects of contrast agents on the integrity of some diseased kidneys, this is a particularly attractive feature of ultrasonography.46 Juvenile diabetics with renal insufficiency (creatinine >1.5 mg./dl.) appear to be at greatest risk for the development of contrast-related acute renal failure. This sequela probably is dose-related47 and may occur after administration of contrast agents for a variety of procedures, including angiography, computed tomography and angiocardiography. The etiology of this complication is not clear at present and there is a good deal of controversy about its frequency and exact role in contributing to the accelerated renal failure seen in some patients who have received contrast medium. Until these uncertainties have been clarified it probably is best to avoid an IVP in that small and select group of patients having severe renal insufficiency of diabetic origin insofar as this is possible. REFERENCES
FIG. 7. IVP during renal failure. Despite laboratory evidence of renal insufficiency (blood urea nitrogen 60, creatinine 6.0) uro-tomogram exposed 15 minutes after 100 cc intravenous contrast medium demonstrates renal size and contour, and non-obstructed collecting systems. Arrowheads demarcate proximal ureters. Pyelographic density cannot always be correlated with degree of renal insufficiency. Pathological diagnosis: chronic glomerulonephritis.
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11. Fry, I. K., Cattell, W.R., Spencer, A.G. and Purkiss, P.: Excretion urography. II-The relation between hypaque excretion and the intravenous urogram. Brit. J. Rad., 40: 572, 1967. 12. Saxton, H. M.: Urography. Brit. J. Rad., 42: 321, 1969. 13. Sherwood, T.: The physiology of intravenous urography. In: The Scientific Basis of Medicine. Annual Reviews 1971. Edited by I. Gilliland and J. Francis. London: The Athlone Press, chapt. 19, pp. 336-348, 1971. 14. Cattell, W. R., Fry, I. K., Lane, R. and Tsay, J. L.: Comparison of the renal excretion of hypaque 45% and urografin 60%. Brit. J. Rad., 43: 309, 1970. 15. McClennan, B. L., Becker, J. A. and Berdon, W. E.: Excretory urography. Choice of contrast material-experimental. Radiology, 100: 585, 1971. 16. McClennan, B. L. and Becker, J. A.: Excretory urography. Choice of contrast material-clinical. Radiology, 100: 591, 1971. 17. Benness, G. T.: Urographic contrast agents. A comparison of sodium and methylglucamine salts. Clin. Rad., 21: 150, 1970. 18. Schencker, B.: Drip infusion pyelography. Indication and applications in urologic roentgen diagnosis. Radiology, 83: 12, 1964. 19. Dure-Smith, P.: The dose of contrast medium in intravenous urography: a physiologic assessment. Amer. J. Roentgen., 108: 691, 1970. 20. Cooke, G. M. and Bartucz, J. P.: Spontaneous extravasation of contrast medium during intravenous urography. Report of 14 cases and a review of the literature. Clin. Rad., 25: 87, 1974. 21. McCrory, W. W., Shibuya, M., Leumann, E. and Karp, R.: Studies of renal function in children with chronic hydronephrosis. Ped. Clin. N. Amer., 18: 445, 1971. 22. Older R. A., Korobkin, M., Cleeve, D. M., Schaaf, R. and Thompson, W.: Contrast-induced acute renal failure: persistent nephrogram as clue to early detection. Amer. J. Roentgen., 134: 339, 1980. 23. Korobkin, M.: The nephrogram of hemorrhagic hypotension. Amer. J. Roentgen., 114: 673, 1972. 24. Katzberg, R. W. and Schabel, S. I.: Bilaterally small kidneys in shock. J.A.M.A., 235: 2213, 1976. 25. Owen, R. H.: The concentration of pyelographic contrast media. A radiographic method of estimation of renal function. Brit. J. Rad., 33: 368, 1960. 26. Ellis, H. L., Klahr, S. and Bricker, N. S.: Intravenous pyelography in unilateral renal disease. Adequacy of contrast visualization despite severe renal involvement. J.A.M.A., 188: 128, 1964. 27. Milewski, P. J.: Radiographic measurements and contralateralrenal size in primary pelvic hydronephrosis. Brit. J. Urol., 50: 289, 1978. 28. Shapiro, S. R. and Bennett, A. H.: Recovery of renal function after prolonged unilateral ureteral obstruction. J. Urol., 115: 136, 1976. 29. Forbes, W. S., Isherwood, I. and Fawcitt, R. A.: Computed tomography in the evaluation of the solitary or unilateral nonfunctioning kidney. J. Comp. Ass. Tomography, 2: 389, 1978. 30. Shapiro, S. R., Woerner, S., Adelman, R. D. and Palmer, J. M.: Diabetes insipidus and hydronephrosis. J. Urol., 119: 715, 1978.
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31. Hodson, C. J.: Round table discussion: radiological changes in the urinary tract associated with pregnancy in relation to the pathogenesis of pyelonephritis. In: Urinary Tract Infections. Edited by F. O'Grady and W. Brumfitt. London: Oxford University Press, pp. 172-175, 1968. 32. Berdon, W. E. and Baker, D. H.: The significance of a distended bladder in the interpretation of intravenous pyelograms obtained on patients with "hydronephrosis". Amer. J. Roentgen., 120: 402, 1974. 33. Gill, W. B. and Curtis, G. A.: The influence of bladder fullness on upper urinary tract dimensions and renal excretory function. J. Urol., 117: 573, 1977. 34. Maxwell, M. H., Gonick, H. C., Wiita, R. and Kaufman, J. J.: Use of the rapid-sequence intravenous pyelogram in the diagnosis of renovascular hypertension. New Engl. J. Med., 270: 213, 1964. 35. Amplatz, K.: Two radiographic tests for assessment ofrenovascular hypertension. A preliminary report. Radiology, 79: 807, 1962. 36. Wolf, G. L. and Wilson, W. J.: Vasodilated excretory urography: an improved screening test for renal arterial stenosis? Amer. J. Roentgen., 114: 684, 1972. 37. Talner, L. B., Stone, R. A., Coel, M. N., Levy, S. B. and Emarine, C. W.: Furosemide-augmented intravenous urography: results in essential hypertension. Amer. J. Roentgen., 130: 257, 1978. 38. Bookstein, J. J., Abrams, H. L., Buenger, R. E., Lecky, J., Franklin, S. S., Reiss, M. D., Bleifer, K. H., Klatte, E. C., Varady, P. D. and Maxwell, M. H.: Radiologic aspects of renovascular hypertension. Part 2. The role of urography in unilateral renovascular disease. J.A.M.A., 220: 1225, 1972. 39. Bricker, N. S., Morrin, P.A. F. and Kime, S. W., Jr.: The pathologic physiology of chronic Bright's disease. An exposition of the "intact nephron hypothesis". Amer. J. Med., 28: 77, 1960. 40. Fry, I. K. and Cattell, W. R.: Excretion urography in advanced renal failure. Brit. J. Rad., 44: 198, 1971. 41. Stage, P., Milman, N. and Brix, E.: High-dose urography in advanced renal failure. I. Evaluation of diagnostic value. Acta Rad. Diag., 14: 689, 1973. 42. Fry, I. K. and Cattell, W. R.: Radiology in the diagnosis of renal failure. Brit. Med. Bull., 27: 148, 1971. 43. Matalon, R. and Eisinger, R. P.: Successful intravenous pyelography in advanced uremia-visualization in the post-dialytic state. New Engl. J. Med., 282: 835, 1970. 44. Becker, J. A.: Before and after dialysis urography. Radiology, 109: 271, 1973. 45. Rees, D. 0., Davies, M., Lloyd, H.J., Jones, J. H. and McLachlan, M. S. F.: Effects of haemodialysis on excretion urography in severe chronic renal failure. Brit. J. Rad., 47: 163, 1974. 46. Vanzee, B. E., Hoy, W. E., Talley, T. E. and Jaenike, J. R.: Renal injury associated with intravenous pyelography in nondiabetic and diabetic patients. Ann. Intern. Med., 89: 51, 1978. 47. Byrd, L. and Sherman, R. L.: Radiocontrast-induced acute renal failure: a clinical and pathophysiologic review. Medicine, 58: 270, 1979.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1980 by The Williams & Wilkins Co.
Review Article EVALUATION OF RENAL FUNCTION BY EXCRETORY OROGRAPHY MARC P. BANNER
AND
HOWARD M. POLLACK
From the Department of Radiology, University of Pennsylvania School of Medicine and Hospital, Philadelphia, Pennsylvania
subclinical dose levels but this is negligible compared to glomerular filtration at clinical dose levels. The concentration of diatrizoate in the glomerular filtrate is the same as it is in plasma. In the proximal tubule isosmotic reabsorption of sodium and water increases diatrizoate concentration 5 to 10 times. Although proximal tubular reabsorption is independent of the state of hydration facultative reabsorption in the distal tubule and collecting duct allows urinary diatrizoate concentrations of 30 to 50 times the plasma value in the presence of antidiuretic hormone. 10 Fluid deprivation before an IVP, by increasing circulating antidiuretic hormone, produces higher urine diatrizoate concentrations9 and, thence, better pyelograms.11 In a discussion of the relationship between the density of contrast medium seen on the radiograph and renal function it is convenient to consider renal parenchymal opacification-the nephrogram-separately from caliceal or pelvic opacificationthe pyelogram.
The capacity of the kidney to excrete circulating organic iodinated compounds in concentrations sufficiently high to render the urine radiopaque provides the basis for excretory urography (IVP). When renal function is normal or only moderately decreased collecting system opacification ordinarily is excellent. On the other hand, when renal function is appreciably impaired visualization of the collecting system on the involved side or sides after a standard dose of contrast medium characteristically is poor or non-existent. Based on these observations the IVP has been recommended as a test of renal function. 1- 3 Unfortunately, however, the physiological determinants underlying renal contrast visualization fail to support the validity of this extrapolation and, moreover, reliance upon it may lead to potentially serious errors in interpretation. Although the excretion of contrast medium used for an IVP is a physiological process that depends, in the broad sense, on the functional status of the kidney, the present day IVP is not a reliable test for either the presence or severity of renal functional impairment. 4- 7 In the past, when contrast media contained less iodine per molecule than do current agents and dosages were limited by fear of toxicity pyelograms were produced whose density was relatively proportional to renal function. However, modem contrast media contain more iodine atoms per molecule than do older agents and are of exceedingly low toxicity. Therefore, they often are used in relatively large amounts and may be so highly concentrated in the blood that even kidneys with significantly decreased function may excrete enough contrast medium to produce diagnostic, if not excellent pyelograms. 6• 8 To appreciate why renal function and an IVP cannot always be equated an understanding of the physiological basis of an IVP is necessary.
NORMAL NEPHROGRAPHIC DENSITY
NORMAL IVP
The currently used urographic agents are hypertonic, water soluble salts derived from an iodinated benzoic acid precursor. Diatrizoate, the anion of sodium diatrizoate and methylglucamine diatrizoate, can be considered the prototype agent. Identical considerations apply to iothalamate, an isomer of diatrizoate and the anion of methylglucamine iothalamate. This agent also is in widespread use for the IVP. After rapid intravenous injection diatrizoate is diluted immediately in the circulating plasma volume and begins to diffuse into the extravascular space, while simultaneously undergoing filtration by the kidneys. Equilibration between the intravascular and extravascular compartment concentrations occurs approximately 10 minutes after injection. The plasma level of diatrizoate at this time is a direct function of the injected dose and body size. As urinary excretion proceeds the plasma diatrizoate level decreases, resulting in re-entry of diatrizoate from the extravascular to the intravascular compartment. 9 Although earlier, now obsolete contrast agents were secreted by the renal tubules present day agents are excreted almost entirely by glomerular filtration and are not reabsorbed. 8 • 9 A small amount of tubular secretion can be demonstrated at 437
Rapid injection of a bolus of contrast medium produces maximum plasma iodine concentration and a faint total-body opacification in which vascular organs (such as the liver, spleen and intestines) become slightly opaque even though they do not excrete the contrast agent. A radiograph of the kidneys approximately 15 seconds after such an injection, as the bolus clears the renal artery on its first circulation, demonstrates a profound nephrogram. The intensity of this purely vascular nephrogram is dependent on renal blood flow and not on the functional status of the renal parenchyma per se. Differential corticomedullary opacification often is present, similar to that seen with renal arteriography. As the vascular component of this nephrogram peaks and then fades a homogeneous tubular or excretory nephrogram follows. This nephrogram is largely a manifestation of contrast material in the proximal tubular lumina and, as such, it depends on the filtered load-the product of the glomerular filtration rate and plasma diatrizoate concentration. Being related to glomerular filtration rate this tubular nephrogram is dependent on renal function. However, it ordinarily is independent of the state of hydration. 12 In normal subjects the nephrogram attains its maximal density by the end of the bolus injection of contrast medium and remains dense for approximately 2 minutes, at which time contrast molecules begin to reach the calices. The nephrogram then fades gradually as the pyelogram develops. At this time patients with a normal glomerular filtration rate may show dense opacification of the papillae related to high concentrations of contrast medium in the collecting tubules, which,is a normal phenomenon and is not to be confused with pathological causes of increased papillary density, such as tubular ectasia or. papillary necrosis. NORMAL PYELOGRAPHIC DENSITY
Pyelographic density is determined mainly by the amount of contrast material in the calices and pelvis at a given time. It is dependent on the concentration of contrast medium in the
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urine and on the volume of urine in the collecting system, that is the total number of iodine atoms in the pathway of the x-ray beam. 13 Either sodium or methylglucamine is used as the cation for the contrast molecules. Since methylglucamine is not reabsorbed it produces a more pronounced osmotic diuresis than does the sodium salt. The result is a greater urinary iodine concentration with the latter but better pyelocaliceal distension with the former. IVPs made with the 2 different cations are remarkably similar in day-to-day practice, 14- 16 although clinical studies have suggested a slight superiority with the sodium salt, 17 especially when abdominal ureteral compression is applied. As noted previously dehydration before an IVP improves pyelographic quality. The technique of a drip infusion IVP, in which a large dose of contrast material is combined with an equal volume of distilled water or glucose and then infused into the patient in several minutes, has achieved considerable popularity since its introduction by Schencker in 1964. 18 Although large doses of contrast material had been used sporadically for an IVP before then it was probably the novelty and convenience of adminis-tration of the drip infusion technique that stimulated a general tendency to use larger doses. No urographic advantage is gained when a large dose of contrast material is given by infusion rather than by bolus injection. 19
contrast medium indicates a high probability of some degree of renal compromise. The finding of such a persistent nephrogram may suggest renal failure induced by contrast medium earlier than the diagnosis is possible clinically. 22 With regard to the filtered load of contrast medium any evaluation of nephrographic density alterations must begin with a knowledge of the amount of contrast medium administered and its delivery time (bolus versus drip). Diminished filtration states can then be considered. These include patients with decreased cardiac output and poor renal perfusion, and those with hypotension, either on the basis of trauma or consequent to a vasovagal response to the injection of urographic contrast material. Reduced cortical blood flow delays and diminishes the early vascular nephrogram; the decreased glomerular filtration rate has the same effect upon the tubular nephrogram. However, as the latter develops it eventually exceeds the density of the normal nephrogram. The time sequence of the paradoxically dense nephrogram in hypotension is similar to that of the obstructive nephrogram. They have in common a
ABNORMAL !VP
Abnormal nephrographic density. Alterations in either axis of the nephrographic time-density relationship are significant. Conditions that delay the arrival of contrast medium at the glomerulus (diminished renal blood flow) and those that prolong its transit time within the tubule (obstruction, acute tubular necrosis and renal vein thrombosis) are examples of time alterations. Changes in either component of the filtered load (plasma contrast concentration or glomerular filtration rate) alter radiographic density. Diminished renal blood flow will be considered primarily in a separate section on the hypertensive IVP. Of the conditions that prolong the transit of contrast material in the tubules obstruction serves as a prototype to illustrate nephrographic alterations. In the immediate post-obstructive period renal blood flow and glomerular filtration rate remain nearly normal and urographic contrast medium freely enters the nephron. Movement of intratubular urine is slowed by the obstruction, permitting increased water reabsorption. This, plus concomitant tubular distension, allows a continuous input of contrast medium into the tubules at a rate far exceeding the ability of urine to be discharged into the renal pelvis. With an acute increase in intrapelvic pressure urine can leak also through small ruptures at the caliceal fornices into the renal sinus and be reabsorbed by renal lymphatics, decreasing intrapelvic pressure and further facilitating glomerular filtration. 20 The time-density curve of the obstructive nephrogram depends on the balance between the rates at which contrast material enters the nephron and leaves the collecting ducts. With acute severe obstruction inflow exceeds outflow, the kidney becomes swollen and large, and the nephrogram becomes progressively denser over a period of hours (fig. 1). However, with chronic obstruction renal blood flow decreases, 21 so that eventually the glomerular filtration rate may not be adequate to deliver sufficient contrast medium to enable the tubules to opacify significantly. Under these circumstances and especially in the presence of a normal contralateral kidney a poor nephrogram will result. Generally speaking, the intensity of the nephrogram is roughly proportional to the remaining integrity of the kidney. Abnormally dense nephrograms may be seen in a variety of conditions, including acute obstruction, hypotension, renal vein thrombosis and acute renal failure (fig. 2). Recent observations suggest that an abnormally persistent nephrogram after the use of iodinated
FIG. 1. Obstructive nephrogram: 4-hour IVP shows persistently dense nephrogram in enlarged right kidney and delayed faint visualization of mildly dilated pyelocaliceal system and proximal ureter (arrowheads) down to obstructing ureteral calculus at L3-IA interspace (curved arrow).
Fm. 2. Acute renal failure secondary to myoglobinuric nephropathy. Bilateral persistently dense nephrograms noted on 24-hour IVP. Presumably, precipitation of myoglobin in renal tubules prevented contrast medium from reaching calices or pelves with resultant absent pyelograms. Note vicarious excretion of contrast medium with subsequent gallbladder visualization (GB). Contrast medium also may be excreted vicariously by intestinal tract.
IVP EVALUATION OF RENAL FUNCTION
markedly slowed rate of flow along the nephron. Maximal tubular reabsorption of sodium and water leaves large amounts of contrast medium in the tubules and, hence, the eventual increased radiopacity of this type of nephrogram (fig. 3).23 A sometimes dramatic consequence of hypotension is an acute reduction in kidney size because of diminished renal blood flow and intratubular volume. Such changes in kidney size may occur quite rapidly and are reversed when blood pressure is restored. Increased blood pressure also clears the nephrogram and fills the calices. 24 Abnormal pyelographic density. Abnormal pyelographic density may be seen with either normal or abnormal renal
FIG. 3. IVP during hypotension, performed for nephrolithiasis. A, 2minute uro-tomogram shows prompt and symmetric nephrograms. Shortly thereafter patient had hypotension and bradycardia and was treated intravenously with 2.5 mg. atropine. B, radiograph at 10 minutes while blood pressure was returning to normal still shows persistent nephrograms and no caliceal filling. Note 3 opaque stones in left kidney (arrowheads). Normally, collecting system should be well filled and densely opaque by this time. C, subsequent radiograph after blood pressure and pulse returned to normal demonstrates good filling of collecting systems. Calculi in left lower pole calices are seen again.
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function. In the presence of normal kidneys it may be caused by any of the diminished filtration states that alter the nephrogram. However, unlike the nephrogram, the pyelogram is sensitive to changes in hydration. Administration of fluids before an IVP may lessen pyelographic density significantly (fig. 4). 13 Diuretics and the presence of diabetes insipidus also can impair pyelographic visualization. 13 The inability to standardize and control the degree of patient dehydration, as exemplified by the marked variation in urine osmolality in normal patients after an overnight fast, is 1 factor that makes the IVP an unsatisfactory test of renal function. 8 Unless doses are standardized on a volume-for-weight basis renal function of any one patient cannot be compared to that of another. Such strict standardization is not used customarily, since the IVP is performed primarily for the delineation of morphology and not function. It is, thus, more advantageous to use large quantities of contrast material rather than the small doses necessary to detect deviations in renal function. Most patients receive a standard dose of 75 or 100 cc contrast medium, which is large enough to obscure reductions in renal function of ~50 per cent. 25 The evaluation of radiographic density is a subjective phenomenon varying from one observer to another. Therefore, it cannot be quantitated accurately. Attempts to do so are further complicated by the superimposition of intestinal gas, fecal material and soft tissue densities, variations in radiographic techniques and, finally, the varying geometries of the renal collecting systems. It is clearly apparent, then, that judging renal function on the basis of pyelocaliceal density is a precarious undertaking. Even radiography of voided urine specimens, as advocated by some, 25 does not materially improve the reliability of the estimate. In patients with obstructive uropathy the dilutional effect of large volumes of urine on the excreted contrast medium must also be taken into consideration. Excellent pyelographic density in the face of renal disease represents another pitfall in the attempt to equate urographic appearance with renal function. This is best exemplified by the unilateral severely contracted kidney, which still exhibits excellent nephrographic and pyelographic density as long as the opposite kidney retains good function. Ellis and associates showed that a unilaterally diseased kidney with a glomerular filtration rate <10 ml. per minute may concentrate adequately because it does not excrete the load of water and solute that would be necessary were both kidneys diseased similarly. 26 In this setting the superimposition of significant nephron loss in the normal kidney results in failure of concentration by the original abnormal side. Thus, the adequacy of contrast visualization in the unilaterally diseased kidney cannot be accepted per se as a quantitative estimate of its true functional state. Certainly, any attempts to predict the potential life-sustaining capability of an abnormal kidney based solely on radiographic impressions of pyelographic density are ill-advised at best and catastrophic at worst (fig. 5). Other causes of unilateral (or bilateral) renal non-visualization on an IVP include 1) virtually complete destruction of the nephron population of the involved kidney, 2) total or high grade occlusion of the renal artery, 3) high grade to total obstruction of urine flow and 4) high rates of solute and water excretion by the involved organ, such as may occur occasionally after relief of urinary tract obstruction. A kidney that fails to excrete contrast material, especially if its ureter is obstructed suddenly, may be a kidney that is actively filtering urine and will revert to an entirely normal appearance after removal of the obstruction. This is true even if the contralateral kidney has undergone compensatory hypertrophy. 27 Return of useful renal function has been observed after ureteral obstruction and renal non-visualization of up to 150 days. 28 The inability of the IVP to ascertain whether nonvisualization is related to reversible or irreversible functional impairment points out the imprecision of designating a kidney
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reflux or from faulty neuromuscular development of the ureter. Uncomplicated urinary tract infection may cause ureteral dilatation through the inhibitory effect of endotoxin on ureteral smooth muscle, and hormonal effect on smooth muscle tone is thought to cause, at least in part, "pregnancy dilatation" of the urinary tract. 31 Conversely, the absence of dilated calices does not always exclude obstruction, as in patients with intermittent hydronephrosis who have no apparent difficulty when urine flow rate is low or moderate but under the stress of diuresis have typical radiological findings and, often, flank pain. The fact that the IVP does not, strictly speaking, depict the urinary tract in its average physiological state is sometimes overlooked. All contrast agents are, by nature of their hyperosmolarity, diuretics of varying potency, capable of causing a temporary dilatation of the readily distensible calices, pelves and ureters. Large doses of contrast medium, especially when administered with added fluid as in an infusion IVP, may even produce a transient hydronephrotic pattern. 18 Acute distension of the bladder with its well known inhibitory effect on ureteral emptying also may have a role in the development of this phenomenon. 32• 33 Finally, abdominal ureteral compression, when effectively applied, temporarily obstructs the upper urinary tract. HYPERTENSIVE IVP
Although, as we have seen, an IVP is more a morphologic than a functional study attempts to modify it have been made
Fm. 4. Effect of hydration on pyelographic density. A, IO-minute IVP shows normal nephrograms out markedly diminished pyelographic density. Careful questioning disclosed that patient had ingested 2 cups of coffee just before study. B, repeat study next day after overnight dehydration with same amount of contrast medium injected as in part A. Note excellent pyelographic density. In absence of urinary tract obstruction intravenous administration of diuretic immediately after study in part B would produce picture similar to part A within 10 to 15 minutes.
as non-functioning rather than non-visualizing. A non-visualizing kidney on an IVP may demonstrate iodine excretion by computed tomography, since that imaging modality is much more sensitive than the IVP in detecting low concentrations of iodine. 29 Regarding obstructive uropathy mention should be made of an interesting and not entirely explained observation. In acute upper urinary tract obstruction, especially when produced by a ureteral calculus, an initial IVP may demonstrate only a dense nephrogram or faint pyelocaliceal visualization on delayed films. However, a repeat IVP several days later often shows a normal nephrogram and more prompt pyelogram even though the calculus has not changed its position (fig. 6). We believe 2 possible explanations are available: 1) initial ureteral edema at the site of the lodged calculus may partially subside, lessening the degree of obstruction, and 2) although still speculative continued upper tract obstruction may allow for the establishment of an increasing number of pyelosinus and pyelolymphatic communications. By lowering intrapelvic pressure these communications would permit filtered urine and contrast medium to exit the collecting system despite the presence of the obstructing stone. The practical implication of these facts is obvious. No decision to either remove or retain a kidney should be based solely on its appearance on an IVP. Urinary tract dilatation cannot always be equated with obstruction. The mega-urinary tract of primary diabetes insipidus develops in the absence of an anatomic obstruction.30 Dilatation is accounted for by the adaptation of the urinary tract to the large volume of urine continually excreted. Hydroureter and hydronephrosis also may result from primary vesicoureteral
Fm. 5. Pyelographic density in unilateral renal disease. A, IVP shows normal right kidney and shrunken left kidney containing ring calcifications in upper and lower pole calices from old renal tuberculosis. Note contrast excretion into clubbed mid pole calices (c). Narrowed renal pelvis and normal proximal ureter (dots) are of comparable density to right collecting system. B, 6 months later right distal ureter became obstructed by bladder tumor. IVP now shows enlarged right kidney with faint visualization of dilated collecting system (dots). Previously diseased left kidney cannot handle increased solute and water load secondary to obstructed right kidney and fails to concentrate contrast material. Calcified calices in small left kidney now readily apparent (compare to part A). Subsequent IVP after relief of rightsided obstruction virtually identical to part A.
IVP EVALUATION OF RENAL FUNCTION
Fm. 6. IVP during acute obstructive uropathy. A, faint visualization of mildly dilated right renal collecting system and ureter noted at time of acute right renal colic. Note obstructing stone in distal right ureter (arrow). B, 3 days later calculus has not moved (arrow) and degree of dilatation is comparable. However, pyelographic visualization is much improved and comparable to normal left side. Note standing column of contrast material in right ureter down to unchanged calculus.
so as to generate reliably selected physiologic data. The rapid sequence or hypertensive IVP represents such an effort. 34 In these studies films are taken at I-minute intervals for the first 5 minutes after contrast injection in an attempt to compare appearance time and density of contrast medium in the parenchyma and the collecting systems of both kidneys. It is hoped that the decreased glomerular filtration rate accompanying renal ischemia may reflect itself as a diminished nephrogram and a delayed pyelogram of decreased density. However, the sensitivity of this radiographic split-function test is considerably lessened by the inconsistency with which diminution in renal blood flow produces detectable nephrographic and pyelographic derangements. Difficulties are produced by the relative insensitivity of radiographic techniques in detecting small differences in iodine concentration, by differences in collecting system geometry between the 2 kidneys and by the contrast-induced diuresis that further obscures differences in urine iodine concentration. Amplatz attempted to take advantage of this latter effect by pointing out that a kidney affected with renal artery stenosis should reabsorb a greater percentage of its filtered water than normal. 35 By further increasing diuresis through the use of urea given at the conclusion of the IVP he demonstrated that the ischemic kidney retains more contrast material in its collecting system (paradoxical hyperconcentration) after the urea washout than does the contralateral kidney. However, this modification has not increased the accuracy of a hypertensive IVP significantly and generally is considered too impractical for general use. Another variation of a hypertensive IVP (vasodilated IVP) is based on the observations that 1) kidneys enlarge in response to diuretics and 2) a kidney with renal artery stenosis enlarges less than one with a normal renal artery. The test is performed by measuring changes in renal size during the IVP after intravenous injection of ethacrynic acid or furosemide. An increase in area of ~5 to 10 per cent is considered normal, while lesser
increases are suggestive of renal ischemia. 36 Although a vasodilated IVP has the advantages of a quantitative study and, theoretically, could detect bilateral renal artery stenosis, recent reports have shown a high incidence of falsely positive and indeterminant results in hypertensive patients without renal artery stenosis. 37 Although 83 per cent of the patients with unilateral renoprival hypertension have a positive hypertensive IVP 17 per cent do not and 10 per cent of the patients with essential hypertension have a falsely positive study. 38 A high percentage of patients with bilateral or segmental arterial stenosis show false results, pointing out the shortcomings of the IVP in the diagnosis of renovascular hypertension. In many centers it is no longer used as a screening procedure for this disease. IVP IN RENAL FAILURE
Although azotemia may be caused by pre-renal factors that diminish renal blood flow or by post-renal urinary tract obstruction the majority of patients with chronic uremia have some form of intrinsic renal disease. The common pathological alteration in this group of patients is loss of nephrons, which results in a depressed glomerular filtration rate. Although the remaining nephrons are normal or even functionally hypertrophied (intact nephron hypothesis) it is characteristic of uremia that urine cannot be concentrated normally. 39 These alterations impair all of the IVP determinants of nephrographic and pyelographic density except one-the plasma iodine concentration. Hence, to compensate for the expectedly poor IVP in the patient with renal failure the injected dose of contrast medium must be increased to increase the plasma iodine concentration and the filtered load. It is important to anticipate the presence ofrenal failure in patients being referred for an IVP. The results of laboratory studies should, therefore, be available before the IVP to determine the dose of contrast medium for the patient. Blood urea nitrogen and creatinine values are helpful if they
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are elevated. However, the glomerular filtration rate may be as low as 25 per cent of normal, while the creatinine and blood urea values remain within the normal range, as typified by the elderly man with prostatic disease and senile renal atrophy. 11 For this reason, it is recommended that, all other things being equal, elderly patients should empirically receive higher doses of contrast material than are normally used for younger patients. Despite predictably suboptimal visualization valuable information can be obtained from an IVP in most cases, despite marked diminution in renal function or severe oliguria. 12 There are no absolute limits of laboratory values above which an IVP should not be performed, since valuable information has been obtained in patients with a blood urea nitrogen as high as 200 mg./100 dl. and creatinine clearance values <10 dl. per minute. 40 Realistically speaking, however, there is little point in pursuing an IVP in most patients with advanced renal failure for several reasons. First, the clinical information most often required, that is the presence or absence of obstruction, can be obtained safely and accurately by ultrasonography. Second, there is a small but apparently real risk of aggravating preexisting renal disease through the use of contrast medium. It must be kept in mind that the blood urea nitrogen may be elevated for reasons unrelated to renal functional impairment. The use of large doses of contrast material in conjunction with tomography almost always yields a nephrogram that allows estimation of renal size and contour. 6• 40 The appearance of a nephrogram indicates that some glomerular filtration exists. 13 Collecting system visualization ranges from trace to poor but is sufficient in most cases to diagnose or exclude obstruction (fig. 7) .12• 40• 41 Pyelographic density in patients with uremia resulting from urinary tract obstruction usually is far greater than that seen with intrinsic renal disease causing a similar degree of uremia because 1) there are likely to be more functioning nephrons than in intrinsic disease, leading to a larger filtered load, 2) the slow flow down the tubules will allow better reabsorption of water and sodium than with polyuric renal failure and 3) the distended pyelocaliceal system provides a greater depth of contrast medium than usual. 42 Matalon and Eisinger showed that the IVP could be improved if the uremic patient underwent vigorous dialysis before the examination. 43 By lowering the blood urea concentration os-
motic diuresis is diminished and the concentration of urine solutes (including contrast material) is increased. An added advantage to dialysis before an IVP is that the patient will be improved clinically and will tolerate the study better. Although Matalon and Eisinger were able to opacify the urinary tract of patients in whom an IVP with the same technique had been unsuccessful previously the results of other observers are less striking despite comparable reductions in blood urea and creatinine levels. 41 • 44• 45 General experience has been that collecting system visualization before dialysis may be enhanced slightly after dialysis. Dialysis usually does not permit visualization of a collecting system not visualized before dialysis nor does it impair visualization of a system seen before dialysis. Fluid deprivation before an IVP will not enhance urinary contrast medium concentration in patients with renal insufficiency and, in fact, may actually be dangerous. 42 Ultrasonography represents an alternative method of imaging the urinary tract of patients in uremia. The desired information about renal size and contour, the presence or absence of parenchymal cystic disease, and the state of the renal pelvis and calices (obstructed or not) can be more easily and rapidly obtained with ultrasound than with an IVP. The tremendous advantage of ultrasonography is its lack of dependence upon renal function. Hence, an efficacious initial evaluation of the urinary tract in the uremic patient need consist only of an abdominal plain film to detect opaque urinary tract calculi and a renal ultrasonogram to differentiate medical from surgical renal disease. An IVP usually can be circumvented. In view of the apparent deleterious effects of contrast agents on the integrity of some diseased kidneys, this is a particularly attractive feature of ultrasonography.46 Juvenile diabetics with renal insufficiency (creatinine >1.5 mg./dl.) appear to be at greatest risk for the development of contrast-related acute renal failure. This sequela probably is dose-related47 and may occur after administration of contrast agents for a variety of procedures, including angiography, computed tomography and angiocardiography. The etiology of this complication is not clear at present and there is a good deal of controversy about its frequency and exact role in contributing to the accelerated renal failure seen in some patients who have received contrast medium. Until these uncertainties have been clarified it probably is best to avoid an IVP in that small and select group of patients having severe renal insufficiency of diabetic origin insofar as this is possible. REFERENCES
FIG. 7. IVP during renal failure. Despite laboratory evidence of renal insufficiency (blood urea nitrogen 60, creatinine 6.0) uro-tomogram exposed 15 minutes after 100 cc intravenous contrast medium demonstrates renal size and contour, and non-obstructed collecting systems. Arrowheads demarcate proximal ureters. Pyelographic density cannot always be correlated with degree of renal insufficiency. Pathological diagnosis: chronic glomerulonephritis.
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