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Renal failure after major angiography
Renal Failure After Major Angiography
RONALD
L. EISENBERG,
WILLIAM
M.D. W. HEDGCOCK.
MARCUS
0.
M.D.
BANK,
M.D.
A recently reported 12 per cent incidence of renal failure following angiography prompted our prospective study to substantiate or repudiate this seemingly excessive rate. In 100consecutive patients, there was no instance of renal failure following angiography. The results of our study indicate that when adequate hydration is maintained angiography does not pose a “significant hazard” of renal failure as previously reported, even in patients with underlying medical problems. Schwartz et al. [l]recently reported a 12 per cent incidence of acute renal failure following angiography. Extrapolation from this study implies that in an average hospital, in which 15 angiograms are performed per week, at least one case of acute renal failure would be encountered each week and at least two cases of severe renal failure each month. Since this was not our experience, we established a prospective study to evaluate the validity of the previous work on both a short-term (100 patients) and a long-term basis. This report evaluates our short-term analysis of the incidence of clinical and biochemical acute renal failure in patients undergoing angiography.
MATERIAL AND METHODS
From the Departments of Radiology, University of California School of Medicine, San Francisco, and the Veterans Administration Medical Center, 4150 Clement Street, San Francisco, California. Requests for reprints should he addressed to Dr. R. L. Eisenberg, Radiology Service, VA Medical Center, 4150 Clement Street, San Francisco. California 94121. Manuscript accepted July 24,1979.
One hundred consecutive patients undergoing cerebral, abdominal or peripheral angiography during a three-month period at our university-affiliated VA Medical Center constituted the population of our short-term study. We maintained a detailed data sheet for each patient which included history, angiography procedure notes, and laboratory studies preceding and following angiography. As in the previously reported study [l], the presence of the following clinical factors before angiography was extracted from the patient charts: (11 preexisting renal insufficiency, defined as a blood urea nitrogen of 30 mg/dl or more, or a serum creatinine of 1.8 mg/dl or more; (2) hepatic cirrhosis or impaired liver function, the latter being defined as an abnormality in any two of the following: serum glutamic oxaloacetic transaminase, alkaline phosphatase and serum total bilirubin; (3) low serum albumin level, defined as a concentration of 3 g/d1 or less: (4) increased urinary concentration as an index of dehydration, defined as a specific gravity of 1.020 or more in the absence of glucosuria or heavy proteinuria; (5) pathologic proteinuria, defined as a “spot” urine protein of 300 mg/liter or more; [s] gout or hyperuricemia, the latter being defined as a serum uric acid of 7 mg/dl or more; and (7) diabetes mellitus, i.e., an abnormality in a glucose tolerance test, or a random blood sugar of 250 mg/dl or more. In addition, the presence or history of hypertension (diastolic pressure llO0 mm Hg) and myocardial infarction or stroke was noted. All patients’ medications were also tabulated. Cerebral angiograms were performed using sodium iothalamate (Conray” 60 per cent)* exclusively, except for aortic arch studies in which meglumine * Conray-60, MaIlinckrodt Chemical Works, St. Louis, MO
January
1980
The American
Journal of Medicine
Volume
88
43
RENAL FAILURE
TABLE I
AFTER MAJOR ANGIOGRAPHY-EISENBERG
Prevalence of Clinical Dlseases %
Disease Prior myocardial
53
infarction/stroke
Hypertension
43
Diabetes mellitus
31
Renal insufficiency
25
Concentrated
21
urine
High uric acid
13
Proteinuria
11
Liver disease
11
and sodium diatrizoate (Renografins 76 per cent]* was used. Abdominal and peripheral angiography were performed with one or both of these agents, depending upon clinical circumstances. All studies were performed from the femoral or axillary route using the Seldinger technique. The amount of contrast material and the time over which it was given were closely monitored; the amount. of fluid administered both by intravenous infusion of normal saline sqlution and during the routine flushing of catheters was carefully recorded. Any reactions to the contrast agent or the angiographic procedure, as well as the administration of any sedative or vasoactive medications during the procedure, were recorded on the patient data sheets. For the purpose of this study, acute renal failure following angiography was defined as an increase in the blood urea nitrogen of 50 per cent or 20 mg/dl, and/or an increase in the serum creatinine of 1 mg/dl, within 24 hours of the angiographic procedure. Laboratory analyses were performed before, immediately after and 24 hours after the angiograms. They included blood urea nitrogen and serum creatinine determinations as well as urinalysis. Each patient was requested to void prior to the study so that urine samples obtained after the examination would more accurately reflect any effect of the procedure. To evaluate the possible effect of contrast material on other systems, blood samples were drawn at the same time for determination of blood glucose, serum uric acid, serum albumin and total protein, serum glutamic oxaloacetic transaminase, alkaline phosphatase and serum total bilirubin. A plain film of the abdomen was obtained 24 hours after the angiogram to look for the presence of a prolonged nephrogram consistent with acute renal failure. The total dose of contrast agent was calculated as well as the derivative dose of contrast material as a function of time, reported in grams of iodine/hour.
RESULTS Following 53 cerebral
and 47 abdominal or peripheral angiograms, there was no instance of clinical or biochemical evidence of acute renal failure. * Renografin-76,
44
E.R. Squibb and Sons, Princeton,
January 1980
NJ.
The American Journal of Medicine
ET AL.
Table I lists the prevalence of clinical diseases in our study population. Fifty-one patients had two or more of the nine clinical abnormalities assessed by history or initial laboratory values. Twenty-three had two or more of the “risk factors” which, according to the previous study [l], increase the likelihood of renal failure. In no case was there any significant difference between the preliminary and post-angiographic values for serum glutamic oxaloacetic transaminase, alkaline phosphatase, serum total bilirubin, serum albumin or total protein, serum uric acid or blood sugar. In 39 patients there was an increase of 0.010 or more in the specific gravity of the urine obtained immediately after angiography. However, in all of these patients the specific gravity had returned to the levels that existed before the examination by the time of the urinalysis 24 hours after angiography. The volume of contrast material administered ranged from 30 to 500 cc Conray 60% (average 125 cc) for cerebral angiograms, to 150 to 400 cc Conray 60% plus Renografin (average 215 cc) for abdominal and peripheral studies. This represented a total dose of contrast material varying from 1 to 5 cc/kg, with an average patient dose of 2 cc/kg. During each hour of procedure time, patients received an average of 550 cc of normal saline solution intravenously and 250 cc of heparinized saline solution given as flush solution. No patient displayed a persistent nephrogram on a plain film of the abdomen obtained 24 hours after the completion of each examination. The calculated total dose of contrast agent ranged from 9 to 60 g of iodine (average 35 g) for cerebral angiograms and from 46 to 120 g (average 66 g) for peripheral angiograms. The derivative dose as a function of time ranged from 20 to 65 g of iodine per hour (average 40 g) for peripheral angiograms. Relating these data to patient weight, the maximum total dose of iodine administered was 2 g/kg with an average patient receiving 0.7 g/kg of iodine. Two minimal allergic reactions (hives) were noted and responded to treatment with intravenous benadryl.* No other serious angiographic complications were encountered. Five patients were given intravenous diazepant during the study for the treatment of varying degrees of apprehension.
COMMENTS Acute renal failure is a recognized complication of angiography. The results of our prospective study of 100 patients indicate that the risk of renal failure developing following careful angiography is far less than the 12 per cent incidence recently reported [l]. In our series, there was no case of either clinically apparent or biochemi* Benadrylm, Parke-Davis, Morris Plains, New Jersey. t Valium@,Roche Laboratories, Nutley, New Jersey.
Volume 88
RENAL FAILtIRE
tally evident renal failure after cerebral, abdominal or peripheral angiography. The patients in our series appear representative of the general population undergoing angiography. The average patient was 60 years of age and had a number of other significant diseases. The incidence of diabetes (31 per cent], renal insufficiency (25 per cent), high uric acid levels (13per cent], liver disease (11per cent), proteinuria (11per cent], increased urine specific gravity (21per cent), hypertension (43 per cent) and atherosclerotic disease (53 per cent with prior myocardial infarction or cerebrovascular ischemic episode) indicates that our patients had a variety of “risk factors” for angiography. Indeed, 51 per cent of our patients had at least two of the clinical factors listed, and 23 per cent had two or more of the “risk factors” previously reported [l]. One reason that may explain the difference between our study and that of Schwartz et al. [l]is the amount of fluid administered to the patient during the angiographic procedure. In addition to the approximately 250 cc/hour of heparinized saline solution given as flush solution, each of our patients received approximately 550 cc/hour of normal saline solution intravenously in order to maintain adequate hydration in the face of the hyperosmotic contrast load. This compares to only 80 cc/hour of 5 per cent dextrose in water administered intravenously during the procedure in the prior study. Not only is this a small volume, but also the use of dextrose in water does nothing to replace the solute lost through excretion related to the contrast load. The administration of iodinated contrast material has been shown to increase urine volume and osmolar clearance [2]. Fluid replacement is, therefore, required to prevent dehydration. Dehydration has been shown to accentuate the risk of renal failure after the administration of contrast materials, especially in patients with diabetes mellitus and other risk factors [3-51, and could play an important role in any of the proposed mechanisms for contrast material-induced renal toxicity, Experimental data have demonstrated that contrast material infused into the normal kidney initially produces a vasodilator response due to hyperosmolarity, but then results in a late renal vasoconstriction response possibly mediated by the renin-angiotensin system [6,7]. This renal vasoconstriction and the increased blood viscosity in the microcirculation induced by contrast material [8,9] may combine to cause a significant decrease in the glomerular filtration rate and associated renal damage in patients with underlying renal disease whose autoregulation of glomerular filtration and/or renal plasma flow may be impaired [lo]. The uricosuric effect of contrast material may result in the precipitation of urate in the tubular lumen [ll], causing obstruction to the flow of urine and possible cellular injury. The maintaining of adequate renal blood flow by preventing dehydration could prevent this precipitation. Similarly, if the possible
AFTER MAJOR ANGIOGRAPHY-EISENBERG
ET AL.
contrast material-induced precipitation of TammHorsfall protein, a normal constituent of urine, can partially block urine flow and cause renal damage [12], adequate hydration would also minimize this effect. If a direct toxic effect of contrast medium on tubular epithelium is postulated [13], adequate hydration and maintained renal blood flow will decrease the period of exposure of epithelial cells to the contrast agent, again decreasing the chance for the development of renal failure. In 43 per cent of our patients, an increase in urine specific gravity of 0.010or more was noted in urine samples obtained immediately after angiography. Although this may merely be due to the presence of iodinated contrast material in the urine, the increased urine specific gravity may reflect the transient dehydration and decreased renal blood flow that occurred even with the relatively large amounts of intravenous fluid and flush solutions given to our patients routinely during angiography. Within 24 hours, the specific gravity of the urine in all these patients returned to levels that existed before angiography, possibly reflecting our routine orders to encourage oral or parenteral fluids after angiography to enhance the normal urinary excretion of contrast material. Although the previous report [l] stated that their data seldom indicated volume depletion or dehydration following the administration of contrast material, no mention is made of measurements of urine specific gravity immediately after angiography. It may well be that even more pronounced changes of transient dehydration and decreased renal blood flow occurred in their patients, especially since they received much less intravenous fluid during angiography. Perhaps this contributed to their higher incidence of acute renal failure. Although large doses of contrast material have been related to an increased incidence of acute renal failure in patients “at risk” [14-161, the data in our series and others [l]fail to support any dose-response relationship. It is not our intention to suggest that acute renal failure does not occasionally occur following angiography. In fact, the purpose of our long-term study is to obtain an accurate incidence for this complication. It is our conviction, however, that an incidence of 10 to 15 per cent (3 to 5 per cent severe) of acute renal failure following angiography is excessive. Since renal failure can occur after angiography, proper precautions should be employed to decrease this possibility. Of critical importance is the adequate hydration of patients before, during and after the procedure [17]. Even though toxicity of contrast material has not definitely been shown to be dose-related, it would seem prudent to limit the dose of contrast material to that required for an adequate diagnostic study [18].
January 1980
The American Journal of Medicine
Volume 68
45
RENAL FAILURE AFTER MAJOR ANGIOGRAPHY-EISENBERG
CONCLUSION
ET AL
our prospective
Angiograpliy is a valuable diagnostic tool, offering the referring physician information currently unavailable with other modalities. Although complications do occur,
study indicates that, if adequate hydration is maintained, angiography does not pose the “significant hazard” of renal failure as previously reported [I], even in patients with underlying medical problems.
REFEREl’kES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
46
Schwartz RD, Rubin JE, Leeming RW, et al.: Renal failure followihg major angiography. Am 1Med 65: 31,1978. Gup AK, Schlegel JLI: Physiologic effects of high dosage excretory urography. J LIroJ 100: 85,1968. Pomeranc MM: Acute renal failure association with administration of radiographic contrast material. JAMA 239: 125,1978. Port FK, Wagoner RD, Fulton RE: Acute renal failure after angiagraphy. Mayo Clin Proc 121: 544,1974. Weinrauch LA, Robertson WS. D’Elia JA: Contrast mediaproduced acute renal failure. JAMA 239: 2018,1978. Chou CC, Hook JB, Hsieh CP, et al.: Effects of radiopaque dyes on renal vascular resistance. J Lab Clin Med 78: 705, 1971. Norby LH, DiBona GF: The renal vascular effects of meglumine diatrizoate. J Pharmacol Exp Ther 193: 932,1975. Dean RE, Andrew JH, Read RC: The red cell factor in renal damage from angiographic media. JAMA 187: 27,1964. Sobin SS, Frasher WG, Johnson G: Nature of adverse reactions to radiopaque agents: preliminary report. JAMA 170: 1546,1968. Shafi T, Chou SY, Porush JG, et al.: Infusion intravenous pyelography and renal function. Effects in patients with chronic renal insufficiency. Arch Intern Med 138: 1218,
January 1980
The American Journal of Medicine
11.
12.
13. 14. 15.
1978. . _ Postlethwaite AE, KelJy WN: Uricosuric effect of radiocontrast agents. Ann Intern Med 74: 854,1971. Berdon WE, Schwartz RH, Becker J, et al.: Tamm-Horsfall proteinuria: its relationship to prolonged nephrogram in infants and children and to renal failure following intravenous urography in adults with multiple myeloma. Radiology 92: 714,1969. Killen D. Lance EM: Experimental appraisal of the agents employed as angiocardiographic and aortographic contrast media. II. Nenhr,otoxicitv. Surgerv 47: 260.1960. Ansari Z, Baldwin DS: Acute renal failure due to radiocontrast agents. Nephron 17: 28.1976. Gruskin AB, Oetliker OH, Wolfish NM, et al.: Effects of anaionraohv on renal function and histolow in infants and pigJets. J “Pediatr 76: 44.1976. Van Zee BE, Hov WE. Tallv TE. et al.: Renal iniurv associated with intravenous pyelography in non-diabetic and diabetic patients. Ann Intern Med 89: 51, 1978. Gelman ML, Rowe JW, Coggins CH, et al.: Effects of angiographic contrast agent on renal function, Cardiovasc Med 4: 313, 1979. Heneghan M: Contrast-induced acute renal failure. Am J Roentgen01 131: 1113.1978. V”
16. 17.
18.
Volume 68
RONALD
L. EISENBERG,
WILLIAM
M.D. W. HEDGCOCK.
MARCUS
0.
M.D.
BANK,
M.D.
A recently reported 12 per cent incidence of renal failure following angiography prompted our prospective study to substantiate or repudiate this seemingly excessive rate. In 100consecutive patients, there was no instance of renal failure following angiography. The results of our study indicate that when adequate hydration is maintained angiography does not pose a “significant hazard” of renal failure as previously reported, even in patients with underlying medical problems. Schwartz et al. [l]recently reported a 12 per cent incidence of acute renal failure following angiography. Extrapolation from this study implies that in an average hospital, in which 15 angiograms are performed per week, at least one case of acute renal failure would be encountered each week and at least two cases of severe renal failure each month. Since this was not our experience, we established a prospective study to evaluate the validity of the previous work on both a short-term (100 patients) and a long-term basis. This report evaluates our short-term analysis of the incidence of clinical and biochemical acute renal failure in patients undergoing angiography.
MATERIAL AND METHODS
From the Departments of Radiology, University of California School of Medicine, San Francisco, and the Veterans Administration Medical Center, 4150 Clement Street, San Francisco, California. Requests for reprints should he addressed to Dr. R. L. Eisenberg, Radiology Service, VA Medical Center, 4150 Clement Street, San Francisco. California 94121. Manuscript accepted July 24,1979.
One hundred consecutive patients undergoing cerebral, abdominal or peripheral angiography during a three-month period at our university-affiliated VA Medical Center constituted the population of our short-term study. We maintained a detailed data sheet for each patient which included history, angiography procedure notes, and laboratory studies preceding and following angiography. As in the previously reported study [l], the presence of the following clinical factors before angiography was extracted from the patient charts: (11 preexisting renal insufficiency, defined as a blood urea nitrogen of 30 mg/dl or more, or a serum creatinine of 1.8 mg/dl or more; (2) hepatic cirrhosis or impaired liver function, the latter being defined as an abnormality in any two of the following: serum glutamic oxaloacetic transaminase, alkaline phosphatase and serum total bilirubin; (3) low serum albumin level, defined as a concentration of 3 g/d1 or less: (4) increased urinary concentration as an index of dehydration, defined as a specific gravity of 1.020 or more in the absence of glucosuria or heavy proteinuria; (5) pathologic proteinuria, defined as a “spot” urine protein of 300 mg/liter or more; [s] gout or hyperuricemia, the latter being defined as a serum uric acid of 7 mg/dl or more; and (7) diabetes mellitus, i.e., an abnormality in a glucose tolerance test, or a random blood sugar of 250 mg/dl or more. In addition, the presence or history of hypertension (diastolic pressure llO0 mm Hg) and myocardial infarction or stroke was noted. All patients’ medications were also tabulated. Cerebral angiograms were performed using sodium iothalamate (Conray” 60 per cent)* exclusively, except for aortic arch studies in which meglumine * Conray-60, MaIlinckrodt Chemical Works, St. Louis, MO
January
1980
The American
Journal of Medicine
Volume
88
43
RENAL FAILURE
TABLE I
AFTER MAJOR ANGIOGRAPHY-EISENBERG
Prevalence of Clinical Dlseases %
Disease Prior myocardial
53
infarction/stroke
Hypertension
43
Diabetes mellitus
31
Renal insufficiency
25
Concentrated
21
urine
High uric acid
13
Proteinuria
11
Liver disease
11
and sodium diatrizoate (Renografins 76 per cent]* was used. Abdominal and peripheral angiography were performed with one or both of these agents, depending upon clinical circumstances. All studies were performed from the femoral or axillary route using the Seldinger technique. The amount of contrast material and the time over which it was given were closely monitored; the amount. of fluid administered both by intravenous infusion of normal saline sqlution and during the routine flushing of catheters was carefully recorded. Any reactions to the contrast agent or the angiographic procedure, as well as the administration of any sedative or vasoactive medications during the procedure, were recorded on the patient data sheets. For the purpose of this study, acute renal failure following angiography was defined as an increase in the blood urea nitrogen of 50 per cent or 20 mg/dl, and/or an increase in the serum creatinine of 1 mg/dl, within 24 hours of the angiographic procedure. Laboratory analyses were performed before, immediately after and 24 hours after the angiograms. They included blood urea nitrogen and serum creatinine determinations as well as urinalysis. Each patient was requested to void prior to the study so that urine samples obtained after the examination would more accurately reflect any effect of the procedure. To evaluate the possible effect of contrast material on other systems, blood samples were drawn at the same time for determination of blood glucose, serum uric acid, serum albumin and total protein, serum glutamic oxaloacetic transaminase, alkaline phosphatase and serum total bilirubin. A plain film of the abdomen was obtained 24 hours after the angiogram to look for the presence of a prolonged nephrogram consistent with acute renal failure. The total dose of contrast agent was calculated as well as the derivative dose of contrast material as a function of time, reported in grams of iodine/hour.
RESULTS Following 53 cerebral
and 47 abdominal or peripheral angiograms, there was no instance of clinical or biochemical evidence of acute renal failure. * Renografin-76,
44
E.R. Squibb and Sons, Princeton,
January 1980
NJ.
The American Journal of Medicine
ET AL.
Table I lists the prevalence of clinical diseases in our study population. Fifty-one patients had two or more of the nine clinical abnormalities assessed by history or initial laboratory values. Twenty-three had two or more of the “risk factors” which, according to the previous study [l], increase the likelihood of renal failure. In no case was there any significant difference between the preliminary and post-angiographic values for serum glutamic oxaloacetic transaminase, alkaline phosphatase, serum total bilirubin, serum albumin or total protein, serum uric acid or blood sugar. In 39 patients there was an increase of 0.010 or more in the specific gravity of the urine obtained immediately after angiography. However, in all of these patients the specific gravity had returned to the levels that existed before the examination by the time of the urinalysis 24 hours after angiography. The volume of contrast material administered ranged from 30 to 500 cc Conray 60% (average 125 cc) for cerebral angiograms, to 150 to 400 cc Conray 60% plus Renografin (average 215 cc) for abdominal and peripheral studies. This represented a total dose of contrast material varying from 1 to 5 cc/kg, with an average patient dose of 2 cc/kg. During each hour of procedure time, patients received an average of 550 cc of normal saline solution intravenously and 250 cc of heparinized saline solution given as flush solution. No patient displayed a persistent nephrogram on a plain film of the abdomen obtained 24 hours after the completion of each examination. The calculated total dose of contrast agent ranged from 9 to 60 g of iodine (average 35 g) for cerebral angiograms and from 46 to 120 g (average 66 g) for peripheral angiograms. The derivative dose as a function of time ranged from 20 to 65 g of iodine per hour (average 40 g) for peripheral angiograms. Relating these data to patient weight, the maximum total dose of iodine administered was 2 g/kg with an average patient receiving 0.7 g/kg of iodine. Two minimal allergic reactions (hives) were noted and responded to treatment with intravenous benadryl.* No other serious angiographic complications were encountered. Five patients were given intravenous diazepant during the study for the treatment of varying degrees of apprehension.
COMMENTS Acute renal failure is a recognized complication of angiography. The results of our prospective study of 100 patients indicate that the risk of renal failure developing following careful angiography is far less than the 12 per cent incidence recently reported [l]. In our series, there was no case of either clinically apparent or biochemi* Benadrylm, Parke-Davis, Morris Plains, New Jersey. t Valium@,Roche Laboratories, Nutley, New Jersey.
Volume 88
RENAL FAILtIRE
tally evident renal failure after cerebral, abdominal or peripheral angiography. The patients in our series appear representative of the general population undergoing angiography. The average patient was 60 years of age and had a number of other significant diseases. The incidence of diabetes (31 per cent], renal insufficiency (25 per cent), high uric acid levels (13per cent], liver disease (11per cent), proteinuria (11per cent], increased urine specific gravity (21per cent), hypertension (43 per cent) and atherosclerotic disease (53 per cent with prior myocardial infarction or cerebrovascular ischemic episode) indicates that our patients had a variety of “risk factors” for angiography. Indeed, 51 per cent of our patients had at least two of the clinical factors listed, and 23 per cent had two or more of the “risk factors” previously reported [l]. One reason that may explain the difference between our study and that of Schwartz et al. [l]is the amount of fluid administered to the patient during the angiographic procedure. In addition to the approximately 250 cc/hour of heparinized saline solution given as flush solution, each of our patients received approximately 550 cc/hour of normal saline solution intravenously in order to maintain adequate hydration in the face of the hyperosmotic contrast load. This compares to only 80 cc/hour of 5 per cent dextrose in water administered intravenously during the procedure in the prior study. Not only is this a small volume, but also the use of dextrose in water does nothing to replace the solute lost through excretion related to the contrast load. The administration of iodinated contrast material has been shown to increase urine volume and osmolar clearance [2]. Fluid replacement is, therefore, required to prevent dehydration. Dehydration has been shown to accentuate the risk of renal failure after the administration of contrast materials, especially in patients with diabetes mellitus and other risk factors [3-51, and could play an important role in any of the proposed mechanisms for contrast material-induced renal toxicity, Experimental data have demonstrated that contrast material infused into the normal kidney initially produces a vasodilator response due to hyperosmolarity, but then results in a late renal vasoconstriction response possibly mediated by the renin-angiotensin system [6,7]. This renal vasoconstriction and the increased blood viscosity in the microcirculation induced by contrast material [8,9] may combine to cause a significant decrease in the glomerular filtration rate and associated renal damage in patients with underlying renal disease whose autoregulation of glomerular filtration and/or renal plasma flow may be impaired [lo]. The uricosuric effect of contrast material may result in the precipitation of urate in the tubular lumen [ll], causing obstruction to the flow of urine and possible cellular injury. The maintaining of adequate renal blood flow by preventing dehydration could prevent this precipitation. Similarly, if the possible
AFTER MAJOR ANGIOGRAPHY-EISENBERG
ET AL.
contrast material-induced precipitation of TammHorsfall protein, a normal constituent of urine, can partially block urine flow and cause renal damage [12], adequate hydration would also minimize this effect. If a direct toxic effect of contrast medium on tubular epithelium is postulated [13], adequate hydration and maintained renal blood flow will decrease the period of exposure of epithelial cells to the contrast agent, again decreasing the chance for the development of renal failure. In 43 per cent of our patients, an increase in urine specific gravity of 0.010or more was noted in urine samples obtained immediately after angiography. Although this may merely be due to the presence of iodinated contrast material in the urine, the increased urine specific gravity may reflect the transient dehydration and decreased renal blood flow that occurred even with the relatively large amounts of intravenous fluid and flush solutions given to our patients routinely during angiography. Within 24 hours, the specific gravity of the urine in all these patients returned to levels that existed before angiography, possibly reflecting our routine orders to encourage oral or parenteral fluids after angiography to enhance the normal urinary excretion of contrast material. Although the previous report [l] stated that their data seldom indicated volume depletion or dehydration following the administration of contrast material, no mention is made of measurements of urine specific gravity immediately after angiography. It may well be that even more pronounced changes of transient dehydration and decreased renal blood flow occurred in their patients, especially since they received much less intravenous fluid during angiography. Perhaps this contributed to their higher incidence of acute renal failure. Although large doses of contrast material have been related to an increased incidence of acute renal failure in patients “at risk” [14-161, the data in our series and others [l]fail to support any dose-response relationship. It is not our intention to suggest that acute renal failure does not occasionally occur following angiography. In fact, the purpose of our long-term study is to obtain an accurate incidence for this complication. It is our conviction, however, that an incidence of 10 to 15 per cent (3 to 5 per cent severe) of acute renal failure following angiography is excessive. Since renal failure can occur after angiography, proper precautions should be employed to decrease this possibility. Of critical importance is the adequate hydration of patients before, during and after the procedure [17]. Even though toxicity of contrast material has not definitely been shown to be dose-related, it would seem prudent to limit the dose of contrast material to that required for an adequate diagnostic study [18].
January 1980
The American Journal of Medicine
Volume 68
45
RENAL FAILURE AFTER MAJOR ANGIOGRAPHY-EISENBERG
CONCLUSION
ET AL
our prospective
Angiograpliy is a valuable diagnostic tool, offering the referring physician information currently unavailable with other modalities. Although complications do occur,
study indicates that, if adequate hydration is maintained, angiography does not pose the “significant hazard” of renal failure as previously reported [I], even in patients with underlying medical problems.
REFEREl’kES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
46
Schwartz RD, Rubin JE, Leeming RW, et al.: Renal failure followihg major angiography. Am 1Med 65: 31,1978. Gup AK, Schlegel JLI: Physiologic effects of high dosage excretory urography. J LIroJ 100: 85,1968. Pomeranc MM: Acute renal failure association with administration of radiographic contrast material. JAMA 239: 125,1978. Port FK, Wagoner RD, Fulton RE: Acute renal failure after angiagraphy. Mayo Clin Proc 121: 544,1974. Weinrauch LA, Robertson WS. D’Elia JA: Contrast mediaproduced acute renal failure. JAMA 239: 2018,1978. Chou CC, Hook JB, Hsieh CP, et al.: Effects of radiopaque dyes on renal vascular resistance. J Lab Clin Med 78: 705, 1971. Norby LH, DiBona GF: The renal vascular effects of meglumine diatrizoate. J Pharmacol Exp Ther 193: 932,1975. Dean RE, Andrew JH, Read RC: The red cell factor in renal damage from angiographic media. JAMA 187: 27,1964. Sobin SS, Frasher WG, Johnson G: Nature of adverse reactions to radiopaque agents: preliminary report. JAMA 170: 1546,1968. Shafi T, Chou SY, Porush JG, et al.: Infusion intravenous pyelography and renal function. Effects in patients with chronic renal insufficiency. Arch Intern Med 138: 1218,
January 1980
The American Journal of Medicine
11.
12.
13. 14. 15.
1978. . _ Postlethwaite AE, KelJy WN: Uricosuric effect of radiocontrast agents. Ann Intern Med 74: 854,1971. Berdon WE, Schwartz RH, Becker J, et al.: Tamm-Horsfall proteinuria: its relationship to prolonged nephrogram in infants and children and to renal failure following intravenous urography in adults with multiple myeloma. Radiology 92: 714,1969. Killen D. Lance EM: Experimental appraisal of the agents employed as angiocardiographic and aortographic contrast media. II. Nenhr,otoxicitv. Surgerv 47: 260.1960. Ansari Z, Baldwin DS: Acute renal failure due to radiocontrast agents. Nephron 17: 28.1976. Gruskin AB, Oetliker OH, Wolfish NM, et al.: Effects of anaionraohv on renal function and histolow in infants and pigJets. J “Pediatr 76: 44.1976. Van Zee BE, Hov WE. Tallv TE. et al.: Renal iniurv associated with intravenous pyelography in non-diabetic and diabetic patients. Ann Intern Med 89: 51, 1978. Gelman ML, Rowe JW, Coggins CH, et al.: Effects of angiographic contrast agent on renal function, Cardiovasc Med 4: 313, 1979. Heneghan M: Contrast-induced acute renal failure. Am J Roentgen01 131: 1113.1978. V”
16. 17.
18.
Volume 68