Oral Cholecystography in Chronic Renal Insufficiency R O B E R T P. P E R R I L L O , MD, G A R Y R. Z U C K E R M A N , DO, R O B E R T K O E H L E R , R O B E R T J. S T A N L E Y , MD
MD, and
Thirty-two patients with chronic renal insufficiency (CRI) had oral cholecystography. Eleven of 15 patients (73%) with moderately advanced renal impairment had diagnostically inadequate single-dose cholecystograms. In contrast, all 11 patients on chronic hemodialysis had diagnostically opacified gallbladders following a single dose of contrast. Six other patients had biliary disease, either calculi (5 patients) or neoplasia (1 patient). These data suggest that CRI diminishes the likelihood of diagnostic gallbladder opacification, even in the absence of gallbladder disease, and that if the metabolic consequences of CRI are controlled by dialysis, the chances of diagnostic opacification are significantly improved (P < 0.005). As oral cholecystography may not only result in inadequate opacification, but also carry the potential of renal toxicity, abdominal ultrasound should prove a safer and possibly more effective alternative in such patients.
Chronic renal failure is becoming an increasingly well recognized medical p r o b l e m (1), and it has been estimated that by 1980-1982 about 50,00060,000 A m e r i c a n s will be receiving t r e a t m e n t for end-stage renal disease (2). While there has been a resurgence of interest in the gastrointestinal compli-. cations of patients with chronic renal failure (3-7), little is known of the overall frequency of biliary tract disease in such individuals. It had been the impression of the authors that patients with chronic renal insufficiency d e m o n s t r a t e d an increased freq u e n c y of nondiagnostic first day oral cholecystograms. Because of this, a study was done at this institution to assess whether inadequate visualization was m o r e c o m m o n in this population and if so, w h e t h e r this indicated biliary disease with the same frequency as has been reported in a general population of patients (8, 9, 10).
From the Department of Medicine and the Mallinckrodt Institute of Radiology, Washington University School of Medicine, St, Louis, Missouri 63110. Address for reprint requests: Dr. R.P. Perrillo , Division of Gastroenterology, Department of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110.
M A T E R I A L S AND METHODS: We reviewed the records of the 402 patients with a diagnosis of CRI at this institution from 1971 to 1975. Of this number, 32 patients with intact gallbladders had undergone standard oral cholecystography and these patients comprised the study population. Study group I was comprised of 11 individuals who had been treated with thrice-weekly hemodialysis on coil-type dialyzers for a period of three months or longer at the time of cholecystogram. All patients in this group had advanced CRI with a group mean serum creatinine of 11.7 mg/dl. Study group II was comprised of 21 patients not being managed with chronic hemodialysis. Nineteen patients in this group had moderate to severe renal insufficiency with a group mean serum creatinine of 7.1 mg/dl at the time of the study. Two patients had relatively mild CRI with serum creatinine less than 2 mg/dl. The usual preparation for oral cholecystography included a light fat-free evening meal preceding ingestion of the contrast agent. Four patients received iopanoic acid, 3 g; nine received sodium tyropanoate, 3 g; and 19 patients received iocetamic acid, 3 g. Dialysis patients were instructed to take the contrast agent at home on the evening prior to dialysis. All other patients received oral cholecystography as in-patients. Ten to 15 hr after ingestion of the cholecystographic agent, standard prone and oblique radiographs and erect spot films of the gallbladder were obtained. When necessary, second (12 patients) and
Digestive Diseases, Val. 23, No. 9 (September 1978) 0002-9211/78/0900-0829505.00/19 1978DigestiveDiseaseSystemsInc.
829
PERRILLO ET AL third day (3 patients) studies were obtained using an additional 3-g dose of the same contrast agent. Cholecystograms were independently reviewed by two radiologists (RK and RS) who were unaware of the clinical status of the patients. Final scores were derived by averaging the interpretations of the two reviewers. Using the grading system in Table 1, studies with diagnostically inadequate levels of opacification had scores of zero or one. Diagnostically adequate opacification scored two or greater. Films were available for scoring in 27 cases. The written reports were employed in the other five patients. RESULTS
Study Group I: Hemodialysis (11 Patients). All patients had adequate opacification of the gallbladder (Table 2) following a single dose of contrast. Gallbladders were normal in appearance in all cases, and the mean score of density of gallbladder opacification was 3.5.
Study Group II: Nonhemodialysis (21 Patients). The mean score for density of gallbladder opacification for all first day studies in patients without biliary disease was only 1.9. Six patients were demonstrated to have biliary disease, only one of whom had adequate gallbladder opacification after a single dose. Five patients had biliary calculi and one had adenocarcinoma of the bile ducts. Of the remaining 15 patients, 11 (73%) had inadequate gallbladder opacification on the first-day examination (Table 3). Nine of these 11 patients went on to have second-day studies with four resulting in adequate levels of opacification and no demonstration of gallbladder calculi. Three patients had third-day studies, two of which resulted in adequate opacification demonstrating normal appearing gallbladders. Of the four patients without evidence of biliary tract disease who showed adequate first-day gallbladder opacification, all had normal-appearing gallbladders. This group included the two patients with mild CRI (serum creatinine < 2 mg/dl). The difference between the results of group II in which there was a 73% incidence of inadequate first-day gallbladder opacification in patients without documented gallbladder disease and the results of group I in which there were no instances of inadequate first-day opacification in dialyzed patients was statistically significant (Fischer exact probability statistic equal P < 0.005).
were only demonstrated to occur slightly more frequently (5/32 or 15.6%) than in the general American population (11). In addition, 13 patients in group II were clinically unlikely to have biliary disease, and 11 of these 13 patients (84.6%) had inadequate opacification following a single dose of contrast. This figure is considerably greater than the generally accepted incidence of inadequately visualizing gallbladders (I5-20%) following a single dose of contrast agent in hospitalized patients with presumably normal gallbladders (8-10). The striking difference between the results of single-day oral cholecystograms in dialyzed and nondialyzed patients as well as the failure to demonstrate a high enough incidence of calculi or other biliary tract disease in our population to explain this difference suggests that impaired visualization in patients with chronic renal insufficiency may often be secondary to metabolic factors arising from uncontrolled renal failure and not to biliary disease itself. Patients on chronic hemodialysis had adequate gallbladder opacification significantly more frequently on a first day study when compared to nondialyzed patients with somewhat less severe renal insufficiency (Table 3). This suggests that if the metabolic consequences of chronic renal failure are controlled, then the chances of single-dose oral cholecystography resulting in diagnostic levels of opacification are significantly improved. What m e c h a n i s m s might a c c o u n t for inadequately visualizing cholecystograms in patients with chronic renal insufficiency? Oral cholecystography is an integrated sequence of events in which a contrast agent undergoes intestinal absorption, transport in the blood, uptake by the liver, biotransformation in the liver, excretion in the bile, and finally concentration in the gallbladder. Several pos-
TABLE 1. CRITERIA USED IN GRADING FILMS FOR CONTRAST DENSITY Numerical value
Grade
Criteria
4
Excellent
3
Good
DISCUSSION
2
Adequate
We have demonstrated a high incidence of inadequate gallbladder visualization in patients with chronic renal insufficiency. However, biliary calculi
1
Poor
0
None
Equal to or exceeding opacity of the cortex of the lumbar vertebral pedicle Greater than the opacity of rib but less than 4 Equal to the opacity of the eleventh or twelfth rib Less than the opacity of the eleventh or twelfth rib Nonvisualization
830
Digestive Diseases, Vol. 23, No. 9 (September t978)
CHOLECYSTOGRAPHY IN RENAL INSUFFICIENCY TABLE 2, DENSITY OF GALLBLADDER OPACIFICATION IN PATIENTS WITH CHRONIC RENAL INSUFFICIENCY
Mean gallbladder density Study group I. Hemodialysis* (10 patients) II. N o Dialysis? No documented biliary disease (12 patients) Biliary disease (5 patients)
First day
Second day
Third day
1.9
2.2
2.7
1.2
0.5
3.5
*Films unavailable for grading in one case. ?Films unavailable for grading in four cases.
sibilities exist in patients with chronic renal failure in which interference with single or multiple steps in this sequence might lead to failure to opacify the gallbladder. While gastric atony and stasis may develop during the uremic state (12) and consequently lead to deficient intestinal absorption of the agent, this did not appear to be the case in our patient population with the exception of one patient in group II who had gastric retention of contrast agent. Moreover, none of our patients with inadequate opacification had diarrhea, nor were any noted to have vomited the contrast agent. Experiments in dogs indicate that poor absorption of iopanoic acid (Telepaque) could be due to a lack of bile salts in the intestinal lumen when the agent reaches the duodenum (13), such as may occur in a fasting patient or one on a low-fat and lowprotein diet. Furthermore, normal individuals given iopanoic acid have been demonstrated to have impaired gallbladder visualization when placed on fatrestricted diets (14). As anorexia and nausea are common complaints of patients with uremia and such patients may restrict their diets, this may contribute to poor opacification due to decreased absorption of contrast agent in the absence of bile salts. Sodium tyropanoate, which is efficiently absorbed even in the fasting state (15), might be the agent of choice in CRI patients. However, several of our patients had poor gallbladder opacification despite use of this agent, and it may be questioned whether deficient contrast absorption played a major role in the poor gallbladder opacification noted. It is perhaps more significant that decreased drug binding by serum albumin occurs during both acute Digestive Diseases, Vol. 23, No. 9 (September 1978)
and chronic renal failure (16-20), and such an effect is maximal in patients with chronic renal failure (16). This altered binding is thought to primarily effect agents which are organic acids (16, 18), and may be secondary to competitive inhibitors which accumulate in uremic serum (19, 20). As contrast media are weak organic acids which are highly bound to albumin (21), it is possible that retained metabolites, including organic anions, might displace the contrast agent from the albumin molecule and thus interfere with the transport of such agents in the blood. Hemodialysis might diminish this displacement effect by removal of these competitive inhibitors. Finally, it is possible that competition for hepatic uptake sites of the contrast media by organic anions or other retained metabolites during the uremic state similar to that which occurs with sulfobromophthalein (22, 23) might alter the rate of hepatic uptake of the agents. Hemodialysis might also diminish this effect through removal of such competitive metabolites. While none of our patients showed evidence of renal toxicity due to the contrast agents used, it is important to note that oral cholecystography is relatively contraindicated in such patients (24, 25) due to the risk of acute renal insufficiency, particularly when large or repeated doses are used. When biliary-tract disease is suspected in patients with CRI, it would be reasonable to evaluate such patients with abdominal sonography, as this technique is not only safe, but has recently been shown to be an effective means of diagnosis of obstructive and nonobstructive disease of the biliary system (26-28). In a recent study, the results from ultrasonic cholecystography compared favorably with the results from standard oral cholecystography (29).
TABLE 3. PERCENTAGE OF PATIENTS WITH ADEQUATE GALLBLADDER OPACIFICATION ON FIRST-DAY ORAL CHOLECYSTOGRAM*
Study Group I. Hemodialysis II. No dialysis No documented biliary disease Biliary disease
Percent adequate opacification 100 27 17
*Includes films on all 32 patients. ?Difference between group I and group II is statistically significant (P < 0.005).
~3 1
PERRILLO ET AL
REFERENCES 1. Kerr DNS: Provision of services to patients with chronic uremia. Kidney lnt 3:197-204, 1973 2. Burton BT: Chronic dialysis, U.S.A.--past, present and future. Ciin. Nephrol 3:3-5, 1975 3. Hampers CL, Schupak E, Lowrie EG, Lazarus JM: LongTerm Hemodialysis--The Management of the Patient with Chronic Renal Failure, 2nd ed. New York, Grune and Stratton, 1973, pp 136-154 4. Wiener SN, Vertes V and Schapiro H: The upper gastrointestinal tract in patients undergoing chronic dialysis. Radiology 92:110-114, 1969 6. Julien PJ, Goldberg HI, Margulis AR, Belzer FO: Gastrointestinal complications following renal transplantation. Radiology 117:37-43, 1975 7. Margolis DM, Etheredge EE, Garza-Garza R, Hruska K, Anderson C: Ischemic bowel disease following bilateral nephrectomy. Surgery 82:667-673, 1977 8. Rosenbaum HD: The value of re-examination in patients with inadequate visualization of the gallbladder following a single dose of telepaque. Am J Roentgenol Radium Ther Nucl Med 82:1011-1015, 1959 9. Berk RN: The consecutive dose phenomenon in oral cholecystography. Am J Roentgenol Radium Ther Nucl Med 110:230-234, 1970 10. Mujahed Z, Evans JA, Whalen JP: The nonopacified gallbladder on oral ctiolecystography. Radiology 112:1-3, 1974 11. Friedman GD, Kannel WB, Dawber TR: The epidemiology of gallbladder disease: Observations in the Framingham study. J Chron Dis 19:273-293, 1966 12. Mesehan I: Roentgen Signs in Clinical Practice, Vol. 2. Philadelphia, W.B. Saunders, 1966, p. 1520 13. Goldberger LE, Berk RN, Loeb PM: Biopharmaceutical factors influencing intestinal absorption of iopanoic acid. Invest Radiol 9:16-22, 1974 14. Zboralske FF, Amberg JR: Cholecyst-cholestasis: A cause of cholecystographic error. Am J Dig Dis 7:339-346, 1962 15. Loeb P, Berk R, Janes J, Perkin L, Moore J: The effect of fasting on oral cholecystography--a controlled study (abstract) Gastroenterology 72:1090, 1977
832
16. Campion DS: Decreased drug binding by serum albumin during renal failure. Toxicol Appl Pharmacol 25:391-397, 1973 17. Reidenberg MM, Affrime M: Influence of disease on binding of drugs to plasma proteins. Ann NY Acad Sci 226:115-126, 1973 18. Reidenberg M: The binding of drugs to plasma proteins and the interpretation of measurements of plasma concentrations of drugs in patients with poor renal function. Am J Med 62:466-469, 1977 19. Sj6holm I, Kober A, Cederl6f IO, Borga O: Protein binding of dixags in uremic and normal serum: The role of endogenous binding inhibitors. Biochem Pharmacol 25:1205-1213, 1976 20. Craig W, Wagnild J: Correction of protein binding defect in uremic sera by charcoal treatment. Clin Res 22:316A, 1974 21. Lang JH, Lasser EC: Binding of roentgenographic contrast media to serum albumin. Invest Radiol 2:396-401, 1967 22. Cornelius C, Ben-Ezzer J, Arias IM: Binding of sulfobromophthalein sodium (BSP) and other organic anions by isolated hepatic cell plasma membranes in vitro. Proc Soc Exp Biol Med 124:665-667, 1967 23. Sanen FJ: Consideration of cholecystographic contrast media. Am J Roentgenol Radium Ther Nucl Med 88:797-802, 1962 i4. Mudge GH: Uricosuric action of cholecystographic agents-a possible factor in nephrotoxicity. N Engl J Med 284:929933, 1971 25. Berk RN, Loeb PM, Go!dberger LE, SokoloffJ: Oral cholecystography with iopanoic acid. N Engl J Med 290:204-210, 1974 26. Andersen JC, Harned RK: Gray scale ultrasonography of the gallbladder: An evaluation of accuracy and report of additional ultrasound signs. Am J Roentgenol 129:975-977, 1977 27. Nieman HL, Mintzer RA: Accuracy of biliary duct ultrasound: Comparison with cholangiography. Am J Roentgenol 129:979-982, 1977 28. Goldberg B: Ultrasonic cholangiography-gray scale B-scan evaluation of the common bile duct. Radiology 118:401-404, 1976 29. Bartrum RJ, Crow HC, Foote SR: Ultrasonic and radiographic cholecystography. N Engl J Med 296:538-541, 1977
Digestive Diseases, Vol. 23, No. 9 (September 1978)
MD, and
Thirty-two patients with chronic renal insufficiency (CRI) had oral cholecystography. Eleven of 15 patients (73%) with moderately advanced renal impairment had diagnostically inadequate single-dose cholecystograms. In contrast, all 11 patients on chronic hemodialysis had diagnostically opacified gallbladders following a single dose of contrast. Six other patients had biliary disease, either calculi (5 patients) or neoplasia (1 patient). These data suggest that CRI diminishes the likelihood of diagnostic gallbladder opacification, even in the absence of gallbladder disease, and that if the metabolic consequences of CRI are controlled by dialysis, the chances of diagnostic opacification are significantly improved (P < 0.005). As oral cholecystography may not only result in inadequate opacification, but also carry the potential of renal toxicity, abdominal ultrasound should prove a safer and possibly more effective alternative in such patients.
Chronic renal failure is becoming an increasingly well recognized medical p r o b l e m (1), and it has been estimated that by 1980-1982 about 50,00060,000 A m e r i c a n s will be receiving t r e a t m e n t for end-stage renal disease (2). While there has been a resurgence of interest in the gastrointestinal compli-. cations of patients with chronic renal failure (3-7), little is known of the overall frequency of biliary tract disease in such individuals. It had been the impression of the authors that patients with chronic renal insufficiency d e m o n s t r a t e d an increased freq u e n c y of nondiagnostic first day oral cholecystograms. Because of this, a study was done at this institution to assess whether inadequate visualization was m o r e c o m m o n in this population and if so, w h e t h e r this indicated biliary disease with the same frequency as has been reported in a general population of patients (8, 9, 10).
From the Department of Medicine and the Mallinckrodt Institute of Radiology, Washington University School of Medicine, St, Louis, Missouri 63110. Address for reprint requests: Dr. R.P. Perrillo , Division of Gastroenterology, Department of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110.
M A T E R I A L S AND METHODS: We reviewed the records of the 402 patients with a diagnosis of CRI at this institution from 1971 to 1975. Of this number, 32 patients with intact gallbladders had undergone standard oral cholecystography and these patients comprised the study population. Study group I was comprised of 11 individuals who had been treated with thrice-weekly hemodialysis on coil-type dialyzers for a period of three months or longer at the time of cholecystogram. All patients in this group had advanced CRI with a group mean serum creatinine of 11.7 mg/dl. Study group II was comprised of 21 patients not being managed with chronic hemodialysis. Nineteen patients in this group had moderate to severe renal insufficiency with a group mean serum creatinine of 7.1 mg/dl at the time of the study. Two patients had relatively mild CRI with serum creatinine less than 2 mg/dl. The usual preparation for oral cholecystography included a light fat-free evening meal preceding ingestion of the contrast agent. Four patients received iopanoic acid, 3 g; nine received sodium tyropanoate, 3 g; and 19 patients received iocetamic acid, 3 g. Dialysis patients were instructed to take the contrast agent at home on the evening prior to dialysis. All other patients received oral cholecystography as in-patients. Ten to 15 hr after ingestion of the cholecystographic agent, standard prone and oblique radiographs and erect spot films of the gallbladder were obtained. When necessary, second (12 patients) and
Digestive Diseases, Val. 23, No. 9 (September 1978) 0002-9211/78/0900-0829505.00/19 1978DigestiveDiseaseSystemsInc.
829
PERRILLO ET AL third day (3 patients) studies were obtained using an additional 3-g dose of the same contrast agent. Cholecystograms were independently reviewed by two radiologists (RK and RS) who were unaware of the clinical status of the patients. Final scores were derived by averaging the interpretations of the two reviewers. Using the grading system in Table 1, studies with diagnostically inadequate levels of opacification had scores of zero or one. Diagnostically adequate opacification scored two or greater. Films were available for scoring in 27 cases. The written reports were employed in the other five patients. RESULTS
Study Group I: Hemodialysis (11 Patients). All patients had adequate opacification of the gallbladder (Table 2) following a single dose of contrast. Gallbladders were normal in appearance in all cases, and the mean score of density of gallbladder opacification was 3.5.
Study Group II: Nonhemodialysis (21 Patients). The mean score for density of gallbladder opacification for all first day studies in patients without biliary disease was only 1.9. Six patients were demonstrated to have biliary disease, only one of whom had adequate gallbladder opacification after a single dose. Five patients had biliary calculi and one had adenocarcinoma of the bile ducts. Of the remaining 15 patients, 11 (73%) had inadequate gallbladder opacification on the first-day examination (Table 3). Nine of these 11 patients went on to have second-day studies with four resulting in adequate levels of opacification and no demonstration of gallbladder calculi. Three patients had third-day studies, two of which resulted in adequate opacification demonstrating normal appearing gallbladders. Of the four patients without evidence of biliary tract disease who showed adequate first-day gallbladder opacification, all had normal-appearing gallbladders. This group included the two patients with mild CRI (serum creatinine < 2 mg/dl). The difference between the results of group II in which there was a 73% incidence of inadequate first-day gallbladder opacification in patients without documented gallbladder disease and the results of group I in which there were no instances of inadequate first-day opacification in dialyzed patients was statistically significant (Fischer exact probability statistic equal P < 0.005).
were only demonstrated to occur slightly more frequently (5/32 or 15.6%) than in the general American population (11). In addition, 13 patients in group II were clinically unlikely to have biliary disease, and 11 of these 13 patients (84.6%) had inadequate opacification following a single dose of contrast. This figure is considerably greater than the generally accepted incidence of inadequately visualizing gallbladders (I5-20%) following a single dose of contrast agent in hospitalized patients with presumably normal gallbladders (8-10). The striking difference between the results of single-day oral cholecystograms in dialyzed and nondialyzed patients as well as the failure to demonstrate a high enough incidence of calculi or other biliary tract disease in our population to explain this difference suggests that impaired visualization in patients with chronic renal insufficiency may often be secondary to metabolic factors arising from uncontrolled renal failure and not to biliary disease itself. Patients on chronic hemodialysis had adequate gallbladder opacification significantly more frequently on a first day study when compared to nondialyzed patients with somewhat less severe renal insufficiency (Table 3). This suggests that if the metabolic consequences of chronic renal failure are controlled, then the chances of single-dose oral cholecystography resulting in diagnostic levels of opacification are significantly improved. What m e c h a n i s m s might a c c o u n t for inadequately visualizing cholecystograms in patients with chronic renal insufficiency? Oral cholecystography is an integrated sequence of events in which a contrast agent undergoes intestinal absorption, transport in the blood, uptake by the liver, biotransformation in the liver, excretion in the bile, and finally concentration in the gallbladder. Several pos-
TABLE 1. CRITERIA USED IN GRADING FILMS FOR CONTRAST DENSITY Numerical value
Grade
Criteria
4
Excellent
3
Good
DISCUSSION
2
Adequate
We have demonstrated a high incidence of inadequate gallbladder visualization in patients with chronic renal insufficiency. However, biliary calculi
1
Poor
0
None
Equal to or exceeding opacity of the cortex of the lumbar vertebral pedicle Greater than the opacity of rib but less than 4 Equal to the opacity of the eleventh or twelfth rib Less than the opacity of the eleventh or twelfth rib Nonvisualization
830
Digestive Diseases, Vol. 23, No. 9 (September t978)
CHOLECYSTOGRAPHY IN RENAL INSUFFICIENCY TABLE 2, DENSITY OF GALLBLADDER OPACIFICATION IN PATIENTS WITH CHRONIC RENAL INSUFFICIENCY
Mean gallbladder density Study group I. Hemodialysis* (10 patients) II. N o Dialysis? No documented biliary disease (12 patients) Biliary disease (5 patients)
First day
Second day
Third day
1.9
2.2
2.7
1.2
0.5
3.5
*Films unavailable for grading in one case. ?Films unavailable for grading in four cases.
sibilities exist in patients with chronic renal failure in which interference with single or multiple steps in this sequence might lead to failure to opacify the gallbladder. While gastric atony and stasis may develop during the uremic state (12) and consequently lead to deficient intestinal absorption of the agent, this did not appear to be the case in our patient population with the exception of one patient in group II who had gastric retention of contrast agent. Moreover, none of our patients with inadequate opacification had diarrhea, nor were any noted to have vomited the contrast agent. Experiments in dogs indicate that poor absorption of iopanoic acid (Telepaque) could be due to a lack of bile salts in the intestinal lumen when the agent reaches the duodenum (13), such as may occur in a fasting patient or one on a low-fat and lowprotein diet. Furthermore, normal individuals given iopanoic acid have been demonstrated to have impaired gallbladder visualization when placed on fatrestricted diets (14). As anorexia and nausea are common complaints of patients with uremia and such patients may restrict their diets, this may contribute to poor opacification due to decreased absorption of contrast agent in the absence of bile salts. Sodium tyropanoate, which is efficiently absorbed even in the fasting state (15), might be the agent of choice in CRI patients. However, several of our patients had poor gallbladder opacification despite use of this agent, and it may be questioned whether deficient contrast absorption played a major role in the poor gallbladder opacification noted. It is perhaps more significant that decreased drug binding by serum albumin occurs during both acute Digestive Diseases, Vol. 23, No. 9 (September 1978)
and chronic renal failure (16-20), and such an effect is maximal in patients with chronic renal failure (16). This altered binding is thought to primarily effect agents which are organic acids (16, 18), and may be secondary to competitive inhibitors which accumulate in uremic serum (19, 20). As contrast media are weak organic acids which are highly bound to albumin (21), it is possible that retained metabolites, including organic anions, might displace the contrast agent from the albumin molecule and thus interfere with the transport of such agents in the blood. Hemodialysis might diminish this displacement effect by removal of these competitive inhibitors. Finally, it is possible that competition for hepatic uptake sites of the contrast media by organic anions or other retained metabolites during the uremic state similar to that which occurs with sulfobromophthalein (22, 23) might alter the rate of hepatic uptake of the agents. Hemodialysis might also diminish this effect through removal of such competitive metabolites. While none of our patients showed evidence of renal toxicity due to the contrast agents used, it is important to note that oral cholecystography is relatively contraindicated in such patients (24, 25) due to the risk of acute renal insufficiency, particularly when large or repeated doses are used. When biliary-tract disease is suspected in patients with CRI, it would be reasonable to evaluate such patients with abdominal sonography, as this technique is not only safe, but has recently been shown to be an effective means of diagnosis of obstructive and nonobstructive disease of the biliary system (26-28). In a recent study, the results from ultrasonic cholecystography compared favorably with the results from standard oral cholecystography (29).
TABLE 3. PERCENTAGE OF PATIENTS WITH ADEQUATE GALLBLADDER OPACIFICATION ON FIRST-DAY ORAL CHOLECYSTOGRAM*
Study Group I. Hemodialysis II. No dialysis No documented biliary disease Biliary disease
Percent adequate opacification 100 27 17
*Includes films on all 32 patients. ?Difference between group I and group II is statistically significant (P < 0.005).
~3 1
PERRILLO ET AL
REFERENCES 1. Kerr DNS: Provision of services to patients with chronic uremia. Kidney lnt 3:197-204, 1973 2. Burton BT: Chronic dialysis, U.S.A.--past, present and future. Ciin. Nephrol 3:3-5, 1975 3. Hampers CL, Schupak E, Lowrie EG, Lazarus JM: LongTerm Hemodialysis--The Management of the Patient with Chronic Renal Failure, 2nd ed. New York, Grune and Stratton, 1973, pp 136-154 4. Wiener SN, Vertes V and Schapiro H: The upper gastrointestinal tract in patients undergoing chronic dialysis. Radiology 92:110-114, 1969 6. Julien PJ, Goldberg HI, Margulis AR, Belzer FO: Gastrointestinal complications following renal transplantation. Radiology 117:37-43, 1975 7. Margolis DM, Etheredge EE, Garza-Garza R, Hruska K, Anderson C: Ischemic bowel disease following bilateral nephrectomy. Surgery 82:667-673, 1977 8. Rosenbaum HD: The value of re-examination in patients with inadequate visualization of the gallbladder following a single dose of telepaque. Am J Roentgenol Radium Ther Nucl Med 82:1011-1015, 1959 9. Berk RN: The consecutive dose phenomenon in oral cholecystography. Am J Roentgenol Radium Ther Nucl Med 110:230-234, 1970 10. Mujahed Z, Evans JA, Whalen JP: The nonopacified gallbladder on oral ctiolecystography. Radiology 112:1-3, 1974 11. Friedman GD, Kannel WB, Dawber TR: The epidemiology of gallbladder disease: Observations in the Framingham study. J Chron Dis 19:273-293, 1966 12. Mesehan I: Roentgen Signs in Clinical Practice, Vol. 2. Philadelphia, W.B. Saunders, 1966, p. 1520 13. Goldberger LE, Berk RN, Loeb PM: Biopharmaceutical factors influencing intestinal absorption of iopanoic acid. Invest Radiol 9:16-22, 1974 14. Zboralske FF, Amberg JR: Cholecyst-cholestasis: A cause of cholecystographic error. Am J Dig Dis 7:339-346, 1962 15. Loeb P, Berk R, Janes J, Perkin L, Moore J: The effect of fasting on oral cholecystography--a controlled study (abstract) Gastroenterology 72:1090, 1977
832
16. Campion DS: Decreased drug binding by serum albumin during renal failure. Toxicol Appl Pharmacol 25:391-397, 1973 17. Reidenberg MM, Affrime M: Influence of disease on binding of drugs to plasma proteins. Ann NY Acad Sci 226:115-126, 1973 18. Reidenberg M: The binding of drugs to plasma proteins and the interpretation of measurements of plasma concentrations of drugs in patients with poor renal function. Am J Med 62:466-469, 1977 19. Sj6holm I, Kober A, Cederl6f IO, Borga O: Protein binding of dixags in uremic and normal serum: The role of endogenous binding inhibitors. Biochem Pharmacol 25:1205-1213, 1976 20. Craig W, Wagnild J: Correction of protein binding defect in uremic sera by charcoal treatment. Clin Res 22:316A, 1974 21. Lang JH, Lasser EC: Binding of roentgenographic contrast media to serum albumin. Invest Radiol 2:396-401, 1967 22. Cornelius C, Ben-Ezzer J, Arias IM: Binding of sulfobromophthalein sodium (BSP) and other organic anions by isolated hepatic cell plasma membranes in vitro. Proc Soc Exp Biol Med 124:665-667, 1967 23. Sanen FJ: Consideration of cholecystographic contrast media. Am J Roentgenol Radium Ther Nucl Med 88:797-802, 1962 i4. Mudge GH: Uricosuric action of cholecystographic agents-a possible factor in nephrotoxicity. N Engl J Med 284:929933, 1971 25. Berk RN, Loeb PM, Go!dberger LE, SokoloffJ: Oral cholecystography with iopanoic acid. N Engl J Med 290:204-210, 1974 26. Andersen JC, Harned RK: Gray scale ultrasonography of the gallbladder: An evaluation of accuracy and report of additional ultrasound signs. Am J Roentgenol 129:975-977, 1977 27. Nieman HL, Mintzer RA: Accuracy of biliary duct ultrasound: Comparison with cholangiography. Am J Roentgenol 129:979-982, 1977 28. Goldberg B: Ultrasonic cholangiography-gray scale B-scan evaluation of the common bile duct. Radiology 118:401-404, 1976 29. Bartrum RJ, Crow HC, Foote SR: Ultrasonic and radiographic cholecystography. N Engl J Med 296:538-541, 1977
Digestive Diseases, Vol. 23, No. 9 (September 1978)
