Cholangitis With Acute Renal Failure:

Priorities in Therapeutics
HENRI BISMUTH M.D., HENRI KUNTZIGER M.D.,* MARVIN B. CORLETTE M.D.t

Obstructive cholangitis with acute renal failure is a dramatic

syndrome which merits individual definition. Twenty-one patients
with acute suppurative cholangitis complicated by rapidly developing renal insufficiency were studied, and the severity of the
renal failure, an acute interstitial tubulopathy, bore no significant
relationship to the serum bilirubin level. The mechanism of renal
damage was clearly related to episodes of septicemia. Increasing
experience has modified the approach to treatment. The dominant septic problem can often be controlled by vigorous antibiotic
and fluid therapy, allowing time for spontaneous improvement in
renal function. All patients thus operated at a distance from the
septic episode survived. If emergency operation is required because of persistent or recrudescent sepsis, the necessity for
dialysis should be considered first; the circumstances demanding
dialysis are defined. The priorities in therapy are then: 1) treatment of the infection, 2) treatment of the renal failure, and finally
3) operation. The moment of the operation depends on the evolution of the sepsis, but should be preceded by dialysis when required.

(RIGINALLY described by Charcot,6 a particularly se%Jvere form of suppurative cholangitis complicated by

acute renal failure has been the subject of numerous
studies Individualized by Caroli4 as "uremigenic cholangitis," the association of biliary sepsis with renal failure
has too often been considered together with a heterogeneous group of hepato-biliary disorders, pre- and postoperative, called variously "cholemic nephroses" or "liver

kidney syndromes.' '16.21

The lack of clarity in the definition of these syndromes
has led to some confusion in treatment. When suppurative cholangitis is associated with renal failure, a variety
Submitted for publication February 12, 1975.
*Charge de Recherche, I.N.S.E.R.M. U-64, H6pital Tenon, 75020
Paris, France.
tVisiting Surgeon, Harvard Surgical Service. Cambridge Hospital,
Cambridge, Massachusetts.
Reprint requests: Henri Bismuth M.D., Unite de Chirurgie HepatoBiliaire, Hopital Paul Brousse, 94800 Villejuif, France.

From the Unit6 de Chirurgie Hepato-Biliaire,

Faculte de Medecine Paris-Sud, Hopital Paul
Brousse, Villejuif, France

of therapeutic attitudes has been recommended, often

based on the conception that the renal failure will remain
refractory if the biliary tree is not surgically decompressed as an emergency.4'9
One purpose of this study is to analyze the elements of
the association of cholangitis with acute renal failure and
their relationship. The second aim is to define the order
of therapeutic priorities in this dramatic illness. Particularly, the moment of operation and the place of renal
dialysis need to be clarified. Our experience with 21
patients with cholangitis and acute renal insufficiency
suggests that certain previous attitudes concerning the
syndrome should be reconsidered.
Clinical Material
From 1966 to 1973, in a service specializing in hepatobiliary surgery,: 283 patients were hospitalized with a
confirmed diagnosis of cholangitis due to an obstruction
of the main bile duct.
In order to study the association of cholangitis with acute
renal failure, and to eliminate other conditions that might
simulate this syndrome, patients were selected from this
group who fulfilled the following criteria: 1) cholangitis,
i.e., the association of signs of biliary retention (clinical
jaundice, total serum bilirubin more than 3.0 mg/100 ml),
and invasive sepsis (temperature of 39 or over and/or
chills, plus white-cell count exceeding 10,000/mm3) due
to an obstruction of the main bile duct. The nature of the
obstacle was verified at operation or autopsy (excepting
one patient refusing surgery in whom the obstacle, a
stone, was demonstrated on intravenous cholangiogram).

881

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882

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CHOLANGITIS WITH ACUTE RENAL FAILURE

Vol. 181 * No. 6

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acute renal insufficiency, defined as an elevation of

BUN over 40 mg/100 ml or serum creatinine exceeding
2.0 mg/100 ml with a ratio of concentration of urine urea
to blood urea (U/P urea) of less than 8, corresponding to
the usual definition of renal failure.10
Several patients meeting these criteria were eliminated
because they presented another element capable, by itself, of influencing renal function. Thus, patients with
acute pancreatitis, intra-abdominal abscess, bile
peritonitis, or cirrhosis were excluded. No postoperative
patients were included. Renal failure occurring only postoperatively, even if authentic cholangitis existed
preoperatively, was not considered a part of the pure
syndrome of uremigenic cholangitis.
Twenty-one of the 283 patients were found to meet
these requirements and were retained for study. Table 1
presents the clinical data concerning the 10 male and 11
female patients. The average age was 72 years.

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Analysis of the Three Elements of the Syndrome

Sepsis
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Biliary Obstruction
The obstruction of the common duct was of two principal etiologies: lithiasis (13 patients), and tumor of the
ampulla of Vater (4 patients). Other tumors about the

lower common duct accounted for the remainder.

Symptoms and signs related to the biliary tree were conJ:t stant
and generally severe. The average bilirubin was
co
20.0 mg/l00 ml and in 5 patients was over 30 mg/100 ml.
0,
Similarly, the serum alkaline phosphatase was elevated
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r. but in a capricious fashion in relation to the bilirubin, and
in 5 cases was only mildly increased. Almost all patients
03
had pain and tenderness in the right upper quadrant; 4
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wo had rigidity. The liver was palpably enlarged in just less
0 than half the patients.
Previous attacks related to the
-a
m
'0 biliary tree were elicited in 12 of the 13 patients with
lithiasis, often dating back several years. In 5 patients the
major febrile episode leading to the renal failure was
heralded by one or more lesser attacks of right upper
quadrant pain and fever in the month preceding.
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The signs of infection were severe, with chills and

fever exceeding 39 and marked leukocytosis occurring in
all patients; septicemia and shock were documented together in 9 patients. Obtundation or coma was observed
in 15 patients. Bile culture was positive in 12 patients and
described as purulent in others at operation. The culture
techniques may have been deficient in view of the reported incidence of near 90%o positive bile cultures in the
presence of common duct stones, and the rising incidence
of recovery of anaerobic organisms with newer
technological advances, as emphasized recently by Gorbach and Bartlett.13

884

BISMUTH, KUNTZIGER AND CORLETTE

BUN mg. 100 ml 1

TOTAL

SERUM

Ann.

Surg.- June

1975

BILIRUBIN

LO- CONCENTRATION

210

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1800

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y=1Ox+82-6
=20* r =0 31 NS

FIG. 2. Relationship be-

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FIG. 1. Relationship between BUN and total

serum bilirubin concentration. (In one patient simultaneous values were not

available)

60-

301
I1

tween total serum bilirubin

and renal status of patients

30-

classified into three groups

by severity of acute renal

failure (see text). Means +
standard error of the
means (SEM) are represented. Differences between the three groups

20-

significant, as asby Student's t-test.

Only 17 patients are included since simultaneous
data sufficient to classify 4
patients seen early in the

were not

10

20

TOTAL SERUM BILIRUBIN

CONCENTRATION mg.100ml1
30
40

sessed
10-

Renal Insufficiency
Twenty patients gave no previous history of renal disease. In one patient there was previous mild chronic
impairment of renal function which was aggravated by
the cholangitis, with renal function diminishing by more
than half, then returning to the previous baseline.
Anuria or oliguria was recorded in 12 patients (urine
output less than 500 ml per 24 hours). Nine patients had
high output renal failure, characterized by a urine urea to
plasma urea ratio (U/P) of less than 8, associated with a
high urinary sodium. The renal problem appeared
promptly (within 48 hours) after the onset of pain and
fever in eleven patients; in the remainder it was
documented later, generally during the second week of
illness. The onset of renal failure coincided with chills or
elevation of temperature above 39.in all patients except
one, and coincided with shock in 9. No patient had
undergone operation before the onset of renal failure.
The severity and duration of the renal disorder was
quite variable. Patients have been arbitrarily classified
into 3 groups of mild, moderate, and severe renal failure,
defined according to the following criteria: 1) oliguria or
anuria (urine volume less than 500 ml per 24 hours); 2)
necessity for dialysis; 3) BUN of 100 mg/100 ml or greater; 4) plasma potassium of 5.0 mEq/litre or over; 5)
plasma bicarbonate of 20 mEq/litre or less. Patients
exhibiting one or none of these 5 features were classified
as having mild renal failure; with more than one but less
than four, moderate; and with 4 or 5 of the criteria, as
severe. Only 17 patients could be classified because data
was not complete for 4 patients seen early in the series.
Thus defined, 6 patients had mild renal failure, 2 severe,
and the remainder moderate.
Six patients underwent preoperative dialysis; 3
peritoneally and 3 by hemodialysis. Four of these patients required dialysis both pre- and postoperatively.
Two patients were dialyzed in the postoperative period
only. In survivors the renal function eventually returned
to pre-illness levels.

series

MILD

MODERATE

(N-6)

(Nu 9)

were not

available.

SEVERE
(No 2)

The renal failure was considered organic in all cases,

and the mechanism appeared related temporally to an
episode of septicemia, which was documented in 10 patients.
The relationship of the serum bilirubin concentration to
BUN and to the severity of renal failure is expressed in
Figures 1 and 2. While there was a tendency for higher
levels of bilirubin to be associated with more severe renal
involvement, the correlation is not statistically significant.

Results of Treatment
Two patients died in shock within a few hours of their
arrival. One patient refused operation. This left 18 patients for evaluation of therapy. All patients were given
vigorous fluid replacement, including blood and plasma
as needed, and furosemide if urine output was low. All
patients were given antibiotics. All of the 18 patients
underwent surgical exploration. The outcomes of therapy
are presented in Table 2.
The first 3 patients, treated early in our experience,
were managed following the then-current doctrine of
emergency operation. In one of these patients, the course
after rehydration and antibiotics was followed for several
hours; as soon as temperature and urinary output returned to normal, operation was performed. All 3 of these
patients died.
The 15 subsequent patients were observed longer
under the influence of fluid and antibiotic therapy. Four
outcomes were seen. In two patients the infection persisted (cases 7 and 8). Both underwent emergency
hemodialysis, then were operated on and both survived.
The second course was seen in two patients (cases 9

Vol. 181-No. 6

CHOLANGMS WITH ACUTE RENAL FAILURE

TABLE 2. Outcome of Treatment in 18 Operated Patients.

Therapeutic Attitude
Emergency Operation:
(cases 4-6)

No. of Patients

Survivors

Deaths
3

Delayed Operation:
1. Sepsis Continues:

2. Improvement,
Then Relapse:
Urgent Operation
(cases 9-10)

3. Improvement:
Operation After
Renal Recovery
(cases 11-17)

4. Improvement,
But Other Major
Organ Failure
(cases 18-21)

Emergency Dialysis
Then Operation
(cases 7-8)

antibiotics but in whom other major organ failure supervened (i.e. cardiac, neurologic).
In one of these 4 (case 18) gastrointestinal hemorrhage
developed requiring emergency operation after dialysis;
this patient survived. Another (case 21) was operated for
recrudescent sepsis in coma after several cardiac arrests
and eventually died of cardiac causes. The remaining two
died postoperatively, one from cardiac failure, and one,
in whom choledochoduodenostomy was performed, from
diffuse hemorrhage associated with a blood clot blocking
the anastomosis. The occurrence of other major organ
failure in these patients, even though they were improving in terms of their sepsis, created a disparate group in
whom the choice and timing of operative biliary drainage
was

and 10) who showed initial improvement which lasted

several days. In one, the jaundice persisted, but her renal
function returned almost to normal (BUN 40 mg/100 ml).
A relapse of sepsis at this point led to emergency operation and recovery. In the other patient the BUN had
fallen markedly to 50 mg/100 ml over a 16 day period. At
this point the fever returned and he was operated on as an
emergency and recovered.
The third outcome was that of sustained improvement
in terms of the infection. In 7 patients fever and elevated
white-cell count fell rapidly and did not return, allowing
time for spontaneous improvement in renal function. All
these patients did show progressive improvement in renal
function. This permitted elective operation at an interval
of from 8 to 36 days (median 15) following the onset of
renal failure, and from 5 to 34 days (median 11) following
admission to our unit. All 7 patients in this group survived. The BUN in these cases averaged 176 mg/100 ml
initially and had returned to an average of 35 mg/100 ml at
the time of operation. Antibiotics were continued in
most, but in some were stopped after 10 days. In none did
signs of sepsis recur. In 4 the signs of biliary obstruction
improved concomitant with improvement in renal function. In 3, the BUN returned towards normal despite
persistence of elevated bilirubin and alkaline phosphatase. At operation the procedure consisted of a bilioenteric anastomosis in the one case of tumoral obstruction, and in cases of lithiasis, was cholecystectomy, removal of stones and drainage via T-tube in 3 and
choledocho-duodenal anastomosis in 3.
The fourth and final evolution observed under antibiotics includes 4 patients who showed improvement with

885

difficult.

Discussion
The selection of patients for this study may seem unnecessarily restrictive. Patients with sepsis and jaundice
in whom a biliary obstacle was not proven have been
eliminated because the absence of demonstrable biliary
obstruction raises a question as to the validity of the
diagnosis. Other lesions, e.g., the jaundice of septicemia
or leptospirosis, can cause a confusingly similar picture.
This requirement almost surely excluded patients with
true cholangitis but in whom the obstacle, e.g., a stone,
had passed spontaneously. Only when it is certain that
one is dealing with a single clinical entity can appropriate
conclusions be drawn regarding its evolution and treatment. Likewise, the presence of any factor that might,
alone, be related to renal insufficiency, such as acute
pancreatitis or sepsis outside the biliary tract, caused
elimination of the patient because the relationship of
biliary retention to the renal failure is then obscured.
Since the postoperative state introduces a variety of factors which can influence renal function, only patients
with preoperative renal failure were included.
The presence of cirrhosis, even the secondary biliary
type, similarly would not allow evaluation of the pure

syndrome.
The etiology of cholangitis with renal failure is primarily lithiasis, followed by ampulloma, as noted by Caroli.4
These causes of biliary obstruction, frequently partial or
intermittent, are most often complicated by sepsis, in
contradistinction to tumors of the pancreas and bile duct
which rarely become infected, as noted by Sherlock and
others.5'20 In this series, ampullomas occurred in younger
males, without previous biliary disease, in contrast to the
typical picture of lithiasis, occurring predominantly in
elderly females with months, sometimes years, of prior
biliary troubles.
Renal failure is occasionally associated with many diseases that produce jaundice. Although the term
"hepato-renal syndrome" was originally coined by
Merklen in 191517 in considering a case of cholangitis with

886

BISMUTH, KUNTZIGER AND CORLEATE

renal failure, a multitude of conditions has been included

under this rubric, and a clearer definition was needed.
Recently Conn7 has argued for restriction of the term
"hepato-renal syndrome" to a type of renal failure occurring in association with cirrhosis, a clarification which we
heartily support.
During the obstructive jaundice, the responsibility of
the liver for the production or non-detoxification of substances noxious to the kidney in controversial. It is most
likely that the renal lesion associated with jaundice in
cholangitis is related to infection, septicemia, and reduced effective renal perfusion.'5 As such, it is not different from the acute interstitial nephropathy seen in a
variety of conditions affecting renal hemodynamics
which it closely resembles clinically, biochemically, and
histologically.8"'

In our patients the onset of renal insufficiency coincided in every case with an infectious state including
shaking chills, and the clinical and laboratory findings
were the same as those described in the tubulopathy
occurring in septic settings without hepato-biliary disease.'4 "8 There was no significant correlation between
degree of bilirubinemia and the gravity of the renal failure, and in several cases the renal lesion improved spontaneously with clearing of infection but without change in
the bilirubin level.
The responsibility of biliary retention, particularly of
conjugated bilirubin, in the production of renal failure has
been suggested."2'9'22 It appears likely that excess conjugated bilirubin renders the kidney more susceptible to
ischemic insult.9 However, in the absence of infection,
such acute renal failure does not occur, even in extreme
degrees of biliary retention, e.g., neoplastic obstruction.3
Renal failure in these juandiced patients with suppurative
cholangitis remains a rare event and this study does not
confirm or deny that icteric patients are any more likely
to develop a renal lesion than others with sepsis. It appears that renal function can improve independent of the
serum bilirubin level.
The renal lesion occurring in obstructive cholangitis
should not be included under the term "hepato-renal
failure," nor should it be considered a special or mystical
form of kidney injury by an ailing liver. It is best considered and treated as an acute interstitial nephropathy
caused by infection-altered renal hemodynamics.
In the treatment of the three components of the syndrome of acute obstructive cholangitis with renal failure,
the infectious element is predominant. In contrast to the
experience of Glenn and Moody, Reynolds and Dargan,
and others,'2"9'20 our experience shows that the sepsis is
not routinely refractory to antibiotic therapy.
Either signs of sepsis regress, or infection persists or
worsens. In the latter case emergency operation is indicated. When sepsis continues, the renal and metabolic
status is evaluated, and if renal failure is moderate or

Ann. Surg. June 1975

-

severe, hemodialysis should be undertaken before operation. We have selected as indications for dialysis a serum
potassium of 5.5 mEq/l or greater, BUN over 100 mg/100
ml or acidosis with a serum bicarbonate less than 15
mEq/l. Some patients exhibit an extremely rapid rate of
change in these metabolic measurements and this should
be taken into account, sometimes dialyzing for a less
severe but rapidly changing disturbance. Following such
a program, no patients have been lost due to complications of the renal failure.
In those patients who initially improve, three courses
were observed: 1) a recrudescence of the signs of sepsis.
At the first sign of returning sepsis, these patients are
managed as are patients with persistent sepsis, i.e.,
dialysis if necessary; urgent operation. 2) Continued improvement of sepsis with existence of other major organ
failure (pulmonary, cardiac, hemorrhage). The indication
for operation remains but the risk is greatly increased.
Judgment of the moment to operate is delicate, weighing
the probable evolution of the other problems against the
likelihood of recurrent sepsis. No guidelines concerning
these patients can be proposed. 3) Continued improvement of sepsis. The number of patients who maintained
improvement is striking. This may be related to spontaneous improvement in the degree of biliary obstruction
in some patients, but this does not seem to be a prerequisite. That germs are not eliminated from the bile duct by
antibiotics is demonstrated by the high number of positive bile duct cultures; one patient, after extensive antibiotherapy and regression of jaundice, still harbored 4
different organisms in his biliary tract. What deserves
emphasis is the fact that sepsis can often be controlled
allowing time for 1) the renal disorder to resolve spontaneously, and 2) the operation, always indicated, to take
place electively under ideal conditions with resultant improvement in mortality (7 survivors of 7). It thus seems to
be most desirable to abstain from operation for as long as
necessary to allow renal status to return to normal.
Operating immediately, or when temperature,
hemodynamic status, and diuresis first become normal,
has not provided encouraging results.
An additional reason for awaiting the maximum patient
improvement depends on the fact that in patients with
choledocholithiasis, cholangitis, and acute renal failure
the obstruction is most often complete, the stones frequently multiple. The stones, if multiple, may involve
the intrahepatic ducts, or a clay-like mold of the bile duct
may form (observed in two of our patients). In such
patients, the simple placement of a T-tube is evidently
insufficient. The extensive procedure of complete opening of the ducts, preferably with cholangiographic control, and frequently with bilioenteric anastomosis, is most
often required, and for this the patient must be in optimal
condition.
Stated otherwise, the moment of surgical intervention

Vol. 181 - No. 6

CHOLANGITIS WITH ACUTE RENAL FAILURE

is determined by the evolution of the sepsis. An operation

will always be required, but its timing should be in relation, first, to the infection, and second, to the renal insufficiency. The biliary obstruction passes to a secondary
role, and the renal insufficiency is treated on its own
independent merits and/or in relation to an emergency
operation when required. The order of priorities is thus:
1) treatment of the infection; 2) treatment of the renal
failure; and last of all, 3) operation. The gravity of the
infection modifies the timing, but not the chronology of
the different steps.
References
1. Aylward, T. T., Schowengerdt, C. G. and Bove, K.: Experimental
Hyperbilirubinemia: Effect on Glomerular Filtration, J. Surg.
Res., 15:1, 1973.
2. Baum, M., Stirling, G. A. and Dawson, J. L.: Further Study into
Obstructive Jaundice and Ischemic Renal Damage. Br. Med. J.,
2:229, 1969.
3. Bismuth, H. and Kuntziger, H.: Les Angiocholites avec Insuffisance Renale Aigue. Journees de Reanimation de L'Hopital
Claude-Bernard, Paris, 1970.
4. Caroli, J.: Les Angiocholites Ictero-uremigenes. Paris Med.,
35:142, 1945.
5. Caroli, J. and Andre, J.: Les Angiocholites Uremigenes. Rev. Int.
Hepat., 3:215, 1953.
6. Charcot, J. M.: L'Abaissement de l'Excretion Urinaire d'Uree au
cours de la Fievre Intermittente Hepatique, in "Lecons sur les
Maladies du Foie, des Voies Biliaries, et des Reins". Progres
Medical, Paris, 1877.
7. Conn, H. O.: A Rational Approach to the Hepato-renal Syndrome.
Gastroenterology, 65:321, 1973.

887

8. Crosnier J., Dormont, J. and de Montera, H.: Les Lesions du

Parenchyme Renal au cours des Septicemies. Rev. Franc. Etud.
Clin. Biol., 8:863, 1963.
9. Dawson, J. L.: Jaundice, Septic Shock, and Acute Renal Failure.
Am. J. Surg., 115:516, 1968.
10. Franklin, S. S. and Merrill, J. P.: Acute Renal Failure. N. Engl. J.
Med., 262:711, 1960.
11. Funck-Brentano, J. L., Chanard, J., Kleinknecht, D. and Barbanel,
C.: Analyse des Facteurs Pronostiques de l'Insuffisance Renale
Aigue dans les Affections Chirurgicales des Voies Biliaries. Ann.
Gastroenterol. Hepatol., 7:157, 1971.
12. Glenn, F. and Moody, F.: Acute Obstructive Suppurative Cholangitis. Surg. Gynecol. Obstet., 113:265, 1961.
13. Gorbach, S. L. and Bartlett, J. G.: Anaerobic Infections. N. Engl.
J. Med., 290:1177, 1974.
14. Hamburger, J., et al. (translated by Walsh, A.): Acute Tubular and
Interstitial Nephritis. Philadelphia, W. B. Saunders Co., Vol. 1,
1968; p. 501.
15. Hamburger, J., Hepp. J. and Crosnier, J., Discussion by Caroli, J.:
Angiocholite Lithiasique Ictero-uremigene Gravissime. Rev.
Med. Chir. Mal. Foie., 33:181, 1958.
16. Helwig, F. C. and Schutz, C. B.: A Liver-Kidney Syndrome. Surg.
Gynecol. Obstet., 55:570, 1932.
17. Merklen, P.: Sur une Forme d'Insuffisance Hepato-Renale Aigue.
Rev. Med. (Paris), 35:172, 1915.
18. Papper, S.: Renal Failure. Med. Clin. North Am., 55:335, 1971.
19. Reynolds, B. M. and Dargan, E. L.: Acute Obstructive Cholangitis.
Ann. Surg., 150:229, 1959.
20. Sherlock, S.: Diseases of the Liver and Biliary System. Oxford,
Blackwell Scientific Publications (4th edition), 1968.
21. Sorenson, F. H., Anderson, J. B., Ornsholt, J. and Skjoldborg, H.:
Acute Renal Failure Complicating Biliary Tract Disorders. Acta.
Chir. Scand., 137:87, 1971.
22. Wardle, E. N. and Wright, N. A.: Endotoxin and Acute Renal
Failure Associated with Obstructive Jaundice. Br. Med. J. 4:472,
1970.