The Hepatorenal Syndrome: Recovery After Portacaval Shunt STEPHEN ARIYAN, M.D.* THOMAS SWEENEY, M.D.,t MORRIS D. KERSTEIN, M.D.t Reversal of the morbid hepato-renal syndrome has been achieved From the Section of General Surgery, Department of in a cirrhotic patient with ascites foUlowing successful side-to-side Surgery, Yale University School of Medicine, and the portacaval shunt. The hepatorenal syndrome is defined as pro- Veterans Administration Hospital, West Haven, Connecticut gressive unresponsive renal failure with previously normal kidneys in the presence of impaired hepatic function. Although the etiologic mechanism has not been defined, it is suggested the Case Report relationship of increased intrahepatic sinusoidal pressure on the This was the second admission to the West Haven thoracic duct and subsequent decreased lymph flow are interVeterans Administration Hospital for this 78-year-old related to increased levels of aldosterone and manifested by (chylous) ascites. Laboratory and clinical evidence suggest that cir- Caucasian man with cirrhosis of unknown etiology. He rhotics with ascites have remarkably high levels of aldosterone was in good health until mid-1971 when he experienced secretion via the rennin-angiotensin-adrenal cortex mechanism. insidious onset of ascites with no history of alcohol ingesThis is the group that develops hepatorenal syndrome. Reduction of the intrahepatic pressure and decompression ofthe portal hyperten- tion or hepatitis. A liver biopsy on that admission was sion can be successfully achieved with a side-to-side shunt which read as mild inflammatory changes. The ascites was conshould return the aldosterone-rennin-angiotensin axis to normal trolled with diuretics, and the patient was discharged. and subsequently reverse the hepatorenal syndrome. He did well until December, 1973, when he had an episode of hematemesis and bright red blood per rectum. piROGRESSIVE renal failure in the presence of impaired On admission to another hospital, Hct. was 20%.
hepatic function has been described in a variety of disorders grouped as the "hepatorenal syndrome." The features of the hepatorenal syndrome (HRS) include azotemia, oliguria, and intense sodium retention in the presence of histologically normal kidneys. Classically the HRS occurs in cirrhotics in whom there is no evidence of pre-existing renal disease. Hecker and Sherlock reported 9 cirrhotic patients who died in renal failure.7 Papper and his associates reported an additional 22 patients with HRS-all of whom died.15 Various attempts at treating this condition have been unsuccessful, and the HRS is usually a terminal event.2' 1718
Esophagoscopy showed 4+ varices without an obvious bleeding point. He required a 13 unit blood replacement after which he had an episode of hepatic coma controlled with neomycin. The ascites flared, and he required
treatment with diuretics. On admission to the West Haven V.A. Hospital, he was noted to have tense ascites with 4+ pitting edema of lower extremities. HAA was negative. A liver scan showed a small liver with enlarged spleen. He was placed on Aldactone, Digitoxin, low salt and protein diet and fluid restriction. Repeat liver biopsy showed fibrosis of the portal tracts. After several weeks, the ascites improved significantly, and he was discharged. Submitted for publication January 3, 1975. One week prior to the second admission at this hospi*Chief Resident in Surgery, Yale-New Haven Hospital. tal, he noticed increasing ascites and 7 lb. weight gain. tResident in Surgery, Yale-New Haven Hospital. tAssistant Professor of Surgery, Yale University School of Medicine. Paracentesis on this admission revealed chylous ascites Chief, Peripheral Vascular Surgery, Veterans Administration Hospital, with 355 mg.% lipids. Attempts at diuresis resulted in a West Haven, Connecticut. Attending Surgeon, Yale-New Haven Hosrise in the BUN from 33 to 51. It was also noted that he pital. had an enlarging umbilical hernia which was beginning to All correspondence to: Dr. Morris D. Kerstein, Department of Surgery, Yale University School of Medicine, 333 Cedar Street, New ulcerate. Haven, Conneticut. 06510. Femoral cath studies revealed a hepatic wedge pres-
847
848 275
o 225-Iz I. 17549
I~0 0 a
5
160140120100-
so8 60 50
32ts 27s 225: -J
,11
175-
-%---.
100: z
3.2
i .j0
.4
z
Ann. Surg.. June 1975
ARIYAN, SWEENEY AND KERSTEIN
2.4
.0L
35
25
sidered the patient to have HRS.5 Baldus and his associates reported recovery in 6 of their 25 patients with HRS.2 However, the azotemia was present for less then 3 weeks in these patients. Goldstein and Boyle reported 4 additional cases of survivors from this syndrome.6 In all these reports, recovery could be correlated with improvement in hepatic function. This is further evidence that the kidneys are structurally normal. It has also been shown that kidneys from patients who have died from the HRS function normally when transplanted into patients with chronic uremia.8 One feature Temains prominent in the review of HRS; the presence of ascites.2 5"7"8 In fact, it may be the sine qua non of the HRS.4 There is evidence to suggest that cirrhotics with ascites have abnormally high aldosterone secretion,' and that this hyperaldosteronism is responsible for the marked salt and water retention. Although the cause of the hyperaldosteronism is not known, patients with cirrhosis but no ascites do not secrete high levels of aldosterone.'9 In a series of laboratory studies on dogs, Orloff and his associates investigated the relationship between ascites and aldosterone secretion. Increased intrahepatic pressure from minimal hepatic outflow occlusion resulted in 150 _
49
z 200
o a
0O 150 a
a 100 49 I
90
a
1
prooperotive
1.I-
6
10 D
A
Y
S
I
1
20
30
-
W
a o
140
-
130 120 100 _
postoperotive
FIG. IA. Laboratory studies pre and post side-to-side portacaval shunt.
50_
_
I
E
sure of 32 mm Hg.; the IVC was within normal limits and no hepatofugal flow. Attempts were made to reduce the
ascites with serial paracenteses and plasma expanders, but his BUN continued to rise, and serum albumin went down. It was decided that a side-to-side portacaval shunt should be performed in light of intractable ascites, ulcerating umbilical hernia and progressive hepatorenal syndrome. Just prior to surgery, an SMA catheter was placed and the venous anatomy outlined. This also served as a means of vasopressin infusion at time of surgery if needed. A successful side-to-side shunt was performed. Postoperatively, the HRS was relieved (Figs. 1 A and B).
Discussion Spontaneous recovery from the HRS is indeed rare. Although Galambos and Wilkinson described the first recovery of a patient with hyponatremia, they never con-
as
cr40
.
-
.
50 z
4011
Z 2.6 2014
i_ 2.2 W
1.8
I.t
145 0
135
130 125 120
-
I
-
90
I
preoperative
10
DAYS
20
30
postoperative
FIG. I B. Laboratory studies pre and post side-to-side portacaval shunt.
849
THE HEPATORENAL SYNDROME
Vol. 181 -No. 6
prompt 4-to-5 fold increase in aldosterone secretion,13
References
which was abolished in nephrectomized dogs,'0 and again increased in normal dogs cross-transfused with blood from nephrectomized dogs undergoing minimal hepatic outflow occlusion."2 They proposed that intrahepatic hypertension played a role in the hyperaldosteronism associated with cirrhotic ascites, presumably through a renin-angiotensin pathway with the adrenal cortex. Further laboratory studies demonstrated that side-toside portacaval shunts in dogs were significantly better than end-to-side shunts in relieving well-established persistent ascites,'4 decompressing liver sinusoidal and thoracic duct pressures," as well as decreasing aldosterone secretion.'0 On the basis of these experimental observations, 9 patients with intractable ascites and hyperaldosteronism were treated with side-to-side portacaval shunts with resolution of the ascites, decrease in aldosterone secretion, and increase in urine output.9 Wolfman and his associates,20 and Burchell, et al. , demonstrated similar results in their experiences with side-to-side shunts. Schroeder and his colleagues reported the first recovery from the HRS following a side-to-side portacaval shunt in a 42-year-old woman with intractable ascites and renal failure secondary to alcoholic cirrhosis.'6 The hyperaldosteronism, renal dilution mechanism, and plasma renins returned to normal after the shunt. Our patient is the second such case to recover from the HRS following a surgical procedure to decompress the portal venous hypertension. It would seem reasonable from previous laboratory and clinical trials that a decompression procedure which would lower intrahepatic pressure would revert the aldosterone levels to normal, as well as alleviate the ascites. In our patient, the abdominal fluid was a chylous ascites. Orloff has shown that the intrahepatic sinusoidal pressure rise also increased the pressure of the thoracic duct and decreased lymphatic flow. In our case, this could be a reflection of actual contribution to the ascites from the thoracic duct or the bowel wall. For these reasons, a side-to-side shunt was used to decompress the portal hypertension to give the maximal and optimal results for the treatment of ascites, chylous fluid, and return the aldosterone and rennin-angiotensin mechanisms of the HRS to normal. Acknowledgment
1. Axelrad, B.J., Cates, J.E., Johnson, B.B., et al.: Aldosterone in Urine of Normal Man and of Patients with Oedema: Its In-
The authors wish to thank Dr. Harold manuscript.
0.
Conn for reviewing the
2.
3. 4. 5. 6. 7. 8.
9.
10. 11.
12.
13. 14.
15. 16. 17. 18. 19. 20.
creased Recovery After Hydrolysis With Acid and B-Glucuronidase. Br. Med. J., 1:196-199, 1955. Baldus, W.P., Feichter, R.N. and Summerskill, W.H.J.: The Kidney in Cirrhosis. I. Clinical and Biochemical Features of Azotemia in Hepatic Failure. Ann. Intern. Med., 60:353-365, 1964. Burchell, A.R., Rousselot, L.M. and Panke, W.F.: A Seven-year experience with Side-to-Side Portacaval Shunt for Cirrhotic Ascites. Ann. Surg., 168: 655-668, 1968. Conn, H.O.: A Rational Approach to the Hepatorenal Syndrome. Gastroenterology, 65:321-340, 1970. Galambos, J.T. and Wilkinson, H.A.: Reversible Hypoatremia and Azotemia in a Patient with Cirrhosis and Ascites. Am. J. Digest. Dis., 7:642-647, 1962. Goldstein, H. and Boyle, J.D.: Spontaneous Recovery From the Hepatorenal Syndrome. N. Engl. J. Med., 272:895-898, 1965. Hecker, R. and Sherlock, S.: Electrolyte and Circulatory Changes in Terminal Liver Failure. Lancet, 2:1121-1125, 1956. Koppel, M.H., Coburn, J.W., Mims, M.M., et al.: Transplantation of Cadaver Kidneys From Patients with Hepatorenal Syndrome. Evidence for the Functional Nature of Renal Failure in Advanced Renal Disease. N. Engl. J. Med., 280:1367-1371, 1969. Orloff, M.J.: Effect of Side-to-Side Portacaval Shunt on Intractable Ascites, Sodium Excretion and Aldosterone Metabolism in Man. Am. J. Surg., 112:287-298, 1966. Orloff, M.J., Baddeley, R.M., Ross, T.H., et al.: Regulations of Aldosterone Secretion by an Hepatic Receptor. Surg. Forum, 15:74-76, 1964. Orloff, M.J., Goodhead, B., Windsor, C.W.O., et al.: Effect of Portacaval Shunts on Lymph Flow in the Thoracic Duct. Experiments with Normal Dogs and Dogs with Cirrhosis and Ascites. Am. J. Surg., 114:212-221, 1967. Orloff, M.J., Lipman, C.A., Noel, S.M., et al.: Hepatic Regulation of Aldosterone Secretion by a Humoral Mediator. Surgery, 58:225-247, 1965. Orloff, M.J., Ross, T.H., Baddeley, R.M., et al.: Experimental Ascites. VI: The Effects of Hepatic Venous Outflow Obstruction and Ascites on Aldosterone Secretion. Surgery, 56:83-98, 1964. Orloff, M.J., Spitz, B.R., Wall, M.H., et al.: Experimental Ascites. IV: Comparison of the Effects of End-to-Side and Side-to-Side Portacaval Shunts on Intractable Ascites. Surgery, 56:784-799, 1964. Papper, S., Belsky, J.L. and Bleifer, K.H.: Renal Failure in Laennec's Cirrhosis of Liver. I. Description of Clinical and Laboratory Features. Ann. Intern. Med., 51:759-773, 1959. Schroeder, E.T., Numann, P.J., Chamberlain, B.E.: Functional Renal Failure in Cirrhosis. Recovery After Portacaval Shunt. Ann. Intern. Med., 72:923-928, 1970. Shear, L., Kleinerman, J., Gabuzda, G.J.: Renal Failure in Patients with Cirrhosis of the Liver. I. Clinical and Pathological Characteristics. Am. J. Med., 39:184-198, 1965. Sherlock, S. and Shaldon, S.: An Etiology and Management of Ascites in Patients with Hepatic Cirrhosis. Gut, 4:95-105, 1963. Wolff, H.P., Koczorek, K.R., Buchborn, E.: Aldosterone and Antidiuretic Hormone (Adiuretin) in Liver Disease. Acta. Endocrinol., 27:45-58, 1958. Wolfman, E.F., Zuidema, G.D., Child, C.G.: Urinary Sodium and Aldosterone Excretion Following Portacaval Shunts for Cirrhosis of Liver and Portal Hypertension: Effect of End-to-Side and Side-to-Side Anastomoses in 16 Cases. Ann. Surg., 164:538-546, 1966.
hepatic function has been described in a variety of disorders grouped as the "hepatorenal syndrome." The features of the hepatorenal syndrome (HRS) include azotemia, oliguria, and intense sodium retention in the presence of histologically normal kidneys. Classically the HRS occurs in cirrhotics in whom there is no evidence of pre-existing renal disease. Hecker and Sherlock reported 9 cirrhotic patients who died in renal failure.7 Papper and his associates reported an additional 22 patients with HRS-all of whom died.15 Various attempts at treating this condition have been unsuccessful, and the HRS is usually a terminal event.2' 1718
Esophagoscopy showed 4+ varices without an obvious bleeding point. He required a 13 unit blood replacement after which he had an episode of hepatic coma controlled with neomycin. The ascites flared, and he required
treatment with diuretics. On admission to the West Haven V.A. Hospital, he was noted to have tense ascites with 4+ pitting edema of lower extremities. HAA was negative. A liver scan showed a small liver with enlarged spleen. He was placed on Aldactone, Digitoxin, low salt and protein diet and fluid restriction. Repeat liver biopsy showed fibrosis of the portal tracts. After several weeks, the ascites improved significantly, and he was discharged. Submitted for publication January 3, 1975. One week prior to the second admission at this hospi*Chief Resident in Surgery, Yale-New Haven Hospital. tal, he noticed increasing ascites and 7 lb. weight gain. tResident in Surgery, Yale-New Haven Hospital. tAssistant Professor of Surgery, Yale University School of Medicine. Paracentesis on this admission revealed chylous ascites Chief, Peripheral Vascular Surgery, Veterans Administration Hospital, with 355 mg.% lipids. Attempts at diuresis resulted in a West Haven, Connecticut. Attending Surgeon, Yale-New Haven Hosrise in the BUN from 33 to 51. It was also noted that he pital. had an enlarging umbilical hernia which was beginning to All correspondence to: Dr. Morris D. Kerstein, Department of Surgery, Yale University School of Medicine, 333 Cedar Street, New ulcerate. Haven, Conneticut. 06510. Femoral cath studies revealed a hepatic wedge pres-
847
848 275
o 225-Iz I. 17549
I~0 0 a
5
160140120100-
so8 60 50
32ts 27s 225: -J
,11
175-
-%---.
100: z
3.2
i .j0
.4
z
Ann. Surg.. June 1975
ARIYAN, SWEENEY AND KERSTEIN
2.4
.0L
35
25
sidered the patient to have HRS.5 Baldus and his associates reported recovery in 6 of their 25 patients with HRS.2 However, the azotemia was present for less then 3 weeks in these patients. Goldstein and Boyle reported 4 additional cases of survivors from this syndrome.6 In all these reports, recovery could be correlated with improvement in hepatic function. This is further evidence that the kidneys are structurally normal. It has also been shown that kidneys from patients who have died from the HRS function normally when transplanted into patients with chronic uremia.8 One feature Temains prominent in the review of HRS; the presence of ascites.2 5"7"8 In fact, it may be the sine qua non of the HRS.4 There is evidence to suggest that cirrhotics with ascites have abnormally high aldosterone secretion,' and that this hyperaldosteronism is responsible for the marked salt and water retention. Although the cause of the hyperaldosteronism is not known, patients with cirrhosis but no ascites do not secrete high levels of aldosterone.'9 In a series of laboratory studies on dogs, Orloff and his associates investigated the relationship between ascites and aldosterone secretion. Increased intrahepatic pressure from minimal hepatic outflow occlusion resulted in 150 _
49
z 200
o a
0O 150 a
a 100 49 I
90
a
1
prooperotive
1.I-
6
10 D
A
Y
S
I
1
20
30
-
W
a o
140
-
130 120 100 _
postoperotive
FIG. IA. Laboratory studies pre and post side-to-side portacaval shunt.
50_
_
I
E
sure of 32 mm Hg.; the IVC was within normal limits and no hepatofugal flow. Attempts were made to reduce the
ascites with serial paracenteses and plasma expanders, but his BUN continued to rise, and serum albumin went down. It was decided that a side-to-side portacaval shunt should be performed in light of intractable ascites, ulcerating umbilical hernia and progressive hepatorenal syndrome. Just prior to surgery, an SMA catheter was placed and the venous anatomy outlined. This also served as a means of vasopressin infusion at time of surgery if needed. A successful side-to-side shunt was performed. Postoperatively, the HRS was relieved (Figs. 1 A and B).
Discussion Spontaneous recovery from the HRS is indeed rare. Although Galambos and Wilkinson described the first recovery of a patient with hyponatremia, they never con-
as
cr40
.
-
.
50 z
4011
Z 2.6 2014
i_ 2.2 W
1.8
I.t
145 0
135
130 125 120
-
I
-
90
I
preoperative
10
DAYS
20
30
postoperative
FIG. I B. Laboratory studies pre and post side-to-side portacaval shunt.
849
THE HEPATORENAL SYNDROME
Vol. 181 -No. 6
prompt 4-to-5 fold increase in aldosterone secretion,13
References
which was abolished in nephrectomized dogs,'0 and again increased in normal dogs cross-transfused with blood from nephrectomized dogs undergoing minimal hepatic outflow occlusion."2 They proposed that intrahepatic hypertension played a role in the hyperaldosteronism associated with cirrhotic ascites, presumably through a renin-angiotensin pathway with the adrenal cortex. Further laboratory studies demonstrated that side-toside portacaval shunts in dogs were significantly better than end-to-side shunts in relieving well-established persistent ascites,'4 decompressing liver sinusoidal and thoracic duct pressures," as well as decreasing aldosterone secretion.'0 On the basis of these experimental observations, 9 patients with intractable ascites and hyperaldosteronism were treated with side-to-side portacaval shunts with resolution of the ascites, decrease in aldosterone secretion, and increase in urine output.9 Wolfman and his associates,20 and Burchell, et al. , demonstrated similar results in their experiences with side-to-side shunts. Schroeder and his colleagues reported the first recovery from the HRS following a side-to-side portacaval shunt in a 42-year-old woman with intractable ascites and renal failure secondary to alcoholic cirrhosis.'6 The hyperaldosteronism, renal dilution mechanism, and plasma renins returned to normal after the shunt. Our patient is the second such case to recover from the HRS following a surgical procedure to decompress the portal venous hypertension. It would seem reasonable from previous laboratory and clinical trials that a decompression procedure which would lower intrahepatic pressure would revert the aldosterone levels to normal, as well as alleviate the ascites. In our patient, the abdominal fluid was a chylous ascites. Orloff has shown that the intrahepatic sinusoidal pressure rise also increased the pressure of the thoracic duct and decreased lymphatic flow. In our case, this could be a reflection of actual contribution to the ascites from the thoracic duct or the bowel wall. For these reasons, a side-to-side shunt was used to decompress the portal hypertension to give the maximal and optimal results for the treatment of ascites, chylous fluid, and return the aldosterone and rennin-angiotensin mechanisms of the HRS to normal. Acknowledgment
1. Axelrad, B.J., Cates, J.E., Johnson, B.B., et al.: Aldosterone in Urine of Normal Man and of Patients with Oedema: Its In-
The authors wish to thank Dr. Harold manuscript.
0.
Conn for reviewing the
2.
3. 4. 5. 6. 7. 8.
9.
10. 11.
12.
13. 14.
15. 16. 17. 18. 19. 20.
creased Recovery After Hydrolysis With Acid and B-Glucuronidase. Br. Med. J., 1:196-199, 1955. Baldus, W.P., Feichter, R.N. and Summerskill, W.H.J.: The Kidney in Cirrhosis. I. Clinical and Biochemical Features of Azotemia in Hepatic Failure. Ann. Intern. Med., 60:353-365, 1964. Burchell, A.R., Rousselot, L.M. and Panke, W.F.: A Seven-year experience with Side-to-Side Portacaval Shunt for Cirrhotic Ascites. Ann. Surg., 168: 655-668, 1968. Conn, H.O.: A Rational Approach to the Hepatorenal Syndrome. Gastroenterology, 65:321-340, 1970. Galambos, J.T. and Wilkinson, H.A.: Reversible Hypoatremia and Azotemia in a Patient with Cirrhosis and Ascites. Am. J. Digest. Dis., 7:642-647, 1962. Goldstein, H. and Boyle, J.D.: Spontaneous Recovery From the Hepatorenal Syndrome. N. Engl. J. Med., 272:895-898, 1965. Hecker, R. and Sherlock, S.: Electrolyte and Circulatory Changes in Terminal Liver Failure. Lancet, 2:1121-1125, 1956. Koppel, M.H., Coburn, J.W., Mims, M.M., et al.: Transplantation of Cadaver Kidneys From Patients with Hepatorenal Syndrome. Evidence for the Functional Nature of Renal Failure in Advanced Renal Disease. N. Engl. J. Med., 280:1367-1371, 1969. Orloff, M.J.: Effect of Side-to-Side Portacaval Shunt on Intractable Ascites, Sodium Excretion and Aldosterone Metabolism in Man. Am. J. Surg., 112:287-298, 1966. Orloff, M.J., Baddeley, R.M., Ross, T.H., et al.: Regulations of Aldosterone Secretion by an Hepatic Receptor. Surg. Forum, 15:74-76, 1964. Orloff, M.J., Goodhead, B., Windsor, C.W.O., et al.: Effect of Portacaval Shunts on Lymph Flow in the Thoracic Duct. Experiments with Normal Dogs and Dogs with Cirrhosis and Ascites. Am. J. Surg., 114:212-221, 1967. Orloff, M.J., Lipman, C.A., Noel, S.M., et al.: Hepatic Regulation of Aldosterone Secretion by a Humoral Mediator. Surgery, 58:225-247, 1965. Orloff, M.J., Ross, T.H., Baddeley, R.M., et al.: Experimental Ascites. VI: The Effects of Hepatic Venous Outflow Obstruction and Ascites on Aldosterone Secretion. Surgery, 56:83-98, 1964. Orloff, M.J., Spitz, B.R., Wall, M.H., et al.: Experimental Ascites. IV: Comparison of the Effects of End-to-Side and Side-to-Side Portacaval Shunts on Intractable Ascites. Surgery, 56:784-799, 1964. Papper, S., Belsky, J.L. and Bleifer, K.H.: Renal Failure in Laennec's Cirrhosis of Liver. I. Description of Clinical and Laboratory Features. Ann. Intern. Med., 51:759-773, 1959. Schroeder, E.T., Numann, P.J., Chamberlain, B.E.: Functional Renal Failure in Cirrhosis. Recovery After Portacaval Shunt. Ann. Intern. Med., 72:923-928, 1970. Shear, L., Kleinerman, J., Gabuzda, G.J.: Renal Failure in Patients with Cirrhosis of the Liver. I. Clinical and Pathological Characteristics. Am. J. Med., 39:184-198, 1965. Sherlock, S. and Shaldon, S.: An Etiology and Management of Ascites in Patients with Hepatic Cirrhosis. Gut, 4:95-105, 1963. Wolff, H.P., Koczorek, K.R., Buchborn, E.: Aldosterone and Antidiuretic Hormone (Adiuretin) in Liver Disease. Acta. Endocrinol., 27:45-58, 1958. Wolfman, E.F., Zuidema, G.D., Child, C.G.: Urinary Sodium and Aldosterone Excretion Following Portacaval Shunts for Cirrhosis of Liver and Portal Hypertension: Effect of End-to-Side and Side-to-Side Anastomoses in 16 Cases. Ann. Surg., 164:538-546, 1966.
