Reversibility of hepatorenal syndrome in an anuric patient with Child C cirrhosis requiring haemodialysis for 7 weeks
Kai-Uwe Eckardt and
Ulrich Frei
Department of Nephrology and Medical Intensive Care, Charité, Campus Virchow-Klinikum, Berlin, Germany
Keywords: Cirrhosis; hepatorenal syndrome; dialysis; liver failure; renal failure; renal replacement therapy
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Introduction
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Hepatorenal syndrome (HRS) is as a specific form of renal failure occurring in patients with advanced hepatic failure and portal hypertension as a consequence of marked renal vasoconstriction [1,2]. It is most common in patients with cirrhosis, but may also develop in other chronic or acute liver diseases. In the most recent definition it has been proposed that HRS should only be diagnosed when other causes of acute renal failure such as haemodynamic shock, drug-induced nephrotoxicity, and ongoing bacterial infection can be excluded and renal function does not improve following plasma volume expansion [1]. In patients with relatively preserved hepatic function the impairment of kidney function may be moderate and stable for several months (type II HRS), but usually renal failure is rapidly progressive (type I HRS). Such progression may be induced by complications or therapeutic intervention, but in approximately half of the patients it develops without any identifiable precipitating factor. Patients with type I HRS are usually in a severe clinical condition and the prognosis is very poor with a median survival time of less than 2 weeks [3]. Vasoconstrictor agents and peritoneo- or portovenous shunts have been reported to improve renal function in cirrhotic patients [1,2]. However, these studies have usually not included anuric patients on dialysis, and whether they prolong patient survival remains unknown.
In patients with HRS awaiting liver transplantation or in those surviving fulminant hepatic failure, temporary renal replacement therapy may be life saving [4] and under both circumstances renal function usually recovers. However, in patients with chronic liver disease and HRS who are not transplanted, haemodialysis is traditionally considered ineffective, because most of them die during treatment. Only a few case reports have documented prolonged survival and improvement of renal function in patients with chronic liver disease treated by dialysis [5].
We report here the unusual course of a patient with type I HRS who was oligo-/anuric for 2 weeks and was treated with regular dialysis for 7 weeks before he could be discharged with markedly improved renal and hepatic function.
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Case
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A 62-year-old man presented himself to a general practitioner after he had noticed increasing jaundice for approximately 1 week. His previous medical history was unremarkable, but he admitted regular alcohol consumption for 20 years. Ultrasonography showed nodular cirrhosis of a normal sized liver with moderate splenomegaly and perihepatic ascites and normal sized, regular shaped kidneys. Laboratory tests revealed marked hyperbilirubinaemia, a moderate elevation of plasma transaminases, a reduced thromboplastin time, and no evidence for viral hepatitis (Table 1
). Seven days later he was admitted to a community hospital after his general condition had worsened and he had noticed a progressive reduction of his diuresis. At that time he was hyponatraemic and his plasma creatinine had increased from 38 to 301 µmol/l (Table 1
). The following day he was transferred to our intensive care unit. His blood pressure was around 100/50 mmHg, heart rate 80/min. The residual urine output was 120 ml/24 h with a sodium concentration of 8 mmol/l. Diuresis then ceased completely despite plasma volume expansion. Abdominal ultrasound confirmed the previous findings and again revealed only moderate perihepatic and perisplenic ascites. There was no evidence for a thrombosis of the portal vein or for urinary-tract obstruction. The patient had not received any drugs and there was no indication of significant gastrointestinal or renal fluid losses. Nor was there any evidence apart from a moderate leukocytosis suggesting ongoing bacterial infection as a possible cause for the deterioration of renal function. The diagnosis of HRS was therefore made according to the recently proposed criteria [1].
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Table 1. Laboratory values 8 and 1 day prior to admission, reflecting deterioration of renal function in the presence of impaired but stable hepatic function with marked cholestasis
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During the subsequent treatment period the patient was gradually volume expanded, as obvious from the increases in body weight (see Figure 1
), accepting that this resulted in a marked progression of his ascites. Accordingly, during the first 4 days intermittent haemodialysis was performed without net ultrafiltration, until incipient respiratory compromise did not allow a further increase in extracellular volume. In an attempt to improve renal perfusion pressure dopamine was given at a dose of 3.8 µg/kg/min. Ornipressin (Pro8®, Novartis), which has previously been reported to improve renal function in some patients with HRS [6], was started on day 8 at a dose of 6 IU/h and continued until day 14, without unwarranted side-effects. In addition, in accordance with a report that head-out water immersion in a bathtub may improve renal haemodynamics [7], the patient was subjected to repetitive whole-body baths for several hours per day.

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Fig. 1. Time course of plasma bilirubin levels, urine output and body weight over the first 21 days and the subsequent 4 weeks in a patient with alcoholic cirrhosis and HRS.
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On day 12 diuresis resumed, 4 days after arterial blood pressure had gradually increased to approximately 130/70 mmHg. Intermittent haemodialysis had to be performed for another 5 weeks. Thereafter renal function improved sufficiently, despite gradual reduction of the previously expanded extracellular fluid volume, to allow discontinuation of dialysis. This improvement of renal function was paralleled by a continuous fall in bilirubin and a slight improvement in liver function, as reflected by an increase in thromboplastin time to 44%. Endoscopy revealed grade III oesophageal varices, but there were no signs of acute bleeding at any time. The patient was discharged after 7 weeks with a plasma creatinine level of around 350 µmol/l, which subsequently declined to 130 µmol/l during the following months. Mean renal resistive index fell to 0.74 and 0.80 in the right and left kidney respectively, reflecting a moderate residual perfusion impairment. The patient stopped alcohol consumption completely. After more than 6 months of abstinence he was evaluated and accepted for liver transplantation and 7 months later he was transplanted successfully.
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Discussion
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Therapeutic efforts in patients with rapidly progressive HRS are frequently considered futile, and renal replacement therapy is usually only recommended in those awaiting liver transplantation in due course or in patients with acute hepatic dysfunction in whom there is reason to believe that the underlying liver disease is reversible [4]. In the present case the potential reversibility of hepatic failure was uncertain because patient history was undocumented and there was no obvious reason for an acute decompensation superimposed on chronic, presumably alcoholic, cirrhosis. Moreover, no potentially reversible factor could be identified that might have precipitated the marked deterioration in renal function within a few days, in the absence of significant further impairment in liver function (Table 1
).
Nevertheless the implementation of regular intermittent haemodialysis allowed a gradual recovery of both hepatic and renal function. This reversibility of HRS is in accordance with classical studies showing that kidneys from cirrhotic patients with HRS regain a normal function when transplanted into patients with chronic renal failure and that HRS is usually reversible after liver transplantation [1,2]. However, despite the functional nature of HRS, spontaneous recovery is very rare. The pathogenesis of HRS is characterized by severe renal hypoperfusion as a consequence of a yet poorly defined imbalance between vasodilatory and vasoconstrictive mechanisms in the kidney, in the presence of arterial hypotension and reduced vascular resistance in the splanchnic circulation [2].
Several approaches were used in the present case in an attempt to improve renal haemodynamics and reverse the maldistribution of blood volume. These included plasma volume expansion, blood pressure support with dopamine [8], water immersion [7] and the infusion of ornipressin, a vasopressin derivative with little antidiuretic activity, that leads to preferential splanchnic vasoconstriction [6] (Figure 1
).
Due to the obvious limitations of such an observational report, it remains unclear to what extent any of these measures, alone or in combination, facilitated the recovery of renal function. Lenz et al. [6] reported a close temporal relationship between the onset of ornipressin infusion and the improvement of renal function, which was not observed in the present case. Similarly to our patient, however, in a more recent trial [9], an increase in diuresis only occurred after prolonged administration of ornipressin in combination with volume expansion. Unfortunately ornipressin is at present not available in Germany, and the difficulty of obtaining sufficient amounts of this agent was the reason for our not commencing treatment before day 8. It has been suggested, however, that other vasopressin analogues, such as terlipressin, may have similar effects [10].
Irrespective of any effect on kidney function, the temporary and controlled extracellular volume expansion undertaken in this case probably contributed to the success of intermittent dialysis without any complications in the presence of a relatively low arterial blood pressure. Together with gastrointestinal bleeding, worsening of arterial hypotension is one of the unwarranted side-effects that limits the use of dialysis in HRS, and under such circumstances continuous therapies may result in improved cardiovascular stability.
Although haemodynamic rather than metabolic consequences of hepatic failure are believed to induce HRS, both clinical and experimental evidence indicates that cholestasis impairs renal function [11], possibly through mechanisms that are partially sensitive to antioxidants [12]. The marked jaundice in the present case may have played an important role in the development of renal failure, all the more so since renal function deteriorated in the absence of gross ascites, which is unusual for patients with chronic liver disease who develop secondary renal failure. In accordance with a significant impact of cholestasis, the recovery of kidney function was paralleled by a continuous fall in plasma bilirubin concentrations (Figure 1
), although the level was still above 30 mg/dl when diuresis recommenced.
In conclusion, this observation shows that temporary, intermittent haemodialysis may lead to the recovery of satisfactory, stable renal function, even after a period of complete anuria, in patients with well-documented HRS in whom hepatic failure is not rapidly progressive. Individual careful selection is necessary to decide on withholding renal replacement therapy in patients with chronic liver disease developing renal failure. In cases with the potential for stabilization or improvement of hepatic function, the implementation of dialysis is warranted, and combined measures to improve renal perfusion should probably be undertaken in order to facilitate the recovery of renal function.
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Notes
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Correspondence and offprint requests to: K. -U. Eckardt MD, Department of Nephrology and Medical Intensive Care, Charité, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany. 
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References
|
---|
-
Arroyo V, Ginès P, Gerbes AL et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Hepatology1996; 23: 164176[ISI][Medline]
-
Eckardt K-U. Renal failure in liver disease. Int Care Med1999; 25: 514[ISI][Medline]
-
Ginès A, Escorsell A, Ginès P et al. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology1993; 105:229236[ISI][Medline]
-
Perez GO, Golper TA, Epstein M et al. Dialysis, hemofiltration and other extracorporeal techniques in the treatment of the renal complications of liver disease. In: Epstein M, ed. The Kidney in Liver Disease, 4th edn. Hanley and Belfus, Philadelphia, 1996; 517528
-
Keller F, Wagner K, Lenz T et al. Haemodialysis in hepatorenal syndrome: report on two cases. Gut1985; 26: 208211[Abstract]
-
Lenz K, Hörtnagl H, Druml W et al. Beneficial effect of 8-ornithin vasopressin on renal dysfunction in decompensated cirrhosis. Gut1989; 30: 9096[Abstract]
-
Yersin B, Burnier M, Magnenat P. Improvement of renal failure with repeated head-out water immersions in patients with hepatorenal syndrome associated with alcoholic hepatitis. Am J Nephrol1995; 15: 260265[ISI][Medline]
-
Barnardo DE, Baldus WP, Maher FT. Effects of dopamine on renal function in patients with cirrhosis. Gastroenterology1970; 58: 524531[ISI][Medline]
-
Guevara M, Ginés P, Fernández-Esparrach G et al. Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion. Hepatology1998; 27: 3541[ISI][Medline]
-
Cervoni J-P, Lecomte T, Cellier C et al. Terlipressin may influence the outcome of hepatorenal syndrome complicating alcoholic hepatitis. Am J Gastroenterol1997; 92: 21132114[ISI][Medline]
-
Bomzon A, Jacob G, Better OS. Jaundice and the kidney. In: Epstein M, ed. The Kidney in Liver Disease, 4th edn. Hanley and Belfus, Philadelphia,1996; 423446
-
Holt S, Marley R, Fernando B et al. Acute cholestasis-induced renal failure: effects of antioxidants and ligands for the thromboxane A2 receptor. Kidney Int1999; 55:271277[ISI][Medline]
Received for publication: 30. 8.99
Revision received 8. 2.00.