Effects of treatment of hepatorenal syndrome before transplantation on posttransplantation outcome. A case-control study☆
Introduction
Transplantation of patients with cirrhosis and hepatorenal syndrome (HRS) represents a major challenge in liver transplantation today due to two main reasons: first, patients with HRS have a very poor short-term prognosis [1], [2] which account for a high mortality while awaiting transplantation. Second, the existence of HRS is associated with a poor outcome after transplantation. Several studies from different transplant centers have convincingly demonstrated that renal function pretransplantation is the most important predictive factor of post-transplant survival [3], [4], [5], [6], [7], [8], [9]. Moreover, the presence of HRS also carries an increased risk of complications post-transplantation, including intraabdominal bleeding and infections, and a greater use of medical resources (longer hospitalizations and prolonged stays in the intensive care unit) [3], [4], [6], [10], [11].
Considering their poor prognosis, patients with HRS are given priority for transplantation in some centers. This was done with the former system of organ allocation used by the United Network for Organ Allocation (UNOS), in which patients with HRS were given the status 2a [12], and is also done by the new system using the model for end-stage liver disease (MELD) score, which includes serum creatinine as one of the variables used to calculate the score [13], [14], [15], [16], [17]. This type of priorization without doubt increases the proportion of patients with HRS reaching transplantation but has probably no impact in improving the overall outcome of patients transplanted with HRS. A second issue in patients with HRS is that of the management of renal failure pretransplantation. In many centers, patients are treated with a number of methods of renal support, including hemodyalisis, hemofiltration, or albumin dialysis [18], [19], [20], [21]. However, there is no information available about the possible beneficial effect of these measures on outcome after transplantation. Therefore, the management of renal failure pretransplantation in patients with HRS is an unsolved issue.
Recently, several vasoconstrictor drugs have been used in the management of patients with HRS with excellent results [22], [23], [24], [25], [26], [27], [28]. The rationale of this treatment is to increase renal perfusion by causing a vasoconstriction of the splanchnic circulation which is extremely vasodilated in patients with HRS [29]. Vasopressin analogues, especially terlipressin, have been used in most studies, but alfa-adrenergic agonists (noradrenaline and midodrine) seem also effective [27], [28]. A positive response with reversal of HRS is obtained in up to 75% of patients treated. Furthermore, responder patients have a significantly longer survival compared with non-responders, which suggests that this therapy improves survival [25], [26]. Theoretically, the administration of vasoconstrictors may be an ideal approach for the management of HRS in patients awaiting liver transplantation, because the improvement of renal function prior to transplantation may improve posttransplantation outcome. However, the evolution of patients transplanted after treatment of HRS has not been investigated. Therefore, the current study was designed to assess the outcome after transplantation of a series of patients with HRS treated with vasopressin analogues prior to transplantation.
Section snippets
Patients and methods
From 1996 to 2001 60 patients with cirrhosis and renal failure admitted to the Liver Unit of the Hospital Clı́nic of Barcelona met the diagnostic criteria of HRS [30]. Thirty-eight patients (63%) had contraindications for transplantation (advanced age in 16 cases, alcohol abuse in 10, and severe extrahepatic diseases in the remaining 12), while 22 (37%) did not have contraindications. All but one of these 22 patients received vasopressin analogues as therapy for HRS in the setting of
Comparison between the two groups
Table 2 shows the demographic, clinical, and biochemical data of patients with HRS, both at the time of treatment and transplantation, and those of the control group of patients without HRS at the time of transplantation. As expected, at transplantation both groups were similar with respect to the matching variables age and severity of liver failure. Moreover, there were no significant differences between the two groups with respect to the other baseline variables except for BUN and serum
Discussion
The current study shows that patients with HRS treated with vasopressin analogues and albumin prior to transplantation have an excellent outcome after transplantation, which is not different from that observed in a control group of patients transplanted without HRS matched by age, type of immunosuppression, and severity of the liver disease.
Both short and long-term survival after transplantation of patients with treated HRS were similar to those of a control group of patients transplanted
Acknowledgements
This work was supported by a grant from the Ministerio de Ciencia y Tecnologia (SAF 2001-0300), Fundació Marató TV3 (U-2000-TV2710), and Fondo de Investigación Sanitaria (FIS 02/0701). Supported also in part by a grant from the Instituto de Salud Carlos III (C03/2).
The authors would like to thank Dara de las Heras MD, Blas Calahorra MD and Raquel Cela RN and the nursing staff of our Unit for their participation in this project.
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The authors state that they have no financial relationship with any of the companies manufacturing drugs used in this study nor have they received any financial support from these companies to carry out this study.