The growing evidence that renal function should be improved in patients with cirrhosis and hepatorenal syndrome before liver transplantation
2003; Elsevier BV; Volume: 40; Issue: 1 Linguagem: Inglês
10.1016/j.jhep.2003.10.024
ISSN1600-0641
Autores Tópico(s)Organ Transplantation Techniques and Outcomes
ResumoHepatorenal syndrome (HRS) is a prerenal failure (i.e. functional renal failure) that complicates end-stage cirrhosis [[1]Arroyo V. Ginès P. Gerbes A.L. Dudley F.J. Gentilini P. Laffi G. et al.Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis.Hepatology. 1996; 23: 164-176Crossref PubMed Google Scholar]. There are two types of HRS: type 1 (the acute form of the syndrome) and type 2 (the chronic form) [[1]Arroyo V. Ginès P. Gerbes A.L. Dudley F.J. Gentilini P. Laffi G. et al.Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis.Hepatology. 1996; 23: 164-176Crossref PubMed Google Scholar]. Since patients with HRS have a very poor short-term prognosis [[2]Ginès A. Escorsell A. Ginès P. Salo J. Jiménez W. Inglada L. et al.Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites.Gastroenterology. 1993; 105: 229-236Abstract PubMed Google Scholar], they are given priority for liver transplantation in some centers [3Kamath P.S. Wiesner R.H. Malinchoc M. Kremers W. Therneau T.M. Kosberg C.L. et al.A model to predict survival in patients with end-stage liver disease.Hepatology. 2001; 33: 464-470Crossref PubMed Scopus (3830) Google Scholar, 4Wiesner R.H. McDiarmid S.V. Kamath P.S. Edwards E.B. Malinchoc M. Kremers W.K. et al.MELD and PELD application of survival models to liver allocation.Liver Transpl. 2001; 7: 567-580Crossref PubMed Scopus (742) Google Scholar, 5Wiesner R. Edwards E. Freeman R. Harper A. Kim R. Kamath P. et al.Model for end-stage liver disease (MELD) and allocation of donor livers.Gastroenterology. 2003; 124: 91-96Abstract Full Text Full Text PDF PubMed Scopus (2004) Google Scholar]. However, patients with type 1 HRS may die very quickly, i.e. before receiving liver transplantation [2Ginès A. Escorsell A. Ginès P. Salo J. Jiménez W. Inglada L. et al.Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites.Gastroenterology. 1993; 105: 229-236Abstract PubMed Google Scholar, 6Moreau R. Durand F. Poynard T. Duhamel C. Cervoni J.P. Ichaı̈ P. et al.Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study.Gastroenterology. 2002; 122: 923-930Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar]. Renal failure per se is an independent predictive factor of death in patients awaiting liver transplantation [[6]Moreau R. Durand F. Poynard T. Duhamel C. Cervoni J.P. Ichaı̈ P. et al.Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study.Gastroenterology. 2002; 122: 923-930Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar]. Moreover, patients with HRS who are transplanted have a higher in-hospital mortality rate than those without HRS [7Cuervas-Mons V. Millan I. Gavaler J.S. Starzl T.E. Van Thiel D.H. Prognostic value of preoperatively obtained clinical and laboratory data in predicting survival following orthotopic liver transplantation.Hepatology. 1986; 6: 922-927Crossref PubMed Scopus (144) Google Scholar, 8Rimola A. Gavaler J.S. Schade R.R. El-Lankanyu S. Starzl T.E. Effects of renal impairment on liver transplantation.Gastroenterology. 1987; 93: 148-156PubMed Google Scholar, 9Gonwa A.T. Klintmalm G.B. Levy M. Jennings L.S. Goldstein R.M. Husberg B.S. Impact of pretransplant renal function on survival after liver transplantation.Transplantation. 1995; 59: 361-365Crossref PubMed Scopus (385) Google Scholar, 10González E. Rimola A. Navasa M. Andreu H. Grande L. Garcia-Valdecasas J.C. et al.Liver transplantation in patients with non-biliary cirrhosis: prognostic value of preoperative factors.J Hepatol. 1998; 28: 320-328Abstract Full Text PDF PubMed Scopus (20) Google Scholar, 11Nair S. Verma S. Thuluvath P.J. Pretransplant renal function predicts survival in patients undergoing orthotopic liver transplantation.Hepatology. 2002; 35: 1179-1185Crossref PubMed Scopus (447) Google Scholar, 12Gonwa A.T. Morris C. Goldstein R.M. Husberg B.S. Klintmalm G.B. Long-term survival and renal function following liver transplantation in patients with and without hepatorenal syndrome. Experience in 300 patients.Transplantation. 1991; 51: 428-430Crossref PubMed Scopus (280) Google Scholar]. In a large series of patients who received liver transplant, a pretransplantation gomerular filtration rate below 29 ml/min per 1.73 m2 of body-surface area (a common finding in patients with HRS) was a risk factor for the development of post-tranplantation chronic renal failure mainly due to calcineurin-inhibitor therapy [[13]Ojo A.O. Held P.J. Port F.K. Wolfe R.A. Leichtman A.B. Young E.W. et al.Chronic renal failure after transplantation of a nonrenal organ.N Engl J Med. 2003; 349: 931-940Crossref PubMed Scopus (1798) Google Scholar]. Together, these findings suggest that in patients with HRS, improvement of renal function may increase survival until liver transplantation and may improve the outcome post-transplantation. In many centers, patients with HRS are treated with renal replacement therapy, including hemofiltration, hemodialysis, or albumin dialysis [14Davis C.L. Gonwa T.A. Wilkinson A.H. Identification of patients best suited for combined liver–kidney transplantation. Part II.Liver Transpl. 2002; 8: 193-211Crossref PubMed Scopus (109) Google Scholar, 15Mitzner S.R. Stange J. Klammt S. Risler T. Erley C.M. Bader B.D. et al.Improvement of hepatorenal syndrome with extracorporeal albumine dialysis MARS: results of a prospective, randomized controlled clinical trial.Liver Transpl. 2000; 6: 277-286Crossref PubMed Scopus (611) Google Scholar]. However, the impact of these techniques on pretransplantation survival is unclear [[16]Moreau R. Lebrec D. Acute renal failure in patients with cirrhosis. Perspectives in the age of MELD.Hepatology. 2003; 37: 233-243Crossref PubMed Scopus (201) Google Scholar]. Moreover, the use of renal replacement therapy before liver transplantation has been shown to be a predictive factor of the development of post-transplantation chronic renal failure (see below) [[13]Ojo A.O. Held P.J. Port F.K. Wolfe R.A. Leichtman A.B. Young E.W. et al.Chronic renal failure after transplantation of a nonrenal organ.N Engl J Med. 2003; 349: 931-940Crossref PubMed Scopus (1798) Google Scholar]. Thus, more information on the effects of renal replacement therapy are needed. It has been suggested that splanchnic vasoconstrictors could be used to treat renal failure in patients with HRS [[16]Moreau R. Lebrec D. Acute renal failure in patients with cirrhosis. Perspectives in the age of MELD.Hepatology. 2003; 37: 233-243Crossref PubMed Scopus (201) Google Scholar]. Drug candidates include agonists of V1a-vasopressin receptors (i.e. the vasopressin analogues terlipressin and ornipressin) [6Moreau R. Durand F. Poynard T. Duhamel C. Cervoni J.P. Ichaı̈ P. et al.Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study.Gastroenterology. 2002; 122: 923-930Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar, 17Guevara M. Ginès P. Fernandez-Esparrach G. Sort P. Salmeron J.M. Jimenez W. et al.Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion.Hepatology. 1998; 27: 35-41Crossref PubMed Scopus (309) Google Scholar, 18Ortega R. Ginès P. Uriz J. Cardenas A. Calahorra B. De Las Heras D. et al.Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study.Hepatology. 2002; 36: 941-948PubMed Google Scholar, 19Alessandria C. Debernardi Venon W. Marzano A. Barletti C. Fadda M. Rizzetto M. Renal failure in cirrhotic patients: role of terlipressin in clinical approach to hepatorenal syndrome type 2.Eur J Gastroenterol Hepatol. 2002; 14: 1363-1368Crossref PubMed Scopus (122) Google Scholar, 20Solanki P. Chawla A. Garg R. Gupta R. Jain M. Sarin S.K. Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial.J Gastroenterol Hepatol. 2003; 18: 152-156Crossref PubMed Scopus (250) Google Scholar], and agonists of α1-adrenoceptors (i.e. midodrine, noradrenaline) [21Angeli P. Volpin R. Gerunda G. Craighero R. Roner P. Merenda R. et al.Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide.Hepatology. 1999; 29: 1690-1697Crossref PubMed Scopus (475) Google Scholar, 22Duvoux C. Zanditenas D. Hezode C. Chauvat A. Monin J.L. Roudot-Thoraval F. et al.Effects of noradrenalin and albumin in patients with type 1 hepatorenal syndrome: a pilot study.Hepatology. 2002; 36: 374-380Crossref PubMed Scopus (311) Google Scholar]. These vasoconstrictors have been used in combination with 20% human albumin [6Moreau R. Durand F. Poynard T. Duhamel C. Cervoni J.P. Ichaı̈ P. et al.Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study.Gastroenterology. 2002; 122: 923-930Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar, 17Guevara M. Ginès P. Fernandez-Esparrach G. Sort P. Salmeron J.M. Jimenez W. et al.Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion.Hepatology. 1998; 27: 35-41Crossref PubMed Scopus (309) Google Scholar, 18Ortega R. Ginès P. Uriz J. Cardenas A. Calahorra B. De Las Heras D. et al.Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study.Hepatology. 2002; 36: 941-948PubMed Google Scholar, 19Alessandria C. Debernardi Venon W. Marzano A. Barletti C. Fadda M. Rizzetto M. Renal failure in cirrhotic patients: role of terlipressin in clinical approach to hepatorenal syndrome type 2.Eur J Gastroenterol Hepatol. 2002; 14: 1363-1368Crossref PubMed Scopus (122) Google Scholar, 20Solanki P. Chawla A. Garg R. Gupta R. Jain M. Sarin S.K. Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial.J Gastroenterol Hepatol. 2003; 18: 152-156Crossref PubMed Scopus (250) Google Scholar, 21Angeli P. Volpin R. Gerunda G. Craighero R. Roner P. Merenda R. et al.Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide.Hepatology. 1999; 29: 1690-1697Crossref PubMed Scopus (475) Google Scholar, 22Duvoux C. Zanditenas D. Hezode C. Chauvat A. Monin J.L. Roudot-Thoraval F. et al.Effects of noradrenalin and albumin in patients with type 1 hepatorenal syndrome: a pilot study.Hepatology. 2002; 36: 374-380Crossref PubMed Scopus (311) Google Scholar]. The rationale for using vasoconstrictor therapy in patients with HRS is strong. Indeed, these patients have marked splanchnic vasodilation resulting in decreased systemic vascular resistance [[23]Fernandez-Seara J. Prieto J. Quiroga J. Zozaya J.M. Cobos M.A. Rodriguez-Eire J.L. et al.Systemic and regional hemodynamics in patients with liver cirrhosis and ascites with and without functional renal failure.Gastroenterology. 1989; 97: 1304-1312PubMed Google Scholar]. This systemic vasodilation triggers a cascade of events leading to renal (preglomerular) vasoconstriction [[16]Moreau R. Lebrec D. Acute renal failure in patients with cirrhosis. Perspectives in the age of MELD.Hepatology. 2003; 37: 233-243Crossref PubMed Scopus (201) Google Scholar]. In addition, systemic vasodilation causes arterial hypotension (below 80 mmHg) and thus decreased renal perfusion pressure [[24]Colle I. Durand F. Pessione F. Rassiat E. Bernuau J. Barrière E. et al.Clinical course, predictive factors and prognosis of hepatorenal syndrome treated with terlipressin: a retrospective analysis.J Gastroenterol Hepatol. 2002; 17: 882-888Crossref PubMed Scopus (135) Google Scholar]. Preglomerular vasoconstriction and decreased renal perfusion pressure play a crucial role in the marked decrease in the glomerular filtration rate [[16]Moreau R. Lebrec D. Acute renal failure in patients with cirrhosis. Perspectives in the age of MELD.Hepatology. 2003; 37: 233-243Crossref PubMed Scopus (201) Google Scholar]. Thus, it is not suprising that splanchnic vasoconstrictors whose target is the central mechanism of prerenal failure in patients with HRS (i.e. splanchnic vasodilation) induced sustained improvement of renal function in 60–80% of patients with HRS [6Moreau R. Durand F. Poynard T. Duhamel C. Cervoni J.P. Ichaı̈ P. et al.Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study.Gastroenterology. 2002; 122: 923-930Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar, 18Ortega R. Ginès P. Uriz J. Cardenas A. Calahorra B. De Las Heras D. et al.Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study.Hepatology. 2002; 36: 941-948PubMed Google Scholar, 19Alessandria C. Debernardi Venon W. Marzano A. Barletti C. Fadda M. Rizzetto M. Renal failure in cirrhotic patients: role of terlipressin in clinical approach to hepatorenal syndrome type 2.Eur J Gastroenterol Hepatol. 2002; 14: 1363-1368Crossref PubMed Scopus (122) Google Scholar, 20Solanki P. Chawla A. Garg R. Gupta R. Jain M. Sarin S.K. Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial.J Gastroenterol Hepatol. 2003; 18: 152-156Crossref PubMed Scopus (250) Google Scholar, 21Angeli P. Volpin R. Gerunda G. Craighero R. Roner P. Merenda R. et al.Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide.Hepatology. 1999; 29: 1690-1697Crossref PubMed Scopus (475) Google Scholar, 22Duvoux C. Zanditenas D. Hezode C. Chauvat A. Monin J.L. Roudot-Thoraval F. et al.Effects of noradrenalin and albumin in patients with type 1 hepatorenal syndrome: a pilot study.Hepatology. 2002; 36: 374-380Crossref PubMed Scopus (311) Google Scholar, 24Colle I. Durand F. Pessione F. Rassiat E. Bernuau J. Barrière E. et al.Clinical course, predictive factors and prognosis of hepatorenal syndrome treated with terlipressin: a retrospective analysis.J Gastroenterol Hepatol. 2002; 17: 882-888Crossref PubMed Scopus (135) Google Scholar]. Moreover, except ornipressin which may induce serious ischemic side-effects [[17]Guevara M. Ginès P. Fernandez-Esparrach G. Sort P. Salmeron J.M. Jimenez W. et al.Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion.Hepatology. 1998; 27: 35-41Crossref PubMed Scopus (309) Google Scholar], the other molecules are safe; which is important since patients with HRS are in poor condition [[25]Moreau R. Hepatorenal syndrome in patients with cirrhosis.J Gastroenterol Hepatol. 2002; 17: 739-747Crossref PubMed Scopus (47) Google Scholar]. Finally, there is evidence that terlipressin may improve the probability of survival and increase the chance of reaching liver tranplantation in patients with HRS [6Moreau R. Durand F. Poynard T. Duhamel C. Cervoni J.P. Ichaı̈ P. et al.Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study.Gastroenterology. 2002; 122: 923-930Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar, 18Ortega R. Ginès P. Uriz J. Cardenas A. Calahorra B. De Las Heras D. et al.Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study.Hepatology. 2002; 36: 941-948PubMed Google Scholar]. Therefore, vasoconstrictor therapy (mainly with terlipressin) can be used as a bridge while waiting for liver tranplantation. It should be emphasized that these findings were obtained mainly in patients with type 1 HRS and that little is known on the effects of vasoconstrictors in patients with type 2 HRS awaiting liver transplantation. In this issue of the Journal, Restuccia et al. from Barcelona have helped complete the puzzle by adding an important piece that was lacking thus far; i.e. information on post-transplantation outcome in patients who received vasoconstrictor therapy for HRS before transplantation [[26]Restuccia T. Ortega R. Guevara M. Ginès P. Alessandria C. Ozdogan O. et al.Effects of treatment of hepatorenal syndrome before transplantation on posttransplantation outcome. A case-control study.J Hepatol. 2004; 40: 140-146Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar]. In this case-control study, the outcome of nine patients with HRS (three with type 1 and six with type 2) treated with vasopressin analogues before transplantation was compared with that of a contemporary group of 27 patients without pretransplantation HRS matched for age, severity of cirrhosis, and type of immunosuppression. At transplantation, cases and controls had similar characteristics, except for serum creatinine and blood urea nitrogen values which were higher in the former. Three years after transplantation, the probability of survival did not significantly differ between the two groups (100 vs. 83%, in cases and controls, respectively). No significant differences were found between the two groups for post-operative acute renal failure which occurred in 22 and 30% of patients, respectively. This renal failure occurred early (most often during the initial hospitalization for transplantation) and was reversible after treatment of the cause and/or reduction of dosage of calcineurin inhibitors. The two groups were also similar for other post-transplantation complications, i.e. severe bacterial infections (22 vs. 33%), acute rejection (33 vs. 41%), transfusion requirements (six units vs. eight units). Together, these results show that patients with HRS treated with vasopressin analogues before liver transplantation have a post-transplantation outcome similar to that of patients who did not have HRS before they received liver transplant. The study of Restuccia et al. supports the treatment of HRS before liver transplantation. Since Restuccia et al. mainly studied patients with type 2 HRS, their findings suggest that vasoconstrictor therapy may be useful in these patients. However, the number of patients studied was small [[26]Restuccia T. Ortega R. Guevara M. Ginès P. Alessandria C. Ozdogan O. et al.Effects of treatment of hepatorenal syndrome before transplantation on posttransplantation outcome. A case-control study.J Hepatol. 2004; 40: 140-146Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar]. Thus, new studies should be performed to confirm the beneficial effects of vasoconstrictor therapy in patients with type 2 HRS before and after liver transplantation. This is important because type 2 HRS is a fairly common complication of cirrhosis. In addition, the effects of vasoconstrictor therapy before transplantation on post-transplantation outcome should be evaluated in a large series of patients with type 1 HRS. As noted above, calcineurin-inhibitor therapy is a main cause of chronic renal dysfunction after the transplantation of nonrenal organs, including the liver [[13]Ojo A.O. Held P.J. Port F.K. Wolfe R.A. Leichtman A.B. Young E.W. et al.Chronic renal failure after transplantation of a nonrenal organ.N Engl J Med. 2003; 349: 931-940Crossref PubMed Scopus (1798) Google Scholar]. Calcineurin inhibitors cause chronic renal failure by inducing tubular atrophy, interstitial fibrosis, and focal hyalinosis of small arteries and arterioles [[27]Myers B.D. Newton L. Cyclosporine-induced chronic nephropathy: an obliterative microvascular injury.J Am Soc Nephrol. 1991; 2: S45-S52PubMed Google Scholar]. During the 5 years following liver transplantation, 18% of patients develop chronic renal failure (defined as a glomerular filtration rate of 29 ml/min per 1.73 m2 of body-surface area or less), with one-third who require maintenance dialysis or kidney transplantation [[13]Ojo A.O. Held P.J. Port F.K. Wolfe R.A. Leichtman A.B. Young E.W. et al.Chronic renal failure after transplantation of a nonrenal organ.N Engl J Med. 2003; 349: 931-940Crossref PubMed Scopus (1798) Google Scholar]. In patients who receive a liver transplant, the occurrence of chronic renal failure is probably an important prognostic factor. Indeed, the occurrence of chronic renal failure in patients who have received a nonrenal transplant has been shown to significantly increase the risk of death [[13]Ojo A.O. Held P.J. Port F.K. Wolfe R.A. Leichtman A.B. Young E.W. et al.Chronic renal failure after transplantation of a nonrenal organ.N Engl J Med. 2003; 349: 931-940Crossref PubMed Scopus (1798) Google Scholar]. The independent predictive factors of the occurrence of chronic renal failure after liver transplantation are: older age, female sex, low pretransplantation glomerular filtration rate value (see above), renal replacement therapy before transplantation, pretransplantation hepatitis C infection, diabetes mellitus before transplantation, acute renal failure during initial hospitalization for transplantation, treatment with cyclosporine compared to treatment with tacrolimus [[13]Ojo A.O. Held P.J. Port F.K. Wolfe R.A. Leichtman A.B. Young E.W. et al.Chronic renal failure after transplantation of a nonrenal organ.N Engl J Med. 2003; 349: 931-940Crossref PubMed Scopus (1798) Google Scholar]. In the study by Restuccia et al. the two groups had several risk factors for post-transplantation chronic renal failure: female sex (56 and 50%, in cases and controls, respectively), pretransplantation hepatitis C virus (44 and 48%, respectively), post-operative acute renal failure (see above), cyclosporine therapy (78% in both groups) [[26]Restuccia T. Ortega R. Guevara M. Ginès P. Alessandria C. Ozdogan O. et al.Effects of treatment of hepatorenal syndrome before transplantation on posttransplantation outcome. A case-control study.J Hepatol. 2004; 40: 140-146Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar]. Despite the presence of these risk factors, none of the patients developed post-transplantation kidney dysfunction [[26]Restuccia T. Ortega R. Guevara M. Ginès P. Alessandria C. Ozdogan O. et al.Effects of treatment of hepatorenal syndrome before transplantation on posttransplantation outcome. A case-control study.J Hepatol. 2004; 40: 140-146Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar]. The reasons for this are unclear. It should be noted that during the post-transplantation period, Restuccia et al. measured serum creatinine but not the glomerular filtration rate, which is more accurate for assessing renal function. Therefore, they may have missed subtle renal impairment after liver transplantation. Thus, new studies should be performed. In particular, it would be important to evaluate the post-transplantation glomerular filtration rate in patients with type 1 or 2 HRS who received vasoconstrictor therapy before liver transplantation. Patients with refractory ascites are candidates for liver transplantation [[1]Arroyo V. Ginès P. Gerbes A.L. Dudley F.J. Gentilini P. Laffi G. et al.Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis.Hepatology. 1996; 23: 164-176Crossref PubMed Google Scholar]. These patients often have a decrease in renal plasma flow and a slight decrease in glomerular filtration rate between 40 and 70 ml/min (without overt type 2 HRS) [[28]Colle I. Moreau R. Pessione F. Rassiat E. Heller J. Chagneau C. et al.Relationships between hemodynamic alterations and the development of ascites or refractory ascites in patients with cirrhosis.Eur J Gastroenterol Hepatol. 2001; 13: 251-256Crossref PubMed Scopus (13) Google Scholar]. Moderate decreases in the pretransplantation glomerular filtration rate have been shown to be associated with an increased risk of post-transplantation chronic renal failure induced by calcineurin-inhibitor therapy [[13]Ojo A.O. Held P.J. Port F.K. Wolfe R.A. Leichtman A.B. Young E.W. et al.Chronic renal failure after transplantation of a nonrenal organ.N Engl J Med. 2003; 349: 931-940Crossref PubMed Scopus (1798) Google Scholar]. Thus, in patients with refractory ascites and moderate decreases in renal perfusion, improvement of renal hemodynamics before transplantation may help prevent kidney dysfunction after liver transplantation. Interestingly, the acute administration of terlipressin alone or combined with atrial natriuretic peptide has been shown to increase renal perfusion in patients with refractory ascites [[29]Gadano A. Moreau R. Vachiery F. Soupison T. Yang S. Cailmail S. et al.Natriuretic response to the combination of atrial natriuretic peptide and terlipressin in patients with cirrhosis and refractory ascites.J Hepatol. 1997; 26: 1229-1234Abstract Full Text PDF PubMed Scopus (47) Google Scholar]. Studies are needed on this topic. Therefore, in patients with end-stage cirrhosis waiting for liver transplantation, improvement of renal function with vasoconstrictor therapy may improve the post-transplantation outcome.
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