Acute renal failure after liver transplantation: The role of dopamine and fenoldopam
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EDITORIAL Acute Renal Failure After Liver Transplantation: The Role of Dopamine and Fenoldopam Nelson Leung and Stephen C. Textor A cute renal failure (ARF) in the immediate periop- erative liver transplant setting is a complex prob- lem. It is well established that when ARF develops either before or after liver transplantation, it has a major impact on the outcomes of the allograft and on patient survival. The pathogenesis of this disorder reflects mul- tiple hemodynamic changes associated with advanced liver disease, ultimately producing hepatorenal syn- drome, and the postoperative stresses after a liver trans- plant. When preoperative renal failure is related directly to hepatorenal syndrome, patient survival is limited (10% at 10 weeks) if orthotopic liver transplantation cannot be accomplished. 1 After orthotopic liver transplanta- tion, ARF continues to impact outcome, as mortality increases from 5 to 41% in those who develop periop- erative ARF. 2 Several studies indicate that reduced pre- transplant kidney function (reflected by glomerular fil- tration rate, usually expressed as creatinine clearance) is the single most consistent predictor of ARF after trans- plant. 3–7 Other predictors are less consistent, including number of units of blood transfused, the need for vaso- pressor support, early allograft dysfunction, and pre- transplant Child class. 3,4,7,8 Subjects with advanced liver disease regularly experience reduced renal perfu- sion and activation of vasoconstrictor mechanisms that raise renal vascular resistance in the face of systemic vasodilation. 9 Renal function may be further threatened by addi- tional hemodynamic injury during multiple phases of liver transplantation, including intraoperative vascular instability related to clamping of central vessels and highly labile volume management for the first several days thereafter. Immunosuppression based upon cal- cineurin inhibitors (such as cyclosporine or tacrolimus) routinely induces renal vasoconstriction, leading to a 30 to 40% fall in glomerular filtration rate (GFR) within the first several days and weeks, despite rising systemic arterial pressures. 10 Whether the perioperative compromise to renal function in this setting can be influenced favorably and whether such maneuvers can improve outcomes is an important question. In this issue, Biancofiore et al. report the results of a prospective trial of 140 consecu- tive liver transplant recipients monitored carefully dur- ing the first 96 hours after transplant during random- ized administration of fenoldopam (0.1 g/kg/ minute), dopamine (3 g/kg/minute) or placebo. Data were collected from the time of anesthesia induction. Importantly, preoperative renal function was near nor- mal (creatinine was required to be less than 1.5 mg/dL, reported mean values: 0.81 – 0.88 mg/dL by group, GFR reported between 102 – 111 mL/minute by group). Renal function reflected by urine flow rates, diuretic and pressor requirements, creatinine clearance, and serum creatinine values was measured at 12-hour intervals for the first 4 days, which included the intro- duction of cyclosporine. Treatment groups at baseline appeared to be well-matched regarding demographic and clinical characteristics. The placebo group experi- enced a moderate fall in creatinine clearance toward the fourth day (–39%), with a rise in cyclosporine level from 0–328 ng/dL. Although serum creatinine levels and cyclo- sporine levels were identical in the dopamine and fenoldo- pam groups, no decrement in calculated creatinine clear- ance was apparent in the fenoldopam group on the fourth day. No differences were apparent regarding any other parameters, including urine outputs, diuretic require- ments, incidence of acute renal failure requiring dialytic support, intensive care unit stay, or mortality. Biancofiore et al. 11 argue that these results indicate a “counterbalancing” of the renal vasoconstrictive effects of cyclosporine in the posttransplant state. While this may be partially correct, it must be emphasized that the results presented here did not include either arterial pressures or renal blood flow. Hence, whether true renal vasodilation occurred cannot be assessed. Most impor- tantly, these results fail to support improved clinical outcomes either regarding early postoperative urinary Abbreviations: ARF, acute renal failure; GFR, glomerular filtra- tion rate. From the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. Address reprint requests to Stephen Textor, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. Telephone: 507-284- 4841; FAX: 507-284-1161; E-mail: [email protected] Copyright © 2004 by the American Association for the Study of Liver Diseases Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/lt.20196 993 Liver Transplantation, Vol 10, No 8 (August), 2004: pp 993 – 994
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Transcript of Acute renal failure after liver transplantation: The role of dopamine and fenoldopam
EDITORIAL
Acute Renal Failure After Liver Transplantation:The Role of Dopamine and Fenoldopam
Nelson Leung and Stephen C. Textor
Acute renal failure (ARF) in the immediate periop-erative liver transplant setting is a complex prob-
lem. It is well established that when ARF developseither before or after liver transplantation, it has a majorimpact on the outcomes of the allograft and on patientsurvival. The pathogenesis of this disorder reflects mul-tiple hemodynamic changes associated with advancedliver disease, ultimately producing hepatorenal syn-drome, and the postoperative stresses after a liver trans-plant.
When preoperative renal failure is related directly tohepatorenal syndrome, patient survival is limited (10%at 10 weeks) if orthotopic liver transplantation cannotbe accomplished.1 After orthotopic liver transplanta-tion, ARF continues to impact outcome, as mortalityincreases from 5 to 41% in those who develop periop-erative ARF.2 Several studies indicate that reduced pre-transplant kidney function (reflected by glomerular fil-tration rate, usually expressed as creatinine clearance) isthe single most consistent predictor of ARF after trans-plant.3–7 Other predictors are less consistent, includingnumber of units of blood transfused, the need for vaso-pressor support, early allograft dysfunction, and pre-transplant Child class.3,4,7,8 Subjects with advancedliver disease regularly experience reduced renal perfu-sion and activation of vasoconstrictor mechanisms thatraise renal vascular resistance in the face of systemicvasodilation.9
Renal function may be further threatened by addi-tional hemodynamic injury during multiple phases ofliver transplantation, including intraoperative vascularinstability related to clamping of central vessels andhighly labile volume management for the first severaldays thereafter. Immunosuppression based upon cal-cineurin inhibitors (such as cyclosporine or tacrolimus)routinely induces renal vasoconstriction, leading to a 30to 40% fall in glomerular filtration rate (GFR) withinthe first several days and weeks, despite rising systemicarterial pressures.10
Whether the perioperative compromise to renalfunction in this setting can be influenced favorably andwhether such maneuvers can improve outcomes is animportant question. In this issue, Biancofiore et al.report the results of a prospective trial of 140 consecu-tive liver transplant recipients monitored carefully dur-
ing the first 96 hours after transplant during random-ized administration of fenoldopam (0.1 �g/kg/minute), dopamine (3 �g/kg/minute) or placebo. Datawere collected from the time of anesthesia induction.Importantly, preoperative renal function was near nor-mal (creatinine was required to be less than 1.5 mg/dL,reported mean values: 0.81–0.88 mg/dL by group,GFR reported between 102–111 mL/minute bygroup). Renal function reflected by urine flow rates,diuretic and pressor requirements, creatinine clearance,and serum creatinine values was measured at 12-hourintervals for the first 4 days, which included the intro-duction of cyclosporine. Treatment groups at baselineappeared to be well-matched regarding demographicand clinical characteristics. The placebo group experi-enced a moderate fall in creatinine clearance toward thefourth day (–39%), with a rise in cyclosporine level from0–328 ng/dL. Although serum creatinine levels and cyclo-sporine levels were identical in the dopamine and fenoldo-pam groups, no decrement in calculated creatinine clear-ance was apparent in the fenoldopam group on the fourthday. No differences were apparent regarding any otherparameters, including urine outputs, diuretic require-ments, incidence of acute renal failure requiring dialyticsupport, intensive care unit stay, or mortality.
Biancofiore et al.11 argue that these results indicate a“counterbalancing” of the renal vasoconstrictive effectsof cyclosporine in the posttransplant state. While thismay be partially correct, it must be emphasized that theresults presented here did not include either arterialpressures or renal blood flow. Hence, whether true renalvasodilation occurred cannot be assessed. Most impor-tantly, these results fail to support improved clinicaloutcomes either regarding early postoperative urinary
Abbreviations: ARF, acute renal failure; GFR, glomerular filtra-tion rate.
From the Division of Nephrology and Hypertension, Mayo Clinic,Rochester, MN.
Address reprint requests to Stephen Textor, Division of Nephrologyand Hypertension, Mayo Clinic, Rochester, MN. Telephone: 507-284-4841; FAX: 507-284-1161; E-mail: [email protected]
Copyright © 2004 by the American Association for the Study ofLiver Diseases
Published online in Wiley InterScience (www.interscience.wiley.com).DOI 10.1002/lt.20196
993Liver Transplantation, Vol 10, No 8 (August), 2004: pp 993–994
outputs, hospitalization, or morbidity. Whether peri-operative preservation of GFR will translate into subse-quent benefits regarding long-term renal function, dueto calcineurin inhibitors or other factors, is unknownand cannot be addressed with these data.
Should dopamine or fenoldopam be used as part of theperioperative support of liver transplant recipients? Unfor-tunately, available data remain ambiguous. The Bianco-fiore study was limited to patients with near-normal renalfunction. It may be argued that the patients at higher riskwere excluded from the outset. A large body of literatureusing “renal doses” of dopamine fails to demonstrate con-sistent improvement in outcomes with this agent, as hasbeen recently reviewed.12 This literature includes prospec-tive studies of patients undergoing liver transplantationand patients with hyperbilirubinemia undergoing abdom-inal surgery. Short-term studies after cardiac bypass oraortic cross-clamping suggest that the immediate fall inGFR may be less in patients treated with fenoldopamduring the procedure.13 No long-term outcome data areavailable to suggest a durable benefit. Fenoldopam isapproved for treatment of hypertension, particularlyhypertensive “urgencies,” and regularly lowers arterialpressures without compromising renal function.14 Pro-spective studies in high-risk patients with reduced kidneyfunction (GFR � 60 mL/minute/1.73 m2) using fenoldo-pam as a renoprotective agent in other settings, such asprevention of contrast nephropathy, fail to demonstrateimportant benefits.15 Based on these data and the findingsof Biancofiore et al., it is hard to justify routine use of eitherfenoldopam or dopamine in this setting. Because the mor-bidity of ARF is so high in the setting of liver transplanta-tion, further studies to identify whether reversal of hemo-dynamic changes before transplant in higher risk patients,e.g., those with incipient hepatorenal failure, are war-ranted.
References
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2. Fraley DS, Burr R, Bernardini J, Angus D, Kramer DJ, JohnsonJP. Impact of acute renal failure on mortality in end-stage liverdisease with or without transplantation. Kidney Int 1998;54:518–524.
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12. Denton M, Brady HR. Dopamine therapy in acute renal failure.In: Brady HR, Wilcox CS, eds. Therapy in nephrology andhypertension. London: WB Saunders, 2003:19–32.
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994 Leung and Textor
