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• W2085263561 abstract "Acute renal failure (ARF) in the immediate perioperative liver transplant setting is a complex problem. 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 multiple hemodynamic changes associated with advanced liver disease, ultimately producing hepatorenal syndrome, and the postoperative stresses after a liver transplant. ARF, acute renal failure; GFR, glomerular filtration rate. 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 transplantation, ARF continues to impact outcome, as mortality increases from 5 to 41% in those who develop perioperative ARF.2 Several studies indicate that reduced pretransplant kidney function (reflected by glomerular filtration rate, usually expressed as creatinine clearance) is the single most consistent predictor of ARF after transplant.3-7 Other predictors are less consistent, including number of units of blood transfused, the need for vasopressor support, early allograft dysfunction, and pretransplant Child class.3, 4, 7, 8 Subjects with advanced liver disease regularly experience reduced renal perfusion and activation of vasoconstrictor mechanisms that raise renal vascular resistance in the face of systemic vasodilation.9 Renal function may be further threatened by additional 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 calcineurin 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 consecutive liver transplant recipients monitored carefully during the first 96 hours after transplant during randomized administration of fenoldopam (0.1 μg/kg/minute), dopamine (3 μg/kg/minute) or placebo. Data were collected from the time of anesthesia induction. Importantly, preoperative renal function was near normal (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 introduction of cyclosporine. Treatment groups at baseline appeared to be well-matched regarding demographic and clinical characteristics. The placebo group experienced 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 cyclosporine levels were identical in the dopamine and fenoldopam groups, no decrement in calculated creatinine clearance was apparent in the fenoldopam group on the fourth day. No differences were apparent regarding any other parameters, including urine outputs, diuretic requirements, 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 importantly, these results fail to support improved clinical outcomes either regarding early postoperative urinary outputs, hospitalization, or morbidity. Whether perioperative preservation of GFR will translate into subsequent benefits regarding long-term renal function, due to calcineurin inhibitors or other factors, is unknown and cannot be addressed with these data. Should dopamine or fenoldopam be used as part of the perioperative support of liver transplant recipients? Unfortunately, available data remain ambiguous. The Biancofiore study was limited to patients with near-normal renal function. It may be argued that the patients at higher risk were excluded from the outset. A large body of literature using “renal doses” of dopamine fails to demonstrate consistent improvement in outcomes with this agent, as has been recently reviewed.12 This literature includes prospective studies of patients undergoing liver transplantation and patients with hyperbilirubinemia undergoing abdominal surgery. Short-term studies after cardiac bypass or aortic cross-clamping suggest that the immediate fall in GFR may be less in patients treated with fenoldopam during the procedure.13 No long-term outcome data are available to suggest a durable benefit. Fenoldopam is approved for treatment of hypertension, particularly hypertensive “urgencies,” and regularly lowers arterial pressures without compromising renal function.14 Prospective studies in high-risk patients with reduced kidney function (GFR < 60 mL/minute/1.73 m2) using fenoldopam as a renoprotective agent in other settings, such as prevention of contrast nephropathy, fail to demonstrate important benefits.15 Based on these data and the findings of Biancofiore et al., it is hard to justify routine use of either fenoldopam or dopamine in this setting. Because the morbidity of ARF is so high in the setting of liver transplantation, further studies to identify whether reversal of hemodynamic changes before transplant in higher risk patients, e.g., those with incipient hepatorenal failure, are warranted." @default.
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• W2085263561 title "Acute renal failure after liver transplantation: The role of dopamine and fenoldopam" @default.
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• W2085263561 doi "https://doi.org/10.1002/lt.20196" @default.
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