Use of fenoldopam to control renal dysfunction early after liver transplantation

Abstract

With the aim of assessing whether fenoldopam can help to preserve renal function after liver transplantation, we randomized 140 consecutive recipients with comparable preoperative renal function to receive fenoldopam 0.1 g/kg/ minute (group F, 46 patients), dopamine 3 g/kg/minute (group D, 48 patients), or placebo (group P, 46 patients) from the time of anesthesia induction to 96 hours postoperatively. There were no differences between the groups in intraoperative urinary output or furosemide administration (both P ‫؍‬ .1). Daily recordings made during the first 4 postoperative days revealed no significant differences in urinary output (P ‫؍‬ .1), serum creatinine (P ‫؍‬ .5), the incidence of renal insufficiency (P ‫؍‬ .7), the need for loop diuretics (P ‫؍‬ .9) or vasoactive drugs (P ‫؍‬ .8). In comparison with preoperative levels, creatinine clearance at the end of the study in the patients receiving fenoldopam remained substantially unchanged, whereas it decreased by 39 and 12.3%, respectively, in the subjects receiving placebo or dopamine (P < .001); blood cyclosporine A (CsA) levels were similar in the 3 groups (P ‫؍‬ .1). Three subjects died in the intensive care unit (1 in each group, P ‫؍‬ .9), 2 of them had renal failure. In conclusion, our results confirm the inefficacy of dopamine in preventing or limiting early renal dysfunction after liver transplantation, and suggest that fenoldopam may preserve creatinine clearance by counterbalancing the renal vasoconstrictive effect of CsA, as it has been reported in previous experimental studies. A cute renal failure (ARF) is defined as a sudden and marked reduction in the amount of renal glomerular filtrate, leading to an accumulation of nitrogen and other toxins that complicates the management of fluids and electrolytes; 1 it affects about 5% of hospitalized patients and approximately 15% of those who are critically ill, thus prolonging their length of hospitalization, increasing the related costs, and considerably affecting their outcomes. 2 Orthotopic liver transplantation (OLT) is burdened by an incidence of ARF that ranges from 10 to 25%, with a mortality rate that exceeds 50% when renal replacement therapy is required; 3 -5 in this setting, even moderate renal dysfunction is significantly associated with shortened graft and recipient survival. 6 As renal failure is a major risk factor capable of seriously compromising OLT outcomes, various strategies have been adopted in an attempt to prevent or at least limit its deleterious effects, but none have yet proved to be really efficacious. 7 -10 In order to refine the effects of dopamine on renal function, a number of analogs have been synthesized. One of these, fenoldopam, has attracted the attention of clinicians because of its ability to selectively vasodilate renal vessels, and has thus renewed interest in the possibility of combating the onset of perioperative ARF by means of intravenous drug infusion.The aim of this study was to evaluate the efficacy of fenoldopam as a "renoprotective" agent in the ear...

A comparison between fenoldopam and low-dose dopamine in early renal dysfunction of critically ill patients*

“…A very recent study reported a beneficial effect of fenoldopam in liver transplant recipients after 72 hrs of infusion (20). Therefore, the 4-day infusion was considered sufficient to give both drugs a chance to produce an appreciable clinical effect.…”

“…Fenoldopam seems to exert a renoprotective effect when administered prophylactically in patients undergoing elective aortic surgery (16,17) or cardiopulmonary bypass (18). Moreover, fenoldopam seems to preserve renal function by counterbalancing the renal vasoconstrictive effects of cyclosporine in kidney (19) and liver (20) transplant patients. The effects of fenoldopam administration in patients at high risk of radiographic contrast nephropathy are controversial.…”

Preserving renal function in liver transplant recipients with rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitors

“…1,2,[8][9][10][11] Various strategies have been investigated to minimize the risk of acute renal failure after orthotopic liver transplantation, such as optimization of hemodynamic conditions in the operative and perioperative periods, but these strategies have not been successful. [12][13][14][15] Delaying the initiation of the nephrotoxic CNIs cyclosporine and tacrolimus until renal function recovers appears to be a logical approach to minimize early renal dysfunction in liver transplantation. Results from recent clinical studies have demonstrated the safety and efficacy of this strategy; [16][17][18][19][20][21] however, there is concern that delaying the initiation of CNI may place patients at risk for early acute rejection.…”

Perioperative fenoldopam for the prevention of acute renal failure in non-cardiac surgery, randomized clinical trial

“…Our results are in accordance with only two previous reports in which fenoldopam was used at a low dosage (9) or for a short period of time. (10) All the other studies (7,8,(13)(14)(15)(16)(17)(18)(19)(20) …”