Fenoldopam mesylate in early acute tubular necrosis: a randomized, double-blind, placebo-controlled clinical trial
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Published on: March 11, 2016
James A Tumlin1, Kevin W Finkel, Patrick T Murray
1Emory University School of Medicine, Renal Division, Atlanta, GA 30322, USA. jtumlin@emory.edu
Background:
Acute tubular necrosis (ATN) occurs commonly in critically ill patients and is associated with increased morbidity and mortality. Fenoldopam is a dopamine receptor alpha1-specific agonist that increases renal blood flow in patients with kidney failure. We hypothesized that administration of low-dose fenoldopam during early ATN would decrease the need for dialysis therapy and/or incidence of death at 21 days.
Methods:
We conducted a prospective, randomized, double-blind, placebo-controlled, clinical trial in 155 patients with early ATN. Patients were considered eligible for enrollment if serum creatinine level increased to 50% greater than admission levels within 24 hours and mean arterial pressure was greater than 70 mm Hg. Patients were randomly assigned to the administration of placebo or fenoldopam for 72 hours.
Results:
Overall, 22 of 80 patients (27.5%) in the fenoldopam group reached the primary end point compared with 29 of 75 patients (38.7%) in the placebo group (P = 0.235). This 11% absolute reduction in the primary end point was not statistically significant (P = 0.23). Similarly, there was no difference in the incidence of dialysis therapy between patients randomly assigned to fenoldopam (13 of 80 patients; 16.25%) versus the placebo group (19 of 75 patients; 25.3%; P = 0.163). Moreover, there was no statistically significant difference in 21-day mortality rates between the 2 groups (fenoldopam, 13.8% versus placebo, 25.3%; P = 0.068). In secondary analyses, fenoldopam tended to reduce the primary end point in patients without diabetes and postoperative cardiothoracic surgery patients with early ATN (fenoldopam patients without diabetes, 14 of 54 patients [25.9%] versus placebo patients without diabetes, 23 of 52 patients [44.2%]; P = 0.048) and postoperative cardiothoracic patients (6 of 34 patients [17.6%] versus 14 of 36 patients [38.8%]; P = 0.049). Conversely, fenoldopam did not improve the primary end point in patients with diabetes or those with acute renal failure from other causes. A larger multicenter trial using separate randomizations for patients with and without diabetes will be needed to determine the efficacy of fenoldopam mesylate in specific subpopulations with ATN.
Conclusion:
Fenoldopam does not reduce the incidence of death or dialysis therapy in intensive care unit patients with early ATN.
Insights
Low-dose fenoldopam did not significantly reduce the need for dialysis or death in patients with acute tubular necrosis (ATN). Further research is needed for specific patient groups, such as those without diabetes.
Area of Science:
- Nephrology
- Critical Care Medicine
- Pharmacology
Background:
- Acute tubular necrosis (ATN) is a common complication in critically ill patients, leading to significant morbidity and mortality.
- Fenoldopam, a selective dopamine receptor agonist, enhances renal blood flow and was investigated for its potential to mitigate ATN outcomes.
- Early intervention with fenoldopam was hypothesized to decrease the need for dialysis and/or 21-day mortality in ATN patients.
Purpose of the Study:
- To evaluate the efficacy of low-dose fenoldopam in reducing dialysis requirements and mortality in patients diagnosed with early acute tubular necrosis.
- To assess the impact of fenoldopam on key clinical outcomes within a 21-day period following diagnosis of early ATN.
Main Methods:
- A prospective, randomized, double-blind, placebo-controlled trial was conducted involving 155 patients with early ATN.
- Eligible patients had a serum creatinine increase of at least 50% within 24 hours and mean arterial pressure >70 mm Hg.
- Participants received either placebo or fenoldopam for 72 hours.
Main Results:
- The primary endpoint (death or dialysis) was reached by 27.5% of fenoldopam recipients versus 38.7% of placebo recipients (P=0.235), a difference that was not statistically significant.
- No significant differences were observed in the incidence of dialysis therapy (16.25% vs 25.3%; P=0.163) or 21-day mortality rates (13.8% vs 25.3%; P=0.068) between the groups.
- Secondary analyses indicated potential benefits in non-diabetic and postoperative cardiothoracic surgery patients (P=0.048 and P=0.049, respectively), but not in diabetic patients or those with other causes of acute renal failure.
Conclusions:
- Fenoldopam administration did not demonstrate a statistically significant reduction in death or the need for dialysis therapy in intensive care unit patients experiencing early acute tubular necrosis.
- Subgroup analyses suggest potential efficacy in specific populations, warranting further investigation in larger, targeted trials.
- The study highlights the need for individualized treatment strategies for acute tubular necrosis based on patient characteristics, such as diabetic status.
