Fenoldopam, a rapid-acting vasodilator of the renal vasculature along with coronary, mesenteric, and peripheral affects, is used to treat severe hypertension. This agonist for D1-like dopamine receptors, which lowers systolic and diastolic systemic pressures and increases heart rate, allows rapid titration to optimal levels, with rapid reverse titration if severe hypotension occurs. This regime is a consideration for patients who are not candidates for hydration with saline because medical contraindications to volume administration or other clinical logistical issues exist. Since this medication produces vasodilation of the renal vasculature, it has been studied as an intravenous treatment for prevention of contrast nephropathy.
Although early studies were suggestive, the CONTRAST trial,1,3 which tested the efficacy of 0.05-0.1 mcg/kg/min of fenoldopam in preventing contrast nephropathy in approximately 300 patients, showed no benefit of the medication over placebo. Unfortunately, the doses of this dopamine receptor agonist chosen for the CONTRAST trial did not improve renal function in patients with renal insufficiency; therefore, the trial may have failed due to inadequate doses. An escalation dose is possible, but is limited by development of severe systemic hypotension and requires time.
A number of leading interventional cardiologists in the United States are studying the effects of bilateral selective intra-renal arterial delivery of fenoldopam and other drugs, such as nesiritide, that have useful renal properties. The systemic effects of this medication tend to curtail the studies.
A recent multi-center randomized controlled trial presented by Dr. Madyoon1 at TCT 2004 demonstrated that bilateral renal infusion of fenoldopam (0.2 mcg/kg/min) for approximately 30 minutes before an invasive cardiac study improved renal function (glomerular filtration rate) significantly, whereas intravenous administration at the same dose had no effect on renal function. Furthermore, because the kidneys cleared much of the fenoldopam on first pass, blood pressures declined significantly less with intra-renal compared to intravenous fenoldopam.
The ability to protect high-risk patients requiring angiography and intervention from renal failure is exciting and promising new technology could be on the horizon.
This article will present a closer look at the Benephit Infusion System (FlowMedica, Inc. Fremont, CA), a system currently being used for the infusion of the renal protective drug fenoldopam.
This infusion system, which is currently under clinical evaluation4 at both St. Joseph’s Medical Center in Stockton, California and at Scripps Hospital, La Jolla, California, is specifically targeted for renal therapy. The system is a 77 cm selective bifurcated infusion catheter that has a nitinol shaft and infusion lumen. The catheter has a tear-away sheath and torque device for easier manipulation into the renal arteries (Figure 1). Its pre-shaped atraumatic bifurcated design (Figure 2) is intended to allow cannulation and simultaneous injection of therapeutic or protective agents to both renal arteries. The 8F introducer sheath comes in four lengths and has two insertion ports in a Y-hub. The ports have a hemostasis valve designed for a 6F diagnostic or guiding catheter. The bifurcated infusion catheter has distal radio-opaque bands for good fluoroscopic and cineangiography documentation of renal cannulation. The tip of the sheath is atraumatic (Figure 3).
A group at Centro Cardiologico Monzino (Milan, Italy) studied 208 patients under a study protocol enrolling patients undergoing primary PCI.5 Of the 208 patients, 165 men and 43 women with mean age 62+ years, 40 (19%) developed contrast-induced nephropathy, defined as an absolute increase in creatinine >0.5 mg/dl after PCI. Patients who developed contrast-induced nephropathy were older, had more frequent presentations of anterior acute myocardial infarctions, lower ejection fractions, long reperfusion times, increased cardiac enzymes and higher baseline creatinine values. It is interesting to note that seven of these patients had no prior history of pre-existing renal insufficiency. Normal renal function did not preclude these patients from developing contrast nephropathy. In addition, the mortality rate was higher in patients that developed contrast-induced nephropathy. Twelve patients (31%) died versus one death (0.6%) in the group that did not develop contrast-induced nephropathy.
In addition, a clinical investigative study with the Benephit Infusion System is pending ethical committee approval for Dr. Antonio Colombo at San Raffaele Hospital, in Milan, Italy. We look forward to further research that promises to offer patients at risk during PCI protection from renal compromise and allow catheter-based interventions safety from contrast toxicity.
The author would like to thank Dr Vandana Mathur, FASN, Woodside, CA for her research in CIN.
Laura Minarsch can be contacted at laura22@mmc-medical.com
1. H. Madyoon, P. Teirstein, D. Baim, L. Croushore, E. Anderson, V. Mathur. Differential Effects Between Intravenous and Local Renal Delivery of Fenoldopam on Renal Function and Blood Pressure: A Randomized, Controlled Trial.
Am J Cardiol, September 30, 2004; TCT-51 (Abstract).
2. Madyoon H. Clinical Experience with the use of fenoldopam for prevention of radiocontrast nephropathy in high-risk patients. Rev Cardiovasc Med. 2001;2(suppl 1):526-530.
3. Stone G, McCullough P, Tumlin J, et al. Fenoldopam mesylate for the prevention of contrast-induced nephropathy: a randomized controlled trial. JAMA 2003;290:2284-2291.
4. Mathur V, Goodson B, Valencia A, et al. Use of Renal First-Passas a Strategy for Optimizing Drugs with Desirable Renal Effects: Pharmacokinetic Studies of Nesiritide and Fenoldopam. J Am Soc Nephrol 2004;15:111A.
5. Marenzi G, Lauri G, Assanelli E, et al. Contrast-Induced Nephropathy in Patients Undergoing Primary Angioplasty for Acute Myocardial Infarction. J Am Coll Cardiol. 2004 Nov 2;44(9):1780-1785.
6. Marenzi G, Bartorelli AL, Lauri G, et al. Continuous veno-venous hemofiltration for the treatment of contrast-induced acute renal failure after percutaneous coronary interventions. Catheter Cardiovasc Intervent 2003 Jan;58(1):59-64.
7. Gruberg L, Mehran R, Dangas G, et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 2002;52:409-416.
8. E. Grube, P. Teirstein, D. Baim, R. Mueller, T. Schmidt, D. Burkhoff. Intra-Renal Fenoldopam Increases Renal Artery Flow Velocity and Causes Less Effects on Blood Pressure Lowering than Intravenous Fenoldopam. Am J Cardiol, September 30, 2004; TCT-379 (Abstract).
9. Tumlin JA, Wang A, Murray PT, Mathur VS. Fenoldopam mesylate blocks reductions in renal plasma flow after radiocontrast dye infusion: a pilot trial in the prevention of contrast nephropathy. Am Heart J. 2002;143:894-903.
10. Beregi JP, Vehier CM, Devos P, Gautier C, Libersa C, McFadden G, Carre A. Doppler Flow Wire Evaluation of Renal Blood Flow Reserve in Hypertensive Patients with Normal Renal Arteries. Cardiovasc Intervention Radiol 2000;23:340-346.
11. Maeder M, Klein M, Fehr T, Rickli H. Contrast Nephropathy: Review Focusing on Prevention. JACC 2004;44(9):1763-1771.
12. Bakris GL, Lass NA, Glock D. Renal Hemodynamics in radiocontrast medium-induced renal dysfunction: a role for dopamine-1 receptors. Kidney Int. 1999;56:206-210.
13. Suehiro K, Shimizu J, Yi G-H, Gu A, Wang J, Keren G, Burkhoff D. Selective Renal Vasodilation and Active Renal Artery Perfusion Improve Renal Function in Dogs with Acute Heart Failure. JPET 2001;298:1154-1160. Submitted Publications: 1. Cohen MG, et al. First Experience with Intra-Renal Fenoldopam in a Patient with Heart Failure. J Invas Cardiol 2004. 2. Teirstein P, et al. Targeted Renal Drug Delivery to Improve Renal Function in Patients Undergoing Cardiac Catheterization: A Multi-center, Randomized, Controlled Trial. American College of Cardiology Scientific Sessions, 2005.
