Intrarenal Fenoldopam May Help Protect Kidneys

HOLLYWOOD, FLA. — Targeted renal therapy with the vasodilating drug fenoldopam was effective for treating acute kidney injury and for preventing contrast-induced nephropathy in results from a pair of studies.

By infusing the drug directly into patients' renal arteries with a specially designed catheter, targeted therapy allows the use of a substantial dose of fenoldopam mesylate while avoiding systemic adverse effects such as hypotension, Dr. James A. Tumlin said at ISET 2009, an international symposium on endovascular therapy.

He reported treating a series of 28 patients with oliguria and diuretic-unresponsive acute kidney injury. Their diuretic unresponsiveness was defined as a failure to double their urine output after a single bolus dose of 80–120 mg furosemide. Their average serum creatinine level at entry into the study was about 1.7 mg/dL. Many of the patients had one or more comorbidities, with 57% having respiratory distress, 46% on mechanical ventilation, 43% having sepsis, and 39% with a left ventricular ejection fraction less than 35%.

All patients received intrarenal fenoldopam via a Benephit peripheral vascular catheter made by FlowMedica Inc. The catheter is designed to infuse both renal arteries with a single device, and was approved by the Food and Drug Administration in late 2008 for targeted renal therapy in patients at risk for developing acute kidney injury. Dr. Tumlin is a consultant to and has received grant support from FlowMedica.

Their goal dosage was a fenoldopam infusion of 0.4 mcg/kg per minute, and the actual average dose used was 0.39 mcg/kg per minute, with a maximum dose given to any patient of 0.8 mcg/kg per minute. The target duration of treatment was 48 hours, and the actual average duration was 42 hours, with a maximum of 72 hours.

Renal recovery, defined as a fall in serum creatinine, occurred in 17 patients (61%) by the fourth day after treatment, and in 27 (96%) of patients by a week after treatment. Three of the patients (11%) died during follow-up, and another four (14%) required dialysis during follow-up. (None of the dialysis patients died.) “This was an unusually low mortality rate,” compared with the historic experience with similar patients who did not undergo renal infusion with fenoldopam, said Dr. Tumlin, a nephrologist and professor of medicine at the University of Tennessee in Chattanooga.

The second experience using intrarenal fenoldopam that was presented at the meeting included data from 593 patients who were enrolled in a targeted renal therapy registry. The series included 340 patients who were treated to prevent contrast-induced nephropathy and another 40 patients who were treated for acute kidney injury that they developed following coronary artery bypass grafting. The patients had been treated by 38 different physicians at 19 medical centers.

Intrarenal fenoldopam was given to 94% of the registry's patients, at a median dosage of 0.4 mcg/kg per minute, with a range of 0.05–0.8 mcg/kg per minute. The remaining patients received another drug, such as sodium bicarbonate, reported Dr. John H. Rundback in a separate talk at the meeting. The median duration of the fenoldopam infusion was 180 minutes.

Bilateral renal-artery catheterization was performed successfully in 95% of the registry patients, a procedure that took an average of 2 minutes. Five of the 593 patients in the registry (0.8%) had a complication from renal-artery catheterization: Three had groin complications (the catheter is often inserted through the femoral artery), one had a renal-artery dissection, and one developed hypotension.

Registry outcomes showed that the 0.4-mcg/kg per minute dosage was much more effective than was a 0.2- mcg/kg per minute dosage for preventing contrast-induced nephropathy, and that treatment for at least an hour was more effective than a briefer infusion, said Dr. Rundback, an interventional radiologist and director of the Interventional Institute at Holy Name Hospital, Teaneck, N.J. Dr. Rundback has been a consultant to and a member of the scientific advisory board of FlowMedica.

The predicted incidence of contrast-induced nephropathy was about 27%, yet the rate among 268 patients who were treated with at least 0.4 mcg/kg per minute of fenoldopam for at least 1 hour was less than 1%, Dr. Rundback said.

Patients who received fenoldopam had 'an unusually low mortality rate.' DR. TUMLIN

HOLLYWOOD, FLA. — Targeted renal therapy with the vasodilating drug fenoldopam was effective for treating acute kidney injury and for preventing contrast-induced nephropathy in results from a pair of studies.

By infusing the drug directly into patients' renal arteries with a specially designed catheter, targeted therapy allows the use of a substantial dose of fenoldopam mesylate while avoiding systemic adverse effects such as hypotension, Dr. James A. Tumlin said at ISET 2009, an international symposium on endovascular therapy.

He reported treating a series of 28 patients with oliguria and diuretic-unresponsive acute kidney injury. Their diuretic unresponsiveness was defined as a failure to double their urine output after a single bolus dose of 80–120 mg furosemide. Their average serum creatinine level at entry into the study was about 1.7 mg/dL. Many of the patients had one or more comorbidities, with 57% having respiratory distress, 46% on mechanical ventilation, 43% having sepsis, and 39% with a left ventricular ejection fraction less than 35%.

All patients received intrarenal fenoldopam via a Benephit peripheral vascular catheter made by FlowMedica Inc. The catheter is designed to infuse both renal arteries with a single device, and was approved by the Food and Drug Administration in late 2008 for targeted renal therapy in patients at risk for developing acute kidney injury. Dr. Tumlin is a consultant to and has received grant support from FlowMedica.

Their goal dosage was a fenoldopam infusion of 0.4 mcg/kg per minute, and the actual average dose used was 0.39 mcg/kg per minute, with a maximum dose given to any patient of 0.8 mcg/kg per minute. The target duration of treatment was 48 hours, and the actual average duration was 42 hours, with a maximum of 72 hours.

Renal recovery, defined as a fall in serum creatinine, occurred in 17 patients (61%) by the fourth day after treatment, and in 27 (96%) of patients by a week after treatment. Three of the patients (11%) died during follow-up, and another four (14%) required dialysis during follow-up. (None of the dialysis patients died.) “This was an unusually low mortality rate,” compared with the historic experience with similar patients who did not undergo renal infusion with fenoldopam, said Dr. Tumlin, a nephrologist and professor of medicine at the University of Tennessee in Chattanooga.

The second experience using intrarenal fenoldopam that was presented at the meeting included data from 593 patients who were enrolled in a targeted renal therapy registry. The series included 340 patients who were treated to prevent contrast-induced nephropathy and another 40 patients who were treated for acute kidney injury that they developed following coronary artery bypass grafting. The patients had been treated by 38 different physicians at 19 medical centers.

Intrarenal fenoldopam was given to 94% of the registry's patients, at a median dosage of 0.4 mcg/kg per minute, with a range of 0.05–0.8 mcg/kg per minute. The remaining patients received another drug, such as sodium bicarbonate, reported Dr. John H. Rundback in a separate talk at the meeting. The median duration of the fenoldopam infusion was 180 minutes.

Bilateral renal-artery catheterization was performed successfully in 95% of the registry patients, a procedure that took an average of 2 minutes. Five of the 593 patients in the registry (0.8%) had a complication from renal-artery catheterization: Three had groin complications (the catheter is often inserted through the femoral artery), one had a renal-artery dissection, and one developed hypotension.

Registry outcomes showed that the 0.4-mcg/kg per minute dosage was much more effective than was a 0.2- mcg/kg per minute dosage for preventing contrast-induced nephropathy, and that treatment for at least an hour was more effective than a briefer infusion, said Dr. Rundback, an interventional radiologist and director of the Interventional Institute at Holy Name Hospital, Teaneck, N.J. Dr. Rundback has been a consultant to and a member of the scientific advisory board of FlowMedica.

The predicted incidence of contrast-induced nephropathy was about 27%, yet the rate among 268 patients who were treated with at least 0.4 mcg/kg per minute of fenoldopam for at least 1 hour was less than 1%, Dr. Rundback said.

Patients who received fenoldopam had 'an unusually low mortality rate.' DR. TUMLIN

HOLLYWOOD, FLA. — Targeted renal therapy with the vasodilating drug fenoldopam was effective for treating acute kidney injury and for preventing contrast-induced nephropathy in results from a pair of studies.

By infusing the drug directly into patients' renal arteries with a specially designed catheter, targeted therapy allows the use of a substantial dose of fenoldopam mesylate while avoiding systemic adverse effects such as hypotension, Dr. James A. Tumlin said at ISET 2009, an international symposium on endovascular therapy.

He reported treating a series of 28 patients with oliguria and diuretic-unresponsive acute kidney injury. Their diuretic unresponsiveness was defined as a failure to double their urine output after a single bolus dose of 80–120 mg furosemide. Their average serum creatinine level at entry into the study was about 1.7 mg/dL. Many of the patients had one or more comorbidities, with 57% having respiratory distress, 46% on mechanical ventilation, 43% having sepsis, and 39% with a left ventricular ejection fraction less than 35%.

All patients received intrarenal fenoldopam via a Benephit peripheral vascular catheter made by FlowMedica Inc. The catheter is designed to infuse both renal arteries with a single device, and was approved by the Food and Drug Administration in late 2008 for targeted renal therapy in patients at risk for developing acute kidney injury. Dr. Tumlin is a consultant to and has received grant support from FlowMedica.

Their goal dosage was a fenoldopam infusion of 0.4 mcg/kg per minute, and the actual average dose used was 0.39 mcg/kg per minute, with a maximum dose given to any patient of 0.8 mcg/kg per minute. The target duration of treatment was 48 hours, and the actual average duration was 42 hours, with a maximum of 72 hours.

Renal recovery, defined as a fall in serum creatinine, occurred in 17 patients (61%) by the fourth day after treatment, and in 27 (96%) of patients by a week after treatment. Three of the patients (11%) died during follow-up, and another four (14%) required dialysis during follow-up. (None of the dialysis patients died.) “This was an unusually low mortality rate,” compared with the historic experience with similar patients who did not undergo renal infusion with fenoldopam, said Dr. Tumlin, a nephrologist and professor of medicine at the University of Tennessee in Chattanooga.

The second experience using intrarenal fenoldopam that was presented at the meeting included data from 593 patients who were enrolled in a targeted renal therapy registry. The series included 340 patients who were treated to prevent contrast-induced nephropathy and another 40 patients who were treated for acute kidney injury that they developed following coronary artery bypass grafting. The patients had been treated by 38 different physicians at 19 medical centers.

Intrarenal fenoldopam was given to 94% of the registry's patients, at a median dosage of 0.4 mcg/kg per minute, with a range of 0.05–0.8 mcg/kg per minute. The remaining patients received another drug, such as sodium bicarbonate, reported Dr. John H. Rundback in a separate talk at the meeting. The median duration of the fenoldopam infusion was 180 minutes.

Bilateral renal-artery catheterization was performed successfully in 95% of the registry patients, a procedure that took an average of 2 minutes. Five of the 593 patients in the registry (0.8%) had a complication from renal-artery catheterization: Three had groin complications (the catheter is often inserted through the femoral artery), one had a renal-artery dissection, and one developed hypotension.

Registry outcomes showed that the 0.4-mcg/kg per minute dosage was much more effective than was a 0.2- mcg/kg per minute dosage for preventing contrast-induced nephropathy, and that treatment for at least an hour was more effective than a briefer infusion, said Dr. Rundback, an interventional radiologist and director of the Interventional Institute at Holy Name Hospital, Teaneck, N.J. Dr. Rundback has been a consultant to and a member of the scientific advisory board of FlowMedica.

The predicted incidence of contrast-induced nephropathy was about 27%, yet the rate among 268 patients who were treated with at least 0.4 mcg/kg per minute of fenoldopam for at least 1 hour was less than 1%, Dr. Rundback said.

Patients who received fenoldopam had 'an unusually low mortality rate.' DR. TUMLIN