Special to Medical Device Daily

HOLLYWOOD, Florida – Doctors suggested that the use of the FlowMedica (Fremont, California) Benephit Intra-Renal Drug Delivery System can get enough drug into the kidneys to allow critically ill patients to recover function.

James Tumlin, MD, professor of medicine-nephrology at the University of Tennessee-Chattanooga, and director of clinical research at Southeast Renal Research Institute, said that the recovery is rapid, once the dual kidney catheter is placed and the vasodilator fenoldopam is administered.

"Over 61% of our patients in this study recovered renal function within four days after treatment with the catheter system," Tumlin said at the 21st annual International Symposium on Endovascular Therapy (ISET) here this week. He enrolled 28 patients with acute kidney injury in the study, and 10.7% regained renal function – the ability to produce two times the baseline urine output – within two days; 36% additional patients recovered function within three days and another 14.3% recover kidney function within four days.

"It is difficult for me to convey from the podium the severity of illness of these patients," said Tumlin as he delivered his report at the proffered papers session of the ISET meeting, which was attended by more than 1,200 doctors, scientists, clinicians and allied healthcare professionals.

Of the 28 patients enrolled in the study, 92% were diagnosed with oliguria and 90% were unresponsive to diuretic therapy. Unresponsiveness was defined as being unable to produce twice the baseline urine after an intravenous bolus of furosemide (80 mg to 120 mg).

He said that 14% of his patients had acute kidney injury as a result of a coronary artery bypass graft; 16% had undergone abdominal aorta aneurysm repair; 35% had reduced ejection fraction; 39% had developed sepsis and 61% had chronic kidney disease. The patients also had numerous co-morbid conditions, including respiratory distress among 57% of the patients; 46% were on mechanical ventilation.

Overall mortality at 28 days was 11%. "Although this is not a controlled trial, this is an unusually low mortality rate in our experience," Tumlin said. "The need for dialysis replacement therapy was 14% and none of the patients who required dialysis expired. The typical rate of death among this type of population is over 60%." Creatinine levers peaked at 2.5 mg/dl and decrease to about 2.05 at Day 7.

"Frankly, we would have expected 40% to 50% of these patients to have died within the 28 days we followed them," he said. "We would have thought that two of the three patients who had to go to dialysis would have died. But they all survived through at least 28 days."

The researchers, including his co-investigator David Allie, MD, director of the Cardiovascular Institute of the South (Lafayette, Louisiana), followed the patients through 28 days, so long-term outcomes were not available.

"The FlowMedica catheter system appears to be a safe and effective means for doing intra-renal fenoldopam infusion," Tumlin said. "We have successfully done this up to a dose of 0.8 micrograms/kg/minute. The standard dose is 0.4 mcg/kg/minute. High-dose intravenous fenoldopam responded with renal output in about 61% of patients within four days of treatment."

He noted that the incidence of acute kidney injury and dialysis-dependant renal failure is rising by the decade. Currently, he said 522 per 100,000 people will require some form of dialysis during their lifetimes. "It has become a very big deal," he said.

Development of acute kidney injury translates to a 22-fold higher post-operative mortality rate if the patients have a pre-operative glomerular filtration rate of less than 60 mm/minute. In coronary artery bypass graft surgery the risk of acute kidney injury is as high as 24%.

"High-dose vasodilator therapy has been attempted to correct the constriction that is inherent in acute kidney injury but its use has been controversial and somewhat disappointing," Tumlin said. Systemic treatment has not allowed for adequate medication to reach the kidney. We hypothesized that intra-renal delivery of fenoldopam would reduce hypotension and secondary renal hypoperfusion. Augmenting renal blood flow may reduce progression to dialysis-dependent acute kidney injury."

He said roadblocks to vasodilator therapy in acute kidney injury include lack of bedside access to reliable biomarkers for early identification of acute kidney injury; lack of the ability to deliver isolated vasodilator therapy to the renal circulation; the need to avoid systemic hypotension and the lack of infrastructure for the timely placement of a catheter.

Tumlin said that the use of the FlowMedica Benephit Intra-Renal Drug Delivery System could be placed by interventional radiologists, cardiologists and possibly even hospital intensives. He explained that the system is introduced into the aorta similarly to cardiac procedures. When the catheter passes above the junction of the kidney arteries, the "ears" of the Benephit system and deploys. As the catheter is pulled back, the ears float into the renal arteries.

"It is a very simple, easy to perform maneuver," Tumlin said. "We think it can be performed at bedside and cause less problems for already critically ill patients who will be spared a trip to the radiology department or the catheter laboratory."

The Benephit Infusion Systems are FDA-cleared and are indicated for the "infusion of physician-specified agents in the peripheral vasculature including, but not limited to, the renal arteries."

FlowMedica was purchased by AngioDynamics (Queensbury, New York) earlier this month.