Intra-Renal Drug Infusion Shows Promise

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SEATTLE—Researchers in California have shown that nesiritide directly increases glomerular filtration rate (GFR) and renal plasma flow (RPF).

 

The finding comes from a pilot study of the renal hemodynamic effects of nesiritide (Natrecor) infused directly into the renal arteries of heart transplant recipients. This method of administering the drug may offer a novel therapeutic approach to improve renal function when systemic adverse effects such as hypotension are a concern, according to the researchers. “The key point is that we can give drugs directly into the kidney,” said lead investigator J. Thomas Heywood, MD, director of the Heart Failure Program at the Scripps Clinic in La Jolla, Calif.

 

He and his colleagues accomplished this by inserting a small, specially designed catheter (Benephit System, Flowmedica) directly into the renal arteries in both kidneys, achieving therapeutic drug levels in those organs without causing adverse effects systemically. The results may open the door for treating a number of acute renal problems.

 

“One of the questions that always comes up is whether the drug's systemic blood-pressure-lowering effects actually negate some of the positive kidney effects it should have, based on our understanding of natriuretic peptide physiology,” said co-investigator Vandana Mathur, MD. “This direct infusion into the kidneys was a means to sort that out. We found that we could give the drug in this way and there was no effect whatsoever on blood pressure. Yet we saw some very good and very quick beneficial effects on the renal function and renal perfusion.”

 

The investigators used insulin clearance to determine GFR and paraaminohippurate clearance to

determine RPF during bilateral renal infusion of 0.01 mcg/kg/min of nesiritide with and without a 2 mcg/kg bolus in 10 heart transplant patients. The patients had a history of calcineurin inhibitor use and were undergoing cardiac catheterization.

 

Co-investigator Andrew Ho, MD, who presented the study findings here at the 10th annual scientific meeting of the Heart Failure Society of America, said while this study only had a small number of heart transplant patients, there may be clinical implications for other renal diseases.

 

The study population was 50% male and had a mean age of 56 years. Patients had received their heart transplants a mean 3.5 years before. Dr. Ho said 60% of the patients were on tacrolimus, 20% on cyclosporine, and 90% on sirolimus. At baseline, patients had a mean serum creatinine level of 1.4 mg/dL, mean GFR of 45.6 mL/min, and mean B-type natriuretic peptide (BNP) level of 111.6 pg/mL. They had a mean right arterial pressure of 6.3 mm Hg and pulmonary wedge pressure of 10.0 mm Hg. Their mean cardiac output was 6.2 L/min.

 

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