Targeted Therapy for CIN May Cut Risk in Diabetics

WASHINGTON -- Targeted renal therapy significantly reduced the incidence of contrast-associated acute kidney injury in patients who underwent peripheral vascular procedures, including a subset of 210 diabetic patients.

The diabetic group was a 40% subset of patients enrolled at 19 sites in the International Be-RITe! (Benephit System Renal Infusion Therapy) Registry, FlowMedica Inc.'s postmarketing observational retrospective data compilation of its Benephit infusion system, a bifurcated catheter that delivers therapeutic agents directly to the kidneys via the renal arteries, Dr. Bret N. Weichmann said at the annual meeting of the Society of Interventional Radiology.

Among the total 593 patients, successful bilateral renal artery cannulation was achieved in 94.9%, with a mean of 8.0 mL of contrast required. Average cannulation time was 2 minutes, with 29% achieved in 1 minute or less. Adverse events were reported in a total of 0.8%, including groin complications in 0.5%, renal artery dissection in 0.2%, and hypotension (most likely drug induced) in 0.2%, said Dr. Weichmann, a radiologist with the North Florida Regional Medical Center, Gainesville.

The predominant use of the Benephit device (in 89% of cases) was to deliver TRT as a periprocedural prophylactic strategy for contrast-induced nephropathy (CIN) in high-risk patients receiving iodinated contrast media as part of a percutaneous or coronary angiographic or interventional procedure. Fenoldopam mesylate, a selective dopamine agonist that increases renal blood flow and glomerular filtration rates, was the drug chosen by the physician in 94% of the cases.

In a subset of 285 patients who were given fenoldopam as the therapeutic agent and for whom 48-hour creatinine follow-up was available, rates of CIN--defined as a 25% or greater rise in creatinine level and/or a level of 0.5 mg/dL or greater above baseline within 48 hours of exposure to contrast media--were compared with rates predicted from a previously published risk score calculation based on a total of 8,357 patients undergoing percutaneous coronary intervention (J. Am. Coll. Cardiol. 2004;44:1393-9).

At a fenoldopam infusion dose of 0.2 mcg/kg per minute, there was no significant difference in CIN rate between the patients receiving TRT and the predicted value (30.3% versus 28.3%, respectively). However, at a fenoldopam dose of 0.4 mcg/kg per minute, CIN occurred in only 3.7% of the TRT group, compared with the 27.7% predicted rate. Similarly, there was no significant difference in CIN rates when TRT duration was less than 1 hour (27.3% versus 27.2% predicted), but CIN rates were significantly lower--just 3.5%--among the patients who received TRT for 1 hour or longer, compared with the predicted rate of 28.1%.

Further analysis focused on the patients with diabetes--40% of the registry total--who underwent peripheral angiographic and interventional procedures with fenoldopam as the therapeutic agent. Among 210 diabetic patients for whom 48-hour creatinine follow-up was available, the best TRT results were obtained by combining the 0.4 mcg/kg per minute with the hour-plus duration. Here, the incidence of CIN was just 1.0%, compared with 28.1% of the predicted rate, based on a total of 225 diabetics patients undergoing percutaneous coronary intervention.

At baseline, all of the 210 patients with creatinine follow-up had some degree of renal insufficiency: 100% had serum creatinine levels above 1.5 mg/dL (mean 1.9 mg/dL), and 98.6% had creatinine clearance values of less than 60 mL/min (mean 35.8 mL/min). Observed CIN in that group was 1.4%, compared with 27.2% predicted by the published risk score--a highly significant difference. Again, the benefit was greatest for the 199 diabetic patients who received 0.4 mcg/kg per minute fenoldopam for an hour or longer. None of those patients had CIN, compared with the 27.6% predicted.

Dr. Weichmann disclosed he receives consulting fees from FlowMedica Inc.

When asked to comment on this story, Dr. Ali F. AbuRahma, Robert C. Byrd Health Sciences Center, West Virginia University, Charleston, stated: "Several studies have investigated medications to mitigate contrast-induced nephropathy (CIN). Initial success of innovative pharmaceutical agents such as N-acetyl cysteine and sodium bicarbonate infusion is well demonstrated. However, meta-analysis and large scale randomized trails have failed to show a significant clinical benefit (JAMA 2004;291:2328-34). The time-tested well-validated mechanism to prevent CIN is 12-hour pre-hydration with 0.9% normal saline in intravenous form (Kidney Int. Suppl. 2006;100:S16-9).

"The Benephit device appears to be a promising device for targeted therapy to the renal artery (TRT). The study by Dr. Weichmann is a registry that utilized TRT with fenoldopam (a selective dopamine agonist) to prevent CIN. The study compares the TRT results with the predicted risk of published data of CIN. This has two drawbacks: (1) it is not a prospective randomized trial, and (2) the baseline characteristics of the TRT should match approximate risk factors of the study and the score calculation of the 8357 patients (J. Am. Coll. Cardiol. 2004;44:1398-9).

"Previous studies utilizing fenoldopam for prevention of CIN were not successful. TRT with fenoldopam showed dramatic results in renal function salvage, such as never seen before. Fenoldopam at one hour did not show any benefit, however beyond one hour, it had outstanding protection.

"The complications of TRT with a device include, but are not limited to, renal artery dissection, renal artery thrombosis, vessel perforation, distal embolization from catheter manipulation, and additional contrast use. I am not certain that these complications would justify TRT using Benephit over the standard recommendations of IV saline therapy." he concluded