NEW YORK (Reuters Health) – Perioperative treatment with low-dose human atrial natriuretic peptide (carperitide) improves outcomes in patients with chronic kidney disease (CKD) who are undergoing coronary artery bypass grafting, a Japanese team reports in the August 23rd issue of the Journal of the American College of Cardiology.
“Perioperative infusion of low-dose carperitide may have a significant role in management of patients with renal dysfunction undergoing on-pump CABG,” conclude Dr. Akira Sezai and colleagues at the Nihon University School of Medicine, Tokyo, Japan.
They note that, at present, carperitide is only available in Japan. On the other hand, nesiritide (BNP) is a similar peptide product that is available in Western countries, although not in Japan, they explain.
The team previously found that carperitide helped maintain creatinine clearance after cardiac surgery in patients with normal renal function. The purpose of the current trial was to see if it benefitted CABG patients with moderate chronic renal insufficiency (eGFR 45-50 mL/min per meter squared), in terms of changes in renal function, need for dialysis, and 1-year outcomes.
The 303 patients were randomized to saline placebo or carperitide infusion from the start of cardiopulmonary bypass at an initial dose of 0.02 mcg/kg/min. The infusion rate was halved when oral meds began and continued for another 12 hours.
From day 1 postop, the carperitide group showed significantly lower serum creatinine values than the placebo group (p <0.01), the authors found. For example, on day 3 postop it was 1.27 and 1.46 mg/dL in the two groups, respectively, and at 1 year corresponding values were 1.21 vs 1.47 mg/dL.
Furthermore, only 1 patient in the carperitide group but 5 patients in the placebo group required dialysis after discharge until 1 year postop, the investigators report.
The 1-year mortality rate was low and no different in the two groups, but fewer carperitide patients had cardiac events (25) than the placebo patients (55), the report indicates.
While carperitide is not thought to have long-term effect, Dr. Sezai and colleagues comment, its cardiorenal protective effects in the acute period lead to long-term benefits. “It was very clear that the cardiorenal events decreased at 1 year post-operatively.”
They conclude, “The results of this study demonstrated that in CKD patients undergoing CABG, perioperative low-dose carperitide infusion has renal protective effects, enabling patients to avoid dialysis and cardiac events not only during the early postoperative stage but also for as long as 1 year post-operatively.”
In a related editorial, Dr. Guido Boerrigter and Dr. John C. Burnett with the Mayo Clinic in Rochester, Minnesota, explain that ANP and BNP exert their pleiotropic effects by activating guanylyl cyclase A (GC-A).
“Sezai et al. remind us that GC-A agonism has shown promising cardiorenal protective effects in several studies,” they write, “and that it remains an attractive therapeutic target worthy of continuing investigation.”
Results of Low-Dose Human Atrial Natriuretic Peptide Infusion in Nondialysis Patients With Chronic Kidney Disease Undergoing Coronary Artery Bypass Grafting: The NU-HIT (Nihon University Working Group Study of Low-Dose hANP Infusion Therapy During Cardiac Surgery) Trial for CKD
J Am Coll Cardiol 2011;58:897–903.