Nihon University Working Group Study of Low-Dose hANP Infusion Therapy During Cardiac Surgery Trial for Chronic Kidney Disease - NU-HIT Trial for CKD


The goal of the trial was to evaluate perioperative infusion of human atrial natriuretic peptide (hANP) compared with placebo among patients with chronic renal insufficiency undergoing coronary artery bypass grafting (CABG).


Infusion of hANP will preserve postoperative renal function.

Study Design

  • Blinded
  • Placebo Controlled
  • Randomized

Patient Populations:

  • Japanese patients with renal insufficiency (eGFR<60 ml/min/1.73 m2) undergoing CABG with cardiopulmonary bypass

    Number of enrollees: 303
    Duration of follow-up: 1 year
    Mean patient age: 69 years
    Percentage female: 13%
    Ejection fraction: 55%


  • Dialysis
  • Cardiogenic shock
  • Off-pump CABG

Primary Endpoints:

  • Freedom from dialysis at 1 year
  • Serum creatinine and eGFR at 0, 1, and 3 days; 1 week; and 1 month

Secondary Endpoints:

  • Early postoperative mortality and complications
  • Overall survival and freedom from cardiac events at 1 year
  • Maximum serum creatinine, the rate of increase of serum creatinine, and an increase of serum creatinine by at least 0.3 mg/dl compared with baseline value
  • ANP, BNP, and cyclicguanosine monophosphate (cGMP) levels on postoperative day 1, week 1, and month 1

Drug/Procedures Used:

Patients with chronic renal insufficiency undergoing CABG were randomized to infusion of hANP [carperitide, 0.02 µg•kg-1•min-1] (n = 151) versus placebo (n = 152).

Study medication was begun at the start of cardiopulmonary bypass, reduced in half when oral medications were started, at which point it was continued for another 12 hours.

Principal Findings:

Overall 303 patients were randomized. In the hANP group, the mean age was 69 years, 13% were women, 51% had diabetes, 71% had hypertension, mean left ventricular ejection fraction was 55%, mean cardiopulmonary bypass time was 116 minutes, and mean infusion of study medication was 2.4 days.

Freedom from dialysis at 1 year was 98.6% in the hANP group versus 91.6% in the placebo group (p = 0.0066).

Serum creatinine 1 week after surgery was 1.2 mg/dl versus 1.4 mg/dl, maximum serum creatinine was 1.5 mg/dl versus 1.9 mg/dl (p < 0.0001), at least a 0.3 mg/dl increase in serum creatinine over baseline occurred in 26% versus 59% (p < 0.0001), while estimated glomerular filtration rate (eGFR) 1 week after surgery was 53 ml/min/1.73 m2 versus 46 ml/min/1.73 m2, respectively.

Total deaths at 1 year were 1 versus 6 (p = 0.059), and patients requiring dialysis at 1 year were 2 versus 13 (p = 0.006), respectively.


Among Japanese patients with chronic renal insufficiency undergoing CABG with cardiopulmonary bypass, the use of hANP (carperitide) was beneficial. Compared with placebo, this medication appeared to improve freedom from dialysis and possibly total deaths at 1 year. Secondary outcomes of serum creatinine and eGFR also favored hANP.

Carperitide is a similar peptide to nesiritide (a B-type natriuretic peptide [BNP]), which has largely been abandoned for treatment of acute congestive heart failure due to lack of efficacy over standard therapies (see ASCEND-HF). Carperitide may deserve further study in a larger and more heterogeneous population.


Sezai A, Hata M, Niino T, et al. 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.

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Hypertension

Keywords: Follow-Up Studies, Kidney Failure, Chronic, Creatinine, Renal Dialysis, Heart Failure, Stroke Volume, Glomerular Filtration Rate, Cardiopulmonary Bypass, Coronary Artery Bypass, Atrial Natriuretic Factor, Hypertension, Diabetes Mellitus, Renal Insufficiency, Chronic, Natriuretic Peptide, Brain

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