ANP and AKI

Few recent questions in the Acute Kidney Injury in Nephsap 2011 suggest ANP as an option for preventing AKI in certain surgical setting. Early animal data had shown promise. The first study to look at human data was in transplant patients showing negative results. Similar study was done in more transplant patients showing more negative results. What is the data for benefit?

Earlier studies might have been promising but the recent data is discouraging. A NEJM study in 1997 showed that it was beneficial in oliguric patients with ATN and showed a potential promise for a treatment for ATN. Another study showed benefit in post cardiac surgery patients in a randomized trial. Despite the large size of the trial, ANP administration had no effect on 21-day dialysis-free survival, mortality, or change in plasma creatinine concentration. A Cochrane review recently suggested perhaps some benefit. Nineteen studies (11 prevention, 8 treatment; 1,861 participants) were included. There was no difference in mortality between ANP and control in either the low or high dose prevention studies. After major surgery there was a significant reduction in RRT requirement with ANP in the prevention studies, but not in the treatment studies. There was no difference in mortality between ANP and control in either the prevention or treatment studies. There was a reduced need for RRT with low dose ANP in patients undergoing cardiovascular surgery. ANP was not associated with outcome improvement in either radio contrast nephropathy or oliguric AKI. A review in CJASN by the same authors and similar analysis suggests no benefit. Thus, although subset analyses separating low-dose from high-dose ANP trials suggest potential benefits, the preponderance of the literature suggests no benefit of ANP therapy for AKI. The side effects of potential hypotension and harm associated with the use of a vasodilator in high-risk perioperative and ICU patients, and a low value on potential benefit which is supported by relatively low-quality evidence from retrospective subset analyses from negative multicenter trials made KDIGO not recommend this treatment. 

  

KDIGO guidelines on ANP and AKI from 2012 read as follows: “Several natriuretic peptides are in clinical use or in  development for treatment of congestive heart failure, (CHF) or renal dysfunction, and could potentially be useful  to prevent or treat AKI. Atrial natriuretic peptide (ANP) is a 28-amino-acid peptide with diuretic, natriuretic, and vasodilatory activity. ANP is mainly produced in atrial myocytes, and the rate of release from the atrium increases in response to atrial stretch. Early animal studies showed that ANP decreases preglomerular vascular resistance and increases postglomerular vascular resistance, leading to increased GFR. It also inhibits renal tubular sodium reabsorption. Increases in GFR and diuresis have also been confirmed in clinical studies. It could thus be expected that ANP might be useful for treatment of AKI, and several RCTs have been conducted to test this hypothesis.  3.5.3: We suggest not using atrial natriuretic peptide (ANP) to prevent (2C) or treat (2B) AKI."