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The effects and clearance of synthetic atrial natriuretic peptide (alpha-hANP) were investigated in eight patients with end-stage renal failure and six normal volunteers. ANP or vehicle was infused for 1 h at 10 pmol.kg-1.min-1 in random order on two separate occasions. During ANP infusions in end-stage renal patients, microhematocrit rose by 9.8 +/- 2% (P less than 0.005, n = 8), from base-line values of 0.24 +/- 0.02. Serum protein and albumin rose consistently. In contrast, during placebo infusions, no significant changes were seen. Blood pressure, heart rate, plasma renin concentration, serum creatinine, and electrolytes did not change significantly during either study phase. In end-stage renal failure patients, metabolic clearance rate of infused ANP was 1.04 +/- 0.095 l/min and its plasma half-life was 4 min 34 s. In normal volunteers, metabolic clearance rate was 2.6 l/min and its plasma half-life 3 min 30 s. The data suggest that ANP promotes contraction of plasma volume via a mechanism independent of renal function and also indicate that the kidney is not the only organ involved in the ANP metabolism.

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The size of our trial was indeed based on a comparison of active with placebo treatment, but, as we pointed out, an assessment of the two active agents was an important secondary objective from the outset. The advantage of the diuretic over the 3 blocker was clear, particularly for coronary events, and is also suggested by other recent results.' Swedberg is surely not suggesting that findings of such immediate clinical relevance should remain unreported.