BACKGROUND: Albumin excretion is increased in persons with congestive heart failure (CHF), but the mechanism of this increase is unknown. Atrial natriuretic peptide (ANP) does not correlate with this albumin excretion, but the other 3 cardiac hormones derived from the ANP prohormone have never been investigated as to whether they can enhance albumin and/or protein excretion in persons with CHF. METHODS AND RESULTS: Long-acting natriuretic peptide (LANP), vessel dilator, and kaliuretic peptide (100 ng/kg body weight/min) given intravenously for 60 minutes to NYHA Class III CHF patients (n = 24) increased the albumin excretion rate 2- to 7-fold (P <.001) and total protein excretion rate 2- to 5-fold (P <.001). These peptide hormones similarly enhanced beta(2)-microglobulin, a specific marker of proximal tubular reabsorption, excretion rate 25- to 40-fold (P <.0005) at the end of their respective infusions. Three hours after stopping their respective infusions, the beta(2)-microglobulin excretion rate was still 11- to 33-fold (P <.0005) increased. CONCLUSIONS: LANP, vessel dilator, and kaliuretic peptide each enhance albumin and total protein excretion in persons with CHF. Part of the mechanism of this enhanced protein excretion is the inhibition of proximal tubular reabsorption of protein as shown by the beta(2)-microglobulin data.