Plasma clearance and effects of alpha-hANP infused in patients with end-stage renal failure

Abstract

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.

Change in Plasma Immunoreactive N-Terminus, C-Terminus, and 4,000-Dalton Midportion of Atrial Natriuretic Factor Prohormone with Hemodialysis

“…The release of the N-terminus, pro ANF 31-67 and ANF are simultaneous to all stimuli known to date (7,8,21,22], We cannot, however, rule out from the data of the present investigation that the Nterminus might be secreted into the plasma at a higher rate than that of the C-terminus (i.e. ANF) in persons with renal failure.The half-life of ANF in persons with chronic renal failure has been reported to be 4 min 34 s versus 3 min 30 s in normal volunteers [24]. A similar 25% increase in the half-life of pro ANF 31-67 and the Nterminus of the ANF prohormone would help to account for their extremely high concentrations pre-and postdial ysis since they circulate at 20-fold higher concentrations than ANF in normal healthy volunteers [7,9] and their half-lives are 10-to 20-fold longer than ANF in healthy volunteers [9,22], The reason that the predialysis values of pro AN F 31-67 in the circulation are much higher than the whole N-terminus are unknown at present but suggest the possibility that pro ANF 31-67 clearance is more dependent on the kidney while the whole N-terminus may be extracted by other tissues such as the lung and liver, as is known to occur with ANF [25,26].…”

Effects of Continuous Venovenous Hemofiltration on the Pharmacology of Carperitide, a Recombinant Human Atrial Natriuretic Peptide

“…In end-stage renal failure patients who received hANP at an infusion rate of 30 ng · kg -1 · min -1 , the metabolic clearance rate of hANP was 1,040 ml/min and the plasma hANP concentration was 1.87 ng/ml, which was more than twice that in healthy adults (0.81 ng/ml). 13 Because the present patients were critically ill, internal metabolic clearance of hANP was thought to be reduced due to multiple organ failure, including severe renal failure and impaired hepatic function. In healthy adults a Cltotal of approximately 50 ml/min is not considered to affect plasma hANP concentration because of its high internal metabolic clearance rate.…”

Plasma Atrial Natriuretic Factor and Blood Pressure Drops during Hemodialysis

“…It has been extensively demonstrated that the plasma atrial natriuretic factor (ANF) is elevated in patients with end-stage chronic renal failure [1][2][3]. There is a double mechanism for this increase: ( I ) The volume of the extracel lular fluids is increased in uremic patients on maintenance hemodialysis (HD), particularly just before the HD ses sions.…”

“…This results in an increase of right atrial pressure, stimulating ANF secretion. (2) The catabolism of ANF which takes place essentially in the kidney [2] is diminished in these patients due to the reduced renal mass. The role of these high plasma ANF levels in the maintenance of ho meostasis in uremia has been suggested, essentially in the control of sodium balance.…”