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N-terminal fragments of the proatrial natriuretic peptide in patients before and after hemodialysis treatment.

BACKGROUND
Fragments derived from the prohormone of alpha-human atrial natriuretic peptide (alpha-ANP) in patients with cardiac failure are more closely related to the disease state than intact alpha-ANP.


METHODS
Specific immunoassays have been developed to detect proANP 1-30, proANP 31-67, and proANP 1-98. Plasma concentrations of these fragments were determined in 122 hemodialysis patients with and without cardiac dysfunction, with and without hypertension, as well as with and without dialysis-associated hypotensive episodes either before or after a regularly scheduled hemodialysis session. The effects of different dialyzer membranes were also evaluated. The results of these assays along with other markers of volume regulation such as alpha-ANP and cyclic 3',5' guanosine monophosphate (cGMP) were compared with those of healthy controls.


RESULTS
Predialytic and postdialytic plasma concentrations of the proANP fragments were markedly higher in uremic patients than in controls (98-fold for proANP 1-98, 56-fold for proANP 31-67, and 35-fold for proANP 1-30). All proANP fragments, alpha-ANP, and cGMP decreased during hemodialysis. A strong linear correlation was found between predialytic and postdialytic plasma levels. There was no correlation, however, with the amount of fluid removed during hemodialysis. Patients with altered left ventricular hemodynamics displayed significantly higher plasma concentrations of all proANP fragments and alpha-ANP, but not cGMP, than patients with normal cardiac function. Hemodialysis patients with moderate or severe hypertension had higher concentrations of proANP fragments, alpha-ANP, and cGMP than patients with normal blood pressure or patients with only mild hypertension. There was no significant difference in circulating levels of proANP peptides, alpha-ANP, and cGMP between patients with and without frequent dialysis-associated hypotensive episodes. Cellulose-triacetate dialyzers reduced plasma levels of proANP 1-30, proANP 31-67, and proANP 1-98 significantly more than polysulfone dialyzers, but alpha-ANP and cGMP levels were not different.


CONCLUSIONS
Circulating alpha-ANP and proANP fragments are influenced by a variety of factors such as end-stage renal disease, hemodialysis treatment, dialyzer membrane material, cardiac dysfunction, and hypertension. Therefore, these are not useful markers to accurately estimate volume status in hemodialysis patients.