Plasma Adrenomedullin Levels in Patients on Hemodialysis

Abstract

Adrenomedullin (AM) is a hypotensive peptide that has recently been isolated from human pheochromocytoma. In this study, we measured plasma AM concentrations in 54 patients on hemodialysis (HD) and examined the clinical significance. We also evaluated the effects of high-flux and low-flux dialysis membranes on plasma AM levels. The average value of plasma AM at pre-HD (4.44 ± 0.16 fmol/ml) was significantly elevated compared with that in 44 healthy volunteers (1.31 ± 1.41 fmol/ml) (p < 0.0001). The plasma AM concentrations at pre-HD showed a negative correlation with age and mean blood pressure (MBP) at pre-HD. The plasma AM concentrations at post-HD showed a negative correlation with MBP at post-HD and a negative correlation with the reduction rate of AM. Multiple regression analysis showed that age and MBP were independent factors associated with plasma AM at pre-HD and that MBP and reduction rate of AM were independent factors associated with plasma AM at post-HD. We investigated the differences between high-flux dialyzers (PS-UW, PS-N and FB-F) and a low-flux dialyzer (AM-BC-F), and we found that high-flux dialyzers removed plasma AM more efficiently than a low-flux dialyzer did. In addition, in 3 patients on HD, plasma AM levels decreased significantly during isovolumic dialysis using a high-flux dialyzer, despite the fact that there were no significant changes in MBP and ANP. In conclusion, elevation in plasma AM level causes a fall in MBP in patients on HD, therefore, removal of AM by HD treatment using a high-flux dialyzer contributes to the stability of blood pressure during HD.

Plasma Levels of Proadrenomedullin N-Terminal 20 Peptide and Adrenomedullin in Patients Undergoing Hemodialysis

“…Thus, plasma levels of PAMP, tAM and mAM seem to be positively related to increases in body fluid volume. Several studies have shown that plasma AM levels before HD are significantly higher as compared with controls [10, 11, 12, 13, 14, 15]. Mallamaci et al [12]reported that plasma AM falls after isolated ultrafiltration, indicating that the plasma concentration of this peptide is influenced by the status of the body fluid volume.…”

“…Protein clearance during HD varies with its molecular size and/or the type of dialysis membrane. In HD patients using cuprophan membranes (low-flux membrane), the plasma concentrations of tAM and mAM did not change during dialysis [10, 11, 14], whereas in patients using synthetic membranes (high-flux membrane), the plasma levels of these peptides decreased after HD [14, 15]. High-flux membranes are generally superior to low-flux ones in terms of removing low-molecular-mass proteins.…”

“…Some reports indicate, however, that the plasma concentrations of AM in HD patients are significantly and inversely correlated with blood pressure [13, 14, 15]. Cases et al [13]considered that AM, as a vasodilator hormone, can be involved in the pathophysiology of chronic hypotension in HD patients, when hypotension is defined as a predialysis systolic blood pressure below 100 mm Hg.…”

“…In addition, both plasma mAM and tAM levels increase in proportion to the severity of these diseases [8, 9]. Recent studies [10, 11, 12, 13, 14, 15]have shown that the levels of circulating AM, including mAM, are significantly increased in patients undergoing hemodialysis (HD). Unlike studies on patients with essential hypertension, some reports have shown that plasma tAM/mAM levels are inversely correlated with blood pressure level in HD patients [13, 14, 15].…”

“…Recent studies [10, 11, 12, 13, 14, 15]have shown that the levels of circulating AM, including mAM, are significantly increased in patients undergoing hemodialysis (HD). Unlike studies on patients with essential hypertension, some reports have shown that plasma tAM/mAM levels are inversely correlated with blood pressure level in HD patients [13, 14, 15]. Mallamaci et al [12]reported that the plasma concentrations of this peptide may be influenced by the status of the body fluid volume.…”