Increased plasma levels of mature form of adrenomedullin in patients with chronic renal failure

Background: Adrenomedullin (AM), a novel vasodilator peptide, is produced b y C-terminal amidation reaction of AM-glycine. AM-glycine, an intermediate form of AM (iAM), is processed from pro AM. AM circulating in the human blo od stream was found to consist of an amidated mature form (mAM) and iAM. Bi ological activity is exerted only by mAM. Methods: To investigate the patho physiological role of mAM in renal disease, we measured plasma concentratio ns of mAM as well as total AM (tAM), representing both mAM and iAM, in pati ents with various renal diseases. In addition, plasma ANP level was measure d in all patients. Results: The concentrations of plasma mAM in renal failu re with dialysis (2.1 +/- 0.2 fmol/ml, mean +/- SEM) and without dialysis ( 1.2 +/- 0.2) were significantly (p < 0.05) higher than those in control gro up (0.5 +/- 0.1). However, the plasma ANP level was increased only in renal failure patients with dialysis. Plasma mAM levels were significantly corre lated positively with serum creatinine levels and negatively with hematocri t. No significant difference was noted in the ratio of mAM/tAM between rena l failure patients and healthy subjects. Conclusion: These results suggest that plasma mAM is increased in renal failure in relation to deterioration of renal function, while the amidation process of PIM seems to be unaffecte d in patients with renal failure.