Mature form of adrenomedullin is a useful marker to evaluate blood volume in hemodialysis patients

Kanozawa, Koichi; Shimosawa, Tatsuo; Nagasawa, Ryuji; Matsuda, Akihiko; Kato, Hitoshi; Matsumura, Osamu; Mitarai, Tetsuya; Isoda, Kazuo; Fujita, Toshiro

doi:10.1053/ajkd.2002.35691

Cited by 15 publications

(9 citation statements)

References 35 publications

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“…Although further studies are needed, similar mechanism(s) may be associated with the pathophysiology of EH during dialysis. Besides vasodilator effect, it is suggested that AM may also be associated with circulating blood volume in HD patients [23]. In our current study, there was no relationship between Ht, one of the markers of circulating blood volume, and hypotension.…”

Section: Discussioncontrasting

confidence: 58%

Plasma Concentrations of Adrenomedullin and Ghrelin in Hemodialysis Patients with Sustained and Episodic Hypotension

et al. 2005

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Abstract. Sustained and/or episodic hypotension during hemodialysis (HD) is an important clinical issue. Plasma adrenomedullin (AM) is increased in HD patients with sustained hypotension, but little is known about its implications for episodic hypotension. Ghrelin may also contribute to the pathophysiology of hypotension in HD patients. We evaluated plasma levels of AM and total ghrelin in sustained hypotensive (SH; n = 23), episodic hypotensive (EH; n = 30) and normotensive (NT; n = 23) HD patients. In the EH group, the relationship between low blood pressure during HD and circulating levels of AM and ghrelin was also evaluated. Plasma levels of AM were significantly higher in SH (34.3 ± 8.3 fmol/ml, p<0.01) than in NT patients (27.6 ± 5.2 fmol/ml), but not in EH patients (30.8 ± 6.1 fmol/ml). There was no significant difference of plasma total ghrelin in SH (548.1 ± 426.5 fmol/ml) and in EH patients (544.6 ± 174.3 fmol/ml), compared with NT patients (400.0 ± 219.7 fmol/ml). On the other hand, in EH patients, the "suppressed blood pressure ratio" during HD significantly correlated with plasma AM (r = 0.77, p<0.001) and with total ghrelin levels (r = 0.44, p<0.05). Our results suggest that ghrelin, as well as AM, may play an important role as vasodilator local hormones and regulation of blood pressure during HD, especially the occurrence of EH. Further studies are necessary to clarify the implication of these hormones in the control of hypotension during HD.Key words: Adrenomedullin, Chronic hypotension, Episodic hypotension, Ghrelin, Hemodialysis, Sustained hypotension (Endocrine Journal 52: 23-28, 2005) SIGNIFICANT hypotension is a major cardiovascular complication in patients with end-stage renal disease undergoing hemodialysis (HD). Two types of hypotension are recognizable in the setting of maintenance HD: episodic hypotension (EH) during HD is the most common manifestation of hemodynamic instability, and occurs in around 30-40% of the dialysis population [1]. A second form is sustained hypotension (SH), characterized by a systolic blood pressure (SBP) lower than 100 mmHg, during the interdialysis period and is present in approximately 5-10% of patients [2,3]. Both groups of patients require a substantial amount of medical and nursing care during and after HD to control hypotension-related symptoms. Although several clinical factors, such as autonomic dysfunction, reduced pressor response to vasopressor agents and cardiac dysfunction, have been shown to be responsible for the occurrence of EH and SH [1], the pathophysiology of chronic hypotension in dialysis patients has yet to be fully clarified.

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Section: Discussioncontrasting

confidence: 58%

Plasma Concentrations of Adrenomedullin and Ghrelin in Hemodialysis Patients with Sustained and Episodic Hypotension

et al. 2005

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“…In clinical setting, plasma AM concentration was increased in patients with cardiovascular diseases such as congestive heart failure, hypertension, septic shock as well as preeclampsia, which are often associated with increased plasma concentrations of renin and angiotensin II [62]. Also it is a new tool for use in diagnosis of extracellular volume in renal insufficiency [63]. AM seems to have the potential to protect organs from damage, since AM supplementation was effective to improve hemodynamics in patients with congestive heart failure and hypertension [64][65][66][67].…”

Section: Ammentioning

confidence: 99%

Adrenomedullin and its Related Peptide

Shimosawa

Fujita

2005

Endocr J

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MORE than 100 years have passed since Riva-Rocci [1] modified the sphygmograph by Marey [2], Mahomed [3] and Von Basch [4] to make conventional blood pressure measurements possible. Two years after the method was established, existence of hypertensive agents, now known as renin, was reported [5]. Since then laboratory investigations as well as clinical and epidemiological studies in hypertension research have been advancing at an exponential rate [6]. Since the 1950s, several circulation-regulating peptides, both hypertensive and hypotensive, were discovered. Among them, a novel vasodilative peptide, adrenomedullin (AM) was isolated from pheochromocytoma tissue in 1993 [7]. Another processing site in a propeptide of AM was found and a new hypotensive peptide, named proadrenomedullin N-terminal 20 peptide (PAMP), was isolated from human plasma and urine [7,8].Blood circulates throughout the body by the pressure force generated by cardiac output and peripheral resistance. Each of these primary determinants of blood pressure is determined by the interaction of an exceedingly complex series of factors. Thus it is crucial to determine this complex of interactions in order to better understand the physiological role of these newly found factors. AM and PAMPAs mentioned above, AM, originally isolated from pheochromocytoma cell, is also produced and secreted in endothelial cells [7,19], and has been shown to exhibit hypotensive action by direct vasodilation via both the elevation of intracellular cAMP and alteration of calcium sensitivity in vascular smooth muscle cells [20]. Besides these actions, recent studies have shown that AM increases nitric oxide synthesis in endothelial cell by elevating intracellular calcium [21][22][23][24]. Studies on the physiological action of AM have also revealed that AM increases intracellular cAMP [22] [28]. Moreover, AM inhibits smooth muscle cell migration and proliferation [29, 30]. AM also shares a slight homology with CGRP and the above mentioned physiological effects are inhibited by CGRP antagonist CGRP(8-37) [21]. Together with the evidence that AM production is increased in failing heart [31, 32], it is speculated that

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“…Another report showed that the mean plasma AM concentration was higher in pre-hemodialysis patients than in healthy volunteers [13]. Additionally, we reported that mAM concentrations in plasma of hemodialysis patients at the beginning and end of the hemodialysis treatment were 3.0 ± 0.3 and 2.8 ± 0.2 fmol/mL, respectively [14]. These values are higher than in healthy subjects [12].…”

Section: Discussionmentioning

confidence: 72%

Adrenomedullin in peritoneal effluent expressed by peritoneal mesothelial cells

et al. 2013

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BackgroundAdrenomedullin (AM) possesses vasodilative and cell-protective properties. Glycine combines with the C-terminal of AM to form mature, physiologically active AM (mAM). AM is reportedly induced by high glucose condition in vascular endothelial or smooth muscle cells; however, little is known on how AM is activated by amidation. To investigate the behavior of AM in patients undergoing peritoneal dialysis (PD), the concentrations of AM, mAM and CA125 were measured. The mAM to AM ratio (mAM/AM ratio) was also evaluated as a marker of amidation activity.MethodsTwenty patients were recruited for this study. The effluent at the time of the peritoneal equilibration test was collected and AM, mAM and CA125 concentrations were measured. The expression of AM in peritoneal mesothelial cells (PMCs) collected from effluent was also examined with an indirect immunofluorescent method.ResultsMean values of AM and mAM in effluent were 18.1 ± 1.6 and 4.1 ± 0.3 fmol/mL, respectively. In plasma, they were 42.6 ± 3.3 and 5.6 ± 0.6 fmol/mL, respectively. AM concentrations in effluent did not correlate with plasma AM level but correlated well with the dialysate-to-plasma ratio of creatinine (D/P ratio of creatinine). Moreover, in 7 of 20 cases, concentrations of the mAM and mAM/AM ratio in effluent were higher than in plasma. In effluent, AM concentration but not the mAM/AM ratio correlated with CA125 concentration. Immunocytological study revealed diffuse, cytoplasmic expression of AM in PMCs which were collected from effluent during PD.ConclusionAM is expressed by PMCs and actively amidated in the abdominal cavity of patients undergoing PD.

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Mature form of adrenomedullin is a useful marker to evaluate blood volume in hemodialysis patients

Cited by 15 publications

References 35 publications

Plasma Concentrations of Adrenomedullin and Ghrelin in Hemodialysis Patients with Sustained and Episodic Hypotension

Plasma Concentrations of Adrenomedullin and Ghrelin in Hemodialysis Patients with Sustained and Episodic Hypotension

Adrenomedullin and its Related Peptide

Adrenomedullin in peritoneal effluent expressed by peritoneal mesothelial cells

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