Immunocytological study revealed that AM was diffusely expressed in the cytoplasm of PMCs of PD patients. As AM is a cytoprotective peptide and is upregulated by high glucose condition, the expression of AM in PMCs during PD might contribute to protect PMCs. Using the same assay as in this study, it was Tariquidar molecular weight reported that plasma AM and mAM concentrations in healthy individuals were 2.80 ± 0.14 and 0.65 ± 0.06 fmol/mL, respectively [12]. 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 AZD6738 ic50 values are higher than in healthy subjects [12]. Although absolute values of mAM and AM were low in effluent, the mAM/AM ratio was higher in learn more effluent than in plasma, suggesting a higher amidation activity

[15]. An amidation enzyme for AM has not been identified but it is possible that amidation is increased in the abdominal cavity of PD patients than in the plasma by high glucose condition. Further study will be necessary to clarify the regulation of amidation activity by glucose. AM level in effluent correlated with CA125, a marker for PMCs number, and immunocytochemistry showed that PMCs in effluent express AM. However, the mAM/AM ratio did not correlate with CA125. This suggests that injured PMCs possess only low amidation activity. The Anacetrapib mAM/AM ratio negatively correlated with the D/P ratio of creatinine, suggesting that injured peritoneum can amidate AM. Clearly further study is required

to identify the cells responsible for amidating AM. The molecular weight of AM is 6,028 Kd and it is conceivable for AM to penetrate the peritoneum [16]. In the present study, AM in effluent correlated with the D/P ratio of creatinine (Fig. 2a). Thus, AM level should be higher than in plasma of patients with deteriorating peritoneal function. However, the AM concentrations in effluent and plasma were not correlated and were even lower than in plasma. AM in effluent is the sum of locally expressed AM and dialyzed AM from blood, and is actively amidated and degradated. Furthermore, AM is diluted by dialysate. We showed that detached PMCs in effluent store AM and that AM level in effluent is correlated with CA125. Taken together, it suggests that AM in effluent might be leakage from injured PMCs, and AM from injured PMCs constitute most of the AM in effluent. The peritoneum was not obtained in this study. Therefore, we could not fully elucidate the organ-protective effect of AM or clinical implications of AM in PD patients. The cells that express and amidate AM in the peritoneum were not identified. Finally the precise mechanism as to how amidation is activated in the peritoneum was not defined. Further studies are required.