Mid-term predictive value of calciprotein particles in maintenance hemodialysis patients based on a gel-filtration assay.

BACKGROUND AND AIMS: Calciprotein particles (CPPs), nano-aggregates containing fetuin-A-bound calcium-phosphate, are associated with aortic stiffness and coronary calcification in maintenance hemodialysis patients. A novel gel-filtration assay can detect low-density small CPPs, which are actually a major form of circulating CPPs in vivo. We sought to investigate whether circulating CPP levels measured by gel-filtration method would accurately predict hard endpoints in maintenance hemodialysis patients. METHODS: This study used a prospective, multicenter, longitudinal, and observational design. One-hundred eight patients enrolled in this study were followed-up for about 2 years. We reported all-cause death and cardiovascular events, which included major adverse cardiac, cerebrovascular, and limb events. RESULTS: Kaplan-Meier analysis showed no significant difference between patients with the higher (>median) and lower (

The renoprotective effect and safety of a DPP-4 inhibitor, sitagliptin, at a small dose in type 2 diabetic patients with a renal dysfunction when changed from other DPP-4 inhibitors: REAL trial.

BACKGROUND: We conducted the multicenter, prospective, open-label study in type 2 diabetic (T2DM) patients with renal dysfunction, to clarify the efficacy and the safety in relation to renal function and glycemic control, and the economic effect when other dipeptidyl peptidase-4 (DPP-4) inhibitors were switched to a small dose of sitagliptin depending on their renal function. METHODS: Vildagliptin, alogliptin, or linagliptin received for more than 2 months were changed to sitagliptin at 25 or 12.5 mg/day depending on their renal function in 49 T2DMs. Renal function and glycemic control, and the drug cost were assessed during 6 months. RESULTS: Estimated glomerular filtration rate was not changed in patients not on hemodialysis (n = 29). The HbA1c levels were not altered in all of the patients including those on hemodialysis (n = 20). The active glucagon-like peptide-1 levels or other renal parameters were not altered significantly. There were no adverse events to be related to the drugs. The daily drug expense was reduced by 88.1 yen per patient. CONCLUSION: Switching to a small dose of sitagliptin according to the renal function in T2DM patients with renal dysfunction demonstrated the same efficacy and safety as those with other full-dose DPP-4 inhibitors, indicating a therapeutic option with a high cost performance.

Adrenomedullin in peritoneal effluent expressed by peritoneal mesothelial cells.

BACKGROUND: Adrenomedullin (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. METHODS: Twenty 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. RESULTS: Mean 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. CONCLUSION: AM is expressed by PMCs and actively amidated in the abdominal cavity of patients undergoing PD.

[Predictive value of ultrasonographical assessments of carotid artery for cardiovascular events in patients under hemodialysis: add on comparison with stroke patients].

BACKGROUND: The prognosis of patients on hemodialysis (HD) was determined with respect to cardiovascular disease. We analyzed the relationships between several parameters of carotid artery echograms and cardiovascular events (CVE) in patients on HD. We also compared the characteristic findings of carotid artery echography in patients with stroke and patients on HD. METHOD: We enrolled 104 patients on HD (male : female, 72: 32; mean age, 63.0 +/- 11.2 years) and 48 with stroke (male : female, 36: 12; mean age, 66.0 +/- 7.7 years) who were admitted to our hospital between 1998 and 2004. We measured intima media thickness (IMT), plaque score (PS), resistive index (RI), common carotid artery (CCA) stenosis and plaque echogenicity using B-mode ultrasonography. The correlation between carotid artery echographic findings and CVE were analyzed over a period of 37.5 +/- 22.9 months of follow-up. The characteristic findings of carotid artery echography were compared among groups of patients on initial HD (iHD) and maintenance HD (mHD) and with stroke accompanied by eGFR > 60 mL/min/1.73 m2. RESULTS: Both PS and RI significantly correlated with CVE (p < 0.005 and p < 0.05, respectively), and CVE occurred at the early phase of follow up in patients with increased PS. Both PS and RI were also higher in mHD than in stroke (p < 0.005). Both PS and CCA stenosis were higher in mHD than in iHD (p < 0.01, p< 0.05). More hard plaques were identified in patients on mHD than in those with stroke (p < 0.005). Multivariate analysis showed that the numbers of soft and hard plaques were significantly associated with CCA stenosis(p < 0.05) and the duration of dialysis (p < 0.05), respectively. CONCLUSIONS: Increasing PS and RI were powerful predictors of CVE in patients on HD. Atherosclerotic changes were equal in patients on iHD and those with stroke. Plaque score, the numbers of hard plaques and CCA stenosis were increased in mHD, suggesting the development of atherosclerotic changes in patients on HD.