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Kyoto, Japan

Moroi M.,National Center for Global Health and Medicine | Tamaki N.,Hokkaido University | Nishimura M.,Tojinkai Hospital | Haze K.,Kashiwara Municipal Hospital | And 15 more authors.
American Journal of Kidney Diseases

Background: Detecting myocardial ischemia in hemodialysis patients is crucial given the high incidence of silent ischemia and the high cardiovascular mortality rates. Abnormal myocardial fatty acid metabolism as determined by imaging with 123I-labeled BMIPP (β-methyl iodophenyl- pentadecanoic acid) might be associated with cardiac-derived death in hemodialysis patients. Study Design: Prospective observational study. Setting & Participants: Asymptomatic hemodialysis patients with one or more cardiovascular risk factors, but without known coronary artery disease, were followed up for 3 years at 48 Japanese hospitals (406 men, 271 women; mean age, 64 years). Predictor: Baseline BMIPP summed scores semiquantified using a 17-segment 5-point system (normal, 0; absent, 4). Outcomes: Cardiac-derived death, including cardiac and sudden death. Measurements: HRs were estimated using a Cox model for associations between BMIPP summed scores and cardiac-derived death, adjusting for potential confounders of age, sex, body mass index, dialysis duration, and cardiovascular risk factors. Results: Rates of all-cause mortality and cardiac-derived death were 18.5% and 6.8%, respectively. Cardiac-derived death (acute myocardial infarction [n = 10], congestive heart failure [n = 13], arrhythmia [n = 2], valvular heart disease [n = 1], and sudden death [n = 20]) accounted for 36.8% of all-cause deaths. Cardiac-derived death (n = 46) was associated with age, history of heart failure, and BMIPP summed scores of 4 or higher (HR, 2.9; P < 0.001). Three-year cardiac-derived death-free survival rates were 95.7%, 90.6%, and 78.8% when BMIPP summed scores were 3 or lower, 4-8, and 9 or higher, respectively. BMIPP summed score also was a predictor of all-cause death (HR, 1.6; P = 0.009). Limitations: Sudden death of unknown cause was considered to have been cardiac derived, although a coronary origin was not confirmed. Conclusions: Abnormal myocardial fatty acid metabolism is associated with cardiac-derived death in hemodialysis patients. BMIPP single-proton emission computed tomography appears clinically useful for predicting cardiac-derived death in this population. © 2013 National Kidney Foundation, Inc. Source

Zen K.,Omihachiman Community Medical Center | Tamaki N.,Hokkaido University | Nishimura M.,Tojinkai Hospital | Nakatani E.,Translational Research Informatics Center | And 4 more authors.
International Journal of Cardiology

Background: The aim of this study was to investigate whether 123I-labelled β-methyl iodophenyl-pentadecanoic acid (BMIPP) imaging as an abnormal myocardial fatty acid metabolism indicator better predicted fatal and non-fatal cardiac events than conventional predictors [e.g. peripheral artery disease (PAD) and diabetes mellitus (DM)] in haemodialysis patients. Methods: In a sub-analysis of the BMIPP SPECT Analysis for Decreasing Cardiac Events in Haemodialysis Patients (B-SAFE) study, 677 asymptomatic patients with ≥ 1 cardiovascular risk factor and without known coronary artery disease were followed for 3 years. The amount of radioactivity in each 17-left ventricular segment was graded visually and assigned a score from 0 (normal) to 4 (absent). Its total values were designated as baseline summed BMIPP scores. Outcome measures were composite cardiac events. Results: Cardiac events correlated with age, PAD [hazard ratio (HR): 2.15; p = 0.003], DM (HR: 1.76; p = 0.006) and summed BMIPP scores (4-8, HR: 1.82; p < 0.001; ≥ 9, HR: 3.49; p < 0.001). Cardiac event-free rates decreased with increasing summed BMIPP scores, PAD and DM. Areas under the receiver operating curves (AUCs) indicated that a BMIPP-based model (AUC: 0.656) was more predictive than DM or PAD models (AUC: 0.591); a model with all three was most predictive (AUC: 0.708). The three-year cardiac event-free rates significantly decreased in patients with PAD and/or DM in all summed BMIPP score categories. Conclusions: Abnormal myocardial fatty acid metabolism strongly predicts cardiac events in haemodialysis patients; those with PAD or DM are at high risk for cardiac events. © 2015 Elsevier Ireland Ltd. All rights reserved. Source

Gejyo F.,Niigata University | Amano I.,Nagoya Vascular Access Amano Memorial Clinic | Ando T.,Hidaka Hospital | Ishida M.,Kitasaito Hospital | And 26 more authors.
Therapeutic Apheresis and Dialysis

Dialysis-related amyloidosis is a serious complication of long-term hemodialysis. Its pathogenic mechanism involves accumulation of β2-microglobulin in the blood, which then forms amyloid fibrils and is deposited in tissues, leading to inflammation and activation of osteoclasts. Lixelle, a direct hemoperfusion column for adsorption of β2-microglobulin, has been available since 1996 to treat dialysis-related amyloidosis in Japan. However, previous studies showing the therapeutic efficacy of Lixelle were conducted in small numbers of patients with specific dialysis methods. Here, we report the results of a nationwide questionnaire survey on the therapeutic effects of Lixelle. Questionnaires to patients and their attending physicians on changes in symptoms of dialysis-related amyloidosis by Lixelle treatment were sent to 928 institutions that had used Lixelle, and fully completed questionnaires were returned from 345 patients at 138 institutions. The patients included 161 males and 184 females 62.9±7.7years age, who had undergone dialysis for 25.9±6.2years and Lixelle treatment for 3.5±2.7years. Based on self-evaluation by patients, worsening of symptoms was inhibited in 84.9-96.5% of patients. Of the patients, 91.3% felt that worsening of their overall symptoms had been inhibited, while attending physicians evaluated the treatment as effective or partially effective for 72.8% of patients. Our survey showed that Lixelle treatment improved symptoms or prevented the progression of dialysis-related amyloidosis in most patients. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis. Source

Sasaki K.,Rinku General Medical Center | Mizuno H.,Surgery | Iwamoto N.,Tojinkai Hospital | Imakita M.,Rinku General Medical Center | And 6 more authors.
Blood Purification

Background: Although laparoscopy may provide more detailed morphological and histological information about peritoneal damage, its significance in patients with long vintage of peritoneal dialysis (PD) is not elucidated. Methods: Findings in 12 patients with PD vintage of 7.3 (5.0-8.4) years who had undergone laparoscopy between 2007 and 2011 were reviewed. Macroscopic (peritoneal change, hypervascular change, adhesion, encapsulation) and histopathological peritoneal findings (interstitial fibrosis, microvascular change, fibrin deposition, inflammatory cell infiltration) were scored and summed as Macro-total score (Macro-TS) and Micro-total score (Micro-TS), respectively. Factors associated with these scores and the relationship between these scores were investigated. Results: Neither Macro-TS nor Micro-TS were related to PD vintage (p = 0.069 and p = 0.769, respectively); moreover, Macro-TS varied from patient to patient regardless of similar PD vintage. However, Macro-TS showed a significant association with duration of acidic dialysate (p = 0.003). Conclusion: Macroscopic and microscopic findings via laparoscopy may help the assessment of peritoneal damage in patients with long PD vintage. © 2015 S. Karger AG, Basel. Source

Sakan H.,Nara Medical University | Nakatani K.,Nara Medical University | Asai O.,Nara Medical University | Imura A.,Kyoto University | And 9 more authors.

Renal α-Klotho (α-KL) plays a fundamental role as a co-receptor for fibroblast growth factor 23 (FGF23), a phosphaturic hormone and regulator of 1,25(OH)2 vitamin D3 (1,25VitD3). Disruption of FGF23-α-KL signaling is thought to be an early hallmark of chronic kidney disease (CKD) involving reduced renal α-KL expression and a reciprocal rise in serum FGF23. It remains unclear, however, whether the rise in FGF23 is related to the loss of renal α-KL. We evaluated α-KL expression in renal biopsy samples and measured levels of several parameters of mineral metabolism, as well as soluble α-KL (sKL), in serum and urinary samples from CKD patients (n = 236). We found that although renal α-KL levels were significantly reduced and serum FGF23 levels were significantly elevated in early and intermediate CKD, serum phosphate levels remained within the normal range. Multiple regression analysis showed that the increases in FGF23 were significantly associated with reduced renal function and elevated serum phosphate, but were not associated with loss of renal a-KL. Moreover, despite falling renal α-KL levels, the increase in FGF23 enhanced urinary fractional excretion of phosphate and reduced serum 1,25VitD3 levels in early and intermediate CKD, though not in advanced CKD. Serum sKL levels also fell significantly over the course of CKD, and renal α-KL was a significant independent determinant of sKL. These results demonstrate that FGF23 levels rise to compensate for renal failure-related phosphate retention in early and intermediate CKD. This enables FGF23-α-KL signaling and a neutral phosphate balance to be maintained despite the reduction in α-KL. In advanced CKD, however, renal α-KL declines further. This disrupts FGF23 signaling, and serum phosphate levels significantly increase, stimulating greater FGF23 secretion. Our results also suggest the serum sKL concentration may be a useful marker of renal α-KL expression levels. © 2014 Sakan et al. Source

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