記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Journal of the American Heart Association  

BACKGROUND: Lower extremity peripheral arterial disease is a potentially lethal cardiovascular complication in patients undergoing hemodialysis. Anemia is a risk factor for cardiovascular disease among the hemodialysis population. However, whether blood hemoglobin concentration is associated with the risk of peripheral arterial disease progression in this population remains undetermined. METHODS AND RESULTS: This is an extension of a 4-year multicenter, prospective, observational cohort study to 10 years. A total of 3504 Japanese patients undergoing maintenance hemodialysis were recruited between 2006 and 2007. The primary exposure was blood hemoglobin concentration at baseline. The main outcome was the first-ever incidence of major adverse limb events (MALE), composed of endovascular treatment, bypass surgery, and amputation. Multivariable-adjusted Cox proportional hazards model, Fine-Gray subdistribution hazards model, restricted cubic spline analysis, and restricted mean survival time analysis were used to determine the association of blood hemoglobin concentration with the incidence of MALE. During a median follow-up of 8.0 years, 257 patients experienced MALE. A Cox proportional hazards model showed that the risk of MALE in patients with blood hemoglobin concentrations <10.0 g/dL was significantly higher than in patients with concentrations of 11.0 to 11.9 g/dL, even after adjusting for confounding factors. In contrast, elevated hemoglobin concentration (≥12.0 g/dL) was not significantly associated with increased risk of MALE. Similar associations were observed when the Fine-Gray subdistribution regression model was used by setting all-cause mortality as the competing risk. CONCLUSIONS: A low blood hemoglobin concentration is an independent risk factor for peripheral arterial disease progression in patients undergoing maintenance hemodialysis.

DOI： 10.1161/JAHA.123.033853

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記述言語：英語   出版者・発行元：Therapeutic Apheresis and Dialysis  

Introduction: Several calcimimetics, other than cinacalcet, are commercially available; however, their effects on calcium and phosphate levels have not yet been fully studied. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the impact of calcimimetics on the management of serum calcium and phosphate levels in patients with secondary hyperparathyroidism undergoing dialysis. Methods: A systematic literature search through October 2023 and a meta-analysis were conducted on the effects of upacicalcet, etelcalcetide, evocalcet, and cinacalcet on serum calcium and phosphate levels in patients with secondary hyperparathyroidism undergoing dialysis; we searched PubMed, Ovid MEDLINE, and the Cochrane Central Register of Controlled Trials, and 21 studies comprising 6371 patients undergoing dialysis were included. Results: Participants treated with calcimimetics had lower serum calcium and phosphate levels than placebo. Conclusion: Calcimimetics significantly reduced serum calcium and phosphate levels compared to placebo in patients with secondary hyperparathyroidism undergoing dialysis, independent of therapeutic strategy or concomitant vitamin D treatment.

DOI： 10.1111/1744-9987.14125

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記述言語：英語   出版者・発行元：Clinical Kidney Journal  

Background: Disturbances in the cardiovascular system, bone and skeletal muscle are independent risk factors for death among patients receiving haemodialysis (HD). However, the combined impact of disorders of these three organs on morbidity and mortality is unclear in the HD population. Methods: A total of 3031 Japanese patients on maintenance HD were prospectively followed. The outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and bone fracture. Patients were divided into four groups (G1-G4) according to the baseline number of diseased organs represented as histories of cardiovascular disease and bone fractures and the presence of low skeletal muscle mass as follows: G1, no organ; G2, one organ; G3, two organs; G4, three organs. Multivariable-adjusted survival models were used to analyse associations between the number of diseased organs and outcomes. Results: During a 4-year follow-up, 499 deaths, 540 MACE and 140 bone fractures occurred. In the Cox proportional hazards model, the risk for all-cause mortality was significantly higher in G2, G3 and G4 than in G1 as the reference {hazard ratio: G2, 2.16 [95% confidence interval (CI) 1.65-2.84], G3, 3.10 [95% CI 2.27-4.23] and G4, 3.11 [95% CI 1.89-5.14]}. Similarly, the risks for developing MACE and bone fractures were significantly elevated as the number of organ disorders increased. Conclusions: Multiple disorders of the cardiovascular-bone-skeletal muscle axis are strong predictors of morbidity and mortality in patients undergoing HD.

DOI： 10.1093/ckj/sfae154

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記述言語：英語   出版者・発行元：Clinical and Experimental Nephrology  

Background: The optimal dialysate calcium (Ca) concentration for patients undergoing hemodialysis remains inconclusive, particularly concerning cardiovascular protection. Methods: We conducted a systematic review of 19 randomized controlled trials (RCTs) and a meta-analysis of eight RCTs to determine the optimal dialysate Ca concentration for cardiovascular protection. We compared outcomes in patients receiving maintenance hemodialysis treated with either a low-Ca dialysate (LCD) (1.125 or 1.25 mmol/L) or a high-Ca dialysate (HCD) (1.5 or 1.75 mmol/L). The outcomes were coronary artery calcification score (CACS), all-cause and cardiovascular death, cardiovascular function and structure, and serum biochemical parameters. Results: There was no significant difference between LCD and HCD concerning CACS (standardized mean difference [SMD] = −0.16, 95% confidence interval [CI]: [−0.38, 0.07]), the risk of all-cause death, and cardiovascular death in patients treated with chronic maintenance hemodialysis. Conversely, LCD was associated with a significantly lower intima-media thickness (SMD = −0.49, 95% CI [−0.94, −0.05]) and pulse wave velocity than HCD (SMD = −0.86, 95% CI [−1.21, −0.51]). Furthermore, LCD significantly decreased serum Ca levels (mean difference [MD] = 0.52 mg/dL, 95% CI [0.19, 0.85]) and increased serum parathyroid hormone levels (MD = 44.8 pg/mL, 95% CI [16.2, 73.3]) compared with HCD. Notably, most RCTs examined in our analysis did not include patients receiving calcimimetics. Conclusions: Our meta-analysis showed no significant differences in cardiovascular calcification and death between LCD and HCD and revealed a paucity of RCTs on dialysate Ca concentrations, including those involving patients on calcimimetics, indicating the urgent need for further studies.

DOI： 10.1007/s10157-024-02460-3

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記述言語：英語   出版者・発行元：(一社)日本腎臓学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Therapeutic Apheresis and Dialysis  

Introduction: Malnutrition–inflammation complex syndrome (MICS) is highly prevalent in patients undergoing hemodialysis. We determined the prognostic value of the Simple MICS score, calculated using a combination of age, body mass index, and serum concentrations of albumin, creatinine, and C-reactive protein. Methods: We retrospectively recruited 218 Japanese patients undergoing maintenance hemodialysis. The primary outcome was all-cause mortality, and the main exposure was the Simple MICS score. Cox proportional hazard regression analysis and logistic regression analysis were used to characterize the relationship between the Simple MICS score and mortality. Results: During a median 4.4-year follow-up period, 56 patients died. Multivariable-adjusted models showed that a higher Simple MICS score was associated with higher risks of mortality. The predictability for all-cause mortality of the Simple MICS score was significantly better than conventional nutrition-related indices. Conclusion: The Simple MICS score can be used to stratify mortality risk in patients undergoing maintenance hemodialysis.

DOI： 10.1111/1744-9987.14085

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記述言語：英語   出版者・発行元：Therapeutic Apheresis and Dialysis  

DOI： 10.1111/1744-9987.14084

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記述言語：英語   出版者・発行元：John Wiley & Sons Australia, Ltd  

記述言語：英語   出版者・発行元：一般社団法人 日本動脈硬化学会  

Aim: Sudden death is one of the most common causes of death among hemodialysis patients. Electrocardiography (ECG) is a noninvasive and inexpensive test that is regularly performed in hemodialysis clinics. However, the association between abnormal ECG findings and the risk of sudden death in hemodialysis patients is yet to be fully elucidated. Thus, the aim of this study was to determine the ECG parameters linked to sudden death in patients undergoing hemodialysis. Methods: The Q-Cohort Study is a multicenter, longitudinal, observational study of hemodialysis patients. In this study, 1,153 Japanese hemodialysis patients aged ≥ 18 years with ECG data recorded within 1 year of study enrollment were followed up for 10 years. Cox proportional hazards models were used to estimate the multivariate-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between ECG parameters and sudden death. Results: During the median follow-up period of 9.0 years, 517 patients died, 76 of whom exhibited sudden death. After adjusting for confounding factors, higher heart rate, QT prolongation, and left ventricular hypertrophy as per the Sokolow–Lyon voltage criteria were found to be independently associated with an increased risk of sudden death. The adjusted HRs [95% CIs] for each abnormal ECG parameter were 2.02 [1.05–3.89], 2.10 [1.30–1.77], and 1.91 [1.18–3.09], respectively. Conclusions: Higher heart rate, QT prolongation, and left ventricular hypertrophy on ECG have been determined to be associated with an increased risk of sudden death. Therefore, regular ECG recording could enable medical practitioners to identify hemodialysis patients who require intervention to prevent lethal arrhythmia.

DOI： 10.5551/jat.64255

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記述言語：英語   出版者・発行元：Journal of Bone and Mineral Metabolism  

Introduction: In patients undergoing dialysis, major bone fracture is associated with a high risk of mortality, including death of cardiovascular (CV) origin. In the present study, we aimed to determine whether a history of fragility fracture is a predictor of CV death in patients undergoing hemodialysis with long-term follow-up. Materials and methods: In total, 3499 patients undergoing hemodialysis were analyzed for 10 years. We evaluated the history of fragility fracture in each patient at enrollment. The primary outcome was CV death. A Cox proportional hazard model and a competing risk approach were applied to determine the association between a history of fragility fracture and CV death. Results: A total of 346 patients had a history of fragility fracture at enrollment. During a median follow-up of 8.8 years, 1730 (49.4%) patients died. Among them, 621 patients experienced CV death. Multivariable Cox analyses after adjustment for confounding variables showed that a history of fragility fracture was associated with CV death (hazard ratio, 1.47; 95% confidence interval, 1.16–1.85). In the Fine–Gray regression model, a history of fragility fracture was an independent risk factor for CV death (subdistribution hazard ratio, 1.36; 95% confidence interval, 1.07–1.72). Conclusion: In a large cohort of patients undergoing hemodialysis, a history of fragility fracture was an independent predictor of CV death.

DOI： 10.1007/s00774-024-01501-x

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記述言語：英語   出版者・発行元：Hypertension Research  

We previously reported that brain atrophy was more severe and progressed more rapidly in patients with end-stage kidney disease on peritoneal dialysis (PD) than those with non-dialysis-dependent chronic kidney disease. However, it remains unknown whether there is a difference between patients on PD and hemodialysis (HD). In total, 73 PD and 34 HD patients who underwent brain magnetic resonance imaging (MRI) were recruited for a cross-sectional analysis. Among them, 42 PD and 25 HD patients who underwent a second brain MRI after 2 years were recruited for a longitudinal analysis. T1-weighted MRI images were analyzed. Total gray matter volume (GMV), total white matter volume, and cerebrospinal fluid volume were segmented, and each volume was quantified using statistical parametric mapping software. The ratio of GMV (GMR) was calculated by dividing GMV by intracranial volume, to adjust for variations in head size. We compared GMR between PD and HD patients in the cross-sectional analysis and the annual change in GMR (AC-GMR) in the longitudinal analysis. In the cross-sectional analysis, age- and sex-adjusted GMR was significantly lower in PD than HD patients [least square mean (LSM): 39.2% vs. 40.0%, P = 0.018]. AC-GMR was significantly greater in PD than HD patients and this difference remained significant even after adjustment for potential confounding factors (LSM: −0.68 vs. −0.28 percentage-points/year, P = 0.011). In conclusion, the present study demonstrated a more rapid progression of brain atrophy in PD patients compared with HD patients. [Figure not available: see fulltext.].

DOI： 10.1038/s41440-023-01530-5

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記述言語：英語   出版者・発行元：(一社)日本動脈硬化学会  

記述言語：英語   出版者・発行元：(一社)日本骨代謝学会  

記述言語：英語   出版者・発行元：CEN Case Reports  

DOI： 10.1007/s13730-023-00793-8

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出版者・発行元：日本メディカルセンター  

DOI： 10.19020/cd.0000002866

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記述言語：英語   出版者・発行元：Arteriosclerosis, Thrombosis, and Vascular Biology  

BACKGROUND: Hyponatremia, frequently observed in patients with chronic kidney disease, is associated with increased cardiovascular morbidity and mortality. Hyponatremia or low osmolality induces oxidative stress and cell death, both of which accelerate vascular calcification (VC), a critical phenotype in patients with chronic kidney disease. Whether hyponatremia or low osmolality plays a role in the pathogenesis of VC is unknown. METHODS: Human vascular smooth muscle cells (VSMCs) and mouse aortic rings were cultured in various osmotic conditions and calcifying medium supplemented with high calcium and phosphate. The effects of low osmolality on phenotypic change and oxidative stress in the cultured VSMCs were examined. Microarray analysis was conducted to determine the main signaling pathway of osmolality-related VC. The transcellular sodium and calcium ions flux across the VSMCs were visualized by live imaging. Furthermore, the effect of osmolality on calciprotein particles (CPPs) was investigated. Associations between arterial intimal calcification and hyponatremia or low osmolality were examined by a cross-sectional study using human autopsy specimens obtained in the Hisayama Study. RESULTS: Low osmolality exacerbated calcification of the ECM (extracellular matrix) of cultured VSMCs and mouse aortic rings. Oxidative stress and osteogenic differentiation of VSMCs were identified as the underlying mechanisms responsible for low osmolality-induced VC. Microarray analysis showed that low osmolality activated the Rac1 (Ras-related C3 botulinum toxin substrate 1)-Akt pathway and reduced NCX1 (Na-Ca exchanger 1) expression. Live imaging showed synchronic calcium ion efflux and sodium ion influx via NCX1 when extracellular sodium ion concentrations were increased. An NCX1 inhibitor promoted calcifying media-induced VC by reducing calcium ion efflux. Furthermore, low osmolality accelerated the generation and maturation steps of CPPs. The cross-sectional study of human autopsy specimens showed that hyponatremia and low osmolality were associated with a greater area of arterial intimal calcification. CONCLUSIONS: Hyponatremia and low osmolality promote VC through multiple cellular processes, including the Rac1-Akt pathway activation.

DOI： 10.1161/ATVBAHA.123.320069

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記述言語：英語   出版者・発行元：一般社団法人 日本動脈硬化学会  

DOI： 10.5551/jat.ed234

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Clinical and Experimental Nephrology  

Background: Angiotensin II receptor blockers (ARBs) reportedly reduce the risk of developing bone fractures; however, this association remains unclear among patients with chronic kidney disease (CKD). Methods: This was a cross-sectional study of 3380 CKD patients enrolled in the Fukuoka Kidney disease Registry Study, a multicenter prospective observational cohort study of non-dialysis-dependent CKD patients. The patients were divided into two groups, those taking ARBs and those who were not. Logistic regression models were used to examine the association between ARBs and bone fracture. Results: Approximately 67.0% of the participants were on ARBs, and 6.3% had a history of bone fracture. The history of bone fracture was significantly lower in patients with prescribed ARB and remained significant even after multivariable adjustment (odds ratio, 0.68; 95% confidence interval, 0.51–0.93). Other antihypertensive drugs, such as thiazide diuretics, which were reportedly helpful in preventing fractures, did not alter the bone fracture history and did not change among ARB users and non-users. Conclusions: The present study showed that administering ARB was significantly associated with a lower frequency of bone fracture history.

DOI： 10.1007/s10157-023-02385-3

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記述言語：英語   出版者・発行元：(一社)日本腎臓学会  

慢性腎臓病(CKD)患者における降圧剤処方と骨折歴の関係を明らかにするため、福岡腎臓病データベース研究に登録されたCKD患者3380例(男性56.2%、平均64.9歳)を対象とする横断研究を実施した。6.3%の患者に骨折歴があった。平均推算糸球体濾過量は43.0mL/分/1.73m2であった。薬物療法に関して、患者の67.0%がアンジオテンシンII受容体拮抗薬(ARB)で治療され、9.2%はアンジオテンシン変換酵素阻害薬(ACEI)で治療された。骨折歴はARB処方患者で有意に少なく、多変量で調整後も有意であった。ACEIでは有意な相違は観察されなかったが、ARBとACEIの併用はARB単独使用よりも少ない骨折歴と関連した。

記述言語：英語   出版者・発行元：Scientific Reports  

Peritoneal calcification is a prominent feature of the later stage of encapsulating peritoneal sclerosis (EPS) in patients undergoing long-term peritoneal dialysis (PD). However, the pathogenesis and preventive strategy for peritoneal calcification remain unclear. Peritoneum samples from EPS patients were examined histologically. Peritoneal calcification was induced in mice by feeding with an adenine-containing diet combined with intraperitoneal administration of lipopolysaccharide and a calcifying solution containing high calcium and phosphate. Excised mouse peritoneum, human mesothelial cells (MeT5A), and mouse embryonic fibroblasts (MEFs) were cultured in calcifying medium. Immunohistochemistry confirmed the appearance of osteoblastic differentiation-marker-positive cells in the visceral peritoneum from EPS patients. Intraperitoneal administration of magnesium suppressed peritoneal fibrosis and calcification in mice. Calcifying medium increased the calcification of cultured mouse peritoneum, which was prevented by magnesium. Calcification of the extracellular matrix was accelerated in Met5A cells and MEFs treated with calcification medium. Calcifying medium also upregulated osteoblastic differentiation markers in MeT5A cells and induced apoptosis in MEFs. Conversely, magnesium supplementation mitigated extracellular matrix calcification and phenotypic transdifferentiation and apoptosis caused by calcifying conditions in cultured MeT5A cells and MEFs. Phosphate loading contributes to the progression of EPS through peritoneal calcification and fibrosis, which can be prevented by magnesium supplementation.

DOI： 10.1038/s41598-023-43657-y

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出版者・発行元：東京医学社  

DOI： 10.24479/kd.0000000874

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：(一社)日本臨床検査医学会  

アルブミン濃度の測定にブロモクレゾールパープル(BCP)法を使用して構築された従来の式では精度に問題があるため、BCP改良法を用いる新たなカルシウム(Ca)推定式を構築した。当院で2014年1月～2017年10月に得ていた20歳以上の患者706名の血液検査値(pH、Ca、イオン化Ca(iCa)、アルブミン)を利用し、3種の推定式を構築した。式1はiCaを直接推定するもの、式2はpH7.4へ補正したiCaを推定するもの、式3はpH7.4へ補正したiCaを指標として評価するもの、とした。構築した式の検証を、当院の血液透析患者50名(男性58%、平均62.2±11.5歳)で行ったところ、補正前のCa値および式1では、iCaまたはpH7.4へ補正したiCaよりも低Ca血症に分類されやすい傾向が認められた。また比較に用いたPayneの式およびKidney Disease Outcomes Quality Initiativeのformula 2では高Ca血症に分類されやすい傾向が認められた。算出した重み付けカッパ係数から判断すると、式3は補正Ca値としてCa状態の評価に最も適していた。よって式3が最も有用であると考えられた。

記述言語：英語   出版者・発行元：一般社団法人 日本動脈硬化学会  

Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Multiple factors account for the increased incidence of cardiovascular morbidity and mortality in patients with CKD. Traditional risk factors for atherosclerosis and arteriosclerosis, including age, hypertension, dyslipidemia, diabetes mellitus, and smoking, are also risk factors for CKD. Non-traditional risk factors specific for CKD are also involved in CVD pathogenesis in patients with CKD. Recently, CKD–mineral and bone disorder (CKD– MBD) has emerged as a key player in CVD pathogenesis in the context of CKD. CKD–MBD manifests as hypocalcemia and hyperphosphatemia in the later stages of CKD; however, it initially develops much earlier in disease course. The initial step in CKD–MBD involves decreased phosphate excretion in the urine, followed by increased circulating concentrations of fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH), which increase urinary phosphate excretion. Simultaneously, the serum calcitriol concentration decreases as a result of FGF23 elevation. Importantly, FGF23 and PTH cause left ventricular hypertrophy, arrhythmia, and cardiovascular calcification. More recently, calciprotein particles, which are nanoparticles composed of calcium, phosphate, and fetuin-A, among other components, have been reported to cause inflammation, cardiovascular calcification, and other clinically relevant outcomes. CKD–MBD has become one of the critical therapeutic targets for the prevention of cardiovascular events and is another link between cardiology and nephrology. In this review, we describe the role of CKD–MBD in the pathogenesis of cardiovascular disorders and present the current treatment strategies for CKD–MBD.

DOI： 10.5551/jat.rv22006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Therapeutic Apheresis and Dialysis  

Introduction: The geriatric nutritional risk index (GNRI) is a widely used tool for nutritional assessment in patients receiving hemodialysis. The simplification of the GNRI calculation would be more useful for easier screening of malnutrition and for providing an intuitive stratification of mortality risk. Methods: We retrospectively evaluated 218 Japanese patients receiving maintenance hemodialysis at two hemodialysis centers. The primary outcome was all-cause mortality. The main exposure was a simplified GNRI (sGNRI) calculated as follows: sGNRI = serum albumin (g/dL) + 0.1 × body mass index (kg/m2). Results: During the median 4.4-year follow-up, 56 patients died. Multivariable-adjusted Cox proportional hazard risk models showed that patients with a lower sGNRI showed a significantly increased mortality risk. No significant difference was observed between the original GNRI and sGNRI regarding mortality predictability. Conclusion: sGNRI is as useful as the original GNRI for screening for malnutrition and stratifying hemodialysis patients at increased mortality risk.

DOI： 10.1111/1744-9987.13908

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記述言語：英語   出版者・発行元：John Wiley & Sons Australia, Ltd  

維持血液透析(HD)患者の低栄養状態をスクリーニングし、死亡リスクを直観的に層別化することを目的とした高齢者栄養リスク指数(GNRI)の有用性をより向上させるため、GNRIの簡略化を試みその性能を調べる後ろ向き観察研究を施行した。2つのHDセンターで維持HDを受けていた日本人患者218名(男性131名、年齢中央値65歳)を後ろ向きに評価した。オリジナルのGNRIでは体重/理想体重の比を計算する必要があり、式中に現れる係数も小数であって煩雑であるが、その比の代わりにBMIを採用し、BMI(kg/m2)の10分の1の値を血清アルブミン値(g/dL)と加算するだけで計算可能な簡易式GNRIを考案した。主要評価項目は全死因死亡とした。経過観察期間中(中央値4.4年間)に56名の患者が死亡していた。多変量調整済Cox比例ハザードリスクモデルでの解析の結果、簡易式GNRIが低値である患者では死亡リスクが有意に増大していることが示された。死亡予測性に関し、オリジナルのGNRIと簡易式GNRIの間に有意差は観察されなかった。HD患者を対象に低栄養状態をスクリーニングし死亡リスクが高い状態にある患者を層別する目的において、簡易式GNRIはオリジナルのGNRIと同程度に有用なものとなった。

記述言語：英語   出版者・発行元：Frontiers in Cardiovascular Medicine  

Background: Patients with chronic kidney disease (CKD) have a high risk of left ventricular hypertrophy (LVH). Fibroblast growth factor 23 (FGF23) and indoxyl sulfate (IS) are associated with LVH in patients with CKD, but the interactions between these molecules remain unknown. We investigated whether IS contributes to LVH associated with FGF23 in cultured cardiomyocytes and CKD mice. Methods and results: In cultured rat cardiac myoblast H9c2 cells incubated with IS, mRNA levels of the LVH markers atrial natriuretic factor, brain natriuretic peptide, and β-myosin heavy chain were significantly upregulated. Levels of mRNA of the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), which regulates FGF23 O-glycosylation, and FGF23 were also upregulated in H9c2 cells. Intact FGF23 protein expression and fibroblast growth factor receptor 4 (FGFR4) phosphorylation were increased in cell lysates by IS administration. In C57BL/6J mice with heminephrectomy, IS promoted LVH, whereas the inhibition of FGFR4 significantly reduced heart weight and left ventricular wall thickness in IS-treated groups. While there was no significant difference in serum FGF23 concentrations, cardiac FGF23 protein expression was markedly increased in IS-injected mice. GALNT3, hypoxia-inducible factor 1 alpha, and FGF23 protein expression was induced in H9c2 cells by IS treatment and suppressed by the inhibition of Aryl hydrocarbon receptor which is the receptor for IS. Conclusion: This study suggests that IS increases FGF23 protein expression via an increase in GALNT3 and hypoxia-inducible factor 1 alpha expression, and activates FGF23-FGFR4 signaling in cardiomyocytes, leading to LVH.

DOI： 10.3389/fcvm.2023.990422

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Clinical and Experimental Nephrology  

Background: Constipation is a common complication in patients with chronic kidney disease (CKD) and is involved in the pathogenesis of dysbiosis and progression of CKD. However, little is known about its association with disorders of the bone–cardiovascular axis in patients with CKD. Methods: We performed a cross-sectional analysis of 3878 patients with CKD using the baseline dataset of the Fukuoka Kidney disease Registry study, as a multicenter, prospective cohort study of pre-dialysis CKD patients. The main exposure of interest was constipation defined as use of at least one type of laxative. The main outcomes were the histories of bone fractures and cardiovascular diseases (CVDs) as manifestations of disorders of the bone–cardiovascular axis. Results: The prevalences of laxative use and histories of bone fractures and CVDs increased as kidney function declined. Among the 3878 patients, 532 (13.7%) patients used laxatives, 235 (6.1%) patients had prior bone fractures, and 1001 (25.8%) patients had prior CVDs. Histories of bone fractures and CVDs were significantly more prevalent among laxative users (P < 0.05). Multivariable-adjusted logistic regression analysis revealed that patients with laxatives had a significantly higher odds ratios for histories of bone fractures and CVDs than those without laxatives [adjusted odds ratios (95% confidence intervals) 1.67 (1.20–2.31) and 1.70 (1.30–2.22), respectively, P < 0.05]. Conclusions: These results suggest that constipation indicated by laxative use is associated with increased prevalences of historical bone fractures and CVDs in pre-dialysis patients with CKD.

DOI： 10.1007/s10157-022-02289-8

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記述言語：英語   出版者・発行元：(一社)日本腎臓学会  

透析治療導入には至っていない慢性腎臓病(CKD)患者において、便秘の存在が骨折および心血管疾患の病歴の増加と関連しているか調べた。非透析CKD患者を対象とした多施設共同の前向きコホート研究である福岡腎臓病データベース研究からベースライン時点のデータセットを取得し、3878名を横断解析した。緩下剤を使用していた患者は532名(13.7%)(男性56.8%、年齢中央値76歳)おり、残り3346名(男性55.6%、年齢中央値66歳)は使用していなかった。腎機能が低下するにつれ、緩下剤使用の陽性率、骨折の受傷歴、心血管疾患の病歴はいずれも増高していた。骨折歴の陽性率は、緩下剤使用集団で12.0%、非使用集団で5.1%であった(P<0.001)。心血管疾患歴の陽性率は上記と同順で46.4%と22.5%であった(P<0.001)。多変量調整を行うロジスティック回帰分析の結果、緩下剤使用患者では骨折歴陽性のオッズ比が1.7(95%CI 1.2～2.3)、心血管疾患歴陽性のオッズ比は1.7(95%CI 1.3～2.2)と、いずれも有意に上昇していた。こうした結果から、非透析CKD患者では、緩下剤使用という情報が指し示すところの便秘の存在が、過去に骨折および心血管疾患を経験していた履歴の陽性率上昇と関連していることが示唆された。

記述言語：英語   出版者・発行元：Therapeutic Apheresis and Dialysis  

DOI： 10.1111/1744-9987.13889

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記述言語：英語   出版者・発行元：Japanese Society of Laboratory Medicine  

  Although the serum calcium concentration is affected by the serum albumin concentration and requires use of
a formula, previous formulas were constructed using the bromocresol green (BCG) method, which has problems
with accuracy. In this study, we constructed a new calcium formula using a modified bromocresol purple method,
which overcame the limitations of the BCG method. The new formulas were constructed with the pH, ionized
calcium (iCa), calcium, and albumin values of 706 patients. Sensitivity, specificity, and weighted kappa coefficient
were evaluated with the values of 50 hemodialysis patients. We developed three formulas: to estimate iCa
directly (Formula 1), to estimate iCa corrected to pH 7.4 (Formula 2), and to evaluate iCa corrected to pH 7.4
as an index (Formula 3). Using hemodialysis patients for validation, Pre-correction calcium and Formula 1 were
tended to be classified as hypocalcemia than iCa or iCa corrected to pH 7.4, while Payne's formula and Kidney
Disease Outcomes Quality Initiative's formula 2 were tended to be classified as hypercalcemia. Based on the
weighted kappa coefficient, Formula 3 as corrected calcium was the best for assessment of calcium conditions.
Since the serum calcium is widely used in daily practice, Formula 3 may be the most useful.

DOI： 10.51041/lmi.2.2_19

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Clinical and Experimental Nephrology  

Background: High serum alkaline phosphatase (ALP) levels are associated with excess all-cause and cardiovascular mortality in patients undergoing hemodialysis (HD). However, the long-term relationship between serum ALP levels and infection-related mortality remains unclear. Methods: A total of 3502 maintenance HD patients were registered in the Q-Cohort Study, an observational cohort study in Japan. The primary outcome was infection-related mortality during a 10-year follow-up period. The covariate of interest was serum ALP levels at baseline. The association between serum ALP levels and infection-related mortality was calculated using a Cox proportional hazards model and a Fine–Gray subdistribution hazards model with non-infection-related death as a competing risk. Results: During the follow-up period, 446 patients died of infection. According to their baseline serum ALP levels, the patients were categorized into sex-specific quartiles (Q1–Q4). Compared with patients in the lowest serum ALP quartile (Q1), those in the highest quartile (Q4) had a significantly higher multivariable-adjusted hazard ratio (HR) of 1.70 [95% confidence interval (CI) 1.24–2.32] for infection-related mortality. Furthermore, the HR for every 50 U/L increase in serum ALP levels was 1.24 (95% CI 1.12–1.36) for infection-related mortality. These associations remained consistent in the competing risk model: subdistribution HR, 1.47; 95% CI 1.07–2.03 for Q4 compared with Q1. Conclusion: Higher serum ALP levels were significantly associated with a higher risk of infection-related mortality in patients undergoing HD.

DOI： 10.1007/s10157-022-02255-4

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記述言語：英語   出版者・発行元：(一社)日本腎臓学会  

日本人血液透析(HD)患者における、血清アルカリホスファターゼ(ALP)濃度と感染関連死亡率との関係について検討した。観察コホート研究であるQコホート研究に登録された維持HD患者3502例(男性2076例、女性1426例、年齢中央値64.2歳)の10年間のフォローアップデータを用い、主要評価項目として当該期間中の感染関連死亡率、関心共変量をベースラインでの血清ALP濃度として検討した。患者群をALP濃度に従い最低レベルの第1四分位(Q1)から最高レベルの第4四分位群(Q4)まで性別毎に分割し、血清ALP濃度と感染関連死亡率との関連性をCox比例ハザードモデルとFine-Gray部分分布ハザードモデルを用いて検討した。経過観察期間中446例が感染で死亡し、10年間生存率は血清ALP増加とともに減少した。Q1群に比べてQ4群の感染関連死亡率の多変数調整ハザード比(HR)は1.70と有意に高かった。また変数調整後モデルにおける、血清ALP濃度50U/L増加毎の感染関連死亡率HRは1.24であった。HD維持療法施行患者における血清ALP高値は、感染関連および全死因死亡のリスクを増加させた。HD維持療法施行患者における血清ALP高値は、感染関連および全死因死亡のリスクを増加させた。

記述言語：英語   出版者・発行元：一般社団法人 日本内科学会  

DOI： 10.2169/internalmedicine.0319-22

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記述言語：英語   出版者・発行元：Clinical and Experimental Nephrology  

Chronic kidney disease–mineral and bone disorder (CKD–MBD) is a systemic disorder that affects multiple organs and systems and increases the risk of morbidity and mortality in patients with CKD, especially those receiving dialysis therapy. CKD–MBD is highly prevalent in CKD patients, and its treatment is gaining attention from healthcare providers who manage these patients. Additional important pathologies often observed in CKD patients are chronic inflammation and malnutrition/protein-energy wasting (PEW). These two pathologies coexist to form a vicious cycle that accelerates the progression of various other pathologies in CKD patients. This concept is integrated into the term “malnutrition–inflammation–atherosclerosis syndrome” or “malnutrition–inflammation complex syndrome (MICS)”. Recent basic and clinical studies have shown that CKD–MBD directly induces inflammation as well as malnutrition/PEW. Indeed, higher circulating levels of inorganic phosphate, fibroblast growth factor 23, parathyroid hormone, and calciprotein particles, as markers for critical components and effectors of CKD–MBD, were shown to directly induce inflammatory responses, thereby leading to malnutrition/PEW, cardiovascular diseases, and clinically relevant complications. In this short review, we discuss the close interplay between CKD–MBD and MICS and emphasize the significance of simultaneous control of these two seemingly distinct pathologies in patients with CKD, especially those receiving dialysis therapy, for better management of the CKD/hemodialysis population.

DOI： 10.1007/s10157-022-02216-x

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記述言語：英語   出版者・発行元：一般社団法人 日本動脈硬化学会  

Aim: Elevated serum alkaline phosphatase (ALP) levels have been associated with increased risks of all-cause and cardiovascular mortality in patients receiving hemodialysis. However, little is known about the impact of serum ALP levels on the development of stroke, such as brain hemorrhage and infarction. Methods: A total of 3,497 patients receiving maintenance hemodialysis registered in the multicenter observational Q-Cohort Study were analyzed. The primary outcomes were the incidences of brain hemorrhage and infarction. The covariate of interest was serum ALP levels. Patients were divided into tertiles based on their serum ALP levels (U/L) at baseline (T1, ＜69.3; T2, 69.3–98.4; T3, ＞98.4). The risks of brain hemorrhage, brain infarction, and composite stroke were estimated using Cox proportional hazards models and competing risk models with all-cause death as a competing risk. Results: A total of 89 patients developed brain hemorrhage and 195 patients developed brain infarction during the 4-year follow-up period. The risk of brain hemorrhage in the highest tertile (T3) was significantly higher than that in the lowest tertile (T1) (multivariable-adjusted hazard ratio [95% confidence interval], 1.93 [1.12– 3.35], subdistribution hazard ratio, 1.91 [1.10–3.30]). However, there was no significant association between serum ALP levels and the risk of brain infarction or composite stroke. Conclusions: Higher serum ALP levels are associated with an increased risk of brain hemorrhage, but not brain infarction, in patients receiving maintenance hemodialysis. High serum ALP level is thus an important risk factor for brain hemorrhage in hemodialysis patients.

DOI： 10.5551/jat.62885

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Calcified Tissue International  

Cellular phosphate transporters play critical roles in the pathogenesis of vascular calcification (VC) in chronic kidney disease (CKD). However, the mechanistic link between VC and xenotropic and polytropic receptor 1 (XPR1), a newly identified phosphate exporter, remains unknown. We developed a new mouse model with rapidly progressive uremic VC in C57BL/6 mice and examined the roles of XPR1. The combination of surgical heminephrectomy and 8 weeks of feeding a customized warfarin and adenine-based diet induced extensive aortic VC in almost all mice. The XPR1 mRNA level in the aorta of CKD mice was significantly lower than those in control mice as early as week 2, when there was no apparent VC, which progressively declined thereafter. Dietary phosphate restriction increased XPR1 mRNA expression in the aorta but reduced aortic VC in CKD mice. In cultured vascular smooth muscle cells (VSMCs), a calcifying medium supplemented with high phosphate and calcium did not affect XPR1 mRNA expression. The XPR1 mRNA expression in cultured VCMCs was also unaffected by administration of indoxyl sulfate or calcitriol deficiency but was decreased by 1–34 parathyroid hormone or fibroblast growth factor 23 supplementation. Furthermore, XPR1 deletion in the cultured VSMCs exacerbated calcification of the extracellular matrix as well as the osteogenic phenotypic switch under the condition of calcifying medium. Our data suggest that XPR1 plays protective roles in the pathogenesis of VC and its decrease in the aorta may contribute to the progression of VC in CKD.

DOI： 10.1007/s00223-022-00947-3

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記述言語：英語   出版者・発行元：(一社)日本動脈硬化学会  

慢性血液透析患者3497例(男性2073例、女性1424例)を対象に、血清アルカリホスファターゼ(ALP)値が脳出血および脳梗塞に及ぼす影響について検討した。対象は慢性血液透析患者における総死亡、心血管疾患、骨折の危険因子を評価する観察研究(Qコホート研究)の登録患者で、主要評価項目は脳出血および脳梗塞の発症とした。患者を血清ALPの3分位数に基づき、69.3U/L未満の第1三分位群(女性32.6%、年齢中央値60.3歳)、69.3～98.4U/Lの第2三分位群(女性38.5%、年齢中央値65.3歳)、第98.4U/L以上の3三分位群(女性51.0%、年齢中央値66.3歳)の3群に分類した。患者背景はALP高値群の方が高齢で、女性が多く、透析期間が長かった(いずれもP<0.001)。平均追跡期間は4年で、脳出血は89例、脳梗塞は195例で発生した。多変量解析で第1三分位群と比較した第3三分位群における脳出血発症のハザード比は1.93(95%CI:1.12～3.35、P=0.01)であった。ところが脳梗塞とALP値の高値の間に有意な関連はなかった(HR:1.06、95%CI:0.72～1.58、P=0.79)。

記述言語：英語   出版者・発行元：Clinical and Experimental Nephrology  

DOI： 10.1007/s10157-021-02175-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Kidney Medicine  

Rationale & Objective: Malnutrition-inflammation complex syndrome (MICS) is common in patients receiving hemodialysis and increases the risks of morbidity and mortality. However, few studies have examined the overall impact of MICS on disorders of the bone-cardiovascular axis. Study Design: Prospective, multicenter, observational cohort study. Setting & Participants: A total of 3,030 patients receiving maintenance hemodialysis registered in the Q-Cohort Study. Predictors: A newly developed score for MICS composed of elements chosen from 8 baseline parameters related to nutrition and inflammation by bootstrap resampling, multivariable-adjusted Cox proportional hazard risk analysis for all-cause mortality, and the risk prediction rule. β-coefficients of each element analyzed in the multivariable-adjusted model were used for the creation of the MICS score. Outcomes: Bone fractures, cardiovascular disease events, and the composite outcome of bone fractures and cardiovascular disease events. Analytical Approach: Cox proportional hazard regression and Fine-Gray proportional subdistribution hazards regression. Results: During a median follow-up of 4 years, 140 patients developed bone fractures and 539 developed cardiovascular disease events. Age; serum levels of creatinine, albumin, and C-reactive protein; and body mass index were selected for the creation of the MICS score. The median (IQR) MICS score was 196 (181-212). The multivariable-adjusted Cox proportional hazard risk model and the competing risk model showed that a higher MICS score was incrementally associated with elevated risks of bone fractures, cardiovascular disease events, and the composite outcome; hazard risks (95% CIs) of fractures, cardiovascular disease events, and the composite outcome for each 10-point increase in the MICS score were 1.18 (1.01-1.38), 1.16 (1.07-1.26), and 1.15 (1.07-1.24), respectively. Limitations: One-time measurement of the parameters used for the creation of the MICS score. Conclusions: Malnutrition and inflammation represented by the MICS score were associated with increased risks of bone-cardiovascular axis disorders in patients receiving maintenance hemodialysis.

DOI： 10.1016/j.xkme.2022.100408

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記述言語：英語   出版者・発行元：Scientific Reports  

Women have a longer life expectancy than men in the general population. However, it has remained unclear whether this advantage is maintained in patients undergoing maintenance hemodialysis. The aim of this study was to compare the risk of mortality, especially infection-related mortality, between male and female hemodialysis patients. A total of 3065 Japanese hemodialysis patients aged ≥ 18 years old were followed up for 10 years. The primary outcomes were all-cause and infection-related mortality. The associations between sex and these outcomes were examined using Cox proportional hazards models. During the median follow-up of 8.8 years, 1498 patients died of any cause, 387 of whom died of infection. Compared with men, the multivariable-adjusted hazard ratios (95% confidence interval) for all-cause and infection-related mortality in women were 0.51 (0.45–0.58, P < 0.05) and 0.36 (0.27–0.47, P < 0.05), respectively. These findings remained significant even when propensity score-matching or inverse probability of treatment weighting adjustment methods were employed. Furthermore, even when the non-infection-related mortality was considered a competing risk, the infection-related mortality rate in women was still significantly lower than that in men. Regarding all-cause and infection-related deaths, women have a survival advantage compared with men among Japanese patients undergoing maintenance hemodialysis.

DOI： 10.1038/s41598-021-03551-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Clinical and Experimental Nephrology  

Background: Protein-energy wasting (PEW) is a risk factor for mortality in patients undergoing hemodialysis. Recently, a nutritional risk index for Japanese hemodialysis patients (NRI-JH) has been proposed as a surrogate index of PEW. However, no study has determined the association of the NRI-JH with long-term mortality in patients undergoing hemodialysis. Furthermore, the validity of the NRI-JH has not been confirmed. Methods: In total, 3046 patients undergoing hemodialysis and registered in the Q-Cohort Study were followed up for 10 years. The NRI-JH was calculated on the basis of body mass index and serum levels of albumin, total cholesterol, and creatinine. The patients were divided into four groups according to the NRI-JH scores: 0–3 (G1, n = 1343), 4–7 (G2, n = 1136), 8–10 (G3, n = 321), and 11–13 (G4, n = 246). We examined the association between the NRI-JH and the 4-year and 10-year risks of all-cause, cardiovascular, and infection-related deaths using the Cox proportional hazards model. Results: During the follow-up period, 647 patients died during the first 4 years, and 1503 patients died within 10 years. The 4-year prognosis was analyzed and compared with the lowest NRI-JH score group. Multivariable-adjusted hazard ratios (95% confidence intervals) for all-cause death were 1.93 (1.57–2.38), 2.68 (2.05–3.50), and 3.16 (2.40–4.16) in the G2, G3, and G4 groups, respectively. Similarly, a higher NRI-JH score was associated with an increased risk of cardiovascular and infection-related deaths. Conclusion: A higher NRI-JH score was associated with an increased risk of long-term mortality in patients undergoing maintenance hemodialysis. Trial registration: The study protocol was registered in the University Hospital Medical Information Network (UMIN) clinical trial registry (UMIN ID: 000000556).

DOI： 10.1007/s10157-021-02124-6

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記述言語：英語   出版者・発行元：(一社)日本腎臓学会  

日本人血液透析患者の栄養リスク指数(NRI-JH)と長期死亡率との関連性およびNRI-JHの妥当性を検討した。Qコホート研究に登録された血液透析患者3046例(平均64.3歳)を10年間追跡調査した。患者をNRI-JHのスコアに従って、0～3(G1群、1343例)、4～7(G2群、1136例)、8～10(G3群、321例)、11～13(G4群、246例)に分類した。追跡期間中、最初の4年間に647例が死亡し、10年以内に1503例が死亡した。全死因死亡の多変量調整後ハザード比(95%CI)は、G2、G3、G4群でそれぞれ1.93(1.57～2.38)、2.68(2.05～3.50)、3.16(2.40～4.16)であった。同様に、NRI-JHスコアの高さは、心血管死亡および感染症関連死亡のリスク上昇と関連していた。以上より、NRI-JHスコアが高いほど、維持血液透析を受けている患者における長期死亡のリスクが高いことが示された。

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

開催年月日： 2020年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：福岡(WEB開催)   国名：日本国  

開催年月日： 2020年5月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：ＷEB上   国名：日本国  

開催年月日： 2019年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：徳島   国名：日本国  

開催年月日： 2019年9月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2019年6月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：愛知県名古屋市 名古屋国際会議場   国名：日本国  

開催年月日： 2019年3月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

開催年月日： 2019年2月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2018年9月

記述言語：英語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2018年6月 - 2018年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：パシフィコ横浜   国名：日本国  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

＜文献概要＞骨は,骨形成と骨吸収の協働作業が絶えず行われ,その成長と発達過程,さまざまな内部環境に応じて,モデリング,リモデリング,ミニモデリングによって構造と機能が終生ダイナミックに変化する臓器である.骨形成と骨吸収を基盤とする骨代謝には,骨芽細胞,骨細胞,破骨細胞,その他の造血幹細胞や間質細胞などの多くの細胞が複雑に関与する.骨代謝の過程において,カルシウムやリンはもちろん,骨基質に埋め込まれた蛋白質,増殖因子,サイトカイン,extracellular vesicle(EV),microRNA,そして近年血管石灰化との関わりで注目されているcalciprotein particles(CPPs)などのさまざまな物質が骨から血中に流出する.これらの骨から放出された物質が遠隔臓器に作用して臓器機能に影響を及ぼす.一方,他臓器由来の液性因子,神経性調節,力学負荷も骨代謝に影響する.このように,骨は他臓器とネットワークを形成し,正常な骨代謝が営まれることは他臓器の健康にも重要である.

記述言語：英語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：英語   出版者・発行元：(一社)日本動脈硬化学会  

記述言語：日本語   出版者・発行元：(株)東京医学社  

＜文献概要＞はじめに　慢性腎臓病に伴う骨・ミネラル代謝異常(chronic kidney disease-mineral and bone disorder:CKD-MBD)は,慢性腎臓病(chronic kidney disease:CKD)の進行に伴ってみられる骨およびミネラル代謝異常で,心血管臓器をはじめとしたさまざまな臓器に障害をきたす全身性疾患である。カルシウム(Ca)は骨の主要な構成成分であるのみでなく,細胞内Ca濃度の変化(Caシグナリング)により細胞機能を制御するなど,生命維持に欠かせないミネラルであり,その血中濃度は厳密に調整されている。一方で,CKDではビタミンD活性化障害,二次性副甲状腺機能亢進症(secondary hyperparathyroidism:SHPT)によるCa代謝異常をきたし,Ca値の変化は患者予後に影響する。本稿では,CKD患者における血中Ca値と患者予後の関係およびCaバランスを考慮したCa管理の方法について概説する。

記述言語：英語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：英語   出版者・発行元：(一社)日本動脈硬化学会  

記述言語：英語   出版者・発行元：John Wiley & Sons Australia, Ltd  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   出版者・発行元：九州人工透析研究会  

CKD-MBD(慢性腎臓病に伴う骨ミネラル代謝異常)の治療薬は過去30年間で非常に充実し、カルシプロテイン粒子(CPP)と線維芽細胞増殖因子23(FGF23)が注目され病態理解が深化した。1)FGF23とCPPを中心としたCKD-MBD診療の潮流、2)血清リン値の厳格管理時代の到来と次世代治療、3)CPPの管理による血管石灰化対策と合併症対策、4)低酸素誘導因子-プロリン水酸化酵素阻害薬の到来で明らかになるCKD-MBDと腎性貧血・鉄代謝のクロストーク、について概説した。

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   出版者・発行元：(公社)日本透析医会  

血管石灰化は慢性腎臓病(chronic kidney disease;CKD)患者の心血管合併症の原因として、極めて重要である。CKD患者は健常人と比べて便秘の頻度が高く、腸内細菌叢の乱れ(dysbiosis)を合併する率が高いことが報告されている。近年、dysbiosisに伴って血中のtrimethylamine-N-oxide(TMAO)が増加し、TMAOが動脈硬化を促進して心血管合併症の発症率を増加させることが基礎実験およびコホート研究によって実証された。我々はCKD患者の血管石灰化の一因に、dysbiosisに伴うTMAOの増加が関係しているという仮説を立てた。まず、アデニン腎症モデルをマウスに適応するためにアデニン含有餌の組成を改良し、CKDの進行に伴って6～8週間で高度の血管石灰化とサルコペニアを同時に発症するマウスモデルを完成させた。本モデルでは便硬度が上昇することも確認した。さらに、血中のTMAOやインドキシル硫酸などの尿毒素物質を測定するために、血液を採取した。培養血管平滑筋細胞を用いた実験系において、TMAOを負荷するとリンによる細胞外マトリックスの石灰化が促進されることを明らかにし、さらに、マウスから摘出した胸部大動脈をリング状に裁断して石灰化培地で培養した場合にも、TMAOを投与すると大動脈リングへの石灰沈着量が増加した。今後、今回開発したCKDモデルにおいて、血中のTMAOが増加していることを確認するとともに、下剤を投薬して便秘や腸内細菌叢の乱れを改善した場合に血中のTMAOの濃度が低下し、さらに血管石灰化の進行やサルコペニアの進展を抑制できるかどうかを検証する。(著者抄録)

記述言語：英語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：英語   出版者・発行元：(一社)日本腎臓学会  

記述言語：英語   出版者・発行元：(一社)日本腎臓学会  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：英語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

種別：大会・シンポジウム等 

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種別：大会・シンポジウム等 

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種別：大会・シンポジウム等 

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種別：大会・シンポジウム等 

参加者数：200

種別：査読等 

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