As previous studies have reported finding an association between hyperuricemia and the development of cardiovascular and chronic kidney disease, hyperuricemia is thought to be an independent risk ...factor for hypertension and diabetic mellitus. However, we have not been able to determine whether the use of xanthine oxidase inhibitors can reduce cardiovascular disease. The present study used the longitudinal data of the Fukushima Cohort Study to investigate the relationship between the use of xanthine oxidase inhibitors and cardiovascular events in patients with cardiovascular risks. During the 3-year period between 2012 and 2014, a total of 2724 subjects were enrolled in the study and followed. A total of 2501 subjects had hypertension, diabetic mellitus, dyslipidemia, or chronic kidney disease, and were identified as having cardiovascular risks. The effects of xanthine oxidase inhibitor use on the development of cardiovascular events was evaluated in these patients using a time to event analysis. During the observational periods (median 2.7 years), the incidence of cardiovascular events was 20.7 in subjects with xanthine oxidase inhibitor and 11.2 (/1000 person-years, respectively) in those without. Although a univariate Cox regression analysis showed that the risk of cardiovascular events was significantly higher in subjects administered xanthine oxidase inhibitors (HR = 1.87, 95% CI 1.19-2.94, p = 0.007), the risk was significantly lower in subjects administered a xanthine oxidase inhibitor after adjustment for covariates (HR = 0.48, 95% CI 0.26-0.91; p = 0.024) compared to those without. Xanthine oxidase inhibitor use was associated with reduced risk of cardiovascular disease in patients with cardiovascular risk factors.
A tandem catalyst composed of V2O5/TiO2 (anatase, 8.5 V nm−2) for preferential oxidation of C3H6 in copresence of CO and Cu/CeO2 for NOCO reaction showed comparable three-way catalytic activity with ...Rh/ZrO2.
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•V2O5/TiO2 (anatase, 8.5 V nm−2) preferentially oxidized C3H6 in copresence of CO.•A combination of V2O5/TiO2 and Cu/CeO2 showed comparable TWC activity as Rh/ZrO2.•Consumption of surface acetate intermediate is the key step for C3H6 oxidation to CO/CO2.•Brønsted acid promoted cleavage of CC bond of acetate intermediate.
For the design of a high-performance platinum group metal-free three-way catalyst, we propose a new C3H6-preferential oxidation (C3H6-PROX) catalyst under stoichiometric automobile exhaust gas (NOCOC3H6O2) using supported vanadia catalysts. Among various V2O5 supported catalysts, V2O5/TiO2 (anatase, coverage of around one monolayer) showed the best activity for C3H6-PROX with preferable formation of CO. The tandem catalyst combination using V2O5/TiO2 as the upstream C3H6-PROX catalyst and Cu/CeO2 as the downstream NOCO reaction catalyst showed comparable activity for NO reduction as a Rh/ZrO2 catalyst. The reaction mechanism of C3H6 oxidation was analyzed using in situ Infrared spectroscopy. The C3H6 oxidation progressed with the formation of surface acetate as an intermediate, and acetate consumption was the key step of C3H6 oxidation. It is suggested that the Brønsted acid promoted the cleavage of the CC bond of acetate, therefore, the number of Brønsted acid sites is one of the critical factors for the higher performance of C3H6-PROX catalysts.
Background
Serum potassium disorders, commonly observed in chronic kidney disease (CKD), are reportedly associated with higher mortality, but their impact on renal outcomes is still controversial.
...Methods
The present study used the longitudinal data of the Fukushima CKD cohort study to investigate the relationships between hypokalemia and hyperkalemia and adverse outcomes such as renal outcomes and all-cause mortality in Japanese patients with non-dialysis-dependent CKD. The study involved 1330 CKD patients followed-up for 2.8 years. The primary endpoint of the present study was a kidney event, defined as a combination of doubling of baseline serum creatinine and end-stage kidney disease.
Results
Hyperkalemia (≥ 5.0 mmol/L) was noted in 10.6% and hypokalemia (< 4.0 mmol/L) in 16.4% of the study population. Significant U-shaped associations were observed between potassium levels and both kidney events and all-cause mortality on univariate Cox regression analyses. After adjustment for covariates, both hypokalemia and hyperkalemia were significantly associated with an increased risk of kidney events, with the lowest risk at a serum potassium of 4.0–4.4 mmol/L. Compared with a reference level of 4.0–4.4 mmol/L, the adjusted hazard ratio for kidney events was 2.49 (1.33–4.66) for serum potassium < 4.0 mmol/L, 1.72 (1.00–2.96) for 4.5–4.9 mmol/L, and 2.16 (1.15–4.06) for ≥ 5.0 mmol/L. There was no significant association between serum potassium levels and mortality after multivariate adjustment.
Conclusion
Hypokalemia and hyperkalemia were associated with an increased risk of CKD progression, but not with mortality in Japanese patients with non-dialysis-dependent CKD.
A combination of two base-metal oxides in tandem configuration can realize three-way reaction without platinum group metals. For this purpose, catalysts for hydrocarbon preferential oxidation ...(HC-PROX) and for NO reduction by CO are required. For the design of HC-PROX catalysts, competitive oxidation of propene and CO on spinel-type MFe
2
O
4
(M = Co, Cu, Mg, Mn, Ni, Zn) was investigated. MnFe
2
O
4
preferentially oxidized propene in the co-presence of CO showing the best propene oxidation activity. Among the series of MFe
2
O
4
, the activity controlling factor was correlated to the M-O bond energy of the second metal oxides, and the preference for HC oxidation was dependent on the electronegativity of the second ion. A tandem catalyst using MnFe
2
O
4
for HC-PROX and CuCo
2
O
4
for NO-CO reaction showed TWC activity comparable to a Rh/CeO
2
.
Background
In patients with chronic kidney disease (CKD), dysbiosis in the gastrointestinal microbiome is thought to be associated with increased production of uremic toxins, such as indoxyl sulfate ...(IS) and
p-
cresyl sulfate (PCS). Sucroferric oxyhydroxide (SFO), an iron-based phosphate binder, may affect the gastrointestinal microbiome and the production of uremic toxins. We aimed to examine whether SFO administration affected distribution of gastrointestinal microbiome and serum uremic toxin levels in CKD patients undergoing hemodialysis.
Methods
In this single-center, open-label, interventional study, 18 maintenance hemodialysis patients with hyperphosphatemia were prescribed with SFO. We collected serum samples before and after 3 months of administration, and serum levels of IS and PCS were measured. A control group of 20 hemodialysis patients without SFO was evaluated. We evaluated gastrointestinal microbiome of patients pre- and post-SFO administration by 16S rDNA sequencing and bioinformatics analysis.
Results
Serum IS and PCS levels were significantly elevated after administration of SFO (IS before 2.52 ± 1.60 mg/dl vs. after 3.13 ± 1.51 mg/dl,
P
= 0.008; PCS before 2.32 ± 2.44 mg/dl vs. after 3.45 ± 2.11 mg/dl,
P
= 0.002), while serum IS and PCS levels did not change in the control group. Microbiome analysis in the SFO group showed no significant change in diversity and major components in phylum, class, order, family, gene, and species.
Conclusion
Administration of SFO increased the serum levels of IS and PCS with no change of major components of gastrointestinal microbiome.
Background
Inadequate blood pressure control is one of the important causes of chronic kidney disease (CKD), but only a limited number of reports have examined blood pressure control in Japanese ...patients with pre-dialysis CKD. Differences in blood pressure control due to underlying renal disease in pre-dialysis patients with CKD were investigated in the present study using the baseline data of the Fukushima CKD cohort study.
Methods
The study involved 1351 CKD patients, classified by underlying disease of primary renal disease, hypertensive nephropathy, diabetic nephropathy, other nephropathies, or unknown. Target blood pressure of CKD patients was defined as < 130/80 mmHg in patients under 75 years old with diabetes and/or proteinuria, and < 140/90 mmHg in other patients.
Results
The achievement rate of target systolic blood pressure was lower in the diabetic and hypertensive nephropathy groups than in the primary renal disease group (33.3%, 46.0% vs. 68.1%,
p
< 0.001). However, the number of antihypertensive medications increased in the diabetic and hypertensive nephropathy groups compared to the primary renal disease group (2.16, 2.04 vs. 1.55,
p
< 0.001). Inadequate blood pressure control was independently related to the underlying renal disease, with a significant difference between diabetic nephropathy and primary renal disease (odds ratio 3.19; 95% confidence interval, 2.16–4.69;
p
< 0.001).
Conclusion
This study showed that blood pressure control differs by the underlying renal disease. Blood pressure control was poor especially in diabetic nephropathy despite multidrug combination antihypertensive treatment. It is necessary to verify whether strict blood pressure control improves patients’ prognosis in diabetic nephropathy.
Objective Although an association between serum inorganic phosphorus levels and a poor prognosis has been noted in dialysis patients, these associations have been insufficiently reported in ...non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. This study attempted to determine the association between serum inorganic phosphorus levels and adverse outcomes in Japanese NDD-CKD patients. Methods We investigated the relationships between serum inorganic phosphorus levels and adverse outcomes, such as kidney events, cardiovascular events, and all-cause death, in Japanese NDD-CKD patients using longitudinal data from the Fukushima CKD Cohort Study with a median follow-up period of 2.8 years. The study evaluated 822 patients with NDD-CKD enrolled between June 2012 and July 2014. A kidney event was defined as a combination of doubling of the baseline serum creatinine or end-stage renal disease. Cox regression was performed to analyze the relationships of the quartile of the serum inorganic phosphorus with kidney events, cardiovascular events, and all-cause death. Results The frequency of kidney events per 1,000 person-years exhibited a U-shaped distribution based on serum inorganic phosphorus levels, with these levels not significantly associated with an increased risk of cardiovascular events and all-cause death. A multivariable Cox regression analysis showed an increased risk of kidney events for the highest quartile of the serum inorganic phosphorus levels (≥3.7 mg/dL) versus the second quartile (2.9-3.2 mg/dL, hazard ratio, 3.30; 95% confidence interval, 1.50-7.28; p=0.003). There were no significant associations between the serum calcium levels and adverse outcomes. Conclusion Serum inorganic phosphorus levels were associated with an increased risk of CKD progression in Japanese NDD-CKD patients.
BACKGROUND
Anti‐KANNO, a broadly reactive RBC alloantibody, is found among some Japanese pregnant women, but the genetic basis of the corresponding antigen remains unclear.
STUDY DESIGN AND METHODS
...We integrated a statistical approach to identify the coding gene for KANNO antigen by conducting a genome‐wide association study (GWAS) on four KANNO‐negative individuals and 415 healthy Japanese. We also applied whole‐exome sequencing to them and performed a replication study to confirm the identified genome variation using independent 14 KANNO‐negative individuals. A monoclonal antibody‐specific immobilization of erythrocyte antigens (MAIEA) assay was used to locate KANNO antigen on RBC‐specific membrane protein. In vivo and in vitro binding assays of anti‐KANNO were further applied to the cells expressing a candidate protein.
RESULTS
The GWAS revealed a genome‐wide significant association of chromosome 20p13 locus (p = 2.76E‐08; odds ratio > 1000 95% confidence interval = 48–23,674). The identified single‐nucleotide polymorphism located in an intronic region of the prion protein (PRNP) gene. Whole‐exome sequencing revealed a missense variant in the PRNP gene (rs1800014, E219K), which is in linkage disequilibrium with the single‐nucleotide polymorphism identified in the GWAS. All 18 KANNO‐negative individuals possessed the homozygous genotype of the missense variant. The MAIEA assay using anti‐KANNO and mouse antihuman prion protein showed a clear difference between KANNO‐positive and KANNO‐negative RBCs. Anti‐KANNO showed direct binding to CHO‐K1 cells expressing wild‐type PRNP but not to those expressing E219K PRNP.
CONCLUSION
We first identified the coding gene of the high‐frequency antigen KANNO located in PRNP and the missense variation (E219K) that affects the seropositivity of the KANNO antigen, which were confirmed by PRNP overexpressed cells.
Background
Mean corpuscular volume (MCV) and red cell distribution width (RDW), as well hemoglobin, are reported to be associated with mortality in various populations. However, associations between ...such hematological parameters and adverse outcomes in patients with CKD have not been sufficiently elucidated.
Methods
A total of 1,320 participants enrolled in the Fukushima CKD Cohort Study were examined to investigate associations between hematological parameters of anemia (MCV and RDW) and adverse outcomes, such as ESKD, all-cause death, and cardiovascular events, in patients with non-dialysis-dependent CKD. Baseline hematological parameters were grouped as follows: hemoglobin into 3 categories (< 11.0 g/dL, 11.0 ≤ − < 13.0 g/dL reference, and ≥ 13.0 g/dL); MCV into 5 categories (< 90 fL, ≥ 90 – < 94 fL reference, ≥ 94 − < 98 fL, ≥ 98 − < 102 fL, and ≥ 102 fL); and RDW into 2 categories (< 13.6% reference vs ≥ 13.6%).
Results
During the median observational period of 4.7 years, 120 patients developed ESKD, 160 developed cardiovascular events, and 122 died. Hemoglobin < 11 g/dL (hazard ratio HR 1.56, 95% confidence interval CI, 1.00–2.42), MCV < 90 fL (HR 2.01, 95% CI 1.14–3.54), and RDW ≥ 13.6% (HR 1.57, 95% CI 1.01–2.42) were significantly associated with higher risks of ESKD. Hemoglobin < 11 g/dL, MCV ≥ 98 fL, and RDW ≥ 13.6% were significantly associated with higher risks of all-cause death. No significant associations between hematological parameters and risk of cardiovascular events were confirmed.
Conclusion
In patients with non-dialysis-dependent CKD, MCV, RDW, and hemoglobin were associated with increased risks of ESKD and all-cause mortality.
The cholinergic system is involved in a broad spectrum of brain function, and its failure has been implicated in Alzheimer＇s disease. Acetylcholine transduces signals through muscarinic and nicotinic ...acetylcholine receptors, both of which influence synaptic plasticity and cognition. However, the mechanisms that relate the rapid gating of nicotinic acetylcholine receptors to persistent changes in brain function have remained elusive. Recent evidence indicates that nicotinic acetylcholine receptors activities affect synaptic morphology and density, which result in persistent rearrangements of neural connectivity. Further investigations of the relationships between nicotinic acetylcholine receptors and rearrangements of neural circuitry in the central nervous system may help understand the pathogenesis of Alzheimer＇s disease.
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