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Article ; Online: Association between trunk flexibility and renal flow pulsatility in middle-aged and older adults

Natsumi Nishitani / Keisei Kosaki / Masahiro Matsui / Takeshi Sugaya / Makoto Kuro-o / Chie Saito / Kunihiro Yamagata / Seiji Maeda

Experimental Gerontology, Vol 172, Iss , Pp 112060- (2023)

2023

Abstract: Background: Recent clinical studies have indicated that poor trunk flexibility is associated with arterial stiffness in the aged. Arterial stiffness leads to elevated renal flow pulsatility, which accelerates age-related renal dysfunction and damages. ... ...

Abstract	Background: Recent clinical studies have indicated that poor trunk flexibility is associated with arterial stiffness in the aged. Arterial stiffness leads to elevated renal flow pulsatility, which accelerates age-related renal dysfunction and damages. However, data indicating the potential link between flexibility fitness and renal flow pulsatility are lacking. This study examined the cross-sectional association between trunk flexibility and renal flow pulsatility in middle-aged and older adults. Methods: A total of 175 middle-aged and older adults (aged 63 ± 9 years) were included in this study. Sit-and-reach tests (SRT) were performed to assess their trunk flexibility. Using a Doppler ultrasound, renal pulsatility index (PI) and resistive index (RI) were measured as parameters of renal flow pulsatility. Results: The study found that, in middle-aged and older adults, the SRT score was an independent determinant of renal PI (β = −0.134, P = 0.027) and RI (β = −0.135, P = 0.027). In the one-way analysis of covariance (ANCOVA), the renal PI and RI in the older group with a lower SRT score were found to be significantly higher than those in the middle-aged group. Conclusions: Trunk flexibility is an independent determinant of renal flow pulsatility in middle-aged and older adults.
Keywords	Trunk flexibility ; Renal flow pulsatility ; Aging ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Association between amorphous calcium-phosphate ratios in circulating calciprotein particles and prognostic biomarkers in hemodialysis patients

Kimihiko Nakamura / Naohito Isoyama / Yuki Nakayama / Toshiya Hiroyoshi / Koki Fujikawa / Yutaka Miura / Hiroshi Kurosu / Hideyasu Matsuyama / Makoto Kuro-o

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 8

Abstract: Abstract Calciprotein particles (CPPs) are circulating colloidal mineral-protein complexes containing crystalline and/or non-crystalline (amorphous) calcium-phosphate (CaPi). Serum CPP levels correlate with vascular stiffness and calcification in ... ...

Abstract	Abstract Calciprotein particles (CPPs) are circulating colloidal mineral-protein complexes containing crystalline and/or non-crystalline (amorphous) calcium-phosphate (CaPi). Serum CPP levels correlate with vascular stiffness and calcification in patients with chronic kidney disease (CKD). In vitro studies showed that CPPs containing crystalline CaPi were more arteriosclerogenic and inflammogenic than CPPs without containing crystalline CaPi. Thus, we hypothesized that not only the quantity but also the quality of CPPs (the phase of CaPi) might affect clinical outcomes. To test this hypothesis, we quantified amorphous CaPi ratio defined as the ratio of the amorphous CaPi amount to the total CaPi amount in serum CPPs from 183 hemodialysis patients and explored its possible correlation with serum parameters associated with prognosis of hemodialysis patients. Multivariate analysis revealed that the amorphous CaPi ratio correlated positively with hemoglobin and negatively with fibroblast growth factor-21 (FGF21), which remained significant after adjusting for the total CaPi amount. Because low hemoglobin and high FGF21 are associated with increased mortality, the present study warrants further studies to determine whether low amorphous CaPi ratio in circulating CPPs may be associated with poor prognosis in hemodialysis patients.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Interleukin‐36α as a potential biomarker for renal tubular damage induced by dietary phosphate load

Yoshitaka Hirano / Hiroshi Kurosu / Kazuhiro Shiizaki / Yoshitaka Iwazu / Shuichi Tsuruoka / Makoto Kuro‐o

FEBS Open Bio, Vol 10, Iss 5, Pp 894-

2020 Volume 903

Abstract: Excessive intake of phosphate has been known to induce renal tubular damage and interstitial inflammation, leading to acute kidney injury or chronic kidney disease in rodents and humans. However, sensitive and early biomarkers for phosphate‐induced ... ...

Abstract	Excessive intake of phosphate has been known to induce renal tubular damage and interstitial inflammation, leading to acute kidney injury or chronic kidney disease in rodents and humans. However, sensitive and early biomarkers for phosphate‐induced kidney damage remain to be identified. Our previous RNA sequencing analysis of renal gene expression identified interleukin‐36α (IL‐36α) as a gene significantly upregulated by dietary phosphate load in mice. To determine the time course and dose dependency of renal IL‐36α expression induced by dietary phosphate load, we placed mice with or without uninephrectomy on a diet containing either 0.35%, 1.0%, 1.5%, or 2.0% inorganic phosphate for 10 days, 4 weeks, or 8 weeks and evaluated renal expression of IL‐36α and other markers of tubular damage and inflammation by quantitative RT‐PCR, immunoblot analysis, and immunohistochemistry. We found that IL‐36α expression was induced in distal convoluted tubules and correlated with phosphate excretion per nephron. The increase in IL‐36α expression was simultaneous with but more robust in amplitude than the increase in tubular damage markers such as Osteopontin and neutrophil gelatinase‐associated lipocalin, preceding the increase in expression of other inflammatory cytokines, including transforming growth factor‐α, interleukin‐1β, and transforming growth factor‐β1. We conclude that IL‐36α serves as a marker that reflects the degree of phosphate load excreted per nephron and of associated kidney damage.
Keywords	dietary phosphate load ; interleukin‐36 ; phosphate excretion per nephron ; renal tubular damage ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Association between circulating fibroblast growth factor 21, aerobic fitness, and aortic blood pressure in middle-aged and older women

Masahiro Matsui / Keisei Kosaki / Nobuhiko Akazawa / Koichiro Tanahashi / Makoto Kuro-o / Seiji Maeda

Journal of Physical Fitness and Sports Medicine, Vol 8, Iss 5, Pp 195-

2019 Volume 201

Abstract: Circulating fibroblast growth factor-21 (FGF21) has been reported to correlate with development and progression of some chronic diseases including diabetes and obesity. However, the association between circulating FGF21 levels, aerobic fitness, and ... ...

Abstract	Circulating fibroblast growth factor-21 (FGF21) has been reported to correlate with development and progression of some chronic diseases including diabetes and obesity. However, the association between circulating FGF21 levels, aerobic fitness, and aortic blood pressure (BP) is still not fully understood. This study aimed to examine potential association between circulating FGF21 levels, aerobic fitness, and aortic BP in 118 middle-aged and older women. Aortic pulse pressure (PP) in the higher FGF21 group was significantly increased when compared to the lower FGF21 group (38.4 ± 1.1 vs. 34.9 ± 0.8 mmHg; P < 0.05). Multivariate analysis found the circulating FGF21 level to be an independent determinant of aortic PP (β = 0.169; P < 0.05); and this finding was also independently determined by VO2peak (β = −0.235; P < 0.01). Such a finding demonstrated that serum FGF21 levels were associated positively with aortic PP and negatively with aerobic fitness. These results have raised the possibility that FGF21 might contribute to an increase in aortic PP, and that the promotion of aerobic fitness might be effective in maintaining low FGF21 levels in middle-aged and older women.
Keywords	cardiovascular disease ; aortic hemodynamics ; hepatokine ; Sports medicine ; RC1200-1245 ; Physiology ; QP1-981
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	Japanese Society of Physical Fitness and Sports Medicine
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Possible contribution of phosphate to the pathogenesis of chronic kidney disease in dolphins

Nourin Jahan / Hiroyuki Ohsaki / Kiyoko Kaneko / Asadur Rahman / Takeshi Nishiyama / Makoto Koizumi / Shuichiro Yamanaka / Kento Kitada / Yuki Sugiura / Kenji Matsui / Takashi Yokoo / Takayuki Hamano / Makoto Kuro-o / Takuya Itou / Miwa Suzuki / Keiichi Ueda / Akira Nishiyama

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 13

Abstract: Abstract This study aimed to investigate whether phosphate contributes to the pathogenesis of chronic kidney disease (CKD) in dolphins. Renal necropsy tissue of an aged captive dolphin was analyzed and in vitro experiments using cultured immortalized ... ...

Abstract	Abstract This study aimed to investigate whether phosphate contributes to the pathogenesis of chronic kidney disease (CKD) in dolphins. Renal necropsy tissue of an aged captive dolphin was analyzed and in vitro experiments using cultured immortalized dolphin proximal tubular (DolKT-1) cells were performed. An older dolphin in captivity died of myocarditis, but its renal function was within the normal range until shortly before death. In renal necropsy tissue, obvious glomerular and tubulointerstitial changes were not observed except for renal infarction resulting from myocarditis. However, a computed tomography scan showed medullary calcification in reniculi. Micro area X-ray diffractometry and infrared absorption spectrometry showed that the calcified areas were primarily composed of hydroxyapatite. In vitro experiments showed that treatment with both phosphate and calciprotein particles (CPPs) resulted in cell viability loss and lactate dehydrogenase release in DolKT-1 cells. However, treatment with magnesium markedly attenuated this cellular injury induced by phosphate, but not by CPPs. Magnesium dose-dependently decreased CPP formation. These data support the hypothesis that continuous exposure to high phosphate contributes to the progression of CKD in captive-aged dolphins. Our data also suggest that phosphate-induced renal injury is mediated by CPP formation in dolphins, and it is attenuated by magnesium administration.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Phosphate-Induced Renal Fibrosis Requires the Prolyl Isomerase Pin1.

Zhong-Jian Shen / Jie Hu / Kazuhiro Shiizaki / Makoto Kuro-o / James S Malter

PLoS ONE, Vol 11, Iss 2, p e

2016 Volume 0150093

Abstract: Tubulo-interstitial fibrosis is a common, destructive endpoint for a variety of kidney diseases. Fibrosis is well correlated with the loss of kidney function in both humans and rodents. The identification of modulators of fibrosis could provide novel ... ...

Abstract	Tubulo-interstitial fibrosis is a common, destructive endpoint for a variety of kidney diseases. Fibrosis is well correlated with the loss of kidney function in both humans and rodents. The identification of modulators of fibrosis could provide novel therapeutic approaches to reducing disease progression or severity. Here, we show that the peptidyl-prolyl isomerase Pin1 is an important molecular contributor that facilitates renal fibrosis in a well-characterized animal model. While wild-type mice fed a high phosphate diet (HPD) for 8-12 weeks developed calcium deposition, macrophage infiltration and extracellular matrix (ECM) accumulation in the kidney interstitium, Pin1 null mice showed significantly less pathology. The serum Pi in both WT and KO mice were significantly increased by the HPD, but the serum Ca was slightly decreased in KO compared to WT. In addition, both WT and KO HPD mice had less weight gain but exhibited normal organ mass (kidney, lung, spleen, liver and heart). Unexpectedly, renal function was not initially impaired in either genotype irrespective of the HPD. Our results suggest that diet containing high Pi induces rapid renal fibrosis before a significant impact on renal function and that Pin1 plays an important role in the fibrotic process.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identification and quantification of plasma calciprotein particles with distinct physical properties in patients with chronic kidney disease

Yutaka Miura / Yoshitaka Iwazu / Kazuhiro Shiizaki / Tetsu Akimoto / Kazuhiko Kotani / Masahiko Kurabayashi / Hiroshi Kurosu / Makoto Kuro-o

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 16

Abstract: Abstract Calciprotein particles (CPP) are solid-phase calcium-phosphate bound to serum protein fetuin-A and dispersed as colloids in the blood. Recent clinical studies indicated that serum CPP levels were increased with decline of renal function and ... ...

Abstract	Abstract Calciprotein particles (CPP) are solid-phase calcium-phosphate bound to serum protein fetuin-A and dispersed as colloids in the blood. Recent clinical studies indicated that serum CPP levels were increased with decline of renal function and associated with inflammation and vascular calcification. However, CPP assays used in these studies measured only a part of CPP over a certain particle size and density. Here we show that such CPP are mostly artifacts generated during processing of serum samples in vitro. The native CPP in fresh plasma are smaller in size and lower in density than those artifactual CPP, composed of fetuin-A carrying amorphous and/or crystalline calcium-phosphate, and increased primarily with serum phosphate levels. We have identified several physicochemical factors that promote aggregation/dissolution of CPP and transition of the calcium-phosphate from the amorphous phase to the crystalline phase in vitro, including addition of anti-coagulants, composition of buffer for sample dilution, the number of freeze-thaw cycles, the speed for sample freezing, and how many hours the samples were left at what temperature. Therefore, it is of critical importance to standardize these factors during sample preparation in clinical studies on CPP and to investigate the biological activity of the native CPP.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Klotho Regulates 14-3-3ζ Monomerization and Binding to the ASK1 Signaling Complex in Response to Oxidative Stress.

Reynolds K Brobey / Mehdi Dheghani / Philip P Foster / Makoto Kuro-O / Kevin P Rosenblatt

PLoS ONE, Vol 10, Iss 10, p e

2015 Volume 0141968

Abstract: The reactive oxygen species (ROS)-sensitive apoptosis signal-regulating kinase 1 (ASK1) signaling complex is a key regulator of p38 MAPK activity, a major modulator of stress-associated with aging disorders. We recently reported that the ratio of free ... ...

Abstract	The reactive oxygen species (ROS)-sensitive apoptosis signal-regulating kinase 1 (ASK1) signaling complex is a key regulator of p38 MAPK activity, a major modulator of stress-associated with aging disorders. We recently reported that the ratio of free ASK1 to the complex-bound ASK1 is significantly decreased in Klotho-responsive manner and that Klotho-deficient tissues have elevated levels of free ASK1 which coincides with increased oxidative stress. Here, we tested the hypothesis that: 1) covalent interactions exist among three identified proteins constituting the ASK1 signaling complex; 2) in normal unstressed cells the ASK1, 14-3-3ζ and thioredoxin (Trx) proteins simultaneously engage in a tripartite complex formation; 3) Klotho's stabilizing effect on the complex relied solely on 14-3-3ζ expression and its apparent phosphorylation and dimerization changes. To verify the hypothesis, we performed 14-3-3ζ siRNA knock-down experiments in conjunction with cell-based assays to measure ASK1-client protein interactions in the presence and absence of Klotho, and with or without an oxidant such as rotenone. Our results show that Klotho activity induces posttranslational modifications in the complex targeting 14-3-3ζ monomer/dimer changes to effectively protect against ASK1 oxidation and dissociation. This is the first observation implicating all three proteins constituting the ASK1 signaling complex in close proximity.
Keywords	Medicine ; R ; Science ; Q
Subject code	500
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The anti-aging factor Klotho protects against acquired long QT syndrome induced by uremia and promoted by fibroblast growth factor 23

José Alberto Navarro-García / Rafael Salguero-Bodes / Laura González-Lafuente / Laura Martín-Nunes / Elena Rodríguez-Sánchez / Teresa Bada-Bosch / Eduardo Hernández / Evangelina Mérida-Herrero / Manuel Praga / Jorge Solís / Fernando Arribas / Héctor Bueno / Makoto Kuro-O / María Fernández-Velasco / Luis Miguel Ruilope / Carmen Delgado / Gema Ruiz-Hurtado

BMC Medicine, Vol 20, Iss 1, Pp 1-

2022 Volume 19

Abstract: Abstract Background Chronic kidney disease (CKD) is associated with increased propensity for arrhythmias. In this context, ventricular repolarization alterations have been shown to predispose to fatal arrhythmias and sudden cardiac death. Between mineral ...

Abstract	Abstract Background Chronic kidney disease (CKD) is associated with increased propensity for arrhythmias. In this context, ventricular repolarization alterations have been shown to predispose to fatal arrhythmias and sudden cardiac death. Between mineral bone disturbances in CKD patients, increased fibroblast growth factor (FGF) 23 and decreased Klotho are emerging as important effectors of cardiovascular disease. However, the relationship between imbalanced FGF23-Klotho axis and the development of cardiac arrhythmias in CKD remains unknown. Methods We carried out a translational approach to study the relationship between the FGF23–Klotho signaling axis and acquired long QT syndrome in CKD-associated uremia. FGF23 levels and cardiac repolarization dynamics were analyzed in patients with dialysis-dependent CKD and in uremic mouse models of 5/6 nephrectomy (Nfx) and Klotho deficiency (hypomorphism), which show very high systemic FGF23 levels. Results Patients in the top quartile of FGF23 levels had a higher occurrence of very long QT intervals (> 490 ms) than peers in the lowest quartile. Experimentally, FGF23 induced QT prolongation in healthy mice. Similarly, alterations in cardiac repolarization and QT prolongation were observed in Nfx mice and in Klotho hypomorphic mice. QT prolongation in Nfx mice was explained by a significant decrease in the fast transient outward potassium (K+) current (I tof ), caused by the downregulation of K+ channel 4.2 subunit (Kv4.2) expression. Kv4.2 expression was also significantly reduced in ventricular cardiomyocytes exposed to FGF23. Enhancing Klotho availability prevented both long QT prolongation and reduced I tof current. Likewise, administration of recombinant Klotho blocked the downregulation of Kv4.2 expression in Nfx mice and in FGF23-exposed cardiomyocytes. Conclusion The FGF23–Klotho axis emerges as a new therapeutic target to prevent acquired long QT syndrome in uremia by minimizing the predisposition to potentially fatal ventricular arrhythmias and sudden cardiac ...
Keywords	CKD ; Dialysis ; FGF23 ; Klotho ; Long QT ; Potassium channels ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Phosphate binding by sucroferric oxyhydroxide ameliorates renal injury in the remnant kidney model

Yoshikazu Nemoto / Takanori Kumagai / Kenichi Ishizawa / Yutaka Miura / Takeshi Shiraishi / Chikayuki Morimoto / Kazuhiro Sakai / Hiroki Omizo / Osamu Yamazaki / Yoshifuru Tamura / Yoshihide Fujigaki / Hiroshi Kawachi / Makoto Kuro-o / Shunya Uchida / Shigeru Shibata

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 11

Abstract: Abstract Recent clinical studies indicate that the disturbed phosphate metabolism in chronic kidney disease (CKD) may facilitate kidney injury; nonetheless, the causal role of phosphate in CKD progression remains to be elucidated. Here, we show that ... ...

Abstract	Abstract Recent clinical studies indicate that the disturbed phosphate metabolism in chronic kidney disease (CKD) may facilitate kidney injury; nonetheless, the causal role of phosphate in CKD progression remains to be elucidated. Here, we show that intestinal phosphate binding by sucroferric oxyhydroxide (SF) ameliorates renal injury in the rat remnant kidney model. Sprague-Dawley rats received 5/6 nephrectomy (RK) and had a normal chow or the same diet containing SF (RK + SF). RK rats showed increased plasma FGF23 and phosphate levels, which were suppressed by SF administration. Of note, albuminuria in RK rats was significantly ameliorated by SF at both 4 and 8 weeks. SF also attenuated glomerulosclerosis and tubulointerstitial injury. Moreover, several different approaches confirmed the protective effects on podocytes, explaining the attenuation of glomerulosclerosis and albuminuria observed in this study. As a possible mechanism, we found that SF attenuated renal inflammation and fibrosis in RK rats. Interestingly, von Kossa staining of the kidney revealed calcium phosphate deposition in neither RK nor RK + SF rats; however, plasma levels of calciprotein particles were significantly reduced by SF. These data indicate that latent positive phosphate balance accelerates CKD progression from early stages, even when overt ectopic calcification is absent.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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