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1. Exploring the implications of blocking renin-angiotensin-aldosterone system and fibroblast growth factor 23 in early left ventricular hypertrophy without chronic kidney disease

Author

Kentaro Watanabe, Hideki Fujii, Kohei Okamoto, Keiji Kono, Shunsuke Goto, and Shinichi Nishi

Subjects
fibroblast growth factor 23, renin-angiotensin-aldosterone system, left ventricular hypertrophy (LVH), aldosterone (Ald), angiotensin-converting enzyme 2 (ACE2), Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

BackgroundWhether fibroblast growth factor 23 (FGF23) directly induces left ventricular hypertrophy (LVH) remains controversial. Recent studies showed an association between FGF23 and the renin-angiotensin-aldosterone system (RAAS). The aim of this study was to investigate changes in FGF23 levels and RAAS parameters and their influences on LVH.MethodsIn the first experiment, male C57BL/6J mice were divided into sham and transverse aortic constriction (TAC) groups. The TAC group underwent TAC at 8 weeks of age. At 1, 2, 3, and 4 weeks after TAC, the mice were sacrificed, and blood and urine samples were obtained. Cardiac expressions of FGF23 and RAAS-related factors were evaluated, and cardiac histological analyses were performed. In the second experiment, the sham and TAC groups were treated with vehicle, angiotensin-converting enzyme (ACE) inhibitor, or FGF receptor 4 (FGFR4) inhibitor and then evaluated in the same way as in the first experiment.ResultsIn the early stage of LVH without chronic kidney disease, serum FGF23 levels did not change but cardiac FGF23 expression significantly increased along with LVH progression. Moreover, serum aldosterone and cardiac ACE levels were significantly elevated, and cardiac ACE2 levels were significantly decreased. ACE inhibitor did not change serum FGF23 levels but significantly decreased cardiac FGF23 levels with improvements in LVH and RAAS-related factors, while FGFR4 inhibitor did not change the values.ConclusionsNot serum FGF23 but cardiac FGF23 levels and RAAS parameters significantly changed in the early stage of LVH without chronic kidney disease. RAAS blockade might be more crucial than FGF23 blockade for preventing LVH progression in this condition.

Published
2023
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2. Comparison of two protocols for steroid pulse therapy in patients with IgA nephropathy: a retrospective observational study

Author

Satoshi Yamatani, Keiji Kono, Hideki Fujii, Ken Hirabayashi, Mao Shimizu, Kentaro Watanabe, Shunsuke Goto, and Shinichi Nishi

Subjects
Hematuria, Immunoglobulin A nephropathy, Proteinuria, Steroid pulse therapy, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Steroid pulse (SP) therapy is one of the immunosuppressive therapies for immunoglobulin A nephropathy (IgAN). Although there are various protocols of SP therapy in IgAN, the intermittent SP (ISP) and consecutive SP (CSP) protocols are prevalently performed in clinical settings. However, there is a lack of evidence of comparisons of the effects on IgAN between these two protocols. Methods A total of 189 patients with IgAN who had received SP therapy were included in this study. They were divided into two groups according to the SP protocols into the intermittent SP (ISP) or consecutive SP (CSP) group as follows: ISP; three-times SP therapy in alternate months, CSP; three-times SP therapy in three consecutive weeks. Kidney function, remission of urinary findings, and side effects of SP therapy were compared between the two groups. The observational period was 12 months after the initiation of SP therapy. Results There was no significant difference in kidney function between the two groups during the observational period. The remission rate of proteinuria and hematuria at 12 months also did not significantly differ between the two groups. Furthermore, even after the adjustment of clinical characteristics using propensity score matching, the remission rate of proteinuria and hematuria at 12 months was similar between the two groups. At 2 months, the remission rate of proteinuria was significantly higher in the CSP group than in the ISP group. There were no critical side effects in both groups. Conclusion The effects of SP therapy on IgAN were similar between the ISP and CSP group at 12 months although CSP therapy could remit proteinuria faster than ISP therapy.

Published
2022
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3. Clinical value of serum cholinesterase levels in Nephrotic syndrome: an observational study

Author

Kimihiko Goto, Keiji Kono, Hideki Fujii, Shunsuke Goto, and Shinichi Nishi

Subjects
Nephrotic syndrome, Cholinesterase, Minimal change nephrotic syndrome, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Nephrotic syndrome (NS) results in massive proteinuria and hypoalbuminemia, which are responsible for a compensatory increase in protein synthesis in the liver. Serum cholinesterase (ChE) also increases in NS. However, its clinical value is not fully elucidated. Methods In this study, 184 patients with NS who underwent kidney biopsy were included. The patients were divided into two groups according to serum ChE levels, as follows: hypercholinesterasemia (HC) and non-hypercholinesterasemia (NHC) groups. The clinical factors were compared between the two groups. Results The HC group had significantly more severe proteinuria and higher prevalence of high selective proteinuria than the NHC group. Furthermore, the prevalence of minimal change nephrotic syndrome (MCNS) was significantly higher in the HC group than that in the NHC group. Multivariate analysis revealed that the severity of proteinuria and MCNS were significantly associated with HC. Conclusion In this study, HC in NS was associated with the severity of proteinuria and MCNS, and could help clinicians predict the histological diagnosis of NS.

Published
2022
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4. Comparison of the effects of lanthanum carbonate and calcium carbonate on the progression of cardiac valvular calcification after initiation of hemodialysis

Author

Kentaro Watanabe, Hideki Fujii, Keiji Kono, Shunsuke Goto, and Shinichi Nishi

Subjects
Lanthanum carbonate, Calcium carbonate, Cardiac valvular calcification, Arterial plaque, Initiation of hemodialysis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Although mineral metabolism disorder influences cardiac valvular calcification (CVC), few previous studies have examined the effects of non-calcium-containing and calcium-containing phosphate binders on CVC in maintenance hemodialysis patients. The aim of the present study was to compare the effects of lanthanum carbonate (LC) with calcium carbonate (CC) on the progression of CVC in patients who initiated maintenance hemodialysis and to investigate clinical factors related to CVC. Methods The current study included 50 subjects (mean age 65 years, 72% males) from our previous randomized controlled trial (LC group, N = 24; CC group, N = 26). CVC was evaluated as CVC score (CVCS) using echocardiography at baseline and 18 months after initiation of hemodialysis. We compared CVCS and the changes between the two groups. We also analyzed the associations between CVCS and any other clinical factors including arterial plaque score (PS) and serum phosphorus levels. Results Baseline characteristics of study participants including CVCS were almost comparable between the two groups. At 18 months, there were no significant differences in mineral metabolic markers or CVCS between the two groups, and CVCS were significantly correlated with PS (r = 0.39, p

Published
2020
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5. Changes in serum indoxyl sulfate levels after acute myocardial infarction and the correlation with kidney injury: an observational study

Author

Shuhei Watanabe, Hideki Fujii, Keiji Kono, Kentaro Watanabe, Shunsuke Goto, Susumu Sakamoto, and Shinichi Nishi

Subjects
Indoxyl sulfate, Acute myocardial infarction, Kidney injury, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Kidney function after acute myocardial infarction (AMI) correlates with patient prognosis. Several studies reported the role that indoxyl sulfate (IS), a uremic toxin, plays in the progression of chronic kidney disease and cardiovascular diseases. This study aims at investigating the serum IS level changes after AMI and their correlation with kidney injury. Methods In this observational study, twenty consecutive patients with AMI who received percutaneous coronary intervention within 2 h after admission were enrolled. We measured serum IS levels on admission (day 1) and day 2–3 and evaluated their clinical characteristics. Further, we measured serum neutrophil gelatinase-associated lipocalin (NGAL) levels at admission as a marker of kidney injury. Results Although estimated glomerular filtration rate (eGFR) decreased at day 2–3 compared to that at day 1, serum IS levels at day 1 were rather higher than those at day 2–3. Further analysis only among patients with preserved kidney function revealed that serum IS levels at day 1 were significantly higher than those at day 2–3, despite a higher eGFR. Additionally, serum NGAL levels at admission were higher in these patients than in healthy subjects. Further, serum NGAL levels were significantly higher in patients with higher serum IS levels compared to those with lower IS levels. Conclusion This study suggests that pathophysiological conditions in patients with AMI may elevate serum IS levels independent of kidney dysfunction and that IS may be one of the contributory factors related to kidney injury in AMI.

Published
2019
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6. Clinical practice guideline for renal rehabilitation: systematic reviews and recommendations of exercise therapies in patients with kidney diseases

Author

Kunihiro Yamagata, Junichi Hoshino, Hitoshi Sugiyama, Norio Hanafusa, Yugo Shibagaki, Yasuhiro Komatsu, Tsuneo Konta, Naohiko Fujii, Eiichiro Kanda, Tadashi Sofue, Kiyonobu Ishizuka, Masashi Kitagawa, Keiji Kono, Norikazu Hinamoto, Takayuki Miyai, Kiyomi Koike, Susumu Toda, Jumpei Hasegawa, Masayuki Yamanouchi, Ryuichi Yoshimura, Ryota Ishii, Shunsuke Goto, Hiroo Kawarazaki, Kentaro Takase, Fumika Taki, Mimiko Matsumura, Yoshihiko Raita, Satoko Sakurai, Tatsuya Shimizu, Suguru Yamanoto, Takehiko Kawaguchi, Hideyo Oguchi, Makoto Tsujita, Masahiko Yazawa, Akiko Uchida, Yasuhiro Ando, Satoru Kaneko, Atsuhiko Matsunaga, Taku Harada, Osamu Ito, and Masahiro Kohzuki

Subjects
Renal rehabilitation, Exercise therapy, CKD, Dialysis, Transplantation, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract In recent years, a concept of renal rehabilitation has become widely known among nephrology specialists, dialysis specialists, kidney transplantation specialists, rehabilitation specialists, nutrition specialists, guideline specialists, nurses, physiotherapists, and representatives of patients. Therefore, in order to make it clear the definition, methods, and effectiveness of renal rehabilitation in Japan, we launched Renal Rehabilitation Guideline Preparation Committee in 2016 as a part of works in the Japanese Society of Renal Rehabilitation, and created a guideline in accordance to the “Minds Handbook for Clinical Practice Guideline Development 2014”. Here, we report systematic reviews and recommendations of exercise therapies in patients with kidney diseases based on the guideline preparation committee works. Six recommendations for the condition of each kidney disorder, groups addressing nephritis/nephrosis, chronic kidney diseases, dialysis therapy, and kidney transplantation were created. All the recommendation grades were determined by a consensus conference participated in by representatives of patients and various professionals. The purpose of this report is to provide an evidence-based, best practice summary to optimize the quality, safety and efficacy, and availability of renal rehabilitation service, and to provide care for maximum patient prognosis, quality of life, and satisfaction.

Published
2019
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7. Relationship Between Type of Hypertension and Renal Arteriolosclerosis in Chronic Glomerular Disease

Author

Keiji Kono, Hideki Fujii, Kentaro Nakai, Shunsuke Goto, Shuhei Watanabe, Kentaro Watanabe, and Shinichi Nishi

Subjects
Masked hypertension, Renal arteriolosclerosis, Glomerular disease, Ambulatory blood pressure, Circadian rhythm of blood pressure, Arteriolosclerosis, Dermatology, RL1-803, Diseases of the circulatory (Cardiovascular) system, RC666-701, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Background/Aims: Hypertension (HT) is a common complication in patients with chronic kidney disease (CKD). However, the relationship between circadian rhythm disorder of blood pressure (BP) and intra-renal damage remains unclear. Methods: Ninety patients with chronic glomerular disease (CGD) were included in the present study. On the basis of the clinic BP (CBP) and 24 h-ambulatory BP (ABP) measurements, the patients were divided into the following groups; normotension (NT), white coat HT (WHT), masked HT (MHT), and sustained HT (SHT). For renal histopathological assessment, we evaluated each biopsy specimen for sclerotic glomeruli (SG), interstitial fibrosis (IF), intimal thickening of intra-lobular arteries (ILA), and arteriolar hyalinosis (AH). Results: The prevalence of NT, WHT, MHT and SHT was 60.0%, 3.3%, 23.3%, and 13.4%, respectively. Compared with circadian BP pattern, all-day HT was most prevalent in the SHT group, whereas nighttime HT was most prevalent in the MHT group. The results of histological analysis showed that the SHT group had more severe SG and IF and the MHT group had more severe IF compared to the NT group. As for renal arteriolosclerosis, the MHT and SHT groups had more severe AH compared with the NT group, whereas ILA was comparable among all four groups. Furthermore, multivariate analysis revealed that ILA was significantly correlated only with age, whereas AH was significantly correlated with age and HT based on ABP, but not HT based on CBP. Conclusions: Our findings suggest that renal AH was severe not only in the SHT group, but also in the MHT group. Careful ABP monitoring should be recommended in patients with CGD.

Published
2016
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8. Statin Use Influence on the Occurrence of Acute Kidney Injury in Patients with Peripheral Arterial Disease

Author

Daisuke Kanai, Hideki Fujii, Kentaro Nakai, Keiji Kono, Kentaro Watanabe, Shunsuke Goto, and Shinichi Nishi

Subjects
Peripheral Arterial Disease, Peripheral artery disease, Risk Factors, Biochemistry (medical), Internal Medicine, Humans, Contrast Media, Statin, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, Retrospective Studies, Acute kidney injury
Abstract

Aim: Acute kidney injury (AKI) is an important clinical issue in the diagnosis and treatment of cardiovascular diseases. The association between pretreatment by statins and the occurrence of AKI in patients with peripheral arterial diseases (PAD) remains unclear. Therefore, we examined the association between statin therapy and the occurrence of AKI in patients with PAD. Methods: We retrospectively analyzed data from the endovascular treatment (EVT) database in our hospital. A total of 295 patients who underwent angiography and/or intervention for PAD between October 2011 and March 2016 were enrolled and divided into two groups: those without statins (control group; N=157) and those with statins (statin group; N=138) for at least 1 month before admission. We examined the occurrence of AKI and its related factors in these patients. Results: The serum creatinine levels, dose of contrast medium, use of a renin-angiotensin system inhibitor, smoking habit, and blood pressure were similar in both groups. The statin group had more diabetes patients, had patients who were significantly younger, had patients with a higher body mass index (BMI), and had patients with lower low-density lipoprotein cholesterol than the control group. With regard to the occurrence of AKI, there was a significantly lower incidence in the statin group compared with the control group (5% vs. 16%, p＜0.05). The result of the multivariate analysis indicated that statin therapy was significantly correlated with lower occurrence rates of AKI (p＜0.05). Conclusions: Our study suggests that statin therapy might prevent the occurrence of AKI after angiography and/or intervention for PAD.

Published
2022
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9. Renal protective effects of astragalus root in rat models of chronic kidney disease

Author

Shunsuke Goto, Hideki Fujii, Kentaro Watanabe, Mao Shimizu, Hidehisa Okamoto, Kazuo Sakamoto, Keiji Kono, and Shinichi Nishi

Subjects
Oxidative stress, Nephrology, Physiology, Astragalus, Chronic kidney disease, Physiology (medical), Renin-angiotensin system
Abstract

Background Astragalus root is a commonly used herb in traditional Chinese medicine. Although renoprotective effects have been reported in some clinical and experimental studies, the details remain unknown. Methods We used 5/6 nephrectomized rats as chronic kidney disease (CKD) models. At 10 weeks, they were divided into four groups, namely, CKD, low-dose astragalus (AR400), high-dose astragalus (AR800), and sham groups. At 14 weeks, they were sacrificed for the evaluation of blood, urine, mRNA expression in the kidney, and renal histopathology. Results Kidney dysfunction was significantly improved following astragalus administration (creatinine clearance: sham group; 3.8 ± 0.3 mL/min, CKD group; 1.5 ± 0.1 mL/min, AR400 group; 2.5 ± 0.3 mL/min, AR800 group; 2.7 ± 0.1 mL/min). Blood pressure, urinary albumin, and urinary NGAL levels were significantly lower in the astragalus-treated groups than those in the CKD group. Excretion of urinary 8-OHdG, an oxidative stress marker, and intrarenal oxidative stress were lower in the astragalus-treated groups than those in the CKD group. Furthermore, the mRNA expression of NADPH p22 phox, NADPH p47 phox, Nox4, renin, angiotensin II type 1 receptor, and angiotensinogen in the kidney was lower in the astragalus-treated groups compared with the CKD group. Conclusion This study suggests that astragalus root slowed CKD progression, possibly through the suppression of oxidative stress and the renin–angiotensin system.

Published
2023
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10. Screening for Fabry disease among male patients on hemodialysis in Awaji Island

Author

Mao Shimizu, Hideki Fujii, Keiji Kono, Kentaro Watanabe, Shunsuke Goto, Kandai Nozu, Kimitoshi Nakamura, and Shinichi Nishi

Subjects
Male, hemodialysis, α-galactosidase A activity, Renal Dialysis, Nephrology, alpha-Galactosidase, Humans, Fabry Disease, Kidney Diseases, Hematology, remote island, Kidney
Abstract

Fabry disease (FD) manifests decreased α-galactosidase A (α-Gal A) activity and multiorgan damage. There are some undiagnosed cases of the condition among patients on dialysis. The prevalence of FD may also vary with the region. Among 227 male patients undergoing maintenance hemodialysis in Awaji Island, a remote island in Japan, 201 (88.5%) were included in this study. Patients with α-Gal A activity

Published
2022
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11. Empagliflozin in Patients with Chronic Kidney Disease

Author

Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel Kraus, Carina Krieger, Margit Schmude, Anne Schreiber, Ewelina Eckrich, Diethelm Tschope, Abdulwahab Arbi, Young Lee-Barkey, Bernd Stratmann, Natalie Prib, Sina Rolfsmeier, Irina Schneider, Lars Rump, Johannes Stegbauer, Christine Pötz, Mara Schemmelmann, Claudia Schmidt, Michael Koch, Sendogan Aker, Annika Küpper, Manuela Martin, Thiemo Pfab, Christian Albert, Michael Haase, Barbara Zander, Claudia Schneider-Danwitz, Wolfgang Seeger, Wolf-Adam Seeger, Britta Zemann, Christoph Stellbrink, Kristin Marx, Ekaterina Stellbrink, Britta Brettschneider, Stephanie Watson, Marion Iselt, Gerhard Klausmann, Inga-Nadine Kummer, Auguste Kutschat, Simone Streitenberger, Matthias Girndt, Silke Markau, Ina Girakossyan, Claudia Hanf, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Andreas Schneider, Roland Veelken, Claudia Donhauser, Luis Becker, Nexhat Miftari, Ricarda Wolfling, Sarah Morlok, Christian Hugo, Alexander Paliege, Jens Passauer, Julian Stumpf, Annegret Fleischer, Kerstin Haaser, Bernhard Kraemer, Jan Jochims, Bernd Kruger, Claudia Foellinger, Anastassiya Reisler, Frank Strutz, Stefan Haack, Ursula Hohenstatt, Martin Busch, Konstantin Herfurth, Gunter Wolf, Rainer Paul, Hermann Haller, Jessica Kaufeld, Jan Menne, Elisabeth Bahlmann-Kroll, Angela Bergner, Horst Weihprecht, Aydin Er, Florian Sonntag, Elif Turan, Michael Wittmann, Franziska Klauser, Eva Voigt, Volker Schettler, Egbert Schulz, Madlen Rohnstock, Elke Schettler, Bernd Schroppel, Rene van Erp, Martin Kachele, Ulla Ludwig, Lena Schulte-Kemna, Waltraud Kmietschak, Elke Preiss, Martina Ruocco, Gunnar Heine, Martin Brzoska, Sebastian Gabel, Christina Büttner, Asma Sabarai, Bernhard Banas, Tobias Bergler, Yvonne Ehrl, Franz Putz, Antonia Schuster, Stefanie Kuhn, Torsten Schramm, Stefan Degenhardt, Gerhard Schmidt, Lea Weiland, Ulrike Giebeln-Hudnell, Jan Kielstein, Gabriele Eden, Brigitte Fuchs, Gina Morig, Manuela Winkler, Harald Darius, Charalampos Kriatselis, Carl-Philipp Roesch, Astrid Maselli, Dominik Alscher, Markus Ketteler, Moritz Schanz, Severin Schricker, Bianka Rettenmaier, Andrea Schwab, Pablo Pergola, Irene Leal, Melissa Cagle, Anna Romo, Anthony Torres, Sucharit Joshi, Kulli Barrett, Alexis Africano, Vicki Dodds, Dorleena Gowen, Ashlee Morris, Juan Fernandez, Guillermo Jimenez, Ricardo Viera, Kendaling Bruce, Ryan Barrios, Maylin Garcia, Kerelyn Garcia, Iradis Leal, David Tietjen, David Bains, Carlo Castillo, Genielle Brewer, Justin Davis, Natalie Freking, Brittany Golson, Sally Ham, Jesslyn Roesch, Pusadee Suchinda, Shameem Beigh, Usah Lilavivat, Joyce Bilton, Kim Bocchicchia, Jeffrey Turner, Neera Dahl, Aldo Peixoto, Yasemin Kavak, Lauren Liberti, Hari Nair, Nicolas Page, Stephanie Rosenberg, Kathryn Simmons, Tamara Isakova, Rebecca Frazier, Rupal Mehta, Anand Srivastava, Patrick Fox, Jonathan Hecktman, Alexander Hodakowski, Carlos Martinez, Rachel Phillips, Alexis Stevenson, Reem Mustafa, Kyle Jansson, Cassandra Kimber, Jason Stubbs, Ahmad Tuffaha, Sri Yarlagadda, Debbie Griffin, Elisabeth Laundy, Zhuo Tang, Radica Alicic, Ann Cooper, Lisa Davis, Ashwini Gore, Rebecca Goldfaden, Leslie Harvill, Lisa Hichkad, Barry Johns, Thomas Jones, Kayla Merritt, Jennifer Sheldon, Jennifer Stanfield, Lindsay Alexander, Kaitlyn Preston, Lindsey Wood, Rajesh Pradhan, Roger DeRaad, Kelli McIntosh, Louis Raymond, Michael Shepperd, Susan McLaughlin, Mary Seifert, Andrew Shepherd, Joseph Aiello, William Durham, Laurie Loudermilk, John Manley, Sabrina Burnette, Stephanie Evans, Tara Johnson, Lance Sloan, Judy Ann Acosta, Stacy Gillham, Katia Sloan, SueAnn Squyres, Michael Rocco, Amret Hawfield, Ben Bagwell, Lauren Richmond, Joseph Soufer, Subha Clarke, Amanda Aliu, Kristine Calabrese, Amanda Davis, Veronica Poma, Tracy Spinola, James Magee, Ricardo Silva, Rushab Choksi, Lorraine Dajani, John Evans, Anil George, Prasanth Krish, Gerard Martins, Mae Sheikh-Ali, David Sutton, Freda Driver, Abraham Hanburry, Laura Hume, Amber Hurst, Matthew Taddeo, Marla Turner, Veronica Yousif, Srinivasan Beddhu, Laith Al-Rabadi, Nikita Abraham, Amalia Caamano, Judy Carle, Victoria Gonce, Kaitlyn Staylor, Na Zhou, Shweta Bansal, Manoj Bhattarai, Kumar Sharma, Subrata Debnath, Aliseiya Garza, Chakradhar Velagapudi, Sergio Rovner, Javier Almeida, Pablo Casares, Verlaine Stewart-Ray, Rene Almaraz, Renata Dayrell, Ana Moncada, Ricardo Pulido, Roxana Rodriquez, Wasim Deeb, Kathryn DeGoursey, Rodel Gloria, Trevor Greene, Robert Miller, Edward Pereira, Miguel Roura, Debbie Domingo, Sasha Dorestin, William Hodge, Cathy Jackson, Deborah Lund, Katrina Taylor, Kenneth Boren, Brittany Cleveland, Sandra Gaiser, Mandeep Sahani, Logan Aldrich, Exodus Edmerson, Edmond Limon, Cole Valletta, Patricia Vasquez, Christopher Provenzano, Navkiranjot Brar, Heather Henderson, Bellovich Keith, Qur Khai, Quresh Khairullah, Gail Makos, Joel Topf, Sherry Gasko, Rosemarie Henschel, Kaitlin Knapp, Teresa Kozlowski, Paula LaFleur, Ashwathy Varughese, Hui Xue, Patricia Wu, Olga Arechiga, Shan Darbeau, Michael Fechter, Stephanie Martinez, Lenita Hanson, Nyla Cooper, Arelis Madera, Jay Cadorna, Rita Sheridan, Helen Sparks, Bradley Eilerman, Susanne Bodine, Wael Eid, Rebecca Flora, Amber Avery, Cashmere Hardy, Mihaela Biscoveanu, Steven Nagelberg, Tracey Cummins, Frederic Rahbari-Oskoui, Anju Oommen, Zohreh Forghani, Stacie Hitchcock, Darya Hosein, Diane Watkins, Minesh Patel, Anthony Lambert, Elizabeth Newman, Autumn Wood, Tammy Ross, Stephany Topping, Jeffrey Mulhern, Lorna Murphy, Ann Vasseur, Gregory Greenwood, Alexander Hadley, Denise Laurienti, Christopher Marshall, Nicholas McLean, Scott Satko, Brandy Caudill, Jacob Maris, Janice Rogers, Cindy Vanhoy, George Thomas, Georges Nakhoul, John O'Toole, Jonathan Taliercio, Leslie Cooperman, Marina Markovic, Barbara Tucky, Devasmita Dev, Alia Hasan, Hima Yalamanchili, Namita Jain, Lesley McNeil, Eric Wines, Jean Park, Adline Ghazi, Mia Hamm, Tejas Patel, Amy Mottl, Emily Chang, Vimal Derebail, Emmie Cole, Anne Froment, Sara Kelley, 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Cipressa, Laura, Fabbri, Gianna, Lorimer, Andrea, Lucci, Donata, Ghavampour, Sharang, Knoppe, Anja, Schmidt-Gurtler, Han, Dumann, Hubert, Merscher, Sybille, Patecki, Margret, Rainer Schlieper, Georg, Torp, Anke, Weber, Bianca, Zietz, Maja, Hohenstein, Bernd, Benck, Ur, Draganova, Diliana, Weinreich, Thoma, Wolf, Lothar, Gaidu, Jasmine, Reiner, Hanna, Visnjic, Mandy, Steffl, Daniel, Breitenfeldt, Marie, Kraemer-Guth, Annette, Braun, Christine, Hagge, Simone, Schomig, Michael, Matthias, Stephan, Stoffler, Dominik, Schumacher, Beate, Sitter, Thoma, Fuessl, Louise, Krappe, Julia, Loutan, Jerome, Vielhauer, Volker, Andriaccio, Luciano, Maurer, Magdalena, Winkelmann, Bernhard, Dursch, Martin, Seifert, Linda, Tenbusch, Linda, Weinmann-Menke, Julia, Boedecker, Simone, Kaluza-Schilling, Wiebke, Kraus, Daniel, Krieger, Carina, Schmude, Margit, Schreiber, Anne, Eckrich, Ewelina, Tschope, Diethelm, Arbi, Abdulwahab, Lee-Barkey, Young, Stratmann, Bernd, Prib, Natalie, Rolfsmeier, Sina, Schneider, Irina, Rump, Lar, Stegbauer, Johanne, Pötz, Christine, Schemmelmann, Mara, Schmidt, Claudia, Koch, Michael, Aker, Sendogan, Küpper, Annika, Martin, Manuela, Pfab, Thiemo, Albert, Christian, Haase, Michael, Zander, Barbara, Schneider-Danwitz, Claudia, Seeger, Wolfgang, Seeger, Wolf-Adam, Zemann, Britta, Stellbrink, Christoph, Marx, Kristin, Stellbrink, Ekaterina, Brettschneider, Britta, Watson, Stephanie, Iselt, Marion, Klausmann, Gerhard, Kummer, Inga-Nadine, Kutschat, Auguste, Streitenberger, Simone, Girndt, Matthia, Markau, Silke, Girakossyan, Ina, Hanf, Claudia, Beige, Joachim, Wendt, Ralph, Schmidt, Ulrike, Schneider, Andrea, Veelken, Roland, Donhauser, Claudia, Becker, Lui, Miftari, Nexhat, Wolfling, Ricarda, Morlok, Sarah, Hugo, Christian, Paliege, Alexander, Passauer, Jen, Stumpf, Julian, Fleischer, Annegret, Haaser, Kerstin, Kraemer, Bernhard, Jochims, Jan, Kruger, Bernd, Foellinger, Claudia, Reisler, Anastassiya, Strutz, Frank, Haack, Stefan, Hohenstatt, Ursula, Busch, Martin, Herfurth, Konstantin, Wolf, Gunter, Paul, Rainer, Haller, Hermann, Kaufeld, Jessica, Menne, Jan, Bahlmann-Kroll, Elisabeth, Bergner, Angela, Weihprecht, Horst, Er, Aydin, Sonntag, Florian, Turan, Elif, Wittmann, Michael, Klauser, Franziska, Voigt, Eva, Schettler, Volker, Schulz, Egbert, Rohnstock, Madlen, Schettler, Elke, Schroppel, Bernd, van Erp, Rene, Kachele, Martin, Ludwig, Ulla, Schulte-Kemna, Lena, Kmietschak, Waltraud, Preiss, Elke, Ruocco, Martina, Heine, Gunnar, Brzoska, Martin, Gabel, Sebastian, Büttner, Christina, Sabarai, Asma, Banas, Bernhard, Bergler, Tobia, Ehrl, Yvonne, Putz, Franz, Schuster, Antonia, Kuhn, Stefanie, Schramm, Torsten, Degenhardt, Stefan, Schmidt, Gerhard, Weiland, Lea, Giebeln-Hudnell, Ulrike, Kielstein, Jan, Eden, Gabriele, Fuchs, Brigitte, Morig, Gina, Winkler, Manuela, Darius, Harald, Kriatselis, Charalampo, Roesch, Carl-Philipp, Maselli, Astrid, Alscher, Dominik, Ketteler, Marku, Schanz, Moritz, Schricker, Severin, Rettenmaier, Bianka, Schwab, Andrea, Pergola, Pablo, Leal, Irene, Cagle, Melissa, Romo, Anna, Torres, Anthony, Joshi, Sucharit, Barrett, Kulli, Africano, Alexi, Dodds, Vicki, Gowen, Dorleena, Morris, Ashlee, Fernandez, Juan, Jimenez, Guillermo, Viera, Ricardo, Bruce, Kendaling, Barrios, Ryan, Garcia, Maylin, Garcia, Kerelyn, Leal, Iradi, Tietjen, David, Bains, David, Castillo, Carlo, Brewer, Genielle, Davis, Justin, Freking, Natalie, Golson, Brittany, Ham, Sally, Roesch, Jesslyn, Suchinda, Pusadee, Beigh, Shameem, Lilavivat, Usah, Bilton, Joyce, Bocchicchia, Kim, Turner, Jeffrey, Dahl, Neera, Peixoto, Aldo, Kavak, Yasemin, Liberti, Lauren, Nair, Hari, Page, Nicola, Rosenberg, Stephanie, Simmons, Kathryn, Isakova, Tamara, Frazier, Rebecca, Mehta, Rupal, Srivastava, Anand, Fox, Patrick, Hecktman, Jonathan, Hodakowski, Alexander, Martinez, Carlo, Phillips, Rachel, Stevenson, Alexi, Mustafa, Reem, Jansson, Kyle, Kimber, Cassandra, Stubbs, Jason, Tuffaha, Ahmad, Yarlagadda, Sri, Griffin, Debbie, Laundy, Elisabeth, Tang, Zhuo, Alicic, Radica, Cooper, Ann, Davis, Lisa, Gore, Ashwini, Goldfaden, Rebecca, Harvill, Leslie, Hichkad, Lisa, Johns, Barry, Jones, Thoma, Merritt, Kayla, Sheldon, Jennifer, Stanfield, Jennifer, Alexander, Lindsay, Preston, Kaitlyn, Wood, Lindsey, Pradhan, Rajesh, Deraad, Roger, Mcintosh, Kelli, Raymond, Loui, Shepperd, Michael, Mclaughlin, Susan, Seifert, Mary, Shepherd, Andrew, Aiello, Joseph, Durham, William, Loudermilk, Laurie, Manley, John, Burnette, Sabrina, Evans, Stephanie, Johnson, Tara, Sloan, Lance, Ann Acosta, Judy, Gillham, Stacy, Sloan, Katia, Squyres, Sueann, Rocco, Michael, Hawfield, Amret, Bagwell, Ben, Richmond, Lauren, Soufer, Joseph, Clarke, Subha, Aliu, Amanda, Calabrese, Kristine, Davis, Amanda, Poma, Veronica, Spinola, Tracy, Magee, Jame, Silva, Ricardo, Choksi, Rushab, Dajani, Lorraine, Evans, John, George, Anil, Krish, Prasanth, Martins, Gerard, Sheikh-Ali, Mae, Sutton, David, Driver, Freda, Hanburry, Abraham, Hume, Laura, Hurst, Amber, Taddeo, Matthew, Turner, Marla, Yousif, Veronica, Beddhu, Srinivasan, Al-Rabadi, Laith, Abraham, Nikita, Caamano, Amalia, Carle, Judy, Gonce, Victoria, Staylor, Kaitlyn, Zhou, Na, Bansal, Shweta, Bhattarai, Manoj, Sharma, Kumar, Debnath, Subrata, Garza, Aliseiya, Velagapudi, Chakradhar, Rovner, Sergio, Almeida, Javier, Casares, Pablo, Stewart-Ray, Verlaine, Almaraz, Rene, Dayrell, Renata, Moncada, Ana, Pulido, Ricardo, Rodriquez, Roxana, Deeb, Wasim, Degoursey, Kathryn, Gloria, Rodel, Greene, Trevor, Miller, Robert, Pereira, Edward, Roura, Miguel, Domingo, Debbie, Dorestin, Sasha, Hodge, William, Jackson, Cathy, Lund, Deborah, Taylor, Katrina, Boren, Kenneth, Cleveland, Brittany, Gaiser, Sandra, Sahani, Mandeep, Aldrich, Logan, Edmerson, Exodu, Limon, Edmond, Valletta, Cole, Vasquez, Patricia, Provenzano, Christopher, Brar, Navkiranjot, Henderson, Heather, Keith, Bellovich, Khai, Qur, Khairullah, Quresh, Makos, Gail, Topf, Joel, Gasko, Sherry, Henschel, Rosemarie, Knapp, Kaitlin, Kozlowski, Teresa, Lafleur, Paula, Varughese, Ashwathy, Xue, Hui, Wu, Patricia, Arechiga, Olga, Darbeau, Shan, Fechter, Michael, Martinez, Stephanie, Hanson, Lenita, Cooper, Nyla, Madera, Areli, Cadorna, Jay, Sheridan, Rita, Sparks, Helen, Eilerman, Bradley, Bodine, Susanne, Eid, Wael, Flora, Rebecca, Avery, Amber, Hardy, Cashmere, Biscoveanu, Mihaela, Nagelberg, Steven, Cummins, Tracey, Rahbari-Oskoui, Frederic, Oommen, Anju, Forghani, Zohreh, Hitchcock, Stacie, Hosein, Darya, Watkins, Diane, Patel, Minesh, Lambert, Anthony, Newman, Elizabeth, Wood, Autumn, Ross, Tammy, Topping, Stephany, Mulhern, Jeffrey, Murphy, Lorna, Vasseur, Ann, Greenwood, Gregory, Hadley, Alexander, Laurienti, Denise, Marshall, Christopher, Mclean, Nichola, Satko, Scott, Caudill, Brandy, Maris, Jacob, Rogers, Janice, Vanhoy, Cindy, Thomas, George, Nakhoul, George, O'Toole, John, Taliercio, Jonathan, Cooperman, Leslie, Markovic, Marina, Tucky, Barbara, Dev, Devasmita, Hasan, Alia, Yalamanchili, Hima, Jain, Namita, Mcneil, Lesley, Wines, Eric, Park, Jean, Ghazi, Adline, Hamm, Mia, Patel, Teja, Mottl, Amy, Chang, Emily, Derebail, Vimal, Cole, Emmie, Froment, Anne, Kelley, Sara, Osmond Foster, Jordan, Mahabadi, Vahid, Jafari, Golriz, Kamarzarian, Anita, Arriaga, Wendy, Arteaga, Daisy, Machicado, Rosario, Naverrete, Genesi, Kumar, Prashant, Nazeer, Imran, Urquia, Karina, Glider, Tammi, Jones, Vickie, Rucker, Savannah, Wiley, Jennifer, Pandey, Rahul, Arroyo, Jesu, Pariani, Harish, Ahmad, Mohammad, Mozaffari, Shahin, Perez, Erika, Budoff, Matthew, Roy, Sion, Birudaraju, Divya, Ghanem, Ahmed, Hamal, Sajad, Aronoff, Stephen, Joye Petr, Elisa, Sachson, Richard, Wiebel, Jaime, Akram, Sana, Jones, Laurie, Knight, Curti, Tarlac, Maurie, Ahmed, Shahbaz, Szerlip, Harold, Akinfolarin, Akinwande, Mehta, Ankit, Camp, Shana, Castro, Cindy, Cooper, Zanaida, Terry, Jessica, Awad, Ahmed, Kothapalli, Bhavya, Lustig, Ryan, Alfaress, Serine, Jasim, Hyder, Parrigon, Mary, Karounos, Denni, Ahmed, Sadiq, Berry, Maggie, Oremus, Ruth, Hernandez-Cassis, Carlo, Ugwu, Elia, Junejo, Nazia, Suazo, Nancy, Segal, Mark, Kazory, Amir, Brown, Sherry, Daniels, Tristan, Dayi, Sofia, Hogan, Renee, Mccray, Kathy, Stickley, Jennifer, Rahman, Mahboob, Dobre, Mirela, Negrea, Lavinia, Padiyar, Aparna, Pradhan, Nishigandha, Rashidi, Arash, Sarabu, Nagaraju, Donley, Vicki, Young, Tricia, Oguchi, Godson, Onyema, Judepatrick, Damianik, Kahla, Dienes, Jack, Plummer-Morgan, Judith, Roman, Marilyn, Skipper, Mauver, Villaruel, Stacey-Ann, Williams, Krystle, Sugimoto, Danny, Dugas, Jeffrey, Ahmed, Ismeal, Bhairoo, Jamie, Rijos, Dolore, Salim, Huzaifa, Gavrila, Madita, Lafferty, Kathryn, Rabara, Ria, Ruse, Sally, Weetman, Maria, Bushnell, Jame, Power, Albert, Jenkins, Alison, Jones, Stefanie, Scott, Amanda, Byrne, Cath, Jesky, Mark, Cowley, Alison, Mchaffie, Emma, Waterfall, Holly, Taylor, Jo, Bough, Laura, Phillips, Thoma, Winter-Goodwin, Barbara, Phin Kon, Sui, Macdougall, Iain, Lioudaki, Eirini, Shah, Sapna, Sharpe, Claire, Aguilar, Francisco, Hernandez Pena, Abegail, Pugay, Conception, Te, Amelia, Finn, Hugh, Hanif, Wasim, Mostafa, Samiul, Aitken, Alice, Draxlbauer, Katharine, Grobovaite, Evelina, Kearney, Jennifer, Mccarthy, Theresa, Gentile, Giorgio, Browne, Duncan, Chellamuthu, Palanichamy, Dugal, Tabinda, Chant, Terri, Jones, Laura, Laity, Emily, Miners, Megan, Muir, Jame, Swanson, Elizabeth, Frankel, Andrew, Tomlinson, Jame, Alegata, Marlon, Almasarwah, Rashid, Apostolidi, Anthoula, Vourvou, Maria, Walters, Thoma, Taal, Maarten, Dukka, Hari, Kolhe, Nitin, Mcdonald, Carly, White, Kelly, Ugni, Shiva, Gunda, Smita, Oluyombo, Rotimi, Brindle, Vicki, Coutts, Ping, Fuller, Tracy, Nadar, Evelyn, Ramadoss, Suresh, Motherwell, Nichola, Pajak, Susannah, Tonks, Louise, Bhandari, Sunil, Bodington, Richard, Hazara, Adil, Fellowes, Dominic, Wong, Christopher, Goldsmith, Christopher, Barnes, Sherald, Bennett, Ann, Burston, Claire, Hope, Samantha, Hunt, Nicola, Kurian, Lini, Fish, Richard, Farrugia, Daniela, Lee, Judy, Sadler, Emma, Turner, Hannah, Hill, Christopher, Brown, Henry, Masengu, Agne, Maxwell, Peter, Bleakley, Nina, Murtagh, Hugh, Petchey, William, Yiu, Vivian, Kellett, Joanne, Williams, Angharad, Clarke, Helen, Carnall, Victoria, Benyon, Sarah, Blake, Caroline, Estcourt, Stephanie, Piper, Jane, Morgan, Neal, Hutchinson, Carolyn, Mckinley, Teresa, Woodman, Alastair, Graham, Judi, Leonard, Niall, Smyth, John, Adell, Vicki, Hagan, Samantha, Caplin, Ben, Oomatia, Amin, Damian, Eleanor, Sobande, Toluleyi, Doulton, Tim, Delaney, Michael, Montasser, Mahmoud, Hansen, Jenny, Loader, David, Moon, Angela, Morris, France, Sinha, Smeeta, Chukwu, Chukwuma, Hudson, Amy, Campbell, Diane, Kershaw, Melanie, Whittaker, Stephanie, Irtiza-Ali, Ayesha, Ghalli, Farid, Nosseir, Heba, Leslie, Allison, Trivedi, Kate, Fraser, Donald, Alhadj Ali, Mohammad, Griffin, Sian, Latif, Farah, Witczak, Justyna, Wonnacott, Alexa, Jeffers, Lynda, Webley, Yvette, Phelan, Paul, Miller-Hodges, Eve, Geddes, Ailsa, Glenwright, Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, Subash, Sood, Bhrigu, Swift, Pauline, Acheampong, Sarah, Ansu, Kwame, Augustin, Martia, Sampson, Anna, Vinall, Lynn, Wren, Kim, Wanninayake, Shamila, Wooding, Nichola, Edwards, Heather, Owen, Lydia, Bolton, Stephanie, Carson, Marion, Matthews, Michael, Brunskill, Nigel, Jesus-Silva, Jorge, Howson, Alex, Quashie-Akponeware, Mary, Tindall, Hilary, Nethaji, Chidambaram, Eldon, Helen, Patel, Rajan, Mark, Patrick, Rankin, Alastair, Sullivan, Michael, Forsyth, Kirsty, Mcdougall, Rowan, Dasgupta, Tanaji, Davies, Louisa, Ryder, Maggie, Grimmer, Philip, Macdonald, Clare, Webster, Mary, Newcastle, Newcastle, Ellam, Timothy, Wong, Edwin, Meshykhi, Christine, Webster, Andrea, Wilson, Peter, Vilar, Enric, Berdeprado, Jocelyn, Doctolero, Eunice, Wilkinson, Lily, Mccarroll, Frank, Ammar, Hesham, Kuan, Ying, Moran, Conor, Shivashankar, Girish, Campbell, Ryan, Glowski, Deborah, Mcdermott, Paula, Ali, Amar, Patel, Zuber, Bond, Christine, Whalley, Gillian, Zhang, Haitao, Yang, Liu, Zhang, Lihua, Kan, Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative

Subjects
chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.)

Published
2023

13. X-chromosome inactivation patterns in females with Fabry disease examined by both ultra-deep RNA sequencing and methylation-dependent assay

Author

Shoichi Maruyama, Kandai Nozu, Tomohiko Yamamura, Tomoko Horinouchi, Takeshi Ninchoji, Yuya Aoto, Shinya Ishiko, Rini Rossanti, Shogo Minamikawa, Eri Okada, Keiji Kono, Atsushi Fukunaga, Noritoshi Kato, China Nagano, Kazumoto Iijima, Hideki Fujii, Nana Sakakibara, and Shinichi Nishi

Subjects
Adult, Nephrology, Heterozygote, medicine.medical_specialty, Physiology, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Severity of Illness Index, X-inactivation, 03 medical and health sciences, 0302 clinical medicine, X Chromosome Inactivation, Physiology (medical), Internal medicine, medicine, Humans, Allele, Gene, Aged, Genetics, Chromosomes, Human, X, Sequence Analysis, RNA, business.industry, RNA, Methylation, DNA Methylation, Middle Aged, medicine.disease, Fabry disease, Phenotype, alpha-Galactosidase, Leukocytes, Mononuclear, Fabry Disease, Female, business
Abstract

Fabry disease is an X-linked inherited lysosomal storage disorder caused by mutations in the gene encoding α-galactosidase A. Males are usually severely affected, while females have a wide range of disease severity. This variability has been assumed to be derived from organ-dependent skewed X-chromosome inactivation (XCI) patterns in each female patient. Previous studies examined this correlation using the classical methylation-dependent method; however, conflicting results were obtained. This study was established to ascertain the existence of skewed XCI in nine females with heterozygous pathogenic variants in the GLA gene and its relationship to the phenotypes. We present five female patients from one family and four individual female patients with Fabry disease. In all cases, heterozygous pathogenic variants in the GLA gene were detected. The X-chromosome inactivation patterns in peripheral blood leukocytes and cells of urine sediment were determined by both classical methylation-dependent HUMARA assay and ultra-deep RNA sequencing. Fabry Stabilization Index was used to determine the clinical severity. Skewed XCI resulting in predominant inactivation of the normal allele was observed only in one individual case with low ⍺-galactosidase A activity. In the remaining cases, no skewing was observed, even in the case with the highest total severity score (99.2%). We conclude that skewed XCI could not explain the severity of female Fabry disease and is not the main factor in the onset of various clinical symptoms in females with Fabry disease.

Published
2021
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15. Relationship between parathyroid hormone and renin–angiotensin–aldosterone system in hemodialysis patients with secondary hyperparathyroidism

Author

Shunsuke Goto, Keiji Kono, Hideki Fujii, Shinichi Nishi, and Kentaro Watanabe

Subjects
Male, 0301 basic medicine, endocrine system, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, chemistry.chemical_element, Parathyroid hormone, Blood Pressure, 030209 endocrinology & metabolism, Calcium, Plasma renin activity, Renin-Angiotensin System, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Renal Dialysis, Internal medicine, Renin–angiotensin system, medicine, Humans, Orthopedics and Sports Medicine, Chronic Kidney Disease-Mineral and Bone Disorder, Parathyroidectomy, Hyperparathyroidism, business.industry, General Medicine, Middle Aged, medicine.disease, Body Fluids, chemistry, Parathyroid Hormone, Potassium, Female, Hyperparathyroidism, Secondary, Secondary hyperparathyroidism, 030101 anatomy & morphology, Hemodialysis, business, hormones, hormone substitutes, and hormone antagonists, Hormone
Abstract

Hyperparathyroidism (HPT) is associated with mortality and cardiovascular disease (CVD) in dialysis patients. However, its mechanism is still unclear. It is suspected that parathyroid hormone (PTH) is associated with the renin–angiotensin–aldosterone system (RAAS) as a possible mechanism. Thus, we examined their hormonal interaction in hemodialysis patients with secondary HPT. Seventeen hemodialysis patients with HPT were included. All patients underwent total parathyroidectomy (PTx). Serum intact PTH (iPTH), calcium and phosphate levels, plasma renin activity (PRA), and plasma aldosterone levels (ALD) were measured pre- and post-PTx. Pre-serum iPTH tended to be correlated with pre-PRA and were significantly correlated with pre-ALD (pre-PRA: r = 0.44, p = 0.07, pre-ALD: r = 0.49, p

Published
2020
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16. Pregnant Patient on Hemodialysis Who Showed Remarkable Improvement of Severe Hyperparathyroidism by Strict Serum Phosphorus Control

Author

Hideki Fujii, Keiji Kono, Shunsuke Goto, Jun Ito, and Shinichi Nishi

Subjects
medicine.medical_specialty, medicine.medical_treatment, Intact parathyroid hormone, Case Report, 030204 cardiovascular system & hematology, Severity of Illness Index, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Refractory, Pregnancy, Renal Dialysis, secondary hyperparathyroidism, Internal medicine, Internal Medicine, Humans, Medicine, Dialysis, Hyperparathyroidism, hemodialysis, intact parathyroid hormone, business.industry, Phosphorus, General Medicine, medicine.disease, Parathyroid Hormone, Calcium, Female, Hyperparathyroidism, Secondary, 030211 gastroenterology & hepatology, Secondary hyperparathyroidism, Hemodialysis, Serum phosphorus, business, hormones, hormone substitutes, and hormone antagonists
Abstract

We encountered a pregnant hemodialysis patient with severe hyperparathyroidism (HPT). Although her disease was considered to be refractory to medical treatment, the serum intact parathyroid hormone (PTH) level remarkably improved without manifestation of hypercalcemia through only strict serum phosphorus control, mainly via intensification of dialysis. The very strong correlation between the serum phosphorus level and serum intact PTH level suggested the possibility of secondary HPT. She ultimately gave birth to a healthy baby. The clinical course of the patient's HPT and the growth of the child have been good for more than six years.

Published
2020
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17. Changes in the whole/intact parathyroid hormone ratio and their clinical implications in patients with chronic kidney disease

Author

Kohei Okamoto, Hideki Fujii, Kentaro Watanabe, Shunsuke Goto, Keiji Kono, and Shinichi Nishi

Subjects
Nephrology, endocrine system, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Urology, Parathyroid hormone, Renal function, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Renal Dialysis, Internal medicine, medicine, Humans, In patient, Renal Insufficiency, Chronic, Kidney transplantation, Dialysis, Creatinine, business.industry, medicine.disease, Kidney Transplantation, chemistry, Parathyroid Hormone, Kidney Failure, Chronic, Calcium, business, hormones, hormone substitutes, and hormone antagonists, Glomerular Filtration Rate, Kidney disease
Abstract

Although a previous study has reported the relationship between intact parathyroid hormone (iPTH) and whole parathyroid hormone (wPTH) levels in patients undergoing dialysis, the w/i PTH ratio (whole/intact PTH ratio) among predialysis chronic kidney disease (CKD) patients remains unclear. The present study therefore aimed to examine the relationship between w/i PTH ratio and kidney function and determine other factors affecting the w/i PTH ratio. An observational study including 773 predialysis CKD patients was conducted. The correlation between w/i PTH ratio and kidney function, as well as clinical factors at different CKD stages, were assessed using univariate and multivariate analyses. In addition, the relationship between w/i PTH ratio and composite renal outcome [kidney transplantation, dialysis, and 30% decline in estimated glomerular filtration rate (eGFR)] was examined. The w/i PTH ratio decreased as the CKD stage progressed. Patients in each CKD stage (1/2, 3, 4, and 5) had a w/i PTH ratio of 0.85, 0.81, 0.78, and 0.59, respectively. The inflection point in the correlation lines between eGFR and w/i PTH ratio was 24.1 mL/min/1.73 m2. In multivariate analysis, the w/i PTH ratio was significantly correlated with serum calcium levels only in the CKD5 group and with eGFR in the CKD3, CKD4 and CKD5 group. Furthermore, w/i PTH ratio, eGFR, serum phosphate levels, and urinary protein/creatinine ratio were determined to be significant independent predictors for composite renal outcome. Our study demonstrated that changes in the w/i PTH ratio were associated with kidney function, abnormal mineral metabolism, and renal outcome.

Published
2020
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19. Characteristics of coronary artery disease in chronic kidney disease

Author

Keiji Kono, Hideki Fujii, and Shinichi Nishi

Subjects
Nephrology, medicine.medical_specialty, Invited Review Article, Physiology, 030232 urology & nephrology, Cardiorenal syndrome, Disease, 030204 cardiovascular system & hematology, urologic and male genital diseases, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, Chronic kidney disease, medicine, Prevalence, Humans, cardiovascular diseases, Endothelial dysfunction, Renal Insufficiency, Chronic, Vascular Calcification, Cause of death, business.industry, Coronary flow reserve, medicine.disease, Cardiovascular disease, Coronary Vessels, Endothelium, Vascular, business, Kidney disease
Abstract

Patients with chronic kidney disease (CKD) commonly experience cardiovascular disease (CVD), and a major cause of death in these patients is CVD. Therefore, the prevention of CVD progression is very crucial in patients with CKD. Recently, this relationship between CKD and CVD has increasingly been examined, and a concept termed “cardiorenal syndrome” has been advocated. Coronary artery disease (CAD) and myocardial injury are crucial factors that contribute to the occurrence of CVD. The initial step CAD is endothelial dysfunction that can be detected as a decrease in the coronary flow reserve (CFR). The previous studies have reported that decreased CFR is significantly correlated to coronary events and mortality. Furthermore, CFR reduces with a decline in the kidney function. Another important presentation of CAD is coronary artery calcification. Vascular calcification is a crucial pathophysiological state, particularly in patients with CKD, and it affects the stability of coronary atherosclerotic plaque. In CKD, not only the traditional risk factors but also CKD-related non-traditional risk factors play key roles in CVD progression. Therefore, the mechanisms responsible for CVD progression are very complex; however, their clarification is crucial to improve the prognosis in patients with CKD.

Published
2019

20. A case of membranous nephropathy characterized by atypical distribution of phospholipase A2 receptor

Author

Shigeo Hara, Kei Saito, Keiji Kono, Toshiki Hyodo, Shinichi Nishi, and Tomoo Itoh

Subjects
Male, Pathology, medicine.medical_specialty, Tubular atrophy, Kidney Glomerulus, 030232 urology & nephrology, Glomerulus (kidney), urologic and male genital diseases, Glomerulonephritis, Membranous, Basement Membrane, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Edema, medicine, Humans, Aged, medicine.diagnostic_test, urogenital system, business.industry, Receptors, Phospholipase A2, Glomerulonephritis, Nephrons, General Medicine, medicine.disease, Staining, Kidney Tubules, medicine.anatomical_structure, Nephrology, Immunohistochemistry, Renal biopsy, medicine.symptom, business
Abstract

A 77-year-old man was referred to our hospital with persistent proteinuria and progressive lower leg edema. Past history was unremarkable except for hypertension. Autoimmune diseases, infections, and malignancies were excluded based on clinical and laboratory test results. Renal biopsy specimens showed membranous nephropathy with segmental distribution of spikes and bubbling appearance. Double contour formation in glomerular tufts was also observed. There were no proliferative changes in the glomeruli. Interstitial fibrosis and tubular atrophy were moderate, and no interstitial inflammation was observed. Arteries showed moderate sclerotic changes with hyalinosis. Immunohistochemical analysis revealed no thrombospondin type 1 domain-containing 7A reactivity. Immunofluorescence staining showed segmental granular positivity of IgG on glomerular tufts and focal staining of IgG on the tubular basement membranes. IgG deposits (subclass distribution: IgG1, 2+; IgG2, -; IgG3, 1+; IgG4, 2+) and phospholipase A2 receptor type 1 (PLA2R1) immunoreactivity showed similar distributions in both glomeruli and renal tubular basement membranes. Electron microscopy revealed subendothelial edema in partially collapsed glomerulus. No subepithelial dense deposits were observed in the glomeruli under an electron microscope. This is the first documented case of membranous nephropathy (MN) with segmental distribution of PLA2R1 in the glomeruli and focal PLA2R1 positivity in renal tubular basement membranes. Our findings extend the pathological presentation of PLA2R1-associated MN. Future studies are required to examine the mechanistic insights of these atypical histopathological features. .

Published
2019
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21. Influence of Coexisting Chronic Kidney Disease and Left Ventricular Hypertrophy on Changes in FGF23 and the Renin-Angiotensin-Aldosterone-System

Author

Keiji Kono, Kohei Okamoto, Shinichi Nishi, Hideki Fujii, Shunsuke Goto, and Kentaro Watanabe

Subjects
medicine.medical_specialty, business.industry, urologic and male genital diseases, medicine.disease, Left ventricular hypertrophy, stomatognathic diseases, Text mining, Internal medicine, Renin–angiotensin system, medicine, Cardiology, cardiovascular diseases, business, Kidney disease
Abstract

Serum fibroblast growth factor 23 (FGF23) levels and the renin-angiotensin-aldosterone system (RAAS) are elevated in chronic kidney disease (CKD) patients, and their association with left ventricular hypertrophy (LVH) has been reported. However, whether the FGF23 elevation is the cause or result of LVH remains unclear. At 10 weeks, male C57BL/6J mice were divided into four groups: Sham, CKD (5/6 nephrectomy), LVH (transaortic constriction), and CKD/LVH group. At 16 weeks, the mice were sacrificed, and blood and urine, cardiac expressions of FGF23 and RAAS-related factors, and cardiac histological analyses were performed. Heart weight, serum FGF23 levels, and cardiac expression of FGF23 and RAAS-related factors, except for angiotensin-converting enzyme 2, more increased in the CKD/LVH group compared to the other groups. A significant correlation between LVH and cardiac expressions of FGF23 and RAAS-related factors was observed. Furthermore, there was a significantly close correlation of the cardiac expression of FGF23 with LVH and RAAS-related factors. The coexisting CKD and LVH increased serum and cardiac FGF23 and RAAS-related factors, and there was a significant correlation between them. A close correlation of cardiac, but not serum FGF23, with LVH and RAAS suggested that local FGF23 may be associated with LVH and the RAAS activation.

Published
2021
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22. Influence of oxidative stress on vascular calcification in the setting of coexisting chronic kidney disease and diabetes mellitus

Author

Kentaro Watanabe, Keiji Kono, Shunsuke Goto, Hideki Fujii, Shuhei Watanabe, and Shinichi Nishi

Subjects
Blood Glucose, Male, Nephrology, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, lcsh:Medicine, Context (language use), 030204 cardiovascular system & hematology, urologic and male genital diseases, medicine.disease_cause, Article, Antioxidants, Streptozocin, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Animals, Renal Insufficiency, Chronic, lcsh:Science, Vascular Calcification, Kidney diseases, Osteoblasts, Multidisciplinary, business.industry, Insulin, lcsh:R, Cell Differentiation, medicine.disease, female genital diseases and pregnancy complications, Rats, Oxidative Stress, Endocrinology, chemistry, Apocynin, Disease Progression, lcsh:Q, business, Biomarkers, Oxidative stress, Kidney disease, Calcification
Abstract

Vascular calcification (VC) is a common complication in patients with chronic kidney disease (CKD). Particularly, CKD patients with diabetes mellitus (DM) develop severe VC. Specific mechanisms of VC remain unclear; this study aimed to investigate them in the context of coexisting CKD and DM, mainly regarding oxidative stress. Sprague Dawley rats were randomly divided into six groups as follows: control rats (Control), 5/6 nephrectomized rats (CKD), streptozotocin-injected rats (DM), 5/6 nephrectomized and streptozotocin-injected rats (CKD + DM), CKD + DM rats treated with insulin (CKD + DM + INS), and CKD + DM rats treated with antioxidant apocynin (CKD + DM + APO). At 18 weeks old, the rats were sacrificed for analysis. Compared to the control, DM and CKD groups, calcification of aortas significantly increased in the CKD + DM group. Oxidative stress and osteoblast differentiation-related markers considerably increased in the CKD + DM group compared with the other groups. Moreover, apocynin considerably reduced oxidative stress, osteoblast differentiation-related markers, and aortic calcification despite high blood glucose levels. Our data indicate that coexisting CKD and DM hasten VC primarily through an increase in oxidative stress; anti-oxidative therapy may prevent the VC progression.

Published
2020
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23. Evaluation of aortic calcification using a three-dimensional volume-rendering method in patients with end-stage kidney disease

Author

Hideki Fujii, Keiji Kono, Shunsuke Goto, Atsushi K. Kono, Tatsuya Nishii, Shinichi Nishi, and Kentaro Watanabe

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Imaging, Three-Dimensional, medicine.artery, Internal medicine, Ascending aorta, medicine, Humans, Orthopedics and Sports Medicine, Aorta, Abdominal, Vascular Calcification, business.industry, Abdominal aorta, General Medicine, Middle Aged, medicine.disease, Coronary Vessels, Pulse pressure, Blood pressure, Descending aorta, Cardiology, Kidney Failure, Chronic, Female, 030101 anatomy & morphology, Hemodialysis, business, Tomography, X-Ray Computed, Calcification, Kidney disease
Abstract

Very few studies have been performed to evaluate both the severity and site of aortic calcification (AC) in both end-stage kidney disease (ESKD) and diabetes mellitus (DM). The purpose of our study was to examine the utility of a newly developed three-dimensional (3D) visualization and quantification method compared with other methods to evaluate vascular calcification in ESKD patients with and without DM. Fifty patients with ESKD before initiating hemodialysis at our hospital were included in the present study. They were divided into the two groups, depending on the presence or absence of DM: Control group (n = 31) and DM group (n = 19). The volume and site of AC were evaluated via computed tomography (CT) scan using a 3D visualization and quantification method. Total calcification volume was significantly greater in the DM group than in the Control group. Calcification volume in the descending and abdominal aortas was greater in the DM group compared to the Control group. There were no significant differences in calcification volume in the aortic root, ascending aorta, and aortic arch. Calcification volume of the whole aorta, the descending aorta, and the abdominal aorta were each significantly correlated with age, diastolic blood pressure and pulse pressure. This study using a 3D visualization and quantification method demonstrated that AC was more severe and occurred more frequently in the abdominal aorta in ESKD patients with DM compared to those without DM. This method would enable us to precisely evaluate the volume and distribution of AC.

Published
2020

24. Histological changes of a kidney in a recipient who received an allograft from a patient with Fabry disease

Author

Keiji Kono, Takeshi Ishimura, Shigeo Hara, Hideki Fujii, and Shinichi Nishi

Subjects
Nephrology, medicine.medical_specialty, Kidney, business.industry, MEDLINE, Urology, medicine.disease, Allografts, Fabry disease, Kidney Transplantation, Tissue Donors, medicine.anatomical_structure, Internal medicine, medicine, Fabry Disease, Humans, business, Kidney transplantation
Published
2020

25. Changes in blood pressure during treatment with the tyrosine kinase inhibitor lenvatinib

Author

Takumi Fukumoto, Ken Hirabayashi, Kentaro Watanabe, Shohei Komatsu, Keiji Kono, Satoshi Yamatani, Shinichi Nishi, Shunsuke Goto, Hideki Fujii, and Kei Saito

Subjects
medicine.medical_specialty, Ambulatory blood pressure, urinary sodium excretion, medicine.drug_class, Urinary system, Urology, Renal function, lenvatinib, 030204 cardiovascular system & hematology, Tyrosine-kinase inhibitor, Excretion, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, tyrosine kinase inhibitor, medicine, AcademicSubjects/MED00340, Transplantation, business.industry, blood pressure, Original Articles, medicine.disease, ambulatory blood pressure monitoring, Blood pressure, chemistry, Nephrology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Lenvatinib, business
Abstract

Background Within the class of tyrosine kinase inhibitors (TKIs), which are used for the treatment of numerous advanced cancers, lenvatinib is associated with a higher prevalence of hypertension (HT) compared with other TKIs. In this study, we investigated the effect of lenvatinib on blood pressure (BP) and associated factors. Methods This single-centre, retrospective observational study included 25 consecutive patients treated with lenvatinib for unresectable hepatocellular carcinoma from April 2018 to December 2018 at the study institution. We assessed changes in BP using ambulatory BP monitoring, urinary sodium excretion, kidney function, use of antihypertensive agents and diuretics, and fluid retention following treatment initiation with lenvatinib. Results At 1 week after treatment initiation, the mean BP and the percentage of patients with riser pattern significantly increased compared with those at the baseline. Although there were no significant changes at 1 week, urinary sodium excretion (153.4 ± 51.7 and 112.5 ± 65.0 mEq/day at 1 and 3 weeks, respectively, P Conclusions Lenvatinib might lead to HT without fluid retention soon after the initiation of treatment, subsequently leading to a reduction in urinary sodium excretion, thereby contributing to a rise in BP by fluid retention.

Published
2020

26. Changes of FGF23 and the Renin-Angiotensin-System in Male Mouse Models of Chronic Kidney Disease and Cardiac Hypertrophy

Author

Kohei Okamoto, Hideki Fujii, Kentaro Watanabe, Shunsuke Goto, Keiji Kono, and Shinichi Nishi

Subjects
stomatognathic diseases, aldosterone, renin-angiotensin-aldosterone system, Endocrinology, Diabetes and Metabolism, cardiovascular diseases, urologic and male genital diseases, AcademicSubjects/MED00250, chronic kidney disease, Research Article, fibroblast growth factor 23, left ventricular hypertrophy
Abstract

Serum fibroblast growth factor 23 (FGF23) levels and the renin-angiotensin-aldosterone system (RAAS) are elevated in chronic kidney disease (CKD) patients, and their association with left ventricular hypertrophy (LVH) has been reported. However, whether the FGF23 elevation is the cause or result of LVH remains unclear. At 10 weeks, male C57BL/6J mice were divided into 4 groups: sham, CKD (5/6 nephrectomy), LVH (transaortic constriction), and CKD/LVH group. At 16 weeks, the mice were euthanized, and blood and urine, cardiac expressions of FGF23 and RAAS-related factors, and cardiac histological analyses were performed. Heart weight, serum FGF23 levels, and cardiac expression of FGF23 and RAAS-related factors, except for angiotensin-converting enzyme 2, were more increased in the CKD/LVH group compared to the other groups. A significant correlation between LVH and cardiac expressions of FGF23 and RAAS-related factors was observed. Furthermore, there was a significantly close correlation of the cardiac expression of FGF23 with LVH and RAAS-related factors. The coexisting CKD and LVH increased serum and cardiac FGF23 and RAAS-related factors, and there was a significant correlation between them. A close correlation of cardiac, but not serum FGF23, with LVH and RAAS suggests that local FGF23 levels may be associated with LVH and RAAS activation.

Published
2022

27. Changes in serum and intracardiac fibroblast growth factor 23 during the progression of left ventricular hypertrophy in hypertensive model rats

Author

Shunsuke Goto, Keiji Kono, Kentaro Watanabe, Hideki Fujii, Shuhei Watanabe, and Shinichi Nishi

Subjects
Male, Nephrology, Fibroblast growth factor 23, medicine.medical_specialty, Physiology, medicine.drug_class, Urinary system, 030232 urology & nephrology, 030204 cardiovascular system & hematology, urologic and male genital diseases, Left ventricular hypertrophy, Rats, Inbred WKY, Bone and Bones, Intracardiac injection, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Rats, Inbred SHR, Physiology (medical), Internal medicine, Natriuretic Peptide, Brain, medicine, Natriuretic peptide, Animals, cardiovascular diseases, Aldosterone, Chronic Kidney Disease-Mineral and Bone Disorder, business.industry, Myocardium, Organ Size, medicine.disease, Peptide Fragments, Fibroblast Growth Factors, Disease Models, Animal, stomatognathic diseases, Endocrinology, Blood pressure, chemistry, Hypertension, Hypertrophy, Left Ventricular, business
Abstract

Recent clinical studies have demonstrated that serum fibroblast growth factor 23 (FGF23) levels have a significant association with left ventricular hypertrophy (LVH). Although LVH is commonly seen in hypertensive patients, the association between FGF23, hypertension, and LVH remains unclear. We aimed to examine the changes in serum and intracardiac FGF23 during the progression of hypertension using spontaneously hypertensive rats (SHR). Male SHR comprised the experimental group (HT group) and Wistar Kyoto rats served as controls. At 10 weeks, urinary and blood biochemical analyses and blood pressure measurements were performed for both the groups. At 18 weeks, the rats were sacrificed: urinary and blood biochemical analyses and real-time PCR were performed. At 18 weeks, the relative heart weight and serum N-terminal pro-brain natriuretic peptide and aldosterone levels were significantly greater in the HT group. Serum calcium and phosphate levels were significantly lower, while serum FGF23 levels were significantly higher in the HT group compared to the control group. Further analyses showed that the mRNA expression of FGF23 in the heart was significantly increased in the HT group compared to the control group. Both serum FGF23 levels and intracardiac mRNA expression of FGF23 showed significant correlation with the relative heart weight. During LVH progression, serum and intracardiac FGF23 increased in hypertension. Although it is unclear whether the change in FGF23 is the cause or result of LVH, the interaction between FGF23 and aldosterone may be associated with the development of LVH in hypertension.

Published
2018
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29. Influence of Uncertain Anticipation on Brain Responses to Aversive Rectal Distension in Patients With Irritable Bowel Syndrome

Author

Patrick Dupont, Huynh Giao Ly, Lukas Van Oudenhove, Shunji Mugikura, Joe Morishita, Kei Takase, Keiji Kono, Tomohiko Muratsubaki, Michiko Kano, and Shin Fukudo

Subjects
Adult, Male, Nociception, medicine.medical_specialty, Adolescent, Brain activity and meditation, Precuneus, Brain mapping, Irritable Bowel Syndrome, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Psychiatry, Applied Psychology, Irritable bowel syndrome, Cerebral Cortex, Brain Mapping, medicine.diagnostic_test, business.industry, Rectum, Uncertainty, Hypervigilance, Anticipation, Psychological, medicine.disease, Magnetic Resonance Imaging, Anticipation, Psychiatry and Mental health, medicine.anatomical_structure, Anesthesia, Female, 030211 gastroenterology & hepatology, medicine.symptom, business, Functional magnetic resonance imaging, Insula, 030217 neurology & neurosurgery
Abstract

Objective We investigated whether certainty and uncertainty of impending aversive visceral sensation differently modulate regional brain activity, both during anticipation and visceral sensation in irritable bowel syndrome (IBS) patients compared with healthy controls. Methods Twenty-six IBS patients (14 women) and 29 healthy controls (15 women) were enrolled in a functional magnetic resonance imaging study. Participants received rectal distention at an individually titrated severe discomfort level that was preceded by visual cues to induce certain (100% chance of distention), uncertain (50% chance), and safe (0% chance) anticipation. Results Subjective ratings of anticipatory fear before and discomfort during distention were similar between IBS and control participants under cued certainty and uncertainty (p > .05). Uncertain anticipation compared with certain anticipation induced greater activation of anterior midcingulate cortex, thalamus, and visual processing areas in IBS patients compared with controls. Rectal distention after the uncertain, but not certain, cue induced higher activity in the posterior- and midcingulate cortices and the precuneus in IBS compared with controls. Controls exhibited bilateral insula activation during the nondistention period after the uncertain cue compared with the safe cue. IBS patients failed to produce this response, which was possibly due to elevated bilateral insular responses during nondistention after the safe cue. Brain data were significant at a voxel-level threshold of puncorrected value of less than .005 combined with a cluster-level threshold of pFWE-corrected value of less than .05. Conclusions Preceding uncertainty differentially modulates the brain processing of physiologically identical rectal stimulation in IBS patients. Cue-dependent alterations in brain responses may underlie hypervigilance to visceral sensations in IBS patients.

Published
2017
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30. Effects of Lanthanum Carbonate on Coronary Artery Calcification and Cardiac Abnormalities After Initiating Hemodialysis

Author

Keiji Kono, Hideki Fujii, Shunsuke Goto, Atsushi K. Kono, Shinichi Nishi, Tatsuya Nishii, and Kentaro Nakai

Subjects
Adult, Male, Fibroblast growth factor 23, medicine.medical_specialty, medicine.drug_class, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030232 urology & nephrology, Parathyroid hormone, chemistry.chemical_element, 030204 cardiovascular system & hematology, Calcium Carbonate, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Lanthanum, Renal Dialysis, Internal medicine, medicine, Humans, Orthopedics and Sports Medicine, Renal Insufficiency, Chronic, Vascular Calcification, Aged, Chelating Agents, Aged, 80 and over, business.industry, Middle Aged, medicine.disease, Coronary Vessels, Phosphate binder, Fibroblast Growth Factor-23, Lanthanum carbonate, Treatment Outcome, Calcium carbonate, chemistry, Parathyroid Hormone, Cardiology, Female, Hemodialysis, business, Kidney disease, medicine.drug
Abstract

It is known that calcium-containing phosphate binders are more closely associated with the progression of vascular calcification than non-calcium-containing phosphate binders. In this study, we investigated the effect of the non-calcium-containing phosphate binder, lanthanum carbonate on the progression of coronary artery calcification and cardiovascular abnormalities compared to that of calcium-containing phosphate binder in chronic kidney disease patients during the early period after initiating hemodialysis. This was a randomized open-label study in which patients were divided into the calcium carbonate or lanthanum carbonate group. We evaluated blood samples, coronary artery calcification using high-resolution computed tomography, and cardiac abnormalities using echocardiography prior to and after initiating hemodialysis. Cardiac dimension and systolic function were significantly improved in the lanthanum carbonate group compared to those in the calcium carbonate group. Although statistically significant differences were not observed in all the patients, only among patients with moderate coronary artery calcification, the changes in coronary artery calcification score at 18 months were significantly smaller in the lanthanum carbonate group than those in the calcium carbonate group. The percent change in coronary artery calcification at 18 months was significantly correlated with the serum fibroblast growth factor 23 levels at 18 months (r = 0.245, P

Published
2017
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31. Hypertension Induced by Tyrosine-Kinase Inhibitors for the Treatment of Renal Cell Carcinoma in Hemodialysis Patients: A Single-Center Experience and Review of the Literature

Author

Kentaro Nakai, Shunsuke Goto, Hideki Fujii, Keiji Kono, and Shinichi Nishi

Subjects
Sorafenib, medicine.medical_specialty, Sunitinib, business.industry, medicine.medical_treatment, 030232 urology & nephrology, Urology, Hematology, 030204 cardiovascular system & hematology, Single Center, medicine.disease, Surgery, Axitinib, 03 medical and health sciences, 0302 clinical medicine, Blood pressure, Nephrology, Renal cell carcinoma, medicine, Hemodialysis, business, Dialysis, medicine.drug
Abstract

Malignancy is a major cause of mortality in dialysis patients. Although molecular-targeted anticancer drugs, including tyrosine-kinase inhibitors, are used for advanced renal cell carcinoma treatment, there are few reports on their effectiveness and safety in dialysis patients. Renal cell carcinoma dialysis patients treated at our hospital from 2010 to 2013 participated in this study. Thirteen patients were treated with tyrosine-kinase inhibitors and 15 patients with surgery only (control group). During treatment, blood pressure changes and dry weight reduction tended to be greater in the tyrosine-kinase inhibitor group than in controls. More intensive management of hypertension was necessary in the tyrosine-kinase inhibitor group than in the controls. Renal cell carcinoma treatment by tyrosine-kinase inhibitors increased blood pressure in hemodialysis patients. We should prevent and manage hypertension carefully by adjusting antihypertensive drugs and dry weight in renal cell carcinoma patients.

Published
2017
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32. A Case of Fibrillary Glomerulonephritis with Fibril Deposition in the Arteriolar Wall and a Family History of Renal Disease

Author

Shuhei Watanabe, Shinichi Nishi, Kentaro Watanabe, Hideki Fujii, Kentaro Nakai, Nozomi Hosokawa, Shigeo Hara, Shunsuke Goto, and Keiji Kono

Subjects
Pathology, medicine.medical_specialty, business.industry, Fibrillary Glomerulonephritis, Familial nephritis, 030232 urology & nephrology, Nephrotic syndrome, Case Report, 030204 cardiovascular system & hematology, Glomerulus (kidney), Fibril, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Nephrology, Mesangium, Glomerulopathy, Hereditary nephritis, medicine, Mesangial proliferative glomerulonephritis, Fibrillary glomerulonephritis, Family history, business
Abstract

Herein, we report a case of fibrillary glomerulonephritis (FGN). FGN usually shows non-amyloidal fibrils in the mesangium and glomerular capillary walls on electron microscopy. Inherited cases of FGN have been reported in only 3 families, and the suspected genetic form was autosomal dominant. In the present case, the deposition of microfibrils in the arteriolar wall as well as the glomerulus is unique. Our patient’s father died of nephrotic syndrome, and his elder brother had a biopsy-proven glomerulopathy. The histological findings of the brothers are similar to mesangial proliferative glomerulonephritis and resemble each other. Therefore, our case is presumed to be familial FGN. Additionally, herein, we review the literature and reconsider the histological and clinical characters of FGN.

Published
2017

33. A case of cryptococcuria involving the delayed development of cryptococcal meningitis after the initiation of hemodialysis

Author

Keiji Kono, Shunsuke Goto, Shuhei Watanabe, Kentaro Nakai, Risa Ishida, Shinichi Nishi, Hideki Fujii, Junji Takiguchi, Junko Nakano, Mao Shimizu, Kentaro Watanabe, Mikiko Yoshikawa, Toru Iwasaki, and Ria Awata

Subjects
03 medical and health sciences, Pediatrics, medicine.medical_specialty, 0302 clinical medicine, business.industry, medicine.medical_treatment, 030232 urology & nephrology, medicine, 030212 general & internal medicine, Hemodialysis, business, Cryptococcal meningitis
Published
2017
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34. Clinical practice guideline for renal rehabilitation: systematic reviews and recommendations of exercise therapies in patients with kidney diseases

Author

Norio Hanafusa, Kiyomi Koike, Akiko Uchida, Shunsuke Goto, Tsuneo Konta, Takayuki Miyai, Naohiko Fujii, Ryuichi Yoshimura, Ryota Ishii, Yoshihiko Raita, Osamu Ito, Tatsuya Shimizu, Satoko Sakurai, Susumu Toda, Jumpei Hasegawa, Junichi Hoshino, Mimiko Matsumura, Yasuhiro Komatsu, Tadashi Sofue, Hitoshi Sugiyama, Masashi Kitagawa, Suguru Yamanoto, Taku Harada, Eiichiro Kanda, Hiroo Kawarazaki, Atsuhiko Matsunaga, Takehiko Kawaguchi, Masayuki Yamanouchi, Satoru Kaneko, Masahiko Yazawa, Keiji Kono, Kentaro Takase, Makoto Tsujita, Masahiro Kohzuki, Norikazu Hinamoto, Hideyo Oguchi, Kunihiro Yamagata, Yasuhiro Ando, Yugo Shibagaki, Kiyonobu Ishizuka, and Fumika Taki

Subjects
Nephrology, medicine.medical_specialty, Urology, medicine.medical_treatment, Exercise therapy, 030232 urology & nephrology, 030204 cardiovascular system & hematology, lcsh:RC870-923, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, CKD, medicine, Intensive care medicine, Kidney transplantation, Dialysis, Transplantation, Rehabilitation, business.industry, Renal rehabilitation, Guideline, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, Systematic review, Kidney disorder, business
Abstract

In recent years, a concept of renal rehabilitation has become widely known among nephrology specialists, dialysis specialists, kidney transplantation specialists, rehabilitation specialists, nutrition specialists, guideline specialists, nurses, physiotherapists, and representatives of patients. Therefore, in order to make it clear the definition, methods, and effectiveness of renal rehabilitation in Japan, we launched Renal Rehabilitation Guideline Preparation Committee in 2016 as a part of works in the Japanese Society of Renal Rehabilitation, and created a guideline in accordance to the “Minds Handbook for Clinical Practice Guideline Development 2014”. Here, we report systematic reviews and recommendations of exercise therapies in patients with kidney diseases based on the guideline preparation committee works. Six recommendations for the condition of each kidney disorder, groups addressing nephritis/nephrosis, chronic kidney diseases, dialysis therapy, and kidney transplantation were created. All the recommendation grades were determined by a consensus conference participated in by representatives of patients and various professionals. The purpose of this report is to provide an evidence-based, best practice summary to optimize the quality, safety and efficacy, and availability of renal rehabilitation service, and to provide care for maximum patient prognosis, quality of life, and satisfaction.

Published
2019
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37. Parasympathetic activity correlates with subjective and brain responses to rectal distension in healthy subjects but not in non-constipated patients with irritable bowel syndrome

Author

Lukas Van Oudenhove, Kei Takase, Mao Yagihashi, Shunji Mugikura, Patrick Dupont, Tomohiko Muratsubaki, Michiko Kano, Makoto Yoshizawa, Motoyori Kanazawa, Shin Fukudo, Keiji Kono, and Joe Morishita

Subjects
Male, Nociception, 0301 basic medicine, INDUCED PAIN, Brain activity and meditation, lcsh:Medicine, Gastroenterology, Irritable Bowel Syndrome, Electrocardiography, Basal (phylogenetics), 0302 clinical medicine, Heart Rate, Neural Pathways, Heart rate variability, lcsh:Science, Irritable bowel syndrome, ASSOCIATIONS, HEART-RATE-VARIABILITY, Multidisciplinary, medicine.diagnostic_test, FUNDAMENTALS, Vagus Nerve, Visceral Pain, Magnetic Resonance Imaging, Healthy Volunteers, 3. Good health, Multidisciplinary Sciences, medicine.anatomical_structure, Science & Technology - Other Topics, Sensory processing, Female, Dilatation, Pathologic, Adult, medicine.medical_specialty, DISORDERS, Gyrus Cinguli, SYMPATHOVAGAL BALANCE, Article, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Pathological, Anterior cingulate cortex, PERCEPTION, Science & Technology, business.industry, lcsh:R, Rectum, AUTONOMIC NERVOUS-SYSTEM, medicine.disease, DYSFUNCTION, 030104 developmental biology, lcsh:Q, Caudate Nucleus, business, Functional magnetic resonance imaging, 030217 neurology & neurosurgery
Abstract

The nociceptive and autonomic nervous systems (ANS) are significantly intertwined. Decoupling of these systems may occur in pathological pain conditions, including irritable bowel syndrome (IBS). We investigated ANS activity and its association with visceral perception and brain activity during rectal distention in 27 patients with non-constipated IBS and 33 controls by assessing heart rate variability (HRV) using electrocardiography at rest, before, and during colorectal distention. Brain responses to colorectal distention were measured using functional magnetic resonance imaging and correlated with individual ANS function parameters. The IBS group displayed blunted sympathovagal balance [low/high-frequency ratio (LF:HF) of HRV] in response to colorectal distention compared with controls (P = 0.003). In controls, basal parasympathetic tone (HF component of HRV) was significantly negatively correlated with toleration threshold to the rectal distention, but not in patients with IBS (group comparison P = 0.04). Further, a positive correlation between baseline HF values and neural responses to rectal distension was found in the right caudate, bilateral dorsolateral anterior cingulate cortex, and pregenual anterior cingulate cortex in the control group but not in the IBS group. The results indicate abnormal interactions between ANS activity and the brain mechanisms underlying visceral perception in patients with IBS.

Published
2019
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38. Effects of lanthanum carbonate on bone markers and bone mineral density in incident hemodialysis patients

Author

Kentaro Watanabe, Shunsuke Goto, Kimihiko Goto, Hideki Fujii, Shinichi Nishi, and Keiji Kono

Subjects
0301 basic medicine, Male, medicine.medical_specialty, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Osteocalcin, 030209 endocrinology & metabolism, Bone and Bones, Bone remodeling, Calcium Carbonate, Phosphates, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Bone Density, Lanthanum, Renal Dialysis, Internal medicine, Medicine, Humans, Orthopedics and Sports Medicine, Renal Insufficiency, Chronic, Aged, Bone mineral, biology, business.industry, Tartrate-Resistant Acid Phosphatase, Acid phosphatase, General Medicine, Middle Aged, Phosphate binder, Lanthanum carbonate, chemistry, Parathyroid Hormone, biology.protein, Sclerostin, Alkaline phosphatase, Calcium, Female, 030101 anatomy & morphology, Bone Remodeling, business, Biomarkers, medicine.drug
Abstract

Recent clinical studies demonstrated the favorable effects of calcium-free phosphate binders on mortality and vascular calcification in hemodialysis (HD) patients. The aim of the present study was to investigate the effects of a calcium-free phosphate binder, lanthanum carbonate (LC), on bone metabolic markers and bone mineral density (BMD), compared with those of calcium carbonate (CC), in subjects new to HD. The present study included 65 subjects from our previous randomized controlled trial (LC group, N = 31; CC group, N = 34). We investigated the effects of LC on serum intact parathyroid hormone (iPTH), osteocalcin (OC), bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRACP-5b), sclerostin levels, and BMD, compared with those of CC in patients new to HD at baseline and at 12 and 18 months. Serum OC levels at 18 months were significantly higher in the LC group than in the CC group. During the study period, serum BAP and TRACP-5b and iPTH levels tended to be higher in the LC group than in the CC group. At 18 months, the percentage of low bone turnover, based on a serum BAP cutoff value, was significantly lower in the LC group than in the CC group. There were no significant differences in the lumbar and femoral BMD between the two groups. The results of the present study suggest that LC has potential in preventing low bone turnover, in comparison to CC, in patients new to HD.

Published
2019

39. One-Year Impact of Kidney Transplantation on Cardiac Abnormalities and Blood Pressure in Hemodialysis Patients

Author

Masato Fujisawa, Hideki Fujii, Shunsuke Goto, Shuhei Watanabe, Shinichi Nishi, Keiji Kono, Takeshi Ishimura, and Kentaro Watanabe

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Concentric hypertrophy, Renal function, Blood Pressure, Disease, 030204 cardiovascular system & hematology, Left ventricular hypertrophy, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Internal medicine, Medicine, Humans, Renal Insufficiency, Chronic, Kidney transplantation, Antihypertensive Agents, Retrospective Studies, business.industry, Hematology, Middle Aged, medicine.disease, Kidney Transplantation, Blood pressure, Nephrology, Cardiovascular Diseases, Echocardiography, Cardiac chamber, Hypertension, Cardiology, Female, Hypertrophy, Left Ventricular, Hemodialysis, business, Follow-Up Studies
Abstract

Cardiac abnormalities, including left ventricular hypertrophy and systolic dysfunction, are frequently observed among patients with CKD, including kidney transplant recipients; they are closely linked to cardiovascular disease and mortality. Although several studies have been performed for elucidating changes and mechanisms of cardiac abnormalities after kidney transplantation, details remain unclear. This study included 43 consecutive patients who underwent HD and received kidney transplantation between 2008 and 2012 at our institution. All subjects underwent echocardiography before and 1 year after kidney transplantation. One year after kidney transplantation, left ventricular mass index, cardiac chamber sizes, BP, and the number of antihypertensive agents were reduced. Although the percentage of patients with concentric hypertrophy did not change, the percentage of those with eccentric hypertrophy significantly decreased after kidney transplantation. Volume reduction due to the recovery of kidney function may be primarily attributed to the improvement of cardiac abnormalities, including left ventricular hypertrophy.

Published
2019

40. Anti-oxidative effect of AST-120 on kidney injury after myocardial infarction

Author

Yuriko Yonekura, Yusuke Yamashita, Shunsuke Goto, Hideki Fujii, Sumie Goto, Kentaro Nakai, Ayako Fujieda, Yoshiharu Ito, Mikio Sugano, Shinichi Nishi, and Keiji Kono

Subjects
Pharmacology, medicine.medical_specialty, Kidney, business.industry, 030232 urology & nephrology, Urine, 030204 cardiovascular system & hematology, medicine.disease, medicine.disease_cause, digestive system, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Blood pressure, Internal medicine, medicine, Kidney injury, Myocardial infarction, Risk factor, business, Oxidative stress, Kidney disease
Abstract

BACKGROUND AND PURPOSE Chronic kidney disease (CKD) is a crucial risk factor for cardiovascular disease (CVD), and combined CKD and CVD further increases morbidity and mortality. Here, we investigated effects of AST-120 on oxidative stress and kidney injury using a model of myocardial infarction (MI) in rats. EXPERIMENTAL APPROACH At 10 weeks, male spontaneously hypertensive rats (SHR) were divided into three groups: SHR (n = 6), MI (n = 8) and MI + AST-120 (n = 8). AST-120 administration was started at 11 weeks after MI. At 18 weeks, the rats were killed, and blood and urine, mRNA expression and renal histological analyses were performed. Echocardiography was performed before and after MI. KEY RESULTS At 18 weeks, the BP was significantly lower in the MI and MI+AST-120 groups than in the SHR group. Elevated levels of indoxyl sulfate (IS), one of the uremic toxins, in serum and urine were reduced by AST-120 treatment, compared with the MI group. Markers of oxidative stress in urine and serum biomarkers of kidney injury were decreased in the MI+AST-120 group compared with the other two groups. Renal expression of mRNAs for kidney injury related-markers were decreased in the MI+AST-120 group, compared with the MI group. In vitro data also supported the influence of IS on kidney injury. Immunohistological analysis showed that intrarenal oxidative stress was reduced by AST-120 administration. CONCLUSIONS AND IMPLICATIONS Serum IS was increased after MI and treatment with AST-120 may have protective effects on kidney injury after MI by suppressing oxidative stress.

Published
2016
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41. Two Cases of Hypophosphatemia with Increased Renal Phosphate Excretion in Legionella Pneumonia

Author

Hideki Fujii, Keiji Kono, Kentaro Nakai, Shuhei Watanabe, Shinichi Nishi, and Shunsuke Goto

Subjects
Fibroblast growth factor 23, medicine.medical_specialty, Hypophosphatemia, Urinary system, Legionella Pneumonia, Parathyroid hormone, 030204 cardiovascular system & hematology, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Renal tubular dysfunction, Internal medicine, Vitamin D and neurology, Medicine, 1,25(OH)2 vitamin D, 030212 general & internal medicine, Legionella pneumonia, business.industry, medicine.disease, respiratory tract diseases, Endocrinology, Nephrology, Published online: March, 2016, Fibroblast growth factor-23, business, Renal phosphate excretion
Abstract

We encountered 2 cases of hypophosphatemia due to Legionella pneumonia. Both cases showed increased urinary phosphate excretion and renal tubular dysfunction, which ameliorated with recovery from Legionella pneumonia. Serum fibroblast growth factor-23 level was suppressed, whereas serum 1,25(OH)2 vitamin D and parathyroid hormone levels were normal. Delayed elevation of serum 1,25(OH)2 vitamin D levels was observed with improvement in renal tubular function. These findings suggested hypophosphatemia might be mediated by renal tubular dysfunction.

Published
2016

42. Comparison of the effects of lanthanum carbonate and calcium carbonate on the progression of cardiac valvular calcification after initiation of hemodialysis

Author

Shunsuke Goto, Kentaro Watanabe, Keiji Kono, Shinichi Nishi, and Hideki Fujii

Subjects
Male, lcsh:Diseases of the circulatory (Cardiovascular) system, Time Factors, medicine.medical_treatment, Arterial plaque, Heart Valve Diseases, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Gastroenterology, Lanthanum carbonate, law.invention, 0302 clinical medicine, Randomized controlled trial, Risk Factors, law, Medicine, Chelating Agents, Randomized Controlled Trials as Topic, Aged, 80 and over, Valvular calcification, Initiation of hemodialysis, Calcinosis, Phosphorus, Middle Aged, Cardiac valvular calcification, Cardiac surgery, Treatment Outcome, Disease Progression, Female, Kidney Diseases, Hemodialysis, Cardiology and Cardiovascular Medicine, Calcium carbonate, Research Article, medicine.drug, medicine.medical_specialty, 03 medical and health sciences, Lanthanum, Renal Dialysis, Internal medicine, Humans, Aged, Angiology, business.industry, Mean age, Maintenance hemodialysis, equipment and supplies, lcsh:RC666-701, business, Biomarkers
Abstract

BackgroundAlthough mineral metabolism disorder influences cardiac valvular calcification (CVC), few previous studies have examined the effects of non-calcium-containing and calcium-containing phosphate binders on CVC in maintenance hemodialysis patients. The aim of the present study was to compare the effects of lanthanum carbonate (LC) with calcium carbonate (CC) on the progression of CVC in patients who initiated maintenance hemodialysis and to investigate clinical factors related to CVC.MethodsThe current study included 50 subjects (mean age 65 years, 72% males) from our previous randomized controlled trial (LC group,N = 24; CC group,N = 26). CVC was evaluated as CVC score (CVCS) using echocardiography at baseline and 18 months after initiation of hemodialysis. We compared CVCS and the changes between the two groups. We also analyzed the associations between CVCS and any other clinical factors including arterial plaque score (PS) and serum phosphorus levels.ResultsBaseline characteristics of study participants including CVCS were almost comparable between the two groups. At 18 months, there were no significant differences in mineral metabolic markers or CVCS between the two groups, and CVCS were significantly correlated with PS (r = 0.39,p r = 0.36,p p ConclusionsIn the present study, there were no significant differences between LC and CC with regard to progression of CVC. However, serum phosphorus levels and arterial plaque seem to be important for the progression and formation of CVC in hemodialysis patients.

Published
2020

43. Pharmacokinetics of Oxaliplatin in a Hemodialysis Patient with Metastatic Colon Cancer

Author

Yoshiaki, Nagatani, primary, Yoshinori, Imamura, additional, Tsutomu, Nakamura, additional, Kazuhiko, Yamashita, additional, Mamoru, Okuno, additional, Hiroyuki, Yasui, additional, Jun, Hiraoka, additional, Riho, Niigata, additional, Keiji, Kono, additional, Yasuko, Hyogo, additional, Hirotaka, Suto, additional, Kei, Takenaka, additional, Yohei, Funakoshi, additional, Masanori, Toyoda, additional, Naomi, Kiyota, additional, and Hironobu, Minami, additional

Published
2019
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44. Anti-oxidative effect of theβ-blocker carvedilol on diabetic nephropathy in non-obese type 2 diabetic rats

Author

Shinichi Nishi, Kentaro Nakai, Keiji Kono, Yuriko Yonekura, Hideki Fujii, Masami Shinohara, and Shunsuke Goto

Subjects
Pharmacology, medicine.medical_specialty, NADPH oxidase, biology, Physiology, Chemistry, Insulin, medicine.medical_treatment, medicine.disease, medicine.disease_cause, Diabetic nephropathy, Excretion, Endocrinology, Blood pressure, Physiology (medical), Internal medicine, medicine, biology.protein, P22phox, Carvedilol, Oxidative stress, medicine.drug
Abstract

Summary Oxidative stress plays an important role in the pathogenesis of diabetic nephropathy. The β-blocker carvedilol has been proven to have an anti-oxidant property. The aim of the present study was to elucidate the effects of carvedilol on diabetic nephropathy. At 20 weeks of age, male Spontaneously Diabetic Torii (SDT) rats were divided into three groups based on treatment: (i) an INS group (administered insulin); (ii) a CAR group (administered 10 mg/kg per day, p.o., carvedilol); and (iii) a diabetic (DM) group (administered vehicle). Rats were treated for a period of 10 weeks and were killed at 30 weeks of age. Urinary albumin excretion, renal histomorphology, and oxidative stress were evaluated. Urinary albumin excretion was significantly lower in the CAR than DM group (42.82 ± 3.94 vs 76.62 ± 13.74 mg/day respectively; P

Published
2015
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45. Effect of cinacalcet cessation on hyperparathyroidism in kidney transcaplant patients after long-term dialysis therapy

Author

Shunsuke Goto, Hideki Fujii, Takeshi Ishimura, Keiji Kono, Yuriko Yonekura, Masato Fujisawa, Masashi Takeda, Shinichi Nishi, Mikiko Yoshikawa, and Kentaro Nakai

Subjects
Adult, Male, Nephrology, Parathyroidectomy, medicine.medical_specialty, Cinacalcet, Physiology, medicine.medical_treatment, Urology, Parathyroid hormone, Calcimimetic Agents, Kidney Function Tests, Parathyroid Glands, Renal Dialysis, Physiology (medical), Internal medicine, Humans, Medicine, Vitamin D, Kidney transplantation, Retrospective Studies, Ultrasonography, Minerals, Kidney, Hyperparathyroidism, business.industry, Middle Aged, medicine.disease, Kidney Transplantation, Substance Withdrawal Syndrome, Transplantation, Endocrinology, medicine.anatomical_structure, Parathyroid Hormone, business, medicine.drug
Abstract

Cinacalcet is a promising therapy widely used in dialysis patients with hyperparathyroidism resistant to conventional therapy. However, reports regarding the influence of cinacalcet cessation after long-term use on kidney transplantation patients are few. This retrospective observational study included 40 dialysis patients who underwent kidney transplantation. Creatinine, corrected calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone levels were assessed before and after kidney transplantation according to pretransplant treatment of chronic kidney disease–mineral and bone disorder. Ultrasonography revealed enlargement of the parathyroid in all patients treated with cinacalcet. Although the data at the time of kidney transplantation were comparable, the serum levels of calcium, alkaline phosphatase, and intact parathyroid hormone after kidney transplantation were higher in patients treated with cinacalcet than in those treated without. However, serum phosphate levels in the cinacalcet group were slightly higher at the time of kidney transplantation and significantly lower 3 months later. Mineral abnormalities persisted in kidney transplant patients with enlarged parathyroid glands after discontinuation of cinacalcet treatment. Parathyroidectomy should be considered in kidney transplant candidates with the risk of developing refractory hyperparathyroidism after transplantation.

Published
2015
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46. Newly Developed Rat Model of Chronic Kidney Disease-Mineral Bone Disorder

Author

Kentaro Nakai, Masami Shinohara, Shuhei Watanabe, Shinichi Nishi, Keiji Kono, Hideki Fujii, Shunsuke Goto, and Kentaro Watanabe

Subjects
Fibroblast growth factor 23, Paricalcitol, Male, medicine.medical_specialty, Urinary system, 030232 urology & nephrology, Renal function, Parathyroid hormone, Blood Pressure, 030204 cardiovascular system & hematology, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Chronic kidney disease-mineral and bone disorder, Internal medicine, Internal Medicine, medicine, Animals, Vitamin D, Vascular Calcification, Chronic Kidney Disease-Mineral and Bone Disorder, Kidney, business.industry, Biochemistry (medical), medicine.disease, Rats, Disease Models, Animal, Chronic kidney disease–mineral bone disorder, medicine.anatomical_structure, Endocrinology, Diabetes Mellitus, Type 2, Chronic kidney disease-mineral bone disorder, Original Article, Cardiology and Cardiovascular Medicine, business, Kidney disease, medicine.drug
Abstract

Aim: Chronic kidney disease–mineral bone disorder (CKD–MBD) is associated with all-cause and cardiovascular morbidity and mortality in patients with CKD. Thus, elucidating its pathophysiological mechanisms is essential for improving the prognosis. We evaluated characteristics of CKD–MBD in a newly developed CKD rat model. Methods: We used male Sprague–Dawley (SD) rats and spontaneously diabetic Torii (SDT) rats, which are used as models for nonobese type 2 diabetes. CKD was induced by 5/6 nephrectomy (Nx). At 10 weeks, the rats were classified into six groups and administered with a vehicle or a low- or high-dose paricalcitol thrice a week. At 20 weeks, the rats were sacrificed; blood and urinary biochemical analyses and histological analysis of the aorta were performed. Results: At 20 weeks, hemoglobin A1c (HbA1c) levels, blood pressure, and renal function were not significantly different among the six groups. Serum calcium and phosphate levels tended to be higher in SDT-Nx rats than in SD-Nx rats. The urinary excretion of calcium and phosphate was significantly greater in SDT-Nx rats than in SD-Nx rats. After administering paricalcitol, serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels were significantly higher in SDT-Nx rats than in SD-Nx rats. The degree of aortic calcification was significantly more severe and the aortic calcium content was significantly greater in SDT-Nx rats than in SD-Nx rats. Conclusions: We suggest that our new CKD rat model using SDT rats represents a useful CKD–MBD model, and this model was greatly influenced by paricalcitol administration. Further studies are needed to clarify the detailed mechanisms underlying this model.

Published
2017

47. CKD NUTRITION, INFLAMMATION AND OXIDATIVE STRESS

Author

Abdelouahed Khalil, Anteo Di Napoli, Stephen Zewinger, Mariusz Flisiński, Domenico Trimboli, Maurizio Bossola, Marina Biagioli, Odile Azoulay, Michele Buemi, Piergiorgio Bolasco, Andreea Ilyes, Ángeles Álvarez, Valeria Cernaro, Polichronis Alivanis, Gabriel Stefan, Mehmet Haberal, Marcelo Costa Batista, Jerzy Chudek, Mujdat Batur Canoz, Branka Mitic, Abdul Rashid Qureshi, Anna Stefańska, Christiaan L. Meuwese, Anna Kamińska, Vera Jankowski, Yeon Soon Jung, Luisa Sereni, Rafał Donderski, Ho Sik Shin, Ciprian Stoica, Peter Stenvinkel, Insa E. Emrich, Rosanna Coppo, Boris Zingerman, Rachid Saile, Sonja Radenkovic, Yener Koc, Ilona Miśkowiec-Wiśniewska, Tatjana Cvetkovic, Danilo Fliser, Grigore Dogaru, Simonetta Palleschi, Milica Bozic, Urszula Spiechowicz-Zatoń, Kevin J. Woollard, Serpil Nebioğlu, Erik W. Holy, Hark Rim, Mahmut Gok, Adriana Arena, Iryna Dudar, Goran Paunovic, Elvira Fernández, Maria Inês Barreto-Silva, Jacek Manitius, Naohito Isoyama, Demet Yavuz, Michael Böhm, Jose M. Valdivielso, Paolo Maria Ghezzi, Silvia Regina Manfredi, Paweł Stróżecki, Yusuf Oguz, Maria L Lusini, Miomir Stojanovic, Gabriel Mircescu, Mikio Sugano, Paula Maria Gliga, Zeynep Bal, Mirela Liana Gliga, Elisa Loiacono, Hilmi Umut Ünal, Viktoria Alekseeva, Sun Chul Kim, Hyun Yul Rhew, José Tarcísio Giffoni de Carvalho, Foteini Lamprianou, Ekrem Kara, Sang-Kyung Jo, Barbara E. Stähli, Abdulkadir Unsal, Francesco Franco, Murat Karaman, Shunsuke Goto, Sumie Goto, Richard J. Johnson, Tamer Sakaci, Christophe Dubois, Roman Junik, Nikolaos Karvouniaris, Nikitas Moschos, Timo Speer, Kathleen Claes, Maria Teresa Ingegneri, Gunnar H. Heine, Pieter Evenepoel, Zahava Gamzo, Juan Jesus Carrero, Keiji Kono, Bertrand Gondouin, Sylwia Rotkegel, Mehmet Kanbay, Sebahattin Sari, Roxanne Darbousset, Shinichi Nishi, Andrzej Brymora, Bahar Gurlek Demirci, Vincenzo Bellizzi, Joanna Siódmiak, Domenico Di Lallo, Ye Na Kim, Latife Atasoy Karakas, Adam M. Zawada, Alexander Akhmedov, Mustafa Sevinc, Tuncay Sahutoglu, Hrvoje Cvija, Giovanni G. Camici, Ayse C Akbasli, Mahmut I Yilmaz, Christos Paliouras, Karolina Paunovic, Bulent Erbay, Carla Cavalheiro da Silva Lemos, Frances Costa-Silva, Marina Davoli, Liesbeth Viaene, Fatma Nurhan Ozdemir, Mehtap Erkmen Uyar, Kentaro Nakai, Adrian Covic, Danijela Tasic, Jarosław Ciepał, Mauro Atti, Gunnar Heine, Stéphane Burtey, Domenico Santoro, Benaya Rozen-Zvi, Simone Vargas, Lucia Rohrer, Gaetano Montalto, Hakki Cetinkaya, Turan Colak, Bert Bammens, Alessandro Amore, Tayfun Eyileten, Paul Leurs, Liliana Viasu, Theodoros Haviatsos, Yalcin Solak, Antonino Sidoti, Carmen de Pablo, Tayfun EyIeten, Vincenzo Savica, Maria Dolores Sanchez-Niño, Yasemin Gulcan Kurt, Gordana Kocic, Joachim Jankowski, Andrea Pisacane, Katarzyna Wyskida, Kenan Keven, Sunna Snaedal, Zorica Dimitrijevic, Nikolaos Papagiannis, Abdülgaffar Vural, Taner Basturk, Mutlu Saglam, Björn Anderstam, Hilmi Umut Unal, Serena Chicca, Aline Trevisan Peres, Maria Eugênia Fernandes Canziani, Alberto Ortiz, Mahmut Ilker Yilmaz, Bengt Lindholm, Stéphane Poitevin, Kiryong Park, Paolo M. Ghezzi, Antonio Pisani, Marialuisa Caiazzo, Noreddine Ghalim, Viktor Krot, Silvia Lucisano, Maria Aparecida Dalboni, Eleonora Riccio, Sarah Seiler, Giorgos Ntetskas, Oskar Svedberg, Carmela Aloisi, Sangeon Gwoo, Peter Bárány, Maria Bożentowicz-Wikarek, Alpaslan Altunoglu, O.M. Loboda, Elbis Ahbap, Dariusz Klein, Tuncer Cayci, Siren Sezer, Rosaria Lupica, Giuseppe Vita, Ruben Poesen, Björn Meijers, Nagba Yendoubé Gbandjaba, Magdalena Olszanecka-Glinianowicz, Burak Sayin, Won Yong Cho, Beata Marie Redublo Quinto, J. J. Carrero, Yuriko Yonekura, Felix C. Tanner, Miguel Cendoroglo, Olof Heimbürger, Cuneyt Akgol, Paola Michelozzi, Sarah Triem, Yoshiharu Ito, Emanouil Anastasakis, GrażYna Odrowa˛ż-Sypniewska, Caren Cristina Grabulosa, Aniceta Brzozowska, Hyung Kyu Kim, Marek Kretowicz, Maria Inês Barreto Silva, Thereza Christina Barja-Fidalgo, Yusuke Yamashita, Hideki Fujii, Simona Stancu, Luigi Tazza, Giuseppe Palladino, Nilufer Bayraktar, Rachel Bregman, Rahman Yavuz, Cengizhan Acikel, Barbara Rossi, Cristina Capusa, Massimo Sabbatini, Myung Gyu Kim, Guido Bellinghieri, Renata de Souza Mendes, Dorin Tarta, Radmila Veličković-Radovanović, Kyrill S. Rogacev, Kostantinos Roufas, and Thomas F. Lüscher

Subjects
Transplantation, medicine.medical_specialty, Framingham Risk Score, Cardiovascular History, business.industry, Hazard ratio, Renal function, medicine.disease, Gastroenterology, Endocrinology, Nephrology, Diabetes mellitus, Internal medicine, medicine, Myocardial infarction, Prospective cohort study, business, Kidney disease
Abstract

Introduction and Aims: Serum p-cresyl sulfate associates with cardiovascular disease in patients at different stages of chronic kidney disease. p-Cresyl sulfate concentrations are determined by intestinal uptake of p-cresol, human metabolism to p-cresyl sulfate and renal clearance. Whether intestinal uptake of p-cresol itself is associated with cardiovascular disease in patients with renal disease has not been studied to date. Methods: We performed a prospective study in patients with chronic kidney disease stage 1-5 (clinicaltrials.gov NCT00441623). Intestinal uptake of p-cresol, under steady state conditions, was estimated from 24h urinary excretion of p-cresyl sulfate. Primary endpoint was time to first cardiovascular event, i.e. cardiac death, myocardial infarction/ischemia, ventricular arythmia, cardiovascular surgery, cerebrovascular accident or symptomatic peripheral arterial disease. Statistical analysis was done using Kaplan Meier estimates and Cox proportional hazard analyses. Results: In a cohort of 200 patients, median 24h urinary excretion of p-cresyl sulfate was 457.47 µmol (IQR 252.68-697.17). After a median follow-up of 52 months, 25 patients reached the primary endpoint (tertile 1/2/3: 5/6/14 events, log rank P 0.0368, see figure). Higher urinary excretion of p-cresyl sulfate was related with cardiovascular events (univariate hazard ratio per 100 µmol increase: 1.112, P 0.0015). In multivariate analysis, urinary excretion of p-cresyl sulfate remained a predictor of cardiovascular events, independent of markers of renal function (Hazard ratio 1.120, P 0.0022) and in different models with other cardiovascular risk factors (Framingham risk factors, cardiovascular history, diabetes mellitus and biochemical parameters). The independent association between urinary excretion of p-cresyl sulfate and outcome persisted after correction for serum p-cresyl sulfate. Conclusions: Intestinal uptake of p-cresol associates with cardiovascular disease independent of renal function. Insights into mechanisms governing intestinal generation and absorption of p-cresol may lead to identification of novel therapeutic targets to reduce cardiovascular disease risk in patients with chronic kidney disease.

Published
2014
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48. Dietary phosphorus restriction by a standard low-protein diet decreased serum fibroblast growth factor 23 levels in patients with early and advanced stage chronic kidney disease

Author

Hideki Fujii, Yuriko Yonekura, Jun Ito, Shunsuke Goto, Shinichi Nishi, Kentaro Nakai, and Keiji Kono

Subjects
Adult, Male, Fibroblast growth factor 23, Nephrology, medicine.medical_specialty, Physiology, medicine.medical_treatment, Parathyroid hormone, Disease, urologic and male genital diseases, Fibroblast growth factor, Severity of Illness Index, Low-protein diet, Physiology (medical), Internal medicine, Diet, Protein-Restricted, Vitamin D and neurology, medicine, Humans, Renal Insufficiency, Chronic, Vitamin D, Aged, business.industry, Contraindications, Phosphorus, Middle Aged, medicine.disease, Fibroblast Growth Factors, Fibroblast Growth Factor-23, stomatognathic diseases, Endocrinology, Parathyroid Hormone, Disease Progression, Phosphorus, Dietary, Female, business, Biomarkers, Kidney disease
Abstract

Elevated serum fibroblast growth factor 23 (FGF23) levels are associated with mortality, cardiovascular disease, and disease progression in patients with chronic kidney disease (CKD). Although recent studies demonstrated that FGF23 levels decreased in response to dietary restriction of phosphorus and/or use of phosphate binders, research on the effects of a standard low-protein diet is lacking.The effects of a standard low-protein diet on serum FGF23, intact parathyroid hormone, and 1,25-dihydroxyvitamin D levels were investigated in patients with early (n = 15) and advanced (n = 20) CKD.Serum FGF23 levels decreased in both groups. Changes in FGF23 levels correlated with changes in 24 h urinary phosphorus excretion in the advanced CKD group. Decreased serum intact parathyroid hormone levels were observed only in the advanced CKD group and increased serum 1,25-dihydroxyvitamin D levels only in the early CKD group.These findings suggest that consuming standard low-protein diet decreased serum FGF23 levels in patients with CKD. Serum FGF23 levels may therefore be a useful marker to monitor the effects of a low-protein diet in early and advanced stage CKD.

Published
2014
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49. Renin-Angiotensin System Inhibitors Reduce Serum Asymmetric Dimethylarginine Levels and Oxidative Stress in Normotensive Patients with Chronic Kidney Disease

Author

Shunsuke Goto, Riko Kitazawa, Masafumi Fukagawa, Hideki Fujii, Keiji Kono, Shinichi Nishi, and Kentaro Nakai

Subjects
Asymmetric dimethylarginine, medicine.medical_specialty, Urinary system, Renal function, lcsh:RC870-923, medicine.disease_cause, Excretion, chemistry.chemical_compound, Chronic kidney disease, Internal medicine, Medicine, Original Paper, medicine.diagnostic_test, business.industry, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, Oxidative stress, Renin-angiotensin system inhibitor, Blood pressure, Endocrinology, chemistry, Nephrology, Renal biopsy, business, Kidney disease
Abstract

Background/Aims: The purpose of our study was to elucidate the relationship between asymmetric dimethylarginine (ADMA) and intrarenal lesions and to determine the effect of renin-angiotensin system inhibitors (RAS-Is) on serum ADMA levels, nitric oxide (NO) synthesis and oxidative stress in normotensive patients with chronic kidney disease (CKD). Methods: This study included 23 normotensive patients with chronic glomerulonephritis and normal or mildly impaired renal function who underwent renal biopsy. We evaluated the relationship between serum ADMA levels and intrarenal lesions, and examined renal function, urinary protein excretion, ADMA levels, NO synthesis, oxidative stress and blood pressure (BP) before and 3 months after starting the treatment with RAS-Is. Results: Serum ADMA levels were correlated only with arterial intimal fibroplastic thickness. Despite comparable renal function and BP, serum ADMA levels and excretion of urinary protein excretion significantly decreased, and urinary NO metabolite excretion significantly increased after starting the treatment with RAS-Is. Oxidative stress markers also tended to be reduced by the treatment. Conclusion: These findings suggest that RAS-Is improve the NO system and decrease oxidative stress in normotensive patients with CKD. In addition, ADMA may be associated with intrarenal lesions and can be a useful marker for the effects of treatment in the early stages of CKD.

Published
2014
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50. Changes in serum indoxyl sulfate levels after acute myocardial infarction and the correlation with kidney injury: an observational study

Author

Hideki Fujii, Susumu Sakamoto, Shuhei Watanabe, Shinichi Nishi, Shunsuke Goto, Kentaro Watanabe, and Keiji Kono

Subjects
Nephrology, medicine.medical_specialty, Urology, medicine.medical_treatment, 030232 urology & nephrology, Renal function, Acute myocardial infarction, 030204 cardiovascular system & hematology, Lipocalin, lcsh:RC870-923, Gastroenterology, Indoxyl sulfate, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Myocardial infarction, Transplantation, business.industry, Percutaneous coronary intervention, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, Pathophysiology, Kidney injury, Observational study, business, Kidney disease
Abstract

Background Kidney function after acute myocardial infarction (AMI) correlates with patient prognosis. Several studies reported the role that indoxyl sulfate (IS), a uremic toxin, plays in the progression of chronic kidney disease and cardiovascular diseases. This study aims at investigating the serum IS level changes after AMI and their correlation with kidney injury. Methods In this observational study, twenty consecutive patients with AMI who received percutaneous coronary intervention within 2 h after admission were enrolled. We measured serum IS levels on admission (day 1) and day 2–3 and evaluated their clinical characteristics. Further, we measured serum neutrophil gelatinase-associated lipocalin (NGAL) levels at admission as a marker of kidney injury. Results Although estimated glomerular filtration rate (eGFR) decreased at day 2–3 compared to that at day 1, serum IS levels at day 1 were rather higher than those at day 2–3. Further analysis only among patients with preserved kidney function revealed that serum IS levels at day 1 were significantly higher than those at day 2–3, despite a higher eGFR. Additionally, serum NGAL levels at admission were higher in these patients than in healthy subjects. Further, serum NGAL levels were significantly higher in patients with higher serum IS levels compared to those with lower IS levels. Conclusion This study suggests that pathophysiological conditions in patients with AMI may elevate serum IS levels independent of kidney dysfunction and that IS may be one of the contributory factors related to kidney injury in AMI.

Published
2019

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