Publications by authors named "Yuka Sugawara"

12 Publications

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Trans-ethnic Mendelian-randomization study reveals causal relationships between cardiometabolic factors and chronic kidney disease.

Int J Epidemiol 2021 Oct 20. Epub 2021 Oct 20.

Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Background: This study was to systematically test whether previously reported risk factors for chronic kidney disease (CKD) are causally related to CKD in European and East Asian ancestries using Mendelian randomization.

Methods: A total of 45 risk factors with genetic data in European ancestry and 17 risk factors in East Asian participants were identified as exposures from PubMed. We defined the CKD by clinical diagnosis or by estimated glomerular filtration rate of <60 ml/min/1.73 m2. Ultimately, 51 672 CKD cases and 958 102 controls of European ancestry from CKDGen, UK Biobank and HUNT, and 13 093 CKD cases and 238 118 controls of East Asian ancestry from Biobank Japan, China Kadoorie Biobank and Japan-Kidney-Biobank/ToMMo were included.

Results: Eight risk factors showed reliable evidence of causal effects on CKD in Europeans, including genetically predicted body mass index (BMI), hypertension, systolic blood pressure, high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein(a), type 2 diabetes (T2D) and nephrolithiasis. In East Asians, BMI, T2D and nephrolithiasis showed evidence of causality on CKD. In two independent replication analyses, we observed that increased hypertension risk showed reliable evidence of a causal effect on increasing CKD risk in Europeans but in contrast showed a null effect in East Asians. Although liability to T2D showed consistent effects on CKD, the effects of glycaemic phenotypes on CKD were weak. Non-linear Mendelian randomization indicated a threshold relationship between genetically predicted BMI and CKD, with increased risk at BMI of >25 kg/m2.

Conclusions: Eight cardiometabolic risk factors showed causal effects on CKD in Europeans and three of them showed causality in East Asians, providing insights into the design of future interventions to reduce the burden of CKD.
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http://dx.doi.org/10.1093/ije/dyab203DOI Listing
October 2021

Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database.

Diabetes Care 2021 Nov 30;44(11):2542-2551. Epub 2021 Sep 30.

Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Objective: Randomized controlled trials have shown kidney-protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy, as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitor initiation modify treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients, is unknown.

Research Design And Methods: Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease.

Results: At baseline, mean age at initiation of the SGLT2 inhibitor ( = 1,033) or other glucose-lowering drug ( = 1,033) was 64.4 years, mean eGFR was 68.1 mL/min per 1.73 m, and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs. other drugs 0.75 mL/min/1.73 m per year [0.51 to 1.00]). During a mean follow-up of 24 months, 103 composite kidney outcomes occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26-0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiation of SGLT2 inhibitors ( ≥ 0.35).

Conclusions: The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.
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http://dx.doi.org/10.2337/dc21-1081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546274PMC
November 2021

Infection prevention measures for patients undergoing hemodialysis during the COVID-19 pandemic in Japan: a nationwide questionnaire survey.

Ren Replace Ther 2021 29;7(1):27. Epub 2021 May 29.

Division of Nephrology and Endocrinology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655 Japan.

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic affecting a variety of medical treatments, including hemodialysis. This study aims to investigate the implementation of infection control measures, to examine the shortage of personal protective equipment (PPE) and disinfectants, and to quantify the number of nosocomial COVID-19 transmissions in hemodialysis facilities in Japan during the pandemic.

Methods: We conducted a nationwide questionnaire survey between 20 October and 16 November 2020 (i.e., between the "second wave" and "third wave" in Japan) in the 4198 dialysis facilities of the Japanese Association of Dialysis Physicians and the Japanese Society for Dialysis Therapy. A total of 2227 facilities (53.0%) responded. The questionnaire consisted of (i) characteristics of facilities, (ii) infection prevention measures in routine dialysis practices, (iii) shortage of PPE, (iv) feasibility of various isolation measures, and (v) nosocomial transmission.

Results: Half of the responding facilities were hospitals with multiple departments, and the other half were clinics specialized in dialysis. Several infection prevention measures such as health checks of staff and patients, donning of masks before and after hemodialysis, and disinfection of frequently contacted areas were implemented during the COVID-19 pandemic. There was a significant improvement in the implementation rate of these measures during the pandemic, compared to before it, which reached over 90%. More than half of the facilities reported a shortage of disposable masks (67.2%) and hand sanitizer alcohol (56.7%). Isolation of COVID-19 patients in private rooms was possible only in 52.7% of the facilities. The majority of facilities (73.3%) could not accept COVID-19 dialysis patients due to lack of space and manpower. Nosocomial transmission of COVID-19 occurred in 4.0% of the facilities. Of those infected, 51.9% were staff.

Conclusions: This survey revealed that most hemodialysis facilities in Japan had improved implementation of infection control measures and had shortage of PPEs and disinfectants, though some facilities did not implement infection prevention measures adequately, mainly due to the limited space of the facility. It may be recommended that each facility immediately establishes isolation measures to prepare for the pandemic of COVID-19.

Supplementary Information: The online version contains supplementary material available at 10.1186/s41100-021-00350-y.
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http://dx.doi.org/10.1186/s41100-021-00350-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164066PMC
May 2021

Nationwide survey of the coronavirus disease 2019 prevention and treatment systems for kidney disease patients: a study of Japanese Society of Nephrology-certified educational facilities.

Clin Exp Nephrol 2021 Sep 31;25(9):996-1002. Epub 2021 May 31.

Division of Nephrology and Endocrinology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: There are no reports of a large-scale survey on the infection prevention measures against coronavirus disease 2019 (COVID-19) in nephrology facilities. This study investigated the facility-level nephrology practices adopted during the COVID-19 pandemic and their associated challenges. Additionally, the treatment patterns and outcomes of chronic kidney disease (CKD) patients with COVID-19 were reviewed.

Methods: We conducted a nationwide questionnaire survey of 704 educational facilities that were certified by the Japanese Society of Nephrology (JSN) from October 20, 2020 to November 16, 2020. The questionnaire reviewed the facility characteristics, infection prevention measures taken during routine nephrology practice, impact of COVID-19 on nephrology practice, experiences in managing CKD patients with COVID-19, and nosocomial transmission in the nephrology unit.

Results: Of the 347 facilities that responded, 95.1% checked outpatients' body temperatures and COVID-19 symptoms at their visits. To reduce face-to-face contact, 80% and 70% of the facilities lengthened the intervals between outpatient visits and introduced online/telephonic consultations, respectively. As a result, more than half of the hospitals experienced a decrease in the numbers of outpatients and inpatients (64% and 50%, respectively). During the study period, 347 facilities managed 479 CKD patients with COVID-19. Oxygen administration and mechanical ventilation were performed for 47.8% and 16.5% of the patients, respectively, with a 9.2% total mortality rate.

Conclusion: This survey demonstrated that JSN-certified educational nephrology facilities adopted multiple measures to manage the COVID-19 pandemic; however, they faced several challenges. Sharing these experiences could standardize these approaches and prepare us better for the future.
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http://dx.doi.org/10.1007/s10157-021-02082-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165509PMC
September 2021

The role of anti-complement factor H antibodies in the development of atypical haemolytic uremic syndrome: a possible contribution to abnormality of platelet function.

Br J Haematol 2020 04 26;189(1):182-186. Epub 2019 Dec 26.

Division of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan.

Atypical haemolytic uremic syndrome (aHUS) is associated with complement system abnormality, such as production of complement factor H (CFH) autoantibodies. The growing evidence indicates complement overactivation on platelets is intimately involved in aHUS pathogenesis, besides endothelial injury. We here showed plasma from patients with anti-CFH antibodies induced aggregation of washed platelets, while purified anti-CFH antibodies suppressed aggregation. This suggested anti-CFH antibody itself suppressed thrombosis, while other plasma factor including complement factors could overactivate the platelets, leading to aggregation, which augmented the notion the state of complement activation influenced by anti-CFH antibodies is important in the aggregation of platelets in aHUS.
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http://dx.doi.org/10.1111/bjh.16297DOI Listing
April 2020

Novel Hybrid in C3 Glomerulopathy Identified by Genomic Structural Variation Analysis.

Kidney Int Rep 2019 Dec 19;4(12):1759-1762. Epub 2019 Sep 19.

Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.ekir.2019.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895660PMC
December 2019

Profiles of Coagulation and Fibrinolysis Activation-Associated Molecular Markers of Atypical Hemolytic Uremic Syndrome in the Acute Phase.

J Atheroscler Thromb 2020 Apr 4;27(4):353-362. Epub 2019 Sep 4.

Division of Nephrology and Endocrinology, the University of Tokyo Graduate School of Medicine.

Aim: Atypical hemolytic uremic syndrome (aHUS), characterized by thrombotic microangiopathy (TMA), is a genetic, life-threatening disease which needs many differential diagnoses. This study aimed to reveal coagulation and fibrinolysis profiles in aHUS and secondary TMA patients. Furthermore, we investigated whether aHUS patients progress to, and meet, disseminated intravascular coagulation (DIC) criteria.

Methods: The acute phase samples were available in 15 aHUS and 20 secondary TMA patients. We measured PT-ratio, activated partial thromboplastin time (APTT), fibrinogen, fibrin degradation product (FDP), fibrin monomer complex (FMC), antithrombin (AT), plasmin-α2 plasmin inhibitor complex (PIC), and von Willebrand factor antigen (VWF:Ag). We examined and compared these tests among aHUS, secondary TMA patients, and healthy volunteer (HV), and evaluated whether patients with aHUS and secondary TMA met DIC criteria.

Results: PT-ratio, APTT, FDP, FMC and PIC in patients with aHUS and secondary TMA were higher than those in HV. Fibrinogen and AT showed no significant difference among three groups. VWF:Ag was higher in only aHUS patients. No tests showed significant difference between aHUS and secondary TMA patients. Three aHUS patients out of 15 met DIC criteria.

Conclusion: We revealed the profiles and distributions of coagulation and fibrinolysis tests of aHUS and secondary TMA patients. All tests were enhanced compared to HV; however, our results showed the no specificities in distinguishing aHUS from secondary TMA patients. We also clarified that some aHUS patients fulfilled DIC diagnostic criteria, indicating that DIC itself cannot be an exclusion criterion of aHUS.
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http://dx.doi.org/10.5551/jat.49494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192816PMC
April 2020

Umbilical Cord Blood Transplantation-associated Nephrotic Syndrome Successfully Treated by Low-density Lipoprotein Apheresis.

Intern Med 2016;55(19):2831-2836. Epub 2016 Oct 1.

Department of Nephrology and Endocrinology, The University of Tokyo, Japan.

The development of nephrotic syndrome (NS) after umbilical cord transplantation (UBT) has been reported in only four cases to date. We herein report the case of a 50-year-old woman who developed NS 94 days after UBT. She fell into oliguria and required dialysis. A kidney biopsy revealed focal and segmental glomerulosclerosis. Although glucocorticoid monotherapy did not improve her condition, the addition of low-density lipoprotein (LDL) apheresis resulted in remission of NS, a drastic improvement in her renal function, and withdrawal from dialysis. To the best of our knowledge, this is the first report of UBT-associated NS treated with LDL apheresis.
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http://dx.doi.org/10.2169/internalmedicine.55.7017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088545PMC
February 2017

Changes in disability-free life expectancy (DFLE) at birth between 2000 and 2010 across Japanese prefectures.

Int J Public Health 2016 Sep 28;61(7):739-49. Epub 2016 Jun 28.

University Research Center, Nihon University, 12-5 Gobancho, Chiyoda-ku, Tokyo, Japan.

Objectives: The second phase of Healthy Japan 21 seeks to increase disability-free life expectancy (DFLE) more than life expectancy (LE) between 2013 and 2022. In the face of the rising incidence of disability, the feasibility of achieving this goal remains unclear.

Methods: We examine changes in DFLE at birth between 2000 and 2010 across 47 prefectures, with particular attention given to changes in the absolute number of years and in the proportion of disability-free life years.

Results: Although LE increased across all prefectures, there is a variation in DFLE. While the number of disability-free life years increased in many parts of the country, some prefectures had decreases in DFLE. Downturns become particularly evident when DFLE is interpreted in relative terms. The proportion of life spent without disability declined in the majority of prefectures.

Conclusions: Results from subnational level analyses suggest that the rate of increase in DFLE lagged behind that in LE across Japanese prefectures during the past decade. More policy attention should be devoted to health-promotion initiatives at the prefecture level to achieve the nationwide health agenda.
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http://dx.doi.org/10.1007/s00038-016-0847-3DOI Listing
September 2016

Marked effect of milnacipran combined with olanzapine for a delusional depressive patient.

Neuropsychiatr Dis Treat 2005 Dec;1(4):373-4

Department of Psychiatry, Akita University School of Medicine, Akita, Japan.

This report is the first to describe the use of milnacipran and olanzapine in combination in the treatment of delusional depression. The patient was a 55-year-old woman, and the combination treatment brought her marked amelioration of delusional depression without significant side effects. This suggests that the combination therapy of milnacipran and olanzapine is efficacious and safe in the treatment of delusional depression.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2424125PMC
December 2005

Response rate obtained using milnacipran depending on the severity of depression in the treatment of major depressive patients.

Clin Neuropharmacol 2006 Jan-Feb;29(1):6-9

Department of Psychiatry, Akita University School of Medicine, Akita, Japan.

Milnacipran--a new specific serotonin and noradrenaline reuptake inhibitor--is as effective as tricyclic antidepressants and exhibits a higher remission rate for major depressive patients than selective serotonin reuptake inhibitors. However, the effectiveness of milnacipran for severe major depressive patients had not been studied adequately. The study included 96 Japanese patients who fulfilled the DSM-IV criteria for the diagnosis of major depressive disorders and whose score on the Montgomery-Asberg Depression Rating Scale (MADRS) was 21 or higher. Of these, 16 patients were excluded because 10 did not complete the study, and 6 showed poor compliance. Finally, 80 patients were included. We defined patients with a baseline MADRS score of > or = 31 points as "severe" (n = 25). The remaining patients were classified as "moderate" (31 > MADRS score > or = 25, n = 30) and "mild" (MADRS score < 25, n = 25) using the median score of those patients as the cutoff. Milnacipran was administered twice daily for 6 weeks. The initial total dose was 50 mg/d; after a week it was increased to 100 mg/d. The response rates were 72%, 70%, and 44% in the "severe," "moderate," and "mild," respectively. No significant differences were found between "severe" and the "moderate"; however, significant differences were observed between "severe" and "mild" and "moderate" and "mild." These results demonstrated that milnacipran is almost equally effective in "severe" and "moderate." This study suggested that milnacipran has a reliable antidepressant effect in treating severe and moderate major depressive patients.
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http://dx.doi.org/10.1097/00002826-200601000-00003DOI Listing
May 2006

Remarkable effect of selegiline (L-deprenyl), a selective monoamine oxidase type-B inhibitor, in a patient with severe refractory depression: a case report.

Clin Neuropharmacol 2005 Jul-Aug;28(4):191-2

Omagari City Hospital, Iida, Japan.

A 34-year-old man presented with severe refractory depression. He had failed to respond to various antidepressants, augmentation therapy with lithium carbonate, and modified electroconvulsive therapy. Switching from amoxapine 150 mg/day to selegiline 7.5 mg/day, a selective monoamine oxidase type-B inhibitor, produced a dramatic reduction in hypobulia and lassitude, leading to a complete remission of all depressive symptoms. The patient reverted to his former position at work after an interval of approximately 3 years. Although the biologic basis of the antidepressant effect of selegiline in this patient is unknown, it is suggested that the enhancement of dopaminergic neurotransmission or elevation of brain-derived neurotrophic factor levels in the brain by administration of selegiline is involved in the recovery of this patient from severe refractory depression. This report indicates the antidepressant effect of selegiline in a refractory depressed patient.
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http://dx.doi.org/10.1097/01.wnf.0000171248.89726.2fDOI Listing
December 2005
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