379 results on '"Naoki KASHIHARA"'
Search Results
52. The renoprotective effect of esaxerenone independent of blood pressure lowering: a post hoc mediation analysis of the ESAX-DN trial
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Yasuyuki Okuda, Sadayoshi Ito, Naoki Kashihara, Kenichi Shikata, Masaomi Nangaku, Takashi Wada, Tomoko Sawanobori, and Masataka Taguri
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Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Abstract
Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are recommended as first-line drugs for hypertension with diabetic nephropathy owing to their renoprotective effect; however, their effect beyond lowering blood pressure (BP) has not been confirmed. Recent studies have shown that aldosterone plays a key role in causing renal injury; therefore, it is likely that mineralocorticoid receptor (MR) blockers inhibit aldosterone-induced renal damage in different ways from ACE inhibitors and ARBs. Therefore, we investigated the mechanism of the effect of an MR blocker on reducing the urinary albumin-to-creatinine ratio (UACR) using data from a randomized, double-blind, placebo-controlled phase 3 study (ESAX-DN) of a new nonsteroidal MR blocker, esaxerenone. This post hoc analysis used a novel statistical method to quantitatively estimate the effect of esaxerenone on UACR reduction mediated, or not mediated, by changes in systolic BP (SBP) and/or estimated glomerular filtration rate (eGFR). The proportion of the mediated effect by SBP changes to the total effect on UACR reduction was 9.8–10.7%; the UACR was reduced to 0.903–0.911 times the baseline at the end of treatment through the SBP-related pathway and to 0.422–0.426 times the baseline through the non-SBP-related pathway. Even considering both SBP and eGFR simultaneously, the proportion of the mediated effect was 21.9–28.1%. These results confirm that esaxerenone has a direct UACR-lowering effect independent of BP lowering and that its magnitude is much larger than that of the BP-dependent effect. Thus, esaxerenone could be a UACR-reducing treatment option for patients with diabetic nephropathy.
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- 2022
53. Analysis of inflammatory cytokines and estimated glomerular filtration rate decline in Japanese patients with diabetic kidney disease: a pilot study
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Yuka Sugawara, Yosuke Hirakawa, Koki Mise, Kosuke Kashiwabara, Ko Hanai, Satoshi Yamaguchi, Akihiro Katayama, Yasuhiro Onishi, Yui Yoshida, Naoki Kashihara, Yutaka Matsuyama, Tetsuya Babazono, Masaomi Nangaku, and Jun Wada
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Japan ,Biochemistry (medical) ,Clinical Biochemistry ,Drug Discovery ,Diabetes Mellitus ,Disease Progression ,Cytokines ,Humans ,Diabetic Nephropathies ,Pilot Projects ,Kidney ,Glomerular Filtration Rate - Abstract
Background: It is important to identify additional prognostic factors for diabetic kidney disease. Materials & methods: Baseline levels of ten cytokines (APRIL/TNFSF13, BAFF/TNFSF13B, chitinase 3-like 1, LIGHT/TNFSF14, TWEAK/TNFSF12, gp130/sIL-6Rβ, sCD163, sIL-6Rα, sTNF-R1, sTNF-R2) were measured in two cohorts of diabetic patients. In one cohort (n = 777), 156 individuals were randomly sampled after stratification and their plasma samples were analyzed; in the other cohort (n = 69), serum samples were analyzed in all the individuals. The levels of cytokines between rapid (estimated glomerular filtration rate decline >5 ml/min/1.73 m2/year) and non-rapid decliners were compared. Results: Multivariate analysis demonstrated significantly high levels of LIGHT/TNFSF14, TWEAK/TNFSF12 and sTNF-R2 in rapid decliners. Conclusion: These three cytokines can be potential biomarkers for the progression of diabetic kidney disease.
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- 2022
54. Evaluation of Neutrophil Dynamics Change by Protective Effect of Tadalafil After Renal Ischemia/Reperfusion Using In Vivo Real-time Imaging
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Kasumi Yoshinaga, Takuya Sadahira, Yuki Maruyama, Yasutomo Nasu, Koichiro Wada, Kengo Kidokoro, Naoki Kashihara, Yosuke Mitsui, Yuji Sogawa, Motoo Araki, Masami Watanabe, and Toyohiko Watanabe
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Neutrophils ,Ischemia ,Pharmacology ,Kidney ,Tadalafil ,Mice ,In vivo ,Enos ,medicine ,Animals ,Transplantation ,biology ,urogenital system ,business.industry ,Acute kidney injury ,Acute Kidney Injury ,medicine.disease ,biology.organism_classification ,medicine.anatomical_structure ,Reperfusion Injury ,Reperfusion ,business ,Reperfusion injury ,medicine.drug - Abstract
BACKGROUND Neutrophils play a major role in ischemia/reperfusion injury (IRI) in renal transplantation and acute kidney injury. However, it has been difficult to observe changes in neutrophil dynamics over time in living mice kidney. We investigate neutrophil dynamics in IRI in living mice using novel in vivo multiphoton microscope imaging techniques and characterize the renoprotective effects of a selective phosphodiesterase (PDE) 5 inhibitor, tadalafil. METHODS Wild-type (WT) and eNOS knockout (eNOS-KO) mice, a model of endothelial dysfunction, were used to establish in vivo real-time imaging in living mouse kidneys. Neutrophils were labeled green with Ly-6G monoclonal antibody, and plasma flow was labeled red with bovine serum albumin. Tadalafil was administered orally 1 h before surgery. Both kidney pedicles were reperfused after 37° warm ischemia for 45 min. RESULTS Our novel approach revealed that neutrophils were trapped in glomerulus within a few minutes after reperfusion. They gradually increased over time and Infiltrated neutrophils were observed in the tubular lumen and peritubular capillary. The neutrophils were clearly visualized rolling on peritubular capillary plexus at 3 μm/min. The administration of tadalafil significantly reduced neutrophil influx into the glomerulus in both WT and eNOS-KO mice. Reduced neutrophil infiltration in tadalafil groups, which was confirmed by flow cytometry, resulted in histopathologically decreased tubular injury. The expression of VCAM-1 and KIM-1 was partially prevented by tadalafil. CONCLUSIONS Use of a novel technique contributed to elucidation of neutrophil dynamics after reperfusion. Tadalafil has a potential for inhibiting neutrophil infiltration in renal IRI.Supplemental Visual Abstract; http://links.lww.com/TP/C223.
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- 2021
55. Glomerular Classification Using Convolutional Neural Networks Based on Defined Annotation Criteria and Concordance Evaluation Among Clinicians
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Kazuhiko Ohe, Akira Shimizu, Ryohei Yamaguchi, Yukako Shintani-Domoto, Yoshimasa Kawazoe, Kiminori Shimamoto, Tatsuo Tsukamoto, Masaomi Nangaku, Hiroshi Uozaki, Hajime Nagasu, Naoki Kashihara, Emiko Y. Shinohara, Michio Nagata, and Tetsuo Ushiku
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Receiver operating characteristic ,business.industry ,Deep learning ,030232 urology & nephrology ,convolutional neural network ,deep learning ,Pattern recognition ,glomerular image ,030204 cardiovascular system & hematology ,artificial intelligence ,Convolutional neural network ,03 medical and health sciences ,0302 clinical medicine ,Cohen's kappa ,Clinical Research ,renal pathology ,Nephrology ,Feature (computer vision) ,Medicine ,Segmentation ,Artificial intelligence ,business ,Kappa ,Test data - Abstract
Introduction Diagnosing renal pathologies is important for performing treatments. However, classifying every glomerulus is difficult for clinicians; thus, a support system, such as a computer, is required. This paper describes the automatic classification of glomerular images using a convolutional neural network (CNN). Method To generate appropriate labeled data, annotation criteria including 12 features e.g., “fibrous crescent”, were defined. The concordance among five clinicians was evaluated for 100 images using kappa coefficient for each feature. Using the annotation criteria, one clinician annotated 10,102 images. We trained the CNNs to classify the features whose average kappa ≧ 0.4 and evaluated their performance using the receiver operating characteristic – area under the curve (ROC–AUC). An error analysis was conducted and the gradient-weighted class activation mapping (Grad-CAM) was also applied; it expresses the CNN’s focusing point with a heat map when the CNN classifies the glomerular image for a feature. Result The average kappa coefficient of the features ranged from 0.28 to 0.50. The ROC–AUC of the CNNs for test data varied from 0.65 to 0.98. Among the features, “capillary collapse” and “fibrous crescent” had high ROC–AUC values of 0.98 and 0.91, respectively. The error analysis and the Grad-CAM visually showed the CNN could not distinguish between two different features that had similar visual structures or occurred simultaneously. Conclusion The differences in the texture or frequency of the co-occurrence between the different features affected the CNN performance; thus, to improve the classification accuracy, methods such as segmentation are required.
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- 2021
56. A rare case of amyloid light-chain amyloidosis with bilateral perirenal hematoma shortly after initiation of peritoneal dialysis
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Naoki Kashihara, Toshiya Yamamoto, Eriko Urabe, Hiroyuki Kadoya, Tamaki Sasaki, and Seiji Itano
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Amyloidosis ,Renal Hemorrhage ,030232 urology & nephrology ,Case Report ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,Surgery ,Peritoneal dialysis ,Angiopathy ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Renal replacement therapy ,Hemodialysis ,Hemoperitoneum ,medicine.symptom ,business ,Kidney disease - Abstract
Peritoneal dialysis (PD) is valuable for patients starting on renal replacement therapy because it preserves residual renal function, maintains hemodynamic stability, and affords higher quality of life than hemodialysis. Amyloid-related kidney disease is a rare condition and a cause of end-stage renal disease, the incidence of which appears to be rising in recent years. Hemoperitoneum is a common complication of PD. In some cases, it requires urgent treatment and careful monitoring for deterioration and potential complications. Although the kidney is a retroperitoneal organ, renal hemorrhage can cause bloody peritoneal dialysate. We encountered a rare case of amyloid light-chain amyloidosis where bilateral perirenal hematoma occurred shortly after initiation of PD. Amyloid angiopathy with increased blood vessel fragility and impaired vasoconstriction may promote bleeding. Therefore, hemoperitoneum in a patient on PD with disease causing fragile blood vessels, such as amyloidosis, should alert the physician to the possibility of underlying angiopathy.
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- 2021
57. A case of pleuroperitoneal communication during long-term steroid therapy for dermatomyositis
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Masanobu Takasu, Hiroyuki Kadoya, Yu Yamanouchi, Yuji Nojima, Toshiya Yamamoto, Seiji Itano, Masao Nakata, Tamaki Sasaki, and Naoki Kashihara
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Peritoneal Dialysis, Continuous Ambulatory ,Nephrology ,Communication ,Hydrothorax ,Humans ,Steroids ,General Medicine ,Peritoneal Dialysis ,Dermatomyositis - Published
- 2022
58. Correlates and Consequences of an Acute Change in eGFR in Response to the SGLT2 Inhibitor Dapagliflozin in Patients with CKD
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Niels, Jongs, Glenn M, Chertow, Tom, Greene, John J V, McMurray, Anna Maria, Langkilde, Ricardo, Correa-Rotter, Naoki, Kashihara, Peter, Rossing, C David, Sjöström, Bergur V, Stefánsson, Robert D, Toto, David C, Wheeler, Hiddo J L, Heerspink, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Kidney Center (GKC)
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Adult ,renal function ,EMPAGLIFLOZIN ,KIDNEY-DISEASE ,General Medicine ,dapagliflozin ,GLOMERULAR-FILTRATION-RATE ,PREDICTS ,Diabetes Mellitus, Type 2 ,Nephrology ,FALL ,Humans ,Albuminuria ,Benzhydryl Compounds ,Renal Insufficiency, Chronic ,Sodium-Glucose Transporter 2 Inhibitors ,chronic kidney disease ,Glomerular Filtration Rate - Abstract
Dapagliflozin reduces kidney failure risk in patients with CKD but can result in a reversible acute reduction in eGFR upon treatment initiation. Determinants of this eGFR reduction and its associations with efficacy and safety outcomes are unknown.The DAPA-CKD trial randomized 4304 adults with CKD and albuminuria to once-daily dapagliflozin 10 mg or placebo, added to standard care. We prespecified an analysis comparing the effects of dapagliflozin among patients who experienced relative reductions in eGFR (gt;10% orgt;0%-10%) or an increase in eGFR from baseline to 2 weeks and assessed long-term efficacy and safety thereafter.A total of 4157 (96.6%) patients had eGFR data available at baseline and at 2 weeks. In the dapagliflozin and placebo groups, 1026 (49.4%) and 494 (23.7%), respectively, experienced an acute reduction in eGFRgt;10%. Among patients receiving dapagliflozin, those with an acute reduction in eGFRgt;10% experienced a long-term eGFR decline of -1.58 ml/min per 1.73 msup2/supper year compared with -2.44 and -2.48 ml/min per 1.73 msup2/supper year among those experiencing a less pronounced reduction or increase in eGFR, respectively (iP/i-interaction=0.05). In the placebo group, long-term eGFR decline was -3.27, -3.84, and -3.77 ml/min per 1.73 msup2/supper year for acute eGFR reduction subgroups ofgt;10%,gt;0%-10%, or increase in eGFR (iP/i-interaction=0.48). Rates of serious adverse events and adverse events of special interest in patients randomized to dapagliflozin were unrelated to the acute eGFR change.Among patients with CKD and albuminuria treated with dapagliflozin, an acute reduction in eGFR (from baseline to 2 weeks) is not associated with higher rates of CKD progression.bClinical Trial registration number:/bA Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (Dapa-CKD) NCT03036150.
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- 2022
59. New-onset and relapse of nephrotic syndrome following COVID-19 vaccination: a questionnaire survey in Japan
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Naoki Nakagawa, Shoichi Maruyama, Naoki Kashihara, Ichiei Narita, and Yoshitaka Isaka
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Male ,COVID-19 Vaccines ,Nephrotic Syndrome ,Japan ,Nephrology ,Physiology ,Recurrence ,Physiology (medical) ,Surveys and Questionnaires ,Vaccination ,COVID-19 ,Humans - Abstract
Background Recent clinical reports indicate a correlation between new-onset and relapse of nephrotic syndrome (NS) following coronavirus 2019 (COVID-19) vaccination in patients with glomerular diseases. However, there are no reports of a nationwide survey on NS following COVID-19 vaccination in Japan. Methods We conducted a web-based survey of council members of the Japanese Society of Nephrology (581 members, 382 facilities) to elucidate the relationship between COVID-19 vaccination and new-onset and relapse of NS. Results Following COVID-19 vaccination, 27 patients (male: 15, 55.6%) with new-onset (n = 6) and relapse (n = 21) of NS were reported. Of them, 12 (44.4%) patients were diagnosed with minimal change disease at the occurrence of NS. Five patients developed a slight increase in serum creatinine levels; however, none progressed to severe renal dysfunction. Conclusion Our findings clarify the clinical features of new-onset and relapse of NS following COVID-19 vaccination. Although there was no obvious progression to severe renal dysfunction, clinicians and pathologists should be aware that NS is a potential adverse effect of the vaccines.
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- 2022
60. A phase 3 multicenter open-label maintenance study to investigate the long-term safety of sodium zirconium cyclosilicate in Japanese subjects with hyperkalemia
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Takeshi Osonoi, Hiromasa Harada, Yoshimitsu Yamasaki, June Zhao, Hyosung Kim, Yugo Shibagaki, Toshitaka Yajima, Nobuaki Sarai, and Naoki Kashihara
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Nephrology ,Adult ,Male ,medicine.medical_specialty ,Constipation ,Hyperkalemia ,Physiology ,Peripheral edema ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Sodium zirconium cyclosilicate ,Adverse effect ,Long-term safety study ,Aged ,Aged, 80 and over ,business.industry ,Silicates ,Middle Aged ,Japanese ,Potassium ,Population study ,Original Article ,Female ,Long term safety ,medicine.symptom ,business - Abstract
Background Hyperkalemia is associated with many chronic diseases and renin-angiotensin-aldosterone system inhibitor therapy. Sodium zirconium cyclosilicate (SZC), an oral, highly selective cation-exchanger, is approved for the treatment of hyperkalemia. Methods This phase 3, multicenter, open-label, single-arm, flexible-dose study assessed the safety and efficacy of SZC in Japanese patients with hyperkalemia during a correction phase of up to 3 days and long-term (1 year) maintenance phase (NCT03172702). Results Overall, 150 patients received treatment during both study phases; the study population was generally representative of hyperkalemic Japanese patients in clinical practice. Most patients (78.7%) had three doses of SZC during the correction phase. All but one patient received SZC for ≤ 48 h before transitioning to the maintenance phase. In the maintenance phase, mean (standard deviation; SD) exposure to the study drug was 319.4 (98.1) days and mean (SD) dose was 7.38 (2.85) g/day. Adverse events (AEs) were reported in 131 patients (87.3%); most were mild. The most common treatment-related AEs as evaluated by investigators were constipation (6.7%), peripheral edema (4.0%), and hypertension (2.7%). In the correction phase, 78.7% of patients were normokalemic at 24 h and 98.7% within 48 h; ≥ 65.5% maintained normokalemia throughout the maintenance phase. Conclusion After a year of exposure, SZC treatment was well tolerated by Japanese patients and potassium levels were well controlled.
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- 2020
61. Correction of serum potassium with sodium zirconium cyclosilicate in Japanese patients with hyperkalemia: a randomized, dose–response, phase 2/3 study
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Hiroshi Mizuno, Naoki Kashihara, Toshitaka Yajima, Yosuke Saka, Takayasu Ohtake, Takeshi Osonoi, Toshiyuki Imasawa, Hyosung Kim, Yugo Shibagaki, Toshiki Nishio, and Nobuaki Sarai
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Male ,Nephrology ,medicine.medical_specialty ,Time Factors ,Hyperkalemia ,Physiology ,Placebo ,Gastroenterology ,chemistry.chemical_compound ,Double-Blind Method ,Japan ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Potassium binder ,Sodium zirconium cyclosilicate ,Adverse effect ,Aged ,Chelating Agents ,Aged, 80 and over ,business.industry ,Silicates ,Middle Aged ,Hypokalemia ,Treatment Outcome ,chemistry ,Serum potassium ,Potassium ,Japanese ,Female ,Original Article ,medicine.symptom ,business ,Biomarkers - Abstract
Background Sodium zirconium cyclosilicate (SZC) is an oral potassium binder approved to treat hyperkalemia in adults in a number of countries, including Japan. Methods This phase 2/3, randomized, double-blind, placebo-controlled, dose–response study (ClinicalTrials.gov: NCT03127644) was designed to determine the efficacy and safety of SZC in Japanese adults with hyperkalemia. Patients with serum potassium (sK+) concentrations ≥ 5.1– ≤ 6.5 mmol/L were randomized 1:1:1 to SZC 5 g, SZC 10 g, or placebo three times daily for 48 h (six doses total). The primary efficacy endpoint was the exponential rate of change in sK+ over 48 h. The proportion of patients with normokalemia (sK+ 3.5–5.0 mmol/L) at 48 h and adverse events (AEs) were also evaluated. Results Overall, 103 patients (mean age, 73.2 years; range 50–89 years) received SZC 5 g (n = 34), SZC 10 g (n = 36), or placebo (n = 33). The exponential rate of sK+ change from 0 to 48 h versus placebo was − 0.00261 (SZC 5 g) and – 0.00496 (SZC 10 g; both P + Conclusion SZC is effective and well tolerated in Japanese patients with hyperkalemia.
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- 2020
62. Association of Arterial Stiffness With Kidney Function Among Adults Without Chronic Kidney Disease
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Yukihito Higashi, Hirofumi Tomiyama, Yuji Sogawa, Kenji Suzuki, Matthew J. Budoff, Hirofumi Makino, Minoru Satoh, Naoki Kashihara, Yuichiro Yano, Yusuke Kobayashi, George L. Bakris, Raymond R. Townsend, Hajime Nagasu, Seiji Itano, and Hiroshi Kanegae
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Male ,medicine.medical_specialty ,hypertension ,Original Contributions ,Clinical Sciences ,030232 urology & nephrology ,Urology ,Renal function ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Kidney ,Kidney Function Tests ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Vascular Stiffness ,Japan ,Internal Medicine ,medicine ,Medical Records, Problem-Oriented ,Humans ,AcademicSubjects/MED00200 ,Ankle Brachial Index ,Renal Insufficiency, Chronic ,Retrospective Studies ,Proteinuria ,Proportional hazards model ,business.industry ,cardio-ankle vascular index ,Hazard ratio ,blood pressure ,Odds ratio ,Middle Aged ,medicine.disease ,Prognosis ,female genital diseases and pregnancy complications ,Editor's Choice ,Blood pressure ,arterial stiffness ,Cardiovascular System & Hematology ,Arterial stiffness ,Disease Progression ,AcademicSubjects/SCI00960 ,Female ,medicine.symptom ,business ,chronic kidney disease ,Kidney disease ,Glomerular Filtration Rate - Abstract
BACKGROUND Our aims were to assess whether arterial stiffness is associated with a higher risk for kidney dysfunction among persons without chronic kidney disease (CKD). METHODS We analyzed data from the national health checkup system in Japan; for our analyses, we selected records of individuals who completed assessments of cardio-ankle vascular index (CAVI) and kidney function from 2005 to 2016. We excluded participants who had CKD at baseline, defined as the presence of proteinuria or estimated glomerular filtration rate (eGFR) RESULTS The mean age of the 24,297 included participants was 46.2 years, and 60% were female. Over a mean follow-up of 3.1 years, 1,435 CKD events occurred. In a multivariable analysis, the hazard ratios with 95% confidence intervals (CIs) for the highest vs. combined lower quartiles of CAVI measurements were 1.3 (1.1, 1.5) for CKD events, 1.3 (0.96, 1.62) for proteinuria, 1.4 (1.1, 1.7) for eGFR CONCLUSIONS Persons with CAVI measurements ≧8.1 had a higher risk for CKD events compared with their counterparts with CAVI measurements
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- 2020
63. Incidence of remission and relapse of proteinuria, end-stage kidney disease, mortality, and major outcomes in primary nephrotic syndrome: the Japan Nephrotic Syndrome Cohort Study (JNSCS)
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Yoshitaka Isaka, Hajime Hasegawa, Takeyuki Hiramatsu, Hitoshi Yokoyama, Ichiei Narita, Naoki Kashihara, Kosuke Masutani, Seiichi Matsuo, Kunihiro Yamagata, Tatsuo Tsukamoto, Hiroshi Sato, Kazuhiko Tsuruya, Yusuke Suzuki, Tomohiko Naruse, Shoichi Maruyama, Hiroshi Sobajima, Shunsuke Goto, Arimasa Shirasaki, Hideo Yasuda, Hirofumi Tamai, Hirokazu Okada, Shunya Uchida, Makoto Mizutani, Takashi Wada, Kiyoki Kitagawa, Satoshi Suzuki, Toshinobu Sato, Keiju Hiromura, Saori Nishio, Yoshio Terada, Kosaku Nitta, Ritsuko Katafuchi, Tomoya Nishino, Eiji Ishimura, Kojiro Nagai, Tsuneo Konta, Tetsushi Mimura, Yugo Shibagaki, Kunio Morozumi, Junichiro James Kazama, Hiroki Hayashi, Hitoshi Sugiyama, Megumu Fukunaga, Shizunori Ichida, Yasuhiro Akai, Toshiyuki Akahori, Takashi Shigematsu, Takafumi Ito, Asami Takeda, Enyu Imai, Satoshi Tanaka, Tatsuya Shoji, Yoshiro Fujita, Tadashi Sofue, Yosuke Saka, Ryohei Yamamoto, and Shouichi Fujimoto
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Male ,Nephrotic Syndrome ,Physiology ,Glomerulonephritis, Membranous ,Cohort Studies ,Primary nephrotic syndrome ,Focal segmental glomerulosclerosis ,Japan ,Recurrence ,Medicine ,Minimal change disease ,Proteinuria ,Glomerulosclerosis, Focal Segmental ,Incidence (epidemiology) ,Incidence ,Remission Induction ,Diabetes ,End-stage kidney disease ,Middle Aged ,Hospitalization ,Nephrology ,Cardiovascular Diseases ,Creatinine ,Female ,Original Article ,medicine.symptom ,Cohort study ,Infection ,Immunosuppressive Agents ,Adult ,medicine.medical_specialty ,Infections ,Membranous nephropathy ,Physiology (medical) ,Internal medicine ,Diabetes Mellitus ,Humans ,Hypoglycemic Agents ,Mortality ,Aged ,business.industry ,Nephrosis, Lipoid ,medicine.disease ,Kidney Failure, Chronic ,business ,Nephrotic syndrome ,Kidney disease ,Follow-Up Studies - Abstract
Background Despite recent advances in immunosuppressive therapy for patients with primary nephrotic syndrome, its effectiveness and safety have not been fully studied in recent nationwide real-world clinical data in Japan. Methods A 5-year cohort study, the Japan Nephrotic Syndrome Cohort Study, enrolled 374 patients with primary nephrotic syndrome in 55 hospitals in Japan, including 155, 148, 38, and 33 patients with minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other glomerulonephritides, respectively. The incidence rates of remission and relapse of proteinuria, 50% and 100% increases in serum creatinine, end-stage kidney disease (ESKD), all-cause mortality, and other major adverse outcomes were compared among glomerulonephritides using the Log-rank test. Incidence of hospitalization for infection, the most common cause of mortality, was compared using a multivariable-adjusted Cox proportional hazard model. Results Immunosuppressive therapy was administered in 339 (90.6%) patients. The cumulative probabilities of complete remission within 3 years of the baseline visit was ≥ 0.75 in patients with MCD, MN, and FSGS (0.95, 0.77, and 0.79, respectively). Diabetes was the most common adverse events associated with immunosuppressive therapy (incidence rate, 71.0 per 1000 person-years). All-cause mortality (15.6 per 1000 person-years), mainly infection-related mortality (47.8%), was more common than ESKD (8.9 per 1000 person-years), especially in patients with MCD and MN. MCD was significantly associated with hospitalization for infection than MN. Conclusions Patients with MCD and MN had a higher mortality, especially infection-related mortality, than ESKD. Nephrologists should pay more attention to infections in patients with primary nephrotic syndrome.
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- 2020
64. Dialysis Care and Dialysis Funding in Asia
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Hung Chun Chen, Hyeong Cheon Park, Aida Lydia, Vivekanand Jha, Sanjib Kumar Sharma, Naoki Kashihara, Maria Gina C. Nazareth, Ehteshamul Hoque, Sydney C.W. Tang, Virithy Lun, Ariunaa Togtokh, Bak Leong Goh, Sakarn Bunnag, Mohammad Ghnaimet, Adrian Liew, Jackson Tan, and Xueqing Yu
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Asia ,medicine.medical_treatment ,Population ,030232 urology & nephrology ,Developing country ,Health Services Accessibility ,Insurance Coverage ,Gross domestic product ,Hospitals, Private ,03 medical and health sciences ,0302 clinical medicine ,Cost of Illness ,Renal Dialysis ,Universal Health Insurance ,Prevalence ,Per capita ,Humans ,Medicine ,Diabetic Nephropathies ,030212 general & internal medicine ,education ,Socioeconomics ,Developing Countries ,Socioeconomic status ,Dialysis ,Health policy ,education.field_of_study ,Hospitals, Public ,business.industry ,Developed Countries ,Health Care Costs ,Kidney Transplantation ,Transplantation ,Nephrology ,Kidney Failure, Chronic ,Health Expenditures ,business ,Procedures and Techniques Utilization - Abstract
Asia is the largest and most populated continent in the world, with a high burden of kidney failure. In this Policy Forum article, we explore dialysis care and dialysis funding in 17 countries in Asia, describing conditions in both developed and developing nations across the region. In 13 of the 17 countries surveyed, diabetes is the most common cause of kidney failure. Due to great variation in gross domestic product per capita across Asian countries, disparities in the provision of kidney replacement therapy (KRT) exist both within and between countries. A number of Asian nations have satisfactory access to KRT and have comprehensive KRT registries to help inform practices, but some do not, particularly among low- and low-to-middle-income countries. Given these differences, we describe the economic status, burden of kidney failure, and cost of KRT across the different modalities to both governments and patients and how changes in health policy over time affect outcomes. Emerging trends suggest that more affluent nations and those with universal health care or access to insurance have much higher prevalent dialysis and transplantation rates, while in less affluent nations, dialysis access may be limited and when available, provided less frequently than optimal. These trends are also reflected by an association between nephrologist prevalence and individual nations’ incomes and a disparity in the number of nephrologists per million population and per thousand KRT patients.
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- 2020
65. Klotho is a novel therapeutic target in peritoneal fibrosis via Wnt signaling inhibition
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Hajime Nagasu, Kengo Kidokoro, Megumi Kondo, Minoru Satoh, Yoshihisa Wada, Tamaki Sasaki, Hiroyuki Kadoya, Yuji Sogawa, Naoki Kashihara, and Yuko Nishi
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0301 basic medicine ,Transgene ,030232 urology & nephrology ,Mice, Transgenic ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Peritoneum ,Fibrosis ,Animals ,Humans ,Medicine ,Klotho Proteins ,Peritoneal Fibrosis ,Klotho ,beta Catenin ,Glucuronidase ,Transplantation ,business.industry ,Wnt signaling pathway ,medicine.disease ,Eukaryotic translation elongation factor 1 alpha 1 ,Mice, Inbred C57BL ,Wnt Proteins ,030104 developmental biology ,medicine.anatomical_structure ,Nephrology ,Cancer research ,Signal transduction ,business ,Peritoneal Dialysis - Abstract
Background Long-term exposure to bioincompatible peritoneal dialysate causes the loss of mesothelial cells and accumulation of matrix proteins, leading to an increase in the thickness of the submesothelial layer, thereby limiting the long-term effectiveness of peritoneal dialysis (PD). However, the detailed molecular mechanisms underlying the process of peritoneal fibrosis have not been clearly elucidated. Wnt/β-catenin signaling pathway activation has been suggested to play a pivotal role in the development of organ fibrosis. Moreover, Klotho protein can regulate Wnt/β-catenin signaling. We examined the role of Klotho protein in reducing peritoneal fibrosis by inhibiting Wnt/β-catenin signaling. Methods The β-catenin-activated transgenic (BAT) driving expression of nuclear β-galactosidase reporter transgenic (BAT-LacZ) mice, the alpha-Klotho gene under control of human elongation factor 1 alpha promoter [Klotho transgenic (KLTG) and C57BL/6 background] and C57BL/6 mice [wild-type (WT)] were used. The mice received daily intraperitoneal (i.p.) injections of 4.25% glucose with lactate (PD solution) or saline as a control for 4 weeks. Other mice received daily i.p. injections of the same volume of saline (normal control). Results After exposure to PD, Wnt signal activation was observed on the peritoneal mesothelial cells in WT-PD mice. The peritoneal fibrosis was also accelerated in WT-PD mice. The protein expression of β-catenin and Wnt-inducible genes were also remarkably increased in WT-PD mice. On the other hand, KLTG-PD mice attenuated activation of Wnt/β-catenin signaling after exposure to PD and ameliorated the progression of peritoneal fibrosis. Conclusions Overexpression of Klotho protein protects the peritoneal membrane through attenuation of the Wnt/β-catenin signaling pathway. The availability of recombinant Klotho protein would provide a novel potential therapeutic target in peritoneal fibrosis.
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- 2020
66. Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial
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Heerspink, H. J.L., Stefansson, B., Chertow, G., Correa-Rotter, R., Greene, Tom, Hou, Fan Fan, Lindberg, Magnus, McMurray, John, Rossing, P., Toto, Roberto, Langkilde, Anna Maria, Wheeler, David C., Wheeler, D. C., Greene, T., Hou, F. F., McMurray, J., Toto, R., Langkilde, A. M., Pfeffer, Marc A., Pocock, Stuart, Swedberg, Karl, Rouleau, Jean L., Chaturvedi, Nishi, Ivanovich, Peter, Levey, Andrew S., Christ-Schmidt, Heidi, Mann, Johannes, Held, Claes, Varenhorst, Christoph, Holmgren, Pernilla, Hallberg, Theresa, Douthat, Walter, Filho, Roberto Pecoits, Cherney, David, Persson, Frederik, Haller, Hermann, Wittmann, István, Khullar, Dinesh, Naoki, Kashihara, Correa-Rotter, Richardo, Escudero, Elizabeth, Isidto, Rey, Nowicki, Michal, Batiushin, Mikhail, Groningen Kidney Center (GKC), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
- Subjects
Male ,Type 2 diabetes ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,sodium-glucose co-transporter inhibitor ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,Glucosides ,Randomized controlled trial ,law ,Chronic kidney disease ,Randomized controlled clinical trial ,Clinical endpoint ,Diabetic Nephropathies ,030212 general & internal medicine ,Dapagliflozin ,randomized controlled clinical trial ,Aged, 80 and over ,sodium–glucose co-transporter inhibitor ,Middle Aged ,Prognosis ,Cardiovascular Diseases ,Research Design ,Nephrology ,Female ,Glomerular Filtration Rate ,Adult ,medicine.medical_specialty ,Adolescent ,Renal function ,Young Adult ,03 medical and health sciences ,Double-Blind Method ,Clinical Research ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Benzhydryl Compounds ,Renal Insufficiency, Chronic ,Sodium-Glucose Transporter 2 Inhibitors ,Aged ,Transplantation ,Creatinine ,business.industry ,dapagliflozin ,medicine.disease ,Sodiumglucose co-transporter inhibitor ,Diabetes Mellitus, Type 2 ,chemistry ,ORIGINAL ARTICLES ,INHIBITORS ,business ,chronic kidney disease ,Kidney disease - Abstract
Background Recent cardiovascular outcome trials have shown that sodium–glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) in patients with type 2 diabetes at high cardiovascular risk. Whether these benefits extend to CKD patients without type 2 diabetes or cardiovascular disease is unknown. The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial (NCT03036150) will assess the effect of the SGLT2 inhibitor dapagliflozin on renal and cardiovascular events in a broad range of patients with CKD with and without diabetes. Methods DAPA-CKD is a randomized, double-blind, placebo-controlled, trial in which ∼4300 patients with CKD Stages 2–4 and elevated urinary albumin excretion will be enrolled. The vast majority will be receiving a maximum tolerated dose of a renin–angiotensin system inhibitor at enrolment. Results After a screening assessment, eligible patients with a urinary albumin:creatinine ratio ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 are randomly assigned to placebo or dapagliflozin 10 mg/day. Enrolment is monitored to ensure that at least 30% of patients do not have diabetes and that no more than 10% have an eGFR >60 mL/min/1.73 m2. The primary endpoint is a composite of a sustained decline in eGFR of ≥50%, end-stage renal disease, renal death or cardiovascular death. The trial will conclude when 681 primary renal events have occurred, providing 90% power to detect a 22% relative risk reduction (α level of 0.05). Conclusion DAPA-CKD will determine whether the SGLT2 inhibitor dapagliflozin, added to guideline-recommended therapies, safely reduces the rate of renal and cardiovascular events in patients across multiple CKD stages with and without diabetes., Graphical Abstract Graphical Abstract
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- 2020
67. Renoprotective effects of sodium-glucose cotransporter-2 inhibitors and underlying mechanisms
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Eiichiro Kanda, Kengo Kidokoro, and Naoki Kashihara
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business.industry ,030232 urology & nephrology ,MEDLINE ,030204 cardiovascular system & hematology ,Pharmacology ,Kidney ,Clinical trial ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Diabetes Mellitus, Type 2 ,Nephrology ,Sodium/Glucose Cotransporter 2 ,Internal Medicine ,Animals ,Humans ,Hypoglycemic Agents ,Medicine ,Diabetic Nephropathies ,business ,Sodium-Glucose Transporter 2 Inhibitors - Abstract
Emerging data have demonstrated that sodium-glucose cotransporter-2 (SGLT2) inhibitors prevent cardiovascular events, especially heart failure-associated endpoints. Cardiovascular outcome trials have also suggested their renoprotective effects. One large clinical trial investigated renal primary endpoints and demonstrated that SGLT2 inhibitors slowed the progression of diabetic kidney disease (DKD). This review summarizes clinical trial data on renal outcomes and discusses potential underlying mechanisms.The EMPA-REG, CANVAS, and DECLARE-TIMI 58 studies revealed that SGLT2 inhibitors reduce the risk of cardiovascular events and concomitantly suggested that these drugs slow the progression of kidney disease in type 2 diabetes. The CREDENCE trial on patients with high-risk type 2 diabetes and chronic kidney disease demonstrated that canagliflozin treatment reduced the relative risk of a composite outcome, including end-stage kidney disease, serum creatinine doubling, and renal/cardiovascular death, by 30% in these patients. Animal experiments revealed that oxidative stress, inflammation, fibrosis, and tubuloglomerular feedback are underlying renoprotective mechanisms behind SGLT2 inhibitors.Recent clinical trials have established the renoprotective effects of SGLT2 inhibitors. Further investigations on mechanisms of these renoprotective effects will provide deeper insights and understanding of pathogenetic properties of DKD.
- Published
- 2020
68. PS-R05-5: A CASE OF SEPTIC PULMONARY EMBOLISM DUE TO MITRAL VALVE ENDOCARDITIS OCCURRING EARLY IN THE INDUCTION PHASE OF HEMODIALYSIS
- Author
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Seiji Kishi, Kenji Nishimura, Naoki Kashihara, and Kojiro Nagai
- Subjects
Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
69. PS-B09-3: EXAMINATION OF ALBUMINURIA REDUCTION EFFECT THROUGH IMPROVEMENT OF ENOS UNCOUPLING BY SGLT2 IN TYPE 2 DIABETIC MICE
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Tsukasa Iwakura, Megumi Kondo, Kengo Kidokoro, and Naoki Kashihara
- Subjects
Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
70. S-41-1: PAST, PRESENT AND FUTURE OF CKD IN JAPAN
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Naoki Kashihara
- Subjects
Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
71. PS-BPB06-1: GLOMERULAR HEMODYNAMIC CHANGES WITH SGLT2 INHIBITION IN TYPE 2 DIABETIC RATS USING IN VIVO IMAGING
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Rie Tatsugawa, Yoshihisa Wada, Kengo Kidokoro, and Naoki Kashihara
- Subjects
Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
72. PS-BPB05-1: DUAL DISRUPTION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE AND APOE GENE ACCELERATES KIDNEY FIBROSIS AND AGING AFTER INJURY
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Seiji Kishi, Kenji Nishimura, and Naoki Kashihara
- Subjects
Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
73. PS-BPB08-6: REGULATORY MECHANISM OF GLOMERULAR FILTRATION RATE BY THE KEAP1/NRF2 PATHWAY
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Kengo Kidokoro, Hiroyuki Kadoya, and Naoki Kashihara
- Subjects
Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
74. PS-B09-2: ENOS-NO PATHWAY MODULATES AKI TO CKD TRANSITION IN IRI MODEL MICE VIA REGULATION OF B;CATENIN TRANSLOCATION
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Masanobu Takasu, Megumi Kondo, Hajime Nagasu, Hiroyuki Kadoya, Seiji Kishi, Kengo Kidokoro, and Naoki Kashihara
- Subjects
Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
75. PS-B09-9: ENOS-NO PATHWAY REGULATES INFLAMMASOME ACTIVATION IN DIABETIC MICE VIA MODULATION OF CEBP TRANSLOCATION
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Hajime Nagasu, Reiko Umeno, Hiroyuki Kadoya, and Naoki Kashihara
- Subjects
Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
76. PS-B06-7: ENDOTHELIAL DYSFUNCTION EXACERBATES KIDNEY DYSFUNCTION IN AGEING KIDNEY VIA ACTIVATION OF INFLAMMASOME
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Yoshihisa Wada, Hajime Nagasu, Hiroyuki Kadoya, and Naoki Kashihara
- Subjects
Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
77. PS-B09-1: ENOS/NO SIGNALING REGULATES RENAL INTERSTITIAL FIBROSIS BY INCREASING CYTOPLASMIC BETA-CATENIN DEGRADATION
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Masanobu Takasu, Hiroyuki Kadoya, Hajime Nagasu, Seiji Kishi, Tamaki Sasaki, and Naoki Kashihara
- Subjects
Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
78. Trans-ethnic Mendelian-randomization study reveals causal relationships between cardiometabolic factors and chronic kidney disease
- Author
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Hong Zhang, Humaira Rasheed, Yukinori Okada, Iona Y Millwood, Zhengming Chen, Tom R. Gaunt, George Davey Smith, Yoichiro Kamatani, Venexia M Walker, Philip C Haycock, Andrew P. Morris, Jie Zheng, Cristian Pattaro, Robyn E Wootton, Yuka Sugawara, Amy E Howell, Masato Akiyama, Koichi Matsuda, Sean J. Barbour, Nora Franceschini, Masahiro Kanai, Matthias Wuttke, Si Fang, Masayuki Yamamoto, Jiachen Li, Naoki Kashihara, Ben Michael Brumpton, Laurent F. Thomas, Maria Carolina Borges, Rebecca Carnegie, Jamie Robinson, Yue-miao Zhang, Stein Hallan, Canqing Yu, Benjamin Elsworth, Stephen Burgess, Yue Leng, Kristian Hveem, Robin G Walters, Yoonsu Cho, Anna Köttgen, Bjørn Olav Åsvold, Qian Yang, Zheng, Jie [0000-0002-6623-6839], Walker, Venexia [0000-0001-5064-446X], Elsworth, Benjamin [0000-0001-7328-4233], Wootton, Robyn E [0000-0003-3961-3202], Yang, Qian [0000-0001-8778-4132], Davey Smith, George [0000-0002-1407-8314], Apollo - University of Cambridge Repository, and Burgess, Stephen [0000-0001-5365-8760]
- Subjects
medicine.medical_specialty ,causality ,Apolipoprotein B ,Epidemiology ,Renal function ,Type 2 diabetes ,urologic and male genital diseases ,Random Allocation ,Internal medicine ,Mendelian randomization ,medicine ,Humans ,AcademicSubjects/MED00860 ,Renal Insufficiency, Chronic ,biology ,business.industry ,trans-ethnic study ,General Medicine ,Mendelian Randomization Analysis ,medicine.disease ,Causality ,cardiometabolic risk factors ,female genital diseases and pregnancy complications ,Blood pressure ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,biology.protein ,business ,Body mass index ,chronic kidney disease ,Genome-Wide Association Study ,Kidney disease - Abstract
Funder: Government Department of Business, Funder: Energy and Industrial Strategy (BEIS), Funder: Vice-Chancellor Fellowship from the University of Bristol, Funder: Shanghai Thousand Talents Program, Funder: Academy of Medical Sciences (AMS) Springboard Award, Funder: BBSRC Innovation fellowship, Funder: NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol, 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 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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- 2021
79. Low Adherence to Kidney Disease: Improving Global Outcomes 2012 CKD Clinical Practice Guidelines Despite Clear Evidence of Utility
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Glen James, Juan Jose Garcia Sanchez, Juan Jesus Carrero, Supriya Kumar, Roberto Pecoits-Filho, Hiddo J.L. Heerspink, Stephen Nolan, Carolyn S.P. Lam, Hungta Chen, Eiichiro Kanda, Naoki Kashihara, Matthew Arnold, Mikhail N. Kosiborod, Mitja Lainscak, Carol Pollock, David C. Wheeler, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Kidney Center (GKC)
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estimated glomerular filtration rate ,Kidney Disease: Improving Global Outcomes ,Nephrology ,urinary albumin-to-creatinine ratio ,DISCOVER CKD ,retrospective ,chronic kidney disease - Abstract
Introduction: Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines classify chronic kidney disease (CKD) risk or prognosis using estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR). We assessed patient characteristics and outcomes according to the KDIGO classification, using data from DISCOVER CKD (NCT04034992). Methods: Data were extracted from the US integrated Limited Claims and Electronic Health Record Dataset and TriNetX databases, and the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics databases. Eligible patients were aged ≥18 years with CKD, and identified by 2 consecutive eGFR measures (5 to 2; ≥90 days apart [maximum 730]) from January 2008. Index date was the second eGFR measurement; patients were categorized using the UACR measure closest to the index. Outcomes included patient characteristics, eGFR or UACR measurement frequency, and clinical outcomes per baseline KDIGO classification. Results: Across databases, only 8.6% of patients with 2 eGFR measures had ≥1 UACR measures. Among 123,807 eligible patients, prevalence of heart failure, hypertension, and type 2 diabetes increased with increasing albuminuria. Incidence rates of mortality and adverse cardiovascular and renal outcomes increased with declining baseline eGFR, and particularly with increasing albuminuria. Median number of eGFR and UACR tests per year post-index ranged from 1.6 to 2.5 and 0.5 to 0.6, respectively, across databases; there was no clear increase in UACR testing frequency following the KDIGO 2012 guidelines. Conclusion: Albuminuria monitoring is critical for optimal risk stratification in CKD, and our findings highlight an imperative for more regular UACR testing in clinical practice.
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- 2021
80. Renal cell carcinoma sharply captured by imaging technology at an early stage in a hemodialysis patient: Usefulness of noninvasive monochrome superb microvascular imaging
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Atsuyuki Tokuyama, Atsushi Obata, Takahiro Obata, Hiroyuki Kadoya, Naoki Kashihara, Rie Ohsawa, Tamaki Sasaki, and Hideaki Kaneto
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medicine.medical_specialty ,renal cell carcinoma ,medicine.medical_treatment ,030232 urology & nephrology ,Case Report ,Type 2 diabetes ,Case Reports ,030204 cardiovascular system & hematology ,Malignancy ,urologic and male genital diseases ,03 medical and health sciences ,0302 clinical medicine ,Vascularity ,Renal cell carcinoma ,medicine ,Stage (cooking) ,hemodialysis ,business.industry ,monochrome superb microvascular imaging ,Hematology ,Blood flow ,ultrasonography ,medicine.disease ,Nephrology ,Imaging technology ,Radiology ,Hemodialysis ,type 2 diabetes ,medicine.symptom ,business - Abstract
It has been drawing much attention that type 2 diabetes mellitus is closely associated with increased incidence of numerous cancers and their poor prognosis. Consequently, malignancy has been recently recognized as one of diabetic complications in addition to various conventional complications. Furthermore, it is well known that the prevalence of renal cell carcinoma (RCC) is drastically increased in hemodialysis (HD) patients. Therefore, screening of RCCs in HD patients is a very important and urgent issue as there are no highly sensitive tumor markers for RCCs. Monochrome superb microvascular imaging (mSMI) is a relatively new Doppler ultrasound technique and is useful especially when evaluating very slow blood flow state, because this allows for imaging microvessels with low velocity in the absence of a contrast agent. Thus, mSMI might be also useful when contrast enhancement is not obvious on CT and/or contrast‐enhanced ultrasonography using perflubutane or contrast agents are contraindicated. Moreover, it has been reported that mSMI could effectively detect vascularity of renal malignant tumor than benign renal mass in nondialysis patients. We propose that mSMI of ultrasonography could become one of the very useful methods for detecting RCCs at an early stage with high sensitivity in HD patients.
- Published
- 2021
81. MP37-09 THE NOVEL IN VIVO REAL-TIME IMAGING TECHNIQUES VISUALIZE THE NEUTROPHIL INFILTRATION FOLLOWING RENAL ISCHEMIA/REPERFUSION
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Yasutomo Nasu, Toyohiko Watanabe, Masami Watanabe, Takuya Sadahira, Moto Araki, Koichiro Wada, Yasuyuki Kobayashi, Kohei Edamura, Kasumi Yoshinaga, Naoki Kashihara, Kengo Kidokoro, Shingo Nishimura, Yosuke Mitsui, and Yuki Maruyama
- Subjects
Pathology ,medicine.medical_specialty ,business.industry ,In vivo ,Urology ,Medicine ,Real time imaging ,business ,medicine.disease ,Renal ischemia reperfusion ,Infiltration (medical) - Published
- 2021
82. Prologue: Special Spotlight Issue on Japan
- Author
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Katsuyuki Miura, Akira Nishiyama, Takashi Hisamatsu, Atsushi Sakima, Naoki Kashihara, Kouihci Node, Toshihiko Ishimitsu, Tetsutaro Matayoshi, Yutaka Imai, Kazuomi Kario, Kouichi Tamura, Hiroshi Itoh, Hisatomi Arima, Hiromi Rakugi, Yuichiro Yano, Takayoshi Ohkubo, Kei Asayama, and Takuya Tsuchihashi
- Subjects
business.industry ,Prologue ,Internal Medicine ,MEDLINE ,Medicine ,business ,Classics - Published
- 2021
83. Comparison of annual eGFR decline among primary kidney diseases in patients with CKD G3b-5: results from a REACH-J CKD cohort study
- Author
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Kei Nagai, Ronald L. Pisoni, Hirayasu Kai, Ichiei Narita, Chie Saito, Christian Combe, Kunitoshi Iseki, Hirokazu Okada, Chiho Iseki, Kunihiro Yamagata, Naoki Kashihara, Masahide Kondo, Koichi Asahi, Ryoya Tsunoda, Bruce M. Robinson, Yukiko Ito, Junichi Hoshino, Takashi Wada, Bioingénierie tissulaire (BIOTIS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)
- Subjects
Male ,Nephrology ,medicine.medical_specialty ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,Physiology ,030232 urology & nephrology ,Renal function ,Disease ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,03 medical and health sciences ,0302 clinical medicine ,Polycystic kidney disease ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Diabetic Nephropathies ,Prospective Studies ,Diabetic kidney disease ,Aged ,Aged, 80 and over ,Polycystic Kidney Diseases ,Kidney ,Proteinuria ,business.industry ,REACH-J ,Middle Aged ,medicine.disease ,female genital diseases and pregnancy complications ,medicine.anatomical_structure ,Kidney Failure, Chronic ,Female ,medicine.symptom ,EGFR decline ,business ,Glomerular Filtration Rate ,Cohort study ,Kidney disease - Abstract
Disease-specific trajectories of renal function in advanced chronic kidney disease (CKD) are not well defined. Here, we compared these trajectories in the estimated glomerular filtration rate (eGFR) by CKD stages. Patients with multiple eGFR measurements during the 5-year preregistration period of the REACH-J study were enrolled. Mean annual eGFR declines were calculated from linear mixed effect models with the adjustment variables of baseline CKD stage, age, sex and the current CKD stage and the level of proteinuria (CKDA1-3). Among 1,969 eligible patients with CKDG3b-5, the adjusted eGFR decline (ml/min/1.73 m2/year) was significantly faster in diabetic kidney disease (DKD) patients and polycystic kidney disease (PKD) patients than in patients with other kidney diseases (DKD, − 2.96 ± 0.13; PKD, − 2.82 ± 0.17; and others, − 1.95 ± 0.05, p
- Published
- 2021
84. Correction: Proteinuria changes in kidney disease patients with clinical remission during the COVID-19 pandemic
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Takashi Yokoo, Takaya Sasaki, Nobuo Tsuboi, and Naoki Kashihara
- Subjects
Nephrology ,Adult ,Male ,medicine.medical_specialty ,Science ,Urinary system ,Angiotensin-Converting Enzyme Inhibitors ,Severity of Illness Index ,Japan ,Internal medicine ,Severity of illness ,medicine ,Odds Ratio ,Outpatient clinic ,Humans ,Renal Insufficiency, Chronic ,Aged ,Retrospective Studies ,Multidisciplinary ,Proteinuria ,Maintenance dose ,business.industry ,SARS-CoV-2 ,Remission Induction ,Correction ,COVID-19 ,Odds ratio ,Middle Aged ,medicine.disease ,Logistic Models ,Medicine ,Female ,medicine.symptom ,business ,Kidney disease - Abstract
BACKGROUNDS: Data on how lifestyle changes due to the coronavirus disease 2019 (COVID-19) pandemic have influenced the clinical features of kidney disease patients remain scarce. METHODS: This study retrospectively analyzed clinical variables in patients with stage G1-G4 chronic kidney disease (CKD) with complete or incomplete remission of proteinuria, who were managed in a nephrology outpatient clinic of a university hospital in Tokyo. The clinical variables during the COVID-19 pandemic (term 1, June-July 2020) were compared to those one year before the pandemic (term 0, June-July 2019). The urinary protein excretion (UPE) was used as the primary outcome measure. RESULTS: This study included 325 patients with stage G1-G4 CKD (mean age 58.5 years old, 37.5% female, 80.6% on renin-angiotensin aldosterone system inhibitors [RAASis], 12.0% on maintenance dose immunosuppression therapy) evaluated at term 0. The UPE at terms 0 and 1 was 247 (92-624) and 203 (84-508) mg/day [median (25th-75th percentile)], respectively; the value in term 1 was 18% lower than that in term 0 (p
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- 2021
85. Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome Activation
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Megumi Kondo, Shun'ichiro Taniguchi, Yoshihisa Wada, Atsuyuki Tokuyama, Hiroyuki Kadoya, Masafumi Takahashi, Tamaki Sasaki, Kengo Kidokoro, Reina Umeno, Naoki Kashihara, and Hajime Nagasu
- Subjects
Male ,Aging ,Inflammasomes ,Kidney ,chemistry.chemical_compound ,Mice ,Enos ,Endothelial dysfunction ,Biology (General) ,Spectroscopy ,Mice, Knockout ,biology ,Inflammasome ,General Medicine ,Computer Science Applications ,Mitochondria ,macrophages ,Chemistry ,senescence-associated secretory phenotype ,medicine.drug ,medicine.medical_specialty ,Nitric Oxide Synthase Type III ,QH301-705.5 ,Mice, Transgenic ,Nitric Oxide ,Catalysis ,Article ,Nitric oxide ,Inorganic Chemistry ,inflammasome ,Internal medicine ,medicine ,Animals ,mitochondria dysfunction ,Endothelium ,Vascular Diseases ,Physical and Theoretical Chemistry ,Molecular Biology ,QD1-999 ,business.industry ,Organic Chemistry ,Wild type ,ASC-deficient mice ,medicine.disease ,biology.organism_classification ,Mice, Inbred C57BL ,Endocrinology ,chemistry ,Ageing ,business ,Function (biology) ,Kidney disease - Abstract
Chronic kidney disease is a common problem in the elderly and is associated with increased mortality. We have reported on the role of nitric oxide, which is generated from endothelial nitric oxide synthase (eNOS), in the progression of aged kidneys. To elucidate the role of endothelial dysfunction and the lack of an eNOS-NO pathway in ageing kidneys, we conducted experiments using eNOS and ASC-deficient mice. C57B/6 J mice (wild type (WT)), eNOS knockout (eNOS KO), and ASC knockout (ASC KO) mice were used in the present study. Then, eNOS/ASC double-knockout (eNOS/ASC DKO) mice were generated by crossing eNOS KO and ASC KO mice. These mice were sacrificed at 17−19 months old. The Masson positive area and the KIM-1 positive area tended to increase in eNOS KO mice, compared with WT mice, but not eNOS/ASC DKO mice. The COX-positive area was significantly reduced in eNOS KO mice, compared with WT and eNOS/ASC DKO mice. To determine whether inflammasomes were activated in infiltrating macrophages, the double staining of IL-18 and F4/80 was performed. IL-18 and F4/80 were found to be co-localised in the tubulointerstitial areas. Inflammasomes play a pivotal role in inflammaging in ageing kidneys. Furthermore, inflammasome activation may accelerate cellular senescence via mitochondrial dysfunction. The importance of endothelial function as a regulatory mechanism suggests that protection of endothelial function may be a potential therapeutic target.
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- 2021
86. Roxadustat and thyroid-stimulating hormone suppression
- Author
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Tamaki Sasaki, Atsushi Obata, Atsuyuki Tokuyama, Hiroyuki Kadoya, Naoki Kashihara, and Takahiro Obata
- Subjects
medicine.medical_specialty ,endocrine system ,Darbepoetin alfa ,endocrine system diseases ,medicine.medical_treatment ,030232 urology & nephrology ,Levothyroxine ,Exceptional Cases ,End stage renal disease ,03 medical and health sciences ,0302 clinical medicine ,Thyroid-stimulating hormone ,Internal medicine ,medicine ,AcademicSubjects/MED00340 ,Transplantation ,Thyroid hormone receptor ,end-stage renal disease ,hemodialysis ,business.industry ,roxadustat ,medicine.disease ,levothyroxine sodium hydrate ,Endocrinology ,Nephrology ,Hemodialysis ,hypothyroidism ,business ,hypoxia-inducible factor prolyl-hydroxylase inhibitor ,Kidney disease ,medicine.drug ,Hormone - Abstract
Hypoxia-inducible factor prolyl-hydroxylase inhibitors belong to a new class of orally administered drugs for treating anemia in patients with chronic kidney disease (CKD). The prevalence of hypothyroidism is disproportionately high in patients with CKD on hemodialysis. We report a rapid suppression of thyroid-stimulating hormone (TSH) and decrease in free triiodothyronine (T3) and free tetraiodothyronine levels after switching from darbepoetin alfa to roxadustat in a hemodialysis patient with hypothyroidism on levothyroxine therapy. This was reversed after stopping roxadustat. Roxadustat has structural similarity with T3 and is a selective activating ligand for thyroid hormone receptor-β possibly suppressing TSH release.
- Published
- 2021
87. The deficient of eNOS-NO pathway exacerbates kidney dysfunction via inflammasome activation in diabetic kidney disease.
- Author
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Reina UMENO, Hajime NAGASU, Masanobu TAKASU, Natsumi INOUE, Rie TATSUGAWA, Eriko KAJIMOTO, Akira HIRANO, Tsukasa IWAKURA, Yoshihisa WADA, Hiroyuki KADOYA, Kengo KIDOKORO, Seiji KISHI, Shun'ichiro TANIGUCHI, Masafumi TAKAHASHI, Tamaki SASAKI, and Naoki KASHIHARA
- Published
- 2023
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88. 17. Regional and Multidisciplinary Cooperation in the Countermeasures against Chronic Kidney Disease (CKD)
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Takafumi Ito and Naoki Kashihara
- Subjects
General Medicine - Published
- 2022
89. Physical functioning in patients with chronic kidney disease stage G3b-5 in Japan: The reach-J CKD cohort study
- Author
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Kei Nagai, Junichi Hoshino, Hirayasu Kai, Chie Saito, Naoki Kashihara, Ryoya Tsunoda, Reiko Okubo, Takashi Wada, Ichiei Narita, Hirokazu Okada, Bruce G. Robinson, Masahide Kondo, and Kunihiro Yamagata
- Subjects
Male ,medicine.medical_specialty ,Activities of daily living ,Disease ,urologic and male genital diseases ,Physical functioning ,Japan ,Renal Dialysis ,Diabetes mellitus ,Internal medicine ,Activities of Daily Living ,Medicine ,Humans ,Prospective Studies ,Stage (cooking) ,Renal Insufficiency, Chronic ,Exercise ,Aged ,business.industry ,Public health ,Incidence ,General Medicine ,medicine.disease ,female genital diseases and pregnancy complications ,Nephrology ,Female ,business ,Cohort study ,Kidney disease ,Follow-Up Studies ,Glomerular Filtration Rate - Abstract
AIM Chronic kidney disease (CKD) is an important public health problem. Recently, CKD has been found to be associated with poor physical functioning in community-dwelling elderly individuals. However, the physical functioning of non-dialysis (ND) patients with advanced CKD treated by nephrologists is unknown. METHODS Patients with ND-CKD stage G3b-5 who participated in a nationwide Reach-J CKD cohort study were included in this study. Physical functioning and physical activity were assessed by the Katz Index, Lawton-Body instrumental activities of daily living (IADL) scale, and Rapid Assessment of Physical Activity questionnaire of the international CKD Outcomes and Practice Patterns Study (CKDopps) questionnaires. Dichotomies between good and poor physical functioning and physical activity scores were explored. RESULTS Among 1628 patients, 84.3% had good physical functioning. Poor physical functioning was more common with older age (p
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- 2021
90. Efficacy of the Self-management Support System DialBetesPlus for Diabetic Kidney Disease: Protocol for a Randomized Controlled Trial (Preprint)
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Yuki Kawai, Akiko Sankoda, Kayo Waki, Kana Miyake, Aki Hayashi, Makiko Mieno, Hiromichi Wakui, Yuya Tsurutani, Jun Saito, Nobuhito Hirawa, Tadashi Yamakawa, Shiro Komiya, Akihiro Isogawa, Shinobu Satoh, Taichi Minami, Uru Osada, Tamio Iwamoto, Tatsuro Takano, Yasuo Terauchi, Kouichi Tamura, Toshimasa Yamauchi, Takashi Kadowaki, Masaomi Nangaku, Naoki Kashihara, and Kazuhiko Ohe
- Abstract
BACKGROUND Diabetic kidney disease (DKD) is one of the main complications of type 2 diabetes mellitus (T2DM). DKD is a known risk factor for end-stage renal disease, cardiovascular disease, and all-cause death. Effective intervention for early-stage DKD is vital to slowing down the progression of kidney disease and improve prognoses. Mobile health (mHealth) is reportedly effective in supporting patients’ self-care and improving glycemic control, but the impact of mHealth on DKD has yet to be shown. OBJECTIVE The purpose of this study is to evaluate the efficacy of standard therapy with the addition of a self-management support system, DialBetesPlus, in patients with DKD and microalbuminuria. METHODS This study is a prospective, randomized, open-label, multicenter clinical trial. The target population consists of 160 patients diagnosed with T2DM accompanied by microalbuminuria. We randomly assigned the patients to 2 groups—the intervention group using DialBetesPlus in addition to conventional therapy and the control group using conventional therapy alone. DialBetesPlus is a smartphone application that supports patients’ self-management of T2DM. The study period was 12 months, with a follow-up survey at 18 months. The primary outcome was a change in albuminuria levels at 12 months. Secondary outcomes included changes in physical parameters, blood test results (glycemic control, renal function, and lipid metabolism), lifestyle habits, self-management scores, medication therapy, and quality of life. RESULTS The study was approved in April 2018. We began recruiting patients in July 2018 and completed recruiting in August 2019. The final 18-month follow-up was conducted in March 2021. We recruited 159 patients and randomly allocated 70 into the intervention group and 61 into the control group, with 28 exclusions due to withdrawal of consent, refusal to continue, or ineligibility. The first results are expected to be available in 2021. CONCLUSIONS This is the first randomized controlled trial assessing the efficacy of mHealth on early-stage DKD. We expect that albuminuria levels will decrease significantly in the intervention group due to improved glycemic control with ameliorated self-care behaviors. CLINICALTRIAL UMIN-CTR UMIN000033261; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000037924 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/31061
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- 2021
91. Kidney vascular congestion exacerbates acute kidney injury in mice
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Yuhei Kirita, Satoaki Matoba, Kengo Kidokoro, Keiichi Tamagaki, Benjamin D. Humphreys, Takashi Kitani, Tomohiro Nakata, Aya Yagi-Tomita, Tetsuro Kusaba, Itaru Nakamura, Kunihiro Nakai, Noriko Uehara-Watanabe, Tomoharu Ida, Naoki Kashihara, Noriyuki Yamashita, and Kisho Ikeda
- Subjects
Pathology ,medicine.medical_specialty ,Ischemia ,Renal function ,Kidney ,Peritubular capillaries ,Inferior vena cava ,Mice ,medicine ,Animals ,Humans ,urogenital system ,business.industry ,Acute kidney injury ,NF-kappa B ,Endothelial Cells ,Acute Kidney Injury ,medicine.disease ,medicine.anatomical_structure ,medicine.vein ,Nephrology ,Renal blood flow ,Reperfusion Injury ,business ,Reperfusion injury - Abstract
Heart failure is frequently accompanied by kidney failure and co-incidence of these organ failures worsens the mortality in patients with heart failure. Recent clinical observations revealed that increased kidney venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in patients with heart failure. However, the underlying pathophysiology is unknown. Here, we found that decreased blood flow velocity in peritubular capillaries by kidney congestion and upregulation of endothelial nuclear factor-κB (NF-κB) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral kidney congestion by constriction of the inferior vena cava between kidney veins. Intravital imaging highlighted the notable dilatation of peritubular capillaries and decreased kidney blood flow velocity in the congestive kidney. Damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes within peritubular capillaries was noted at the acute phase after injury. Similar results were obtained in vitro, in which polymorphonuclear leukocytes adhesion on activated endothelial cells was decreased in flow velocity-dependent manner but cancelled by inhibition of NF-κB signaling. Pharmacological inhibition of NF-κB for the mice subjected by both kidney congestion and ischemia reperfusion injury ameliorated the accumulation of polymorphonuclear leukocytes and subsequent exacerbation of kidney injury. Thus, our study demonstrates the importance of decreased blood flow velocity accompanying activated NF-κB signaling in aggravation of kidney injury. Hence, inhibition of NF-κB signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased kidney venous pressure.
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- 2021
92. Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database
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Kazuhiko Ohe, Takashi Wada, Tadashi Sofue, Yuichiro Yano, Hirokazu Okada, Hiromi Kataoka, Masaomi Nangaku, Akira Nishiyama, Yuji Tani, Jun Wada, Hitoshi Sugiyama, Toshiaki Nakano, Eiichiro Kanda, Motoko Yanagita, Mihoko Okada, Yosuke Hirakawa, Takashi Shigematsu, Naoki Kashihara, Yuka Sugawara, Naoki Nakashima, Naoki Nakagawa, Hiddo J.L. Heerspink, Kouichi Tamura, Kohjiro Ueki, Kazuhiko Tsuruya, Ichiei Narita, Takafumi Ito, Yoshio Terada, Hajime Nagasu, Kunihiro Yamagata, Seiji Itano, Hiroshi Kanegae, and Shoichi Maruyama
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Renal function ,Kidney ,law.invention ,Randomized controlled trial ,Japan ,law ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Renal Insufficiency, Chronic ,Sodium-Glucose Transporter 2 Inhibitors ,Advanced and Specialized Nursing ,Proteinuria ,Emerging Therapies: Drugs and Regimens ,business.industry ,Hazard ratio ,medicine.disease ,Clinical trial ,medicine.anatomical_structure ,Glucose ,Diabetes Mellitus, Type 2 ,medicine.symptom ,business ,Kidney disease ,Glomerular Filtration Rate - Abstract
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 (n = 1,033) or other glucose-lowering drug (n = 1,033) was 64.4 years, mean eGFR was 68.1 mL/min per 1.73 m2, 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 m2 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 (Pheterogeneity ≥ 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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- 2021
93. Cardiovascular and Renal Outcomes Associated With Hyperkalemia in Chronic Kidney Disease: A Hospital-Based Cohort Study
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Naoki Kashihara, Eiichiro Kanda, Shun Kohsaka, Toshitaka Yajima, and Suguru Okami
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Medicine (General) ,medicine.medical_specialty ,Hyperkalemia ,business.industry ,medicine.medical_treatment ,Hazard ratio ,Renal function ,Retrospective cohort study ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,R5-920 ,0302 clinical medicine ,Heart failure ,Internal medicine ,medicine ,030212 general & internal medicine ,Renal replacement therapy ,medicine.symptom ,business ,Kidney disease ,Cohort study - Abstract
Objective To examine the association between hyperkalemia and long-term cardiovascular and renal outcomes in patients with chronic kidney disease. Patients and Methods An observational retrospective cohort study was performed using a Japanese hospital claims registry, Medical Data Vision (April 1, 2008, to September 30, 2018). Of 1,208,894 patients with at least 1 potassium measurement, 167,465 patients with chronic kidney disease were selected based on International Classification of Diseases, Tenth Revision codes or estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. Hyperkalemia was defined as at least 2 potassium measurements of 5.1 mmol/L or greater within 12 months. Normokalemic controls were patients without a record of potassium levels of 5.1 mmol/L or greater and 3.5 mmol/L or less. Changes in eGFRs and hazard ratios of death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction were assessed between propensity score–matched hyperkalemic patients and normokalemic controls. Results Of 16,133 hyperkalemic patients and 11,898 normokalemic controls eligible for analyses, 5859 (36.3%) patients and 5859 (49.2%) controls were selected after propensity score matching. The mean follow-up period was 3.5 years. The 3-year eGFR change in patients and controls was −5.75 and −1.79 mL/min/1.73 m2, respectively. Overall, hyperkalemic patients had higher risks for death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction than controls, with hazard ratios of 4.40 (95% CI, 3.74 to 5.18), 1.95 (95% CI, 1.59 to 2.39), 5.09 (95% CI, 4.17 to 6.21), and 7.54 (95% CI, 5.73 to 9.91), respectively. Conclusion Hyperkalemia was associated with significant risks for mortality and adverse clinical outcomes, with more rapid decline of renal function. These findings underscore the significance of hyperkalemia as a predisposition to future adverse events in patients with chronic kidney disease.
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- 2021
94. Prologue: Special Spotlight Issue on Japan
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Yuichiro, Yano, Akira, Nishiyama, Toshihiko, Ishimitsu, Naoki, Kashihara, Hiromi, Rakugi, Kouichi, Tamura, Hiroshi, Itoh, Takuya, Tsuchihashi, Atsushi, Sakima, Hisatomi, Arima, Tetsutaro, Matayoshi, Yutaka, Imai, Katsuyuki, Miura, Takashi, Hisamatsu, Kei, Asayama, Takayoshi, Ohkubo, Kouihci, Node, and Kazuomi, Kario
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- 2021
95. MO148A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED, PARALLEL GROUP, PHASE III STUDY TO EVALUATE THE EFFICACY AND SAFETY OF LNP023 IN PRIMARY IGA NEPHROPATHY PATIENTS
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Naoki Kashihara, Bart Maes, Olympia Papachristofi, Wenyan Wang, Matthias Meier, Jonathan Barratt, Dana V. Rizk, Brad H. Rovin, Alan Charney, Dmitrij Kollins, Vlado Perkovic, and Hong Zhang
- Subjects
Double blind ,Transplantation ,medicine.medical_specialty ,Nephrology ,business.industry ,Internal medicine ,Maximum tolerated dose ,medicine ,business ,Placebo ,Primary IgA nephropathy - Abstract
Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is an autoimmune disease characterized by deposits of IgA1-containing immune complexes in the glomerular mesangium leading to local inflammation and subsequent decline in kidney function. Currently, there are no targeted therapies for IgAN. The KDIGO guidelines (2012) recommend optimized long-term supportive care including inhibition of the RAS (ACEi or ARB) as well as lifestyle modification for blood pressure control and proteinuria reduction. Patients who remain at high risk of progressive CKD despite maximal supportive care might be considered for high-dose corticosteroids or immunosuppressants. In recent years, mounting evidence has supported an important role for complement activation in disease onset and progression of IgAN. The alternative complement pathway (AP) and lectin complement pathway (LP) are found to be activated in 75-90% and 17-25% of IgAN patients, respectively (Floege et al 2014, Maillard et al 2015). Factor B (FB) is an essential component of C3- and C5-convertases. Iptacopan (LNP023) is an oral, first-in-class, highly potent selective inhibitor of FB and thereby blocks the activity of AP C3 and C5 convertases, inhibiting the AP as well as the amplification of the classic and lectin complement pathways. Currently, iptacopan is being evaluated in an ongoing adaptive seamless double-blind and placebo-controlled dose-ranging Phase 2 study (CLNP023X2203, Part 1 and Part 2) in patients with biopsy-confirmed IgAN and elevated proteinuria [urine protein to creatinine ratio (UPCR) ≥ 0.75 g/g]. An interim analysis (IA) at 90 days of treatment in the Part 1 study showed that iptacopan administered up to 200 mg b.i.d for 90 days was safe, well tolerated and may be effective in reducing proteinuria. A further IA combining participants in Part 1 and Part 2 will be completed in early 2021 and the pivotal phase 3 trial is to start in early 2021. Aim APPLAUSE-IgAN (NCT04578834; CLNP023A2301) is a multicenter, randomized, double-blind, placebo-controlled parallel-group Phase 3 study which aims to evaluate the efficacy and safety of iptacopan (LNP023) compared with placebo in addition to supportive therapy on proteinuria reduction and slowing kidney disease progression in primary IgAN patients. Method Adult patients diagnosed with primary IgAN (based on kidney biopsy and elevated proteinuria [UPCR ≥ 1 g/day]) will be recruited. A run-in period will ensure that patients have received ACEi/ARB at a maximally tolerated dose for at least 90 days and receive required vaccinations at least 2 weeks prior to first dosing. Patients will be randomized in a 1:1 ratio to either iptacopan 200 mg b.i.d or matching placebo for a 24-month treatment period. The trial will enroll approximately 450 participants, aiming for 430 with eGFR ≥30 mL /min/1.73m2 (main study population). About 20 participants with eGFR 20 to Primary objectives 1) At IA (when approximately 250 patients have completed the 9 months visit): To demonstrate superiority of iptacopan vs. placebo in the reduction of proteinuria. The IA results may be submitted to support accelerated/conditional approval. 2) At final analysis (when approximately 430 patients have completed 24 months of active treatment): to demonstrate superiority of iptacopan vs. placebo in slowing kidney disease progression measured by the annualized total slope of eGFR decline over 24 months. Results Recruitment will start in Q1 2021. Conclusion This trial will evaluate the efficacy of iptacopan, a promising new therapy for IgAN, in reducing proteinuria and slowing loss of kidney function over 2 years.
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- 2021
96. Drastic change in protein intake may cause a rapid decline of residual renal function after initiation of peritoneal dialysis
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Naoki Kashihara, Yuji Sogawa, and Hiroyuki Kadoya
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medicine.medical_specialty ,Nephrology ,business.industry ,medicine.medical_treatment ,medicine ,Urology ,Renal function ,Hematology ,Protein intake ,business ,Peritoneal dialysis - Published
- 2020
97. New measures against chronic kidney diseases in Japan since 2018
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Akira Fukui, Naoki Kashihara, Masaomi Nangaku, and Takashi Yokoo
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Nephrology ,medicine.medical_specialty ,Exacerbation ,Referral ,Physiology ,media_common.quotation_subject ,medicine.medical_treatment ,030232 urology & nephrology ,Chronic kidney disease (CKD) ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Renal Dialysis ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Renal Insufficiency, Chronic ,Intensive care medicine ,Special Report ,Health Education ,Referral and Consultation ,Dialysis ,media_common ,Government ,Primary Health Care ,business.industry ,Ministry of health, Labor and welfare ,Health Policy ,Primary care physician ,Age Factors ,Key performance indicators (KPIs) ,medicine.disease ,Criteria for referral ,Disease Progression ,Interdisciplinary Communication ,business ,Welfare ,Delivery of Health Care ,Goals ,Kidney disease ,Program Evaluation - Abstract
Since 2008, the Japanese government has started measures against chronic kidney disease (CKD), and steady changes have been achieved, including a decrease in the age-adjusted rate of new dialysis introduction. However, the total number of dialysis patients has not declined because of the progression of aging. Therefore, the Japanese government has started more concrete measures since 2018. It aims to prevent CKD exacerbation mainly by early referrals to nephrologists using “criteria for referral from a primary care physician to a kidney specialist/specialized medical institution”. In addition, key performance indicators are set to reduce the number of new dialysis patients from 39,000 in 2016 to ≤ 35,000 by 2028. We hope that you can refer to this measure all over the world and proceed with CKD measures. This report has been originally notified from the Ministry of Health, Labor and Welfare in Japanese. This is the English version of it.
- Published
- 2019
98. Bardoxolone methyl analog attenuates proteinuria-induced tubular damage by modulating mitochondrial function
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Masayuki Yamamoto, Naoki Kashihara, Toshiya Yamamoto, Tamaki Sasaki, Joel W. Proksch, Kengo Kidokoro, W. Christian Wigley, Yuji Sogawa, Minoru Satoh, Colin J. Meyer, Takafumi Suzuki, Hajime Nagasu, and Seiji Itano
- Subjects
0301 basic medicine ,Mitochondrial ROS ,Male ,NF-E2-Related Factor 2 ,Nephrosis ,Inflammation ,Mitochondrion ,Biochemistry ,Nrf2 ,Kidney Tubules, Proximal ,03 medical and health sciences ,Mice ,0302 clinical medicine ,dh404 ,Genetics ,medicine ,Animals ,Humans ,Bardoxolone methyl ,Oleanolic Acid ,reactive oxidative species ,Molecular Biology ,Cells, Cultured ,chemistry.chemical_classification ,Reactive oxygen species ,Mice, Inbred ICR ,Activator (genetics) ,Research ,Glomerulonephritis ,medicine.disease ,Cell biology ,Mitochondria ,Proteinuria ,030104 developmental biology ,chemistry ,inflammation ,medicine.symptom ,Reactive Oxygen Species ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Multiple clinical studies have shown that bardoxolone methyl, a potent activator of nuclear factor erythroid 2-related factor 2 (Nrf2), is effective in increasing glomerular filtration rate in patients with chronic kidney disease. However, whether an Nrf2 activator can protect tubules from proteinuria-induced tubular damage via anti-inflammatory and antioxidative stress mechanisms is unknown. Using an Institute of Cancer Research-derived glomerulonephritis (ICGN) mouse model of nephrosis, we examined the effects of dihydro-CDDO-trifluoroethyl amide (dh404), a rodent-tolerable bardoxolone methyl analog, in protecting the tubulointerstitium; dh404 markedly suppressed tubular epithelial cell damage in the renal interstitium of ICGN mice. The tubular epithelial cells of ICGN mice showed a decrease in the size and number of mitochondria, as well as the breakdown of the crista structure, whereas the number and ultrastructure of mitochondria were maintained by the dh404 treatment. To further determine the effect of dh404 on mitochondrial function, we used human proximal tubular cells in vitro. Stimulation with albumin and free fatty acid increased mitochondrial reactive oxygen species (ROS). However, dh404 administration diminished mitochondrial ROS. Our data show that dh404 significantly reduced proteinuria-induced tubular cell mitochondrial damage, suggesting that improved redox balance and mitochondrial function and suppression of inflammation underlie the cytoprotective mechanism of Nrf2 activators, including bardoxolone methyl, in diabetic kidney disease.-Nagasu, H., Sogawa, Y., Kidokoro, K., Itano, S., Yamamoto, T., Satoh, M., Sasaki, T., Suzuki, T., Yamamoto, M., Wigley, W. C., Proksch, J. W., Meyer, C. J., Kashihara, N. Bardoxolone methyl analog attenuates proteinuria-induced tubular damage by modulating mitochondrial function.
- Published
- 2019
99. Correction to: Gross hematuria after SARS-CoV-2 vaccination: questionnaire survey in Japan
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Yoshihito Nihei, Ichiei Narita, Hitoshi Suzuki, Masao Kihara, Naoki Kashihara, Takashi Yokoo, Yusuke Suzuki, Keiichi Matsuzaki, and Ryousuke Aoki
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2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Physiology ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,MEDLINE ,Questionnaire ,Gross hematuria ,Vaccination ,Nephrology ,Physiology (medical) ,Internal medicine ,Medicine ,business - Published
- 2021
100. Statement of the Asian Hypertension Society Network: the Okinawa Declaration on the unity of hypertension societies in Asian countries and regions to overcome hypertension and hypertension-related diseases
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Tzung-Dau Wang, Ji-Guang Wang, Hsien-Li Kao, Koichi Node, Hirotaka Shibata, Yook Chin Chia, Naoki Kashihara, Deborah Ignacia D. Ona, Satoko Nakamura, Boon Wee Teo, Toshihiko Ishimitsu, S. N. Narasingan, Kouichi Tamura, Hiroshi Itoh, Apichard Sukonthasarn, Atsuhiro Ichihara, Mohd Arifin Mohd Ali, Tomohiro Katsuya, Erwinanto Erwinanto, Akira Nishiyama, Katsuyuki Miura, Godwin Constantine, Saulat Siddique, Sang-Hyun Ihm, Huynh Van Minh, Tatsuo Shimosawa, Masashi Mukoyama, Tsolmon Unurjargal, Kazuomi Kario, Kazunori Toyoda, Hisashi Kai, Mitsuru Ohishi, Yusuke Ohya, Hiromi Raukgi, and Shigeyuki Saito
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Economic growth ,Asia ,Physiology ,Statement (logic) ,Declaration ,Asian People ,Political science ,Hypertension ,Internal Medicine ,Asian country ,Humans ,Societies ,Cardiology and Cardiovascular Medicine ,Societies, Medical - Published
- 2021
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