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1. Association between roxadustat use and suppression of thyroid function: a systematic review and meta-analysis

Author: Yuki Nakano, Satoru Mitsuboshi, Kazuhiro Tada, and Kosuke Masutani
Subjects: Adverse drug event, Thyroid function, Hypothyroidism, Meta-analysis, Roxadustat, Risk assessment, Therapeutics. Pharmacology, RM1-950, Pharmacy and materia medica, RS1-441
Abstract: Abstract Background Based on several case reports and observational studies, there is a growing concern regarding the potential association between roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor, and suppression of thyroid function. In this systematic review and meta-analysis (PROSPERO: CRD42023471516), we aimed to evaluate the relationship between roxadustat use and suppression of thyroid function. Methods We conducted a comprehensive search of MEDLINE via PubMed, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials databases using the search term “roxadustat” to identify all relevant studies. The study population comprised adults with renal anemia who participated in a randomized controlled trial or observational study, with roxadustat as the intervention and a placebo or erythropoiesis-stimulating agent (ESA) as the comparator. The primary outcome was suppression of thyroid function and the secondary outcome was hypothyroidism. A meta-analysis was conducted using the DerSimonian–Laird random effects model based on the size of the intention-to-treat population, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. Two reviewers independently screened the articles, extracted data, and assessed studies using the ROBINS-I tool. Results Of the six studies eligible for inclusion, a meta-analysis was performed using data from two observational studies comparing roxadustat and ESA. The meta-analysis showed that the incidence of suppression of thyroid function was significantly higher with roxadustat use than with ESA use (OR: 6.45; 95% CI: 3.39–12.27; I 2 = 12%). Compared with ESA, roxadustat seemed to potentially increase the risk for suppression of thyroid function in patients with renal anemia. Conclusions Our findings highlighted the importance of monitoring thyroid function in patients treated with roxadustat. The results of this review may enhance the safety of using roxadustat to treat renal anemia through advance recognition of the risk for suppression of thyroid function.
Published: 2024
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2. Relationship between abdominal circumference and the incidence of hyperuricemia in the general Japanese population

Author: Kazumi Kawano, Tamami Ueno, Toshiki Maeda, Chihiro Nohara, Kaori Maki, Kazuyo Iwanaga, Akiko Morinaga, Shunsuke Funakoshi, Makiko Abe, Atsushi Satoh, Miki Kawazoe, Chikara Yoshimura, Koji Takahashi, Kazuhiro Tada, Kenji Ito, Tetsuhiko Yasuno, Shigeaki Mukobara, Daiji Kawanami, Kosuke Masutani, and Hisatomi Arima
Subjects: Medicine, Science
Abstract: Abstract In this study, we aimed to separately evaluate the relationship between waist circumference and the incidence of hyperuricemia in men and women in the general Japanese population. We performed a population-based longitudinal study using data from the annual health examination of residents of Iki City, Japan. A total of 5567 participants without hyperuricemia at baseline were included in the analysis. The men and women were placed into groups according to the tertile of waist circumference. The outcome was incident hyperuricemia (uric acid > 416 µmol/L [7.0 mg/dL]). The relationship between waist circumference and the incidence of hyperuricemia was investigated using Cox proportional hazards models. During the follow-up period, hyperuricemia developed in 697 people (551 men and 146 women). The incidence (per 1000 person-years) of hyperuricemia increased with increasing waist circumference in the men (34.9 for tertile 1, 49.9 for tertile 2 and 63.3 for tertile 3; P trend
Published: 2024
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3. Reply to 'letter to the editor: Measuring renal hemodynamics during exercise using Doppler ultrasound'

Author: Shotaro Kawakami, Tetsuhiko Yasuno, Saki Kawakami, Ai Ito, Kanta Fujimi, Takuro Matsuda, Shihoko Nakashima, Kosuke Masutani, Yoshinari Uehara, Yasuki Higaki, and Ryoma Michishita
Subjects: Physiology, QP1-981
Published: 2024
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4. A case of acute kidney injury due to native kidney BK polyomavirus-associated nephropathy in a human T-lymphotropic virus type 1 carrier

Author: Keita Takae, Yuki Ueno, Masumi Shojima, Hiroshi Nagae, Takako Nakano, Shohei Takata, Ritsuko Katafuchi, Kosuke Masutani, Toshiaki Nakano, and Yusuke Kuroki
Subjects: BK polyomavirus, Kidney injury, Human T-lymphotropic virus type 1, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Abstract Background BK polyomavirus-associated nephropathy (BKPyVAN) has become a major cause of kidney dysfunction and graft loss in kidney transplant recipients. On rare occasion, polyomavirus has also been known to affect native kidneys of immunocompromised individuals. Only a small number of opportunistic infections have been reported in the carrier phase of human T-lymphotropic virus type 1 (HTLV-1). This is the first reported case of BKPyVAN in native kidneys of an HTLV-1 carrier. Case presentation A 61-year-old man was referred to our hospital from a primary care physician for work-up and treatment of pneumonia. He was diagnosed with Pneumocystis pneumonia and identified as a HTLV-1 carrier who had not yet developed adult T-cell leukemia (ATL). The pneumonia was successfully treated with sulfamethoxazole-trimethoprim. He had never been diagnosed with any kind of kidney dysfunction. Laboratory investigations showed a serum creatinine of 5.3 mg/dL, and urinary sediment showed cells with nuclear enlargement and inclusion bodies suggesting viral infection. The urinary Papanicolaou stain showed inclusions in swollen, ground-glass nuclei, typical of “decoy cells”. Renal biopsy showed degeneration of tubules with epithelial enlargement, vacuolar degeneration, nuclear inclusion bodies, and detachment from the tubular basement membrane. Tubular nuclei showed positive staining positive for simian virus 40 large-T antigen. Polymerase chain reaction tests for BK polyomavirus DNA of both urine and plasma were positive. These findings confirmed a diagnosis of BKPyVAN. Intravenous immunoglobulin therapy did not improve renal function, necessitating maintenance hemodialysis therapy. Conclusions BKPyVAN should be considered when acute kidney injury occurs with opportunistic infection. HTLV-1 carriers can develop opportunistic infections even before the onset of ATL.
Published: 2023
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5. Skipping Breakfast and Progression of Chronic Kidney Disease in the General Japanese Population: The Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD)

Author: Koji Takahashi, Yori Inoue, Kazuhiro Tada, Hiroto Hiyamuta, Kenji Ito, Tetsuhiko Yasuno, Takashi Sakaguchi, Shiori Katsuki, Yukiko Shinohara, Chihiro Nohara, Shota Okutsu, Makiko Abe, Atsushi Satoh, Miki Kawazoe, Toshiki Maeda, Chikara Yoshimura, Shigeaki Mukoubara, Hisatomi Arima, and Kosuke Masutani
Subjects: chronic kidney disease, cohort study, eating habit, skipping breakfast, Dermatology, RL1-803, Diseases of the circulatory (Cardiovascular) system, RC666-701, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Introduction: Breakfast-skipping habits are associated with adverse health outcomes including coronary heart disease, metabolic syndrome, and diabetes mellitus. However, it remains uncertain whether skipping breakfast affects chronic kidney disease (CKD) risk. This study aimed to examine the association between skipping breakfast and progression of CKD. Methods: We retrospectively conducted a population-based cohort study using the data from the Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD). Between 2008 and 2019, we included 922 participants aged 30 years or older who had CKD (estimated glomerular filtration rate
Published: 2024
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6. Elevation in white blood cell count and development of hyper LDL cholesterolemia

Author: Shota Okutsu, Yoshifumi Kato, Hiroaki Takeoka, Shunsuke Funakoshi, Toshiki Maeda, Chikara Yoshimura, Miki Kawazoe, Atsushi Satoh, Kazuhiro Tada, Koji Takahashi, Kenji Ito, Tetsuhiko Yasuno, Hideyuki Fujii, Shigeaki Mukoubara, Keijiro Saku, Shohta Kodama, Daiji Kawanami, Kosuke Masutani, Hisatomi Arima, and Shigeki Nabeshima
Subjects: Medicine, Science
Abstract: Abstract To investigate the relationship between white blood cell (WBC) count and incidence of hyper-low-density lipoprotein (LDL) cholesterolemia in a population-based longitudinal study. This is a retrospective study using data of annual health check-ups for residents of Iki City, Japan. A total of 3312 residents (≥ 30 years) without hyper-LDL cholesterolemia at baseline were included in this analysis. Primary outcome was incidence of hyper-LDL cholesterolemia (LDL cholesterol levels ≥ 3.62 mmol/L and/or use of lipid lowering drugs). During follow-up (average 4.6 years), 698 participants development of hyper-LDL cholesterolemia (incidence 46.8 per 1000 person-years). Higher incidence of hyper-LDL cholesterolemia was observed among participants with higher leukocyte count (1st quartile group: 38.5, 2nd quartile group: 47.7, 3rd quartile group: 47.3, and 4th quartile group: 52.4 per 1,000 person-years, P = 0.012 for trend). Statistically significant relation was observed even after adjustment for age, gender, smoking, alcohol intake, leisure-time exercise, obesity, hypertension and diabetes: hazard ratio 1.24 (95% confidence interval 0.99 to 1.54) for 2nd quartile group, 1.29 (1.03–1.62) for 3rd quartile group and 1.39 (1.10–1.75) for 4th quartile group, compared with 1st quartile group (P for trend = 0.006). Increased WBC count was related to incidence of hyper-LDL cholesterolemia in general Japanese population.
Published: 2023
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7. Efficacy of pre-emptive kidney transplantation for adults with end-stage kidney disease: a systematic review and meta-analysis

Author: Tatsuhiko Azegami, Noriyuki Kounoue, Tadashi Sofue, Masahiko Yazawa, Makoto Tsujita, Kosuke Masutani, Yuki Kataoka, and Hideyo Oguchi
Subjects: Transplantation, meta-analysis, systematic review, pre-emptive kidney transplantation, mortality, graft failure, Diseases of the genitourinary system. Urology, RC870-923
Abstract: AbstractBackground Pre-emptive kidney transplantation (PEKT), i.e., transplantation performed before initiation of maintenance dialysis, is considered an ideal renal replacement therapy because there is no exposure to long-term dialysis therapy. Therefore, we summarized advantages/disadvantages of PEKT to assist in deciding whether kidney transplantation should be performed pre-emptively.Methods This study was registered with PROSPERO, CRD42021269163. Observational studies comparing clinical outcomes between PEKT and non-PEKT were included; those involving only pediatric recipients or simultaneous multi-organ transplantations were excluded. The PubMed/MEDLINE, Cochrane Library, and Ichushi-Web databases were searched on 1 August 2021. Studies were pooled using the generic inverse-variance method with random effects model, and risk of bias was assessed using ROBINS-I.Results Seventy-six studies were included in the systematic review (sample size, 23–121,853; enrollment year, 1968–2019). PEKT patients had lower all-cause mortality (adjusted HR: 0.78 [95% CI 0.66–0.92]), and lower death-censored graft failure (0.81 [0.67–0.98]). Unadjusted RRs for the following outcomes were comparable between the two patient groups: cardiovascular disease, 0.90 (0.58–1.40); biopsy-proven acute rejection, 0.75 (0.55–1.03); cytomegalovirus infection, 1.04 (0.85–1.29); and urinary tract infection, 0.89 (0.61–1.29). Mean differences in post-transplant QOL score were comparable in both groups. The certainty of evidence for mortality and graft failure was moderate and that for other outcomes was very low following the GRADE classification.Conclusions The present meta-analysis shows the potential benefits of PEKT, especially regarding patient and graft survival, and therefore PEKT is recommended for adults with end-stage kidney disease.
Published: 2023
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8. Association between serum ALT levels and incidence of new-onset diabetes in general population of Japanese: a longitudinal observational study (ISSA-CKD)

Author: Hisatomi Arima, Koji Takahashi, Akiko Morinaga, Toshiki Maeda, Shunsuke Funakoshi, Kazuhiro Tada, Masayoshi Tsuji, Atsushi Satoh, Miki Kawazoe, Chikara Yoshimura, Makiko Abe, Kazuyo Iwanaga, Kaori Maki, Tamami Ueno, Kazumi Kawano, Toshitaka Yamanokuchi, Kenji Ito, Tetsuhiko Yasuno, Daiji Kawanami, and Kosuke Masutani
Subjects: Medicine
Abstract: Objective We aimed to clarify the relationship between serum alanine transaminase (ALT) levels and incidence of new-onset diabetes in a Japanese general population.Setting Population-based retrospective cohort study using annual health check-up data for residents of Iki City, Nagasaki Prefecture, Japan.Participants A total of 5330 Japanese individuals (≥30 years old) without diabetes at baseline were analysed.Primary and secondary outcome measures Serum ALT levels were determined using an enzymatic method and were classified into gender-specific quartile groups as follows: group 1 (3–16 U/L in men and 3–13 U/L in women), group 2 (17–21 U/L in men and 14–16 U/L in women), group 3 (22–29 U/L in men and 17–22 U/L in women) and group 4 (30–428 U/L in men and 23–268 U/L in women). The study outcome was the incidence of diabetes (fasting glucose ≥7.0 mmol/L, non-fasting glucose ≥11.1 mmol/L, glycated haemoglobin ≥6.5% or use of glucose-lowering therapies).Results After an average follow-up period of 5.0 years, 279 individuals developed diabetes. The incidence rate of diabetes increased with elevation of serum ALT levels (0.7% per 100 person-years in group 1, 0.9% in group 2, 0.9% in group 3 and 1.7% in group 4) (p
Published: 2023
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9. Predictors of early remission of proteinuria in adult patients with minimal change disease: a retrospective cohort study

Author: Ryohei Yamamoto, Enyu Imai, Shoichi Maruyama, Hitoshi Yokoyama, Hitoshi Sugiyama, Asami Takeda, Shunya Uchida, Tatsuo Tsukamoto, Kazuhiko Tsuruya, Yasuhiro Akai, Kosaku Nitta, Megumu Fukunaga, Hiroki Hayashi, Kosuke Masutani, Takashi Wada, Tsuneo Konta, Ritsuko Katafuchi, Saori Nishio, Shunsuke Goto, Hirofumi Tamai, Arimasa Shirasaki, Tatsuya Shoji, Kojiro Nagai, Tomoya Nishino, Kunihiro Yamagata, Junichiro J. Kazama, Keiju Hiromura, Hideo Yasuda, Makoto Mizutani, Tomohiko Naruse, Takeyuki Hiramatsu, Kunio Morozumi, Hiroshi Sobajima, Yosuke Saka, Eiji Ishimura, Daisuke Ichikawa, Takashi Shigematsu, Tadashi Sofue, Shouichi Fujimoto, Takafumi Ito, Hiroshi Sato, Ichiei Narita, Yoshitaka Isaka, and JNSCS Investigators
Subjects: Medicine, Science
Abstract: Abstract Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.
Published: 2022
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10. Effect of chronic kidney disease on the association between hyperuricemia and new‐onset hypertension in the general Japanese population: ISSA‐CKD study

Author: Miki Kawazoe, Shunsuke Funakoshi, Shintaro Ishida, Chikara Yoshimura, Atsushi Satoh, Toshiki Maeda, Masayoshi Tsuji, Soichiro Yokota, Kazuhiro Tada, Koji Takahashi, Kenji Ito, Tetsuhiko Yasuno, Hideyuki Fujii, Shota Okutsu, Shigeaki Mukobara, Daiji Kawanami, Shigeki Nabeshima, Seiji Kondo, Kosuke Masutani, and Hisatomi Arima
Subjects: blood pressure, chronic kidney disease, epidemiology, hypertension, hyperuricemia, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract We aimed to investigate the association between serum uric acid (SUA) level and development of hypertension as well as the interaction effect of chronic kidney disease (CKD) on this relationship in the general Japanese population. We included 7895 participants aged ≥30 years from the ISSA‐CKD study, a population‐based retrospective cohort study that used annual health check‐up data of residents from Iki Island, Japan. After the exclusion of 1881 with l
Published: 2021
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11. Significance of nutrition in hemodialysis patients with peripheral arterial disease evaluated by skin perfusion pressure

Author: Maho Watanabe, Asami Fuji, Sayuri Tokushima, Keiko Uemoto, Masayo Ueno, Yuko Shimomura, Kenji Ito, Tetsuhiko Yasuno, Kosuke Masutani, and Takao Saito
Subjects: Hemodialysis, Peripheral artery disease, Skin perfusion pressure, Nutrition management, Geriatric nutritional risk index, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Abstract Background Peripheral artery disease (PAD) is a serious complication in hemodialysis (HD) patients. Low skin perfusion pressure (SPP) is a useful marker for detecting PAD. Malnutrition is an important cause of intractable complications. We examined the relationship between low SPP and various indicators of nutritional status. Methods A total of 120 patients on maintenance HD were enrolled for SPP measurement. SPP was measured at the soles of both feet during HD, and patients were divided into low SPP (L-SPP) and normal SPP (N-SPP) groups by 50 mmHg. The following values were determined by averaging four blood samples taken before SPP measurements every 3 months for one year: hemoglobin, total protein, albumin (Alb), total cholesterol, urea nitrogen, creatinine (Cr), potassium, calcium, phosphate, intact parathyroid hormone, iron (Fe), transferrin saturation (T-SAT), and C-reactive protein (CRP). We calculated the percent Cr production rate, dialysis index (Kt/V), normalized protein catabolic rate (nPCR), geriatric nutritional risk index (GNRI), and estimated salt intake using the required formulas. In addition, the age, body mass index, and presence of diabetes mellitus (DM) were compared between both groups along with all other measurements. Data were expressed as the mean ± standard deviation or median with interquartile range as appropriate. Differences in continuous variables between the two groups were analyzed by Student’s t-test or Wilcoxon’s rank-sum test, as appropriate. Multivariate logistic analysis and receiver operating curve (ROC) analysis were performed for significant variables. The results were expressed as odds ratios with respective 95% confidence intervals (CIs). Results The enrolled patients were 82 men and 38 women, with a mean age of 66.9 ± 13.3 years and HD duration of 4.76 (2.13–12.28) years (median interquartile range). Twenty patients belonged to the L-SPP group, suggesting PAD. Comparison between the L-SPP and N-SPP groups showed significant differences in age, Cr, Fe, T-SAT, CRP, nPCR, GNRI, DM, and estimated salt intake. When the GNRI, estimated salt intake, CRP, and DM were applied as independent variables for multiple logistic regression analysis, the GNRI (odds ratio: 0.857, 95% CI 0.781–0.941, p = 0.001), CRP (2.406, 1.051–3.980, p = 0.035), and DM (9.194, 2.497–33.853, p = 0.001) were found to be significant for L-SPP, and a cutoff level of 92.1 (sensitivity 80%, specificity 72%, AUC: 0.742, 95% CI 0.626–0.858, p = 0.001) in the GNRI obtained by ROC was consistent with the risk index in the elderly presented previously. Conclusions SPP measurement is an essential tool for detecting high-risk PAD in maintenance HD, which is affected by malnutrition, DM, and inflammation. The GNRI is important for the determination of malnutrition.
Published: 2021
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12. The moderate‐intensity continuous exercise maintains renal blood flow and does not impair the renal function

Author: Shotaro Kawakami, Tetsuhiko Yasuno, Saki Kawakami, Ai Ito, Kanta Fujimi, Takuro Matsuda, Shihoko Nakashima, Kosuke Masutani, Yoshinari Uehara, Yasuki Higaki, and Ryoma Michishita
Subjects: moderate‐intensity continuous exercise, renal function, renal hemodynamics, renal injury, Physiology, QP1-981
Abstract: Abstract Exercise is restricted for individuals with reduced renal function because exercising reduces blood flow to the kidneys. Safe and effective exercise programs for individuals with reduced renal function have not yet been developed. We previously examined the relationship between exercise intensity and renal blood flow (RBF), revealing that moderate‐intensity exercise did not reduce RBF. Determining the effects of exercise duration on RBF may have valuable clinical applications. The current study examined the effects of a single bout of continuous exercise at lactate threshold (LT) intensity on renal hemodynamics. Eight adult males participated in this study. Participants underwent 30 min of aerobic exercise at LT intensity using a cycle ergometer. Evaluation of renal hemodynamics was performed before and after exercise, in the recovery phase using ultrasound echo. Furthermore, blood and urine samplings were conducted before and after exercise, in the recovery phase. Compared with resting, RBF was not significantly changed immediately after continuous exercise (319 ± 102 vs. 308 ± 79 ml/min; p = 0.976) and exhibited no significant changes in the recovery phase. Moreover, urinary kidney injury molecule‐1 (uKIM‐1) level exhibited no significant change immediately after continuous exercise (0.52 ± 0.20 vs. 0.46 ± 0.27 μg/g creatinine; p = 0.447). In addition, the results revealed no significant change in urinary uKIM‐1 in 60‐min after exercise. Other renal injury biomarkers exhibited a similar pattern. These findings indicate that a single bout of moderate‐intensity continuous exercise maintains RBF and does not induce renal injury.
Published: 2022
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13. Casual serum triglyceride concentrations and new-onset chronic kidney disease in the general Japanese population: the Iki city epidemiological study of atherosclerosis and chronic kidney disease study

Author: Koji Takahashi, Yoshihiro Nishida, Soichiro Yokota, Kazuhiro Tada, Hiroto Hiyamuta, Kenji Ito, Tetsuhiko Yasuno, Tosihki Maeda, Hisatomi Arima, and Kosuke Masutani
Subjects: Dermatology, RL1-803, Diseases of the circulatory (Cardiovascular) system, RC666-701, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Introduction: Non-fasting triglyceride (TG) concentrations are useful for predicting various diseases, but most epidemiological studies investigated the association between fasting TG concentrations and chronic kidney disease (CKD). This study aimed to examine the association between casual (fasting or non-fasting) serum TG concentrations and new-onset CKD in the general Japanese population. Methods: We conducted a population-based, retrospective cohort study using annual health check-up data of residents of Iki City, Nagasaki Prefecture, Japan. Between 2008 and 2019, participants without CKD (estimated glomerular filtration rate
Published: 2023
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14. White blood cell count and incidence of hypertension in the general Japanese population: ISSA-CKD study.

Author: Shintaro Ishida, Seiji Kondo, Shunsuke Funakoshi, Atsushi Satoh, Toshiki Maeda, Miki Kawazoe, Chikara Yoshimura, Kazuhiro Tada, Koji Takahashi, Kenji Ito, Tetsuhiko Yasuno, Kosuke Masutani, Hitoshi Nakashima, and Hisatomi Arima
Subjects: Medicine, Science
Abstract: ObjectivesThis study aimed to clarify the relationship between the white blood cell (WBC) count and hypertension in the general Japanese population.MethodsWe conducted a population-based retrospective cohort study using annual health check-up data of residents of Iki City, Nagasaki Prefecture, Japan. A total of 2935 participants without hypertension at baseline were included in the present analysis. WBC counts were classified as tertile 1 (ResultDuring an average follow-up of 4.5 years, 908 participants developed hypertension. The incidence (per 100 person-years) of hypertension increased with an elevation in the WBC count (6.3 in tertile 1, 7.0 in tertile 2, and 7.4 in tertile 3). This association was significant, even after adjustment for other risk factors, including age, sex, current smoking habits, current alcohol intake, exercise habits, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia. The hazard ratios were 1.07 for tertile 2 (95% CI 0.90-1.26) and 1.27 for tertile 3 (95% CI 1.06-1.51) compared with the reference group of tertile 1 (p = 0.009).ConclusionThe WBC count was associated with future development of hypertension in the general Japanese population.
Published: 2021
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15. Bacterial meningitis and multiple abscess formation in the iliopsoas, erector spinae, and vastus lateralis muscle in a maintenance hemodialysis patient treated with continuous epidural anesthesia for herpes zoster-related pain control: a case report and review of the literature

Author: Shunsuke Yamada, Narihito Tatsumoto, Noriko Nakamura, Kosuke Masutani, Toshiro Maeda, Takanari Kitazono, and Kazuhiko Tsuruya
Subjects: Abscess, Epidural catheter, Erector spinae muscle, Hemodialysis, Iliopsoas muscle, Vastus lateralis muscle, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Abstract Background Infection is the second leading cause of mortality in patients who undergo maintenance hemodialysis. In this population, impairment in both cellular and humoral immunity contributes to the increased incidence of infection and infection-related hospitalization. However, these artificial devices occasionally enhance the risk of deep organ infection including muscle abscess, frequently leading to disability and mortality in hemodialysis patients. Case presentation A 54-year-old male undergoing maintenance hemodialysis was hospitalized because of the acute onset pain in the back and bilateral legs and declining consciousness which started at 7 days after the treatment of herpes zoster-related neuralgia with continuous epidural anesthesia. Physical examination revealed purulent discharge from the insertion site of the catheter. Serum biochemical tests showed increased inflammatory response and malnutrition. Magnetic resonance imaging revealed meningitis and multiple abscesses in the iliopsoas, erector spinae, gluteus medius, and vastus lateralis muscles, where conventional antibiotic treatment often fails to cure. Staphylococcus aureus was detected in the cerebrospinal fluid. Combination of intravenous antibiotics treatment and aggressive open surgical drainage of the muscle abscesses finally cured meningitis and multiple deep muscle abscesses in this patient. Conclusions Treatment with sensitive antibiotics and timely open surgical drainage is necessary to cure catheter-related meningitis and secondary deep muscle abscesses in hemodialysis patients. Our case also suggests that epidural anesthesia may not be a good therapeutic option for herpes zoster because patients with herpes zoster are immunologically more compromised during and shortly after reactivation of varicella zoster virus.
Published: 2018
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16. Positive association of residual kidney function with hemoglobin level in patients on peritoneal dialysis independent of endogenous erythropoietin concentration

Author: Kazuhiko Tsuruya, Kumiko Torisu, Hisako Yoshida, Shunsuke Yamada, Shigeru Tanaka, Akihiro Tsuchimoto, Masahiro Eriguchi, Kiichiro Fujisaki, Kosuke Masutani, and Takanari Kitazono
Subjects: Anemia, Creatinine clearance, Erythropoietin, Hemoglobin, Kt/V, Residual kidney function, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Abstract Background How residual kidney function (RKF) functions in the prevention of anemia in peritoneal dialysis (PD) patients is unclear. In this study, we investigated the association between RKF and hemoglobin (Hb) level. Methods We performed a cross-sectional analysis of the association between RKF, defined as the mean renal creatinine and urea clearance (rCUC), and the Hb level in 50 PD patients registered retrospectively. The independent variable was mean rCUC as continuous or categorical variable by tertile, and the dependent variable was Hb level as continuous or dichotomous variable using Hb cutoff of 10 g/dL. We conducted a multivariable regression analysis and calculated the c-statistic for Hb level
Published: 2017
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17. Effects of Weight Gain after 20 Years of Age and Incidence of Hyper-Low-Density Lipoprotein Cholesterolemia: The Iki Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD)

Author: Shota Okutsu, Yoshifumi Kato, Shunsuke Funakoshi, Toshiki Maeda, Chikara Yoshimura, Miki Kawazoe, Atsushi Satoh, Soichiro Yokota, Kazuhiro Tada, Koji Takahashi, Kenji Ito, Tetsuhiko Yasuno, Hideyuki Fujii, Shigeaki Mukoubara, Hitoshi Nakashima, Daiji Kawanami, Kosuke Masutani, Hisatomi Arima, and Shigeki Nabeshima
Subjects: weight gain, LDL cholesterol, hyper-LDL cholesterolemia, longitudinal study, general population, Medicine
Abstract: The aim of this study was to investigate the effects of long-term weight gain from the age of 20 on incidence of hyper-low-density-lipoprotein (LDL) cholesterolemia in the general population of Japanese people. Methods: We conducted a population-based retrospective cohort study using annual health checkup data for residents of Iki City, Nagasaki Prefecture, Japan. A total of 3179 adult (≥30 years old) men and women without hyper-LDL cholesterolemia at baseline, who underwent two or more health checkups were included in the analysis. Information on weight gain (≥10 kg) after 20 years of age was obtained using questionnaire. The outcome of this study was development of hyper-LDL cholesterolemia defined as LDL-cholesterol level ≥3.62 mmol/L and/or initiation of lipid-lowering medications. Results: During a mean follow-up period of 4.53 years, 665 of the 3179 participants developed hyper-LDL cholesterolemia (46.5/1000 person-years). The incidence of hyper-LDL cholesterolemia was higher in participants with a weight gain of ≥10 kg (55.3/1000 person-years) than among those with a weight gain of p = 0.006). Conclusion: A weight gain of ≥10 after 20 years of age affected the development of hyper-LDL cholesterol regardless of age, sex, and obesity in a general population of Japanese.
Published: 2021
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18. Eating Speed and Incidence of Diabetes in a Japanese General Population: ISSA-CKD

Author: Hideyuki Fujii, Shunsuke Funakoshi, Toshiki Maeda, Atsushi Satoh, Miki Kawazoe, Shintaro Ishida, Chikara Yoshimura, Soichiro Yokota, Kazuhiro Tada, Koji Takahashi, Kenji Ito, Tetsuhiko Yasuno, Shota Okutsu, Shigeaki Mukoubara, Hitoshi Nakashima, Shigeki Nabeshima, Seiji Kondo, Masaki Fujita, Kosuke Masutani, Hisatomi Arima, and Daiji Kawanami
Subjects: diabetes, eating speed, primary prevention, lifestyle, Medicine
Abstract: Background: We investigated whether eating speed was associated with the incidence of diabetes in a Japanese general population. Methods: A total of 4853 Japanese individuals without diabetes at baseline were analyzed. Self-reported eating speed was categorized as slow, medium, and fast on the basis of questionnaire responses. The study outcome was the incidence of diabetes. Results: After an average follow-up period of 5.1 years, 234 individuals developed diabetes. The incidence of diabetes per 1000 person-years was 4.9 in the slow eating speed group, 8.8 in the medium eating speed group, and 12.5 in the fast eating speed group, respectively (*** p < 0.001 for trend). The HRs were 1.69 (95%CI 0.94–3.06) for the medium eating speed and 2.08 (95%CI 1.13–3.84) for the fast eating speed, compared to the slow eating speed (* p = 0.014 for trend) after adjustment for age, gender, smoking status, drinking, exercise, obesity, hypertension, and dyslipidemia. Conclusion: Faster eating speed increased a risk for the incidence of diabetes in a general Japanese population.
Published: 2021
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19. Effects of Telmisartan and Candesartan on the Metabolism of Lipids and Glucose in Kidney Transplant Patients: A Prospective, Randomized Crossover Study

Author: Yoshifumi Miura, MD, Hiroshi Noguchi, MD, PhD, Yasuhiro Okabe, MD, Kosuke Masutani, MD, PhD, Shoji Tokunaga, PhD, and Masafumi Nakamura, MD, PhD
Subjects: Surgery, RD1-811
Abstract: Background. The risk of cardiovascular events remains after kidney transplantation (KT). Abnormal glucose metabolism and hyperlipidemia contribute partly to this risk. Among angiotensin II type-1 receptor blockers, telmisartan alone has been shown to ameliorate these effects on glucose and lipid metabolism (GLM). We investigated the effects of telmisartan on GLM in KT patients. Methods. This trial had a crossover design. Forty-six KT patients with well-controlled hypertension under angiotensin II type-1 receptor blockers were randomized into telmisartan and candesartan groups. After a 12-week treatment, crossover was initiated, and additional 12-week treatment was administered without a washout period. We examined the laboratory parameters of GLM, blood pressure and graft function before and after each treatment period. Results. Forty patients completed the scheduled treatment regimen. Serum levels of triglyceride were significantly lower (114.3 ± 50.8 mg/dL vs 136.5 ± 66.8 mg/dL; P = 0.019), and the estimated glomerular filtration rate was significantly higher (50.4 ± 15.1 mL/min per 1.73 m2 vs 48.5 ± 12.5 mL/min per 1.73 m2; P = 0.038) after telmisartan treatment than after candesartan treatment. There were no significant differences between the 2 treatment groups with regard to the other parameters studied (including serum adiponectin levels and parameters of glucose metabolism). Conclusions. These data suggest that telmisartan can improve serum triglyceride levels and graft function for KT patients better than candesartan.
Published: 2019
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20. Association between serum albumin level and incidence of end-stage renal disease in patients with Immunoglobulin A nephropathy: A possible role of albumin as an antioxidant agent.

Author: Yasuhiro Kawai, Kosuke Masutani, Kumiko Torisu, Ritsuko Katafuchi, Shigeru Tanaka, Akihiro Tsuchimoto, Koji Mitsuiki, Kazuhiko Tsuruya, and Takanari Kitazono
Subjects: Medicine, Science
Abstract: Serum albumin is the major intravascular antioxidant. Though oxidative stress plays an important role in the pathophysiology of Immunoglobulin A nephropathy (IgAN), the association between serum albumin and the progression of IgAN is not entirely understood. This retrospective cohort study of 1,352 participants with biopsy-proven IgAN determined the associations between serum albumin level and the incidence of end-stage renal disease (ESRD) using a Cox proportional hazards model. Patients were divided into three groups by tertiles of serum albumin level: Low, Middle, and High group (≤3.9 g/dL, 4.0-4.3 g/dL, ≥4.4 g/dL, respectively). During the median 5.1-year follow-up period, 152 patients (11.2%) developed ESRD. Participants in the Low group had a 1.88-fold increased risk for ESRD compared with those in the High group after adjustment for clinical parameters, including urinary protein excretion, and pathological parameters (Oxford classification). We also experimentally proved the antioxidant capacity of albumin on mesangial cells. The intracellular reactive oxygen species and mitochondrial injury, induced by hydrogen peroxide were significantly attenuated in albumin-pretreated mouse mesangial cells and human kidney cells compared with γ-globulin-pretreated cells. Low serum albumin level is an independent risk factor for ESRD in patients with IgAN. The mechanism could be explained by the antioxidant capacity of serum albumin.
Published: 2018
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21. Asymptomatic Brain Edema after Hemodialysis Initiation in a Patient with Severe Uremia

Author: Kiichiro Fujisaki, Kaneyasu Nakagawa, Hiroshi Nagae, Toshiaki Nakano, Masatomo Taniguchi, Kosuke Masutani, Takanari Kitazono, and Kazuhiko Tsuruya
Subjects: Medicine
Abstract: A 66-year-old man with severe renal insufficiency presented with mild confusion associated with uremia. Cranial magnetic resonance imaging (MRI) showed no remarkable changes. The patient was placed on short-duration hemodialysis (2 hours) with smaller surface area and low blood flow (100 mL/min) to avoid dialysis disequilibrium syndrome (DDS). His consciousness gradually improved and he did not develop apparent DDS symptoms. However, T2-weighted FLAIR MRI showed increased signal intensities bilaterally in the cortical and subcortical areas of the occipital lobe on day 15. In other words, cranial MRI showed cerebral edema, indicating asymptomatic DDS. On day 29, cranial MRI showed a return to findings on admission. In this case, because the patient did not have apparent DDS symptoms despite MRI changes, we diagnosed asymptomatic cerebral edema. The patient was discharged on regular intermittent HD without any neurological deficits. No further neurological disturbances were noted during 1-year follow-up. MRI findings in ESKD patients without DDS symptoms help to clarify the diagnosis of cerebral edema. In this case, the patient did not have apparent DDS symptoms and was therefore diagnosed with asymptomatic cerebral edema.
Published: 2017
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22. Ulcerative Colitis Presented as Fever and Bloody Diarrhea at Initiation of Dialysis in an Elderly Patient with End-Stage Kidney Disease

Author: Shunsuke Yamada, Yuka Kanazawa, Noriko Nakamura, Kosuke Masutani, Motohiro Esaki, Takanari Kitazono, and Kazuhiko Tsuruya
Subjects: Medicine
Abstract: Ulcerative colitis (UC) is a chronic inflammatory bowel disorder that mainly affects the colon and rectum. Immunological derangements are associated with the pathogenesis of UC. Many patients with UC also have chronic kidney disease, associated with immunological disorders and/or pharmacotherapy for UC. Some patients with UC may develop end-stage renal disease (ESRD) and require renal replacement therapy. However, little is known clinically about ESRD patients who develop UC or about patients with UC who develop ESRD. This report describes an elderly patient with ESRD who presented with fever and bloody diarrhea and was finally diagnosed as UC (pancolitis type) at dialysis initiation. The patient was successfully treated with a series of immunosuppressive agents. This report highlights the importance of considering UC as a potential cause of bloody stool and fever in patients with ESRD.
Published: 2015
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23. Dysbiosis of Gut Microbiota in Patients with Chronic Kidney Disease.

Author: Tetsuhiko Yasuno, Koji Takahashi, Kazuhiro Tada, Hiroto Hiyamuta, Maho Watanabe, Kenji Ito, Hisatomi Arima, and Kosuke Masutani
Published: 2024
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24. Antibody acquisition after second and third SARS-CoV-2 vaccinations in Japanese kidney transplant patients: a prospective study

Author: Hidetaka Deguchi, Atsuhiko Sakamoto, Nobuyuki Nakamura, Yasuhiro Okabe, Yoshifumi Miura, Takeshi Iida, Michinobu Yoshimura, Nobuhiro Haga, Shigeki Nabeshima, and Kosuke Masutani
Subjects: Nephrology, Physiology, Physiology (medical)
Published: 2023

25. Serum triglyceride levels and incidence of hypertension in a general Japanese population: ISSA-CKD study

Author: Shintaro Ishida, Seiji Kondo, Shunsuke Funakoshi, Makiko Abe, Atsushi Satoh, Miki Kawazoe, Toshiki Maeda, Chikara Yoshimura, Yoshihiro Nishida, Kazuhiro Tada, Koji Takahashi, Kenji Ito, Tetsuhiko Yasuno, Daiji Kawanami, Shin-ichiro Miura, Shohta Kodama, Keijiro Saku, Shigeaki Mukobara, Kosuke Masutani, and Hisatomi Arima
Subjects: Physiology, Internal Medicine, Cardiology and Cardiovascular Medicine
Published: 2023

26. Allograft adenovirus nephritis accompanied by Crohn’s disease in a kidney transplant recipient: a novel case report

Author: Yoko Fujita, Rie Fujishima, Kenji Ueki, Akihiro Tsuchimoto, Takuya Matsuda, Masaki Kato, Kosuke Masutani, Kazunobu Shinoda, and Masahiko Yazawa
Subjects: Case Report, General Medicine
Abstract: Excessive immunosuppression after kidney transplantation (KT) is often encountered in patients undergoing therapy for anti-rejection or autoimmune disease that requires further treatment using immunosuppressive medications (IMs), including biologic agents. We report a novel case wherein a kidney transplant recipient developed severe acute allograft injury and hemorrhagic cystitis at 4.5 years after KT due to adenovirus nephritis after treatment with infliximab for Crohn's disease. The diagnosis was made based on adenovirus immunohistochemistry staining and urine polymerase chain reaction tests. The patient was successfully treated by reducing IMs and administration of immunoglobulin even though allograft function was eventually partially recovered. When new immunosuppressive agents, particularly biologic agents, are initiated for other diseases in addition to maintenance IMs, the following points need to be regarded: (1) pay attention to opportunistic infections even in the late phase of KT, and (2) maintain communication with other specialists who prescribe biologics to ensure appropriate administration of IMs.
Published: 2022

27. A case of crescentic glomerulonephritis induced by afatinib for lung adenocarcinoma

Author: Daisuke Morita, Kenji Ito, Nobumitsu Ikeuchi, Yoshihiro Nishida, Fumiyasu Igata, Tsubasa Nakamura, Hiroyuki Murayama, Maho Watanabe, Koji Takahashi, Tetsuhiko Yasuno, Noriko Uesugi, Masaki Fujita, Takashi Oda, and Kosuke Masutani
Subjects: Case Report, General Medicine
Abstract: Afatinib is a second-generation, oral, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). One of the most common adverse effects of affatinib is diarrhea, which may lead to acute kidney injury (AKI) due to severe plasma volume loss; however, no case of glomerular injury directly induced by afatinib has been reported to date. Here, we describe the case of a 53-year-old Japanese male patient with advanced lung adenocarcinoma who twice developed AKI requiring dialysis, once after starting and once after increasing the dose of afatinib. Although serum anti-neutrophil cytoplasmic antibodies were negative, crescentic glomerulonephritis with no immune deposits was confirmed on kidney biopsy. No vasculitis-like signs were observed in other organs, such as lung, skin, or peripheral nerves. Afatinib was considered the cause of glomerular damage and was immediately discontinued; corticosteroids were administered. Renal function gradually recovered thereafter, with serum creatinine levels at ~ 2.3 mg/dL after second-line therapy with bevacizumab and atezolizumab. Several cases of cutaneous leukocytoclastic vasculitis have been reported in patients treated with other EGFR-TKIs; therefore, afatinib-induced vasculitis may lead to crescentic glomerulonephritis. Although afatinib-induced glomerular injury is extremely rare and has an unclear mechanism, renal function and urinary findings need to be closely monitored.
Published: 2022

28. Deep learning analysis of clinical course of primary nephrotic syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS)

Author: Tomonori Kimura, Ryohei Yamamoto, Mitsuaki Yoshino, Ryuichi Sakate, Enyu Imai, Shoichi Maruyama, Hitoshi Yokoyama, Hitoshi Sugiyama, Kosaku Nitta, Tatsuo Tsukamoto, Shunya Uchida, Asami Takeda, Toshinobu Sato, Takashi Wada, Hiroki Hayashi, Yasuhiro Akai, Megumu Fukunaga, Kazuhiko Tsuruya, Kosuke Masutani, Tsuneo Konta, Tatsuya Shoji, Takeyuki Hiramatsu, Shunsuke Goto, Hirofumi Tamai, Saori Nishio, Kojiro Nagai, Kunihiro Yamagata, Hideo Yasuda, Shizunori Ichida, Tomohiko Naruse, Tomoya Nishino, Hiroshi Sobajima, Toshiyuki Akahori, Takafumi Ito, Yoshio Terada, Ritsuko Katafuchi, Shouichi Fujimoto, Hirokazu Okada, Tetsushi Mimura, Satoshi Suzuki, Yosuke Saka, Tadashi Sofue, Kiyoki Kitagawa, Yoshiro Fujita, Makoto Mizutani, Naoki Kashihara, Hiroshi Sato, Ichiei Narita, and Yoshitaka Isaka
Subjects: Cohort Studies, Proteinuria, Nephrotic Syndrome, Deep Learning, Japan, Nephrology, Physiology, Creatinine, Physiology (medical), Humans, Hematuria
Abstract: Background Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. Methods Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder–decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. Results Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. Conclusions Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.
Published: 2022

29. Empagliflozin in Patients with Chronic Kidney Disease

Author: Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel Kraus, Carina Krieger, Margit Schmude, Anne Schreiber, Ewelina Eckrich, Diethelm Tschope, Abdulwahab Arbi, Young Lee-Barkey, Bernd Stratmann, Natalie Prib, Sina Rolfsmeier, Irina Schneider, Lars Rump, Johannes Stegbauer, Christine Pötz, Mara Schemmelmann, Claudia Schmidt, Michael Koch, Sendogan Aker, Annika Küpper, Manuela Martin, Thiemo Pfab, Christian Albert, Michael Haase, Barbara Zander, Claudia Schneider-Danwitz, Wolfgang Seeger, Wolf-Adam Seeger, Britta Zemann, Christoph Stellbrink, Kristin Marx, Ekaterina Stellbrink, Britta Brettschneider, Stephanie Watson, Marion Iselt, Gerhard Klausmann, Inga-Nadine Kummer, Auguste Kutschat, Simone Streitenberger, Matthias Girndt, Silke Markau, Ina Girakossyan, Claudia Hanf, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Andreas Schneider, Roland Veelken, Claudia Donhauser, Luis Becker, Nexhat Miftari, Ricarda Wolfling, Sarah Morlok, Christian Hugo, Alexander Paliege, Jens Passauer, Julian Stumpf, Annegret Fleischer, Kerstin Haaser, Bernhard Kraemer, Jan Jochims, Bernd Kruger, Claudia Foellinger, Anastassiya Reisler, Frank Strutz, Stefan Haack, Ursula Hohenstatt, Martin Busch, Konstantin Herfurth, Gunter Wolf, Rainer Paul, Hermann Haller, Jessica Kaufeld, Jan Menne, Elisabeth Bahlmann-Kroll, Angela Bergner, Horst Weihprecht, Aydin Er, Florian Sonntag, Elif Turan, Michael Wittmann, Franziska Klauser, Eva Voigt, Volker Schettler, Egbert Schulz, Madlen Rohnstock, Elke Schettler, Bernd Schroppel, Rene van Erp, Martin Kachele, Ulla Ludwig, Lena Schulte-Kemna, Waltraud Kmietschak, Elke Preiss, Martina Ruocco, Gunnar Heine, Martin Brzoska, Sebastian Gabel, Christina Büttner, Asma Sabarai, Bernhard Banas, Tobias Bergler, Yvonne Ehrl, Franz Putz, Antonia Schuster, Stefanie Kuhn, Torsten Schramm, Stefan Degenhardt, Gerhard Schmidt, Lea Weiland, Ulrike Giebeln-Hudnell, Jan Kielstein, Gabriele Eden, Brigitte Fuchs, Gina Morig, Manuela Winkler, Harald Darius, Charalampos Kriatselis, Carl-Philipp Roesch, Astrid Maselli, Dominik Alscher, Markus Ketteler, Moritz Schanz, Severin Schricker, Bianka Rettenmaier, Andrea Schwab, Pablo Pergola, Irene Leal, Melissa Cagle, Anna Romo, Anthony Torres, Sucharit Joshi, Kulli Barrett, Alexis Africano, Vicki Dodds, Dorleena Gowen, Ashlee Morris, Juan Fernandez, Guillermo Jimenez, Ricardo Viera, Kendaling Bruce, Ryan Barrios, Maylin Garcia, Kerelyn Garcia, Iradis Leal, David Tietjen, David Bains, Carlo Castillo, Genielle Brewer, Justin Davis, Natalie Freking, Brittany Golson, Sally Ham, Jesslyn Roesch, Pusadee Suchinda, Shameem Beigh, Usah Lilavivat, Joyce Bilton, Kim Bocchicchia, Jeffrey Turner, Neera Dahl, Aldo Peixoto, Yasemin Kavak, Lauren Liberti, Hari Nair, Nicolas Page, Stephanie Rosenberg, Kathryn Simmons, Tamara Isakova, Rebecca Frazier, Rupal Mehta, Anand Srivastava, Patrick Fox, Jonathan Hecktman, Alexander Hodakowski, Carlos Martinez, Rachel Phillips, Alexis Stevenson, Reem Mustafa, Kyle Jansson, Cassandra Kimber, Jason Stubbs, Ahmad Tuffaha, Sri Yarlagadda, Debbie Griffin, Elisabeth Laundy, Zhuo Tang, Radica Alicic, Ann Cooper, Lisa Davis, Ashwini Gore, Rebecca Goldfaden, Leslie Harvill, Lisa Hichkad, Barry Johns, Thomas Jones, Kayla Merritt, Jennifer Sheldon, Jennifer Stanfield, Lindsay Alexander, Kaitlyn Preston, Lindsey Wood, Rajesh Pradhan, Roger DeRaad, Kelli McIntosh, Louis Raymond, Michael Shepperd, Susan McLaughlin, Mary Seifert, Andrew Shepherd, Joseph Aiello, William Durham, Laurie Loudermilk, John Manley, Sabrina Burnette, Stephanie Evans, Tara Johnson, Lance Sloan, Judy Ann Acosta, Stacy Gillham, Katia Sloan, SueAnn Squyres, Michael Rocco, Amret Hawfield, Ben Bagwell, Lauren Richmond, Joseph Soufer, Subha Clarke, Amanda Aliu, Kristine Calabrese, Amanda Davis, Veronica Poma, Tracy Spinola, James Magee, Ricardo Silva, Rushab Choksi, Lorraine Dajani, John Evans, Anil George, Prasanth Krish, Gerard Martins, Mae Sheikh-Ali, David Sutton, Freda Driver, Abraham Hanburry, Laura Hume, Amber Hurst, Matthew Taddeo, Marla Turner, Veronica Yousif, Srinivasan Beddhu, Laith Al-Rabadi, Nikita Abraham, Amalia Caamano, Judy Carle, Victoria Gonce, Kaitlyn Staylor, Na Zhou, Shweta Bansal, Manoj Bhattarai, Kumar Sharma, Subrata Debnath, Aliseiya Garza, Chakradhar Velagapudi, Sergio Rovner, Javier Almeida, Pablo Casares, Verlaine Stewart-Ray, Rene Almaraz, Renata Dayrell, Ana Moncada, Ricardo Pulido, Roxana Rodriquez, Wasim Deeb, Kathryn DeGoursey, Rodel Gloria, Trevor Greene, Robert Miller, Edward Pereira, Miguel Roura, Debbie Domingo, Sasha Dorestin, William Hodge, Cathy Jackson, Deborah Lund, Katrina Taylor, Kenneth Boren, Brittany Cleveland, Sandra Gaiser, Mandeep Sahani, Logan Aldrich, Exodus Edmerson, Edmond Limon, Cole Valletta, Patricia Vasquez, Christopher Provenzano, Navkiranjot Brar, Heather Henderson, Bellovich Keith, Qur Khai, Quresh Khairullah, Gail Makos, Joel Topf, Sherry Gasko, Rosemarie Henschel, Kaitlin Knapp, Teresa Kozlowski, Paula LaFleur, Ashwathy Varughese, Hui Xue, Patricia Wu, Olga Arechiga, Shan Darbeau, Michael Fechter, Stephanie Martinez, Lenita Hanson, Nyla Cooper, Arelis Madera, Jay Cadorna, Rita Sheridan, Helen Sparks, Bradley Eilerman, Susanne Bodine, Wael Eid, Rebecca Flora, Amber Avery, Cashmere Hardy, Mihaela Biscoveanu, Steven Nagelberg, Tracey Cummins, Frederic Rahbari-Oskoui, Anju Oommen, Zohreh Forghani, Stacie Hitchcock, Darya Hosein, Diane Watkins, Minesh Patel, Anthony Lambert, Elizabeth Newman, Autumn Wood, Tammy Ross, Stephany Topping, Jeffrey Mulhern, Lorna Murphy, Ann Vasseur, Gregory Greenwood, Alexander Hadley, Denise Laurienti, Christopher Marshall, Nicholas McLean, Scott Satko, Brandy Caudill, Jacob Maris, Janice Rogers, Cindy Vanhoy, George Thomas, Georges Nakhoul, John O'Toole, Jonathan Taliercio, Leslie Cooperman, Marina Markovic, Barbara Tucky, Devasmita Dev, Alia Hasan, Hima Yalamanchili, Namita Jain, Lesley McNeil, Eric Wines, Jean Park, Adline Ghazi, Mia Hamm, Tejas Patel, Amy Mottl, Emily Chang, Vimal Derebail, Emmie Cole, Anne Froment, Sara Kelley, Jordan Osmond Foster, Vahid Mahabadi, Golriz Jafari, Anita Kamarzarian, Wendy Arriaga, Daisy Arteaga, Rosario Machicado, Genesis Naverrete, Prashant Kumar, Imran Nazeer, Karina Urquia, Tammi Glider, Vickie Jones, Savannah Rucker, Jennifer Wiley, Rahul Pandey, Jesus Arroyo, Harish Pariani, Mohammad Ahmad, Shahin Mozaffari, Erika Perez, Matthew Budoff, Sion Roy, Divya Birudaraju, Ahmed Ghanem, Sajad Hamal, Stephen Aronoff, Elisa Joye Petr, Richard Sachson, Jaime Wiebel, Sana Akram, Laurie Jones, Curtis Knight, Maurie Tarlac, Shahbaz Ahmed, Harold Szerlip, Akinwande Akinfolarin, Ankit Mehta, Shana Camp, Cindy Castro, Zanaida Cooper, Jessica Terry, Ahmed Awad, Bhavya Kothapalli, Ryan Lustig, Serine Alfaress, Hyder Jasim, Mary Parrigon, Dennis Karounos, Sadiq Ahmed, Maggie Berry, Ruth Oremus, Carlos Hernandez-Cassis, Elias Ugwu, Nazia Junejo, Nancy Suazo, Mark Segal, Amir Kazory, Sherry Brown, Tristan Daniels, Sofia Dayi, Renee Hogan, Kathy McCray, Jennifer Stickley, Mahboob Rahman, Mirela Dobre, Lavinia Negrea, Aparna Padiyar, Nishigandha Pradhan, Arash Rashidi, Nagaraju Sarabu, Vicki Donley, Tricia Young, Godson Oguchi, Judepatricks Onyema, Kahla Damianik, Jack Dienes, Judith Plummer-Morgan, Marilyn Roman, Mauver Skipper, Stacey-Ann Villaruel, Krystle Williams, Danny Sugimoto, Jeffrey Dugas, Ismeal Ahmed, Jamie Bhairoo, Dolores Rijos, Huzaifa Salim, Madita Gavrila, Kathryn Lafferty, Ria Rabara, Sally Ruse, Maria Weetman, James Bushnell, Albert Power, Alison Jenkins, Stefanie Jones, Amanda Scott, Cath Byrne, Mark Jesky, Alison Cowley, Emma McHaffie, Holly Waterfall, Jo Taylor, Laura Bough, Thomas Phillips, Barbara Winter-Goodwin, Sui Phin Kon, Iain MacDougall, Eirini Lioudaki, Sapna Shah, Claire Sharpe, Francisco Aguilar, Abegail Hernandez Pena, Conception Pugay, Amelia Te, Hugh Finn, Wasim Hanif, Samiul Mostafa, Alice Aitken, Katharine Draxlbauer, Evelina Grobovaite, Jennifer Kearney, Theresa McCarthy, Giorgio Gentile, Duncan Browne, Palanichamy Chellamuthu, Tabinda Dugal, Terri Chant, Laura Jones, Emily Laity, Megan Miners, James Muir, Elizabeth Swanson, Andrew Frankel, James Tomlinson, Marlon Alegata, Rashid Almasarwah, Anthoula Apostolidi, Maria Vourvou, Thomas Walters, Maarten Taal, Hari Dukka, Nitin Kolhe, Carly McDonald, Kelly White, Shiva Ugni, Smita Gunda, Rotimi Oluyombo, Vicki Brindle, Ping Coutts, Tracy Fuller, Evelyn Nadar, Suresh Ramadoss, Nichola Motherwell, Susannah Pajak, Louise Tonks, Sunil Bhandari, Richard Bodington, Adil Hazara, Dominic Fellowes, Christopher Wong, Christopher Goldsmith, Sherald Barnes, Ann Bennett, Claire Burston, Samantha Hope, Nicola Hunt, Lini Kurian, Richard Fish, Daniela Farrugia, Judy Lee, Emma Sadler, Hannah Turner, Christopher Hill, Henry Brown, Agnes Masengu, Peter Maxwell, Nina Bleakley, Hugh Murtagh, William Petchey, Vivian Yiu, Joanne Kellett, Angharad Williams, Helen Clarke, Victoria Carnall, Sarah Benyon, Caroline Blake, Stephanie Estcourt, Jane Piper, Neal Morgan, Carolyn Hutchinson, Teresa 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Irina, Rump, Lar, Stegbauer, Johanne, Pötz, Christine, Schemmelmann, Mara, Schmidt, Claudia, Koch, Michael, Aker, Sendogan, Küpper, Annika, Martin, Manuela, Pfab, Thiemo, Albert, Christian, Haase, Michael, Zander, Barbara, Schneider-Danwitz, Claudia, Seeger, Wolfgang, Seeger, Wolf-Adam, Zemann, Britta, Stellbrink, Christoph, Marx, Kristin, Stellbrink, Ekaterina, Brettschneider, Britta, Watson, Stephanie, Iselt, Marion, Klausmann, Gerhard, Kummer, Inga-Nadine, Kutschat, Auguste, Streitenberger, Simone, Girndt, Matthia, Markau, Silke, Girakossyan, Ina, Hanf, Claudia, Beige, Joachim, Wendt, Ralph, Schmidt, Ulrike, Schneider, Andrea, Veelken, Roland, Donhauser, Claudia, Becker, Lui, Miftari, Nexhat, Wolfling, Ricarda, Morlok, Sarah, Hugo, Christian, Paliege, Alexander, Passauer, Jen, Stumpf, Julian, Fleischer, Annegret, Haaser, Kerstin, Kraemer, Bernhard, Jochims, Jan, Kruger, Bernd, Foellinger, Claudia, Reisler, Anastassiya, Strutz, Frank, Haack, Stefan, Hohenstatt, Ursula, Busch, Martin, Herfurth, Konstantin, Wolf, Gunter, Paul, Rainer, Haller, Hermann, Kaufeld, Jessica, Menne, Jan, Bahlmann-Kroll, Elisabeth, Bergner, Angela, Weihprecht, Horst, Er, Aydin, Sonntag, Florian, Turan, Elif, Wittmann, Michael, Klauser, Franziska, Voigt, Eva, Schettler, Volker, Schulz, Egbert, Rohnstock, Madlen, Schettler, Elke, Schroppel, Bernd, van Erp, Rene, Kachele, Martin, Ludwig, Ulla, Schulte-Kemna, Lena, Kmietschak, Waltraud, Preiss, Elke, Ruocco, Martina, Heine, Gunnar, Brzoska, Martin, Gabel, Sebastian, Büttner, Christina, Sabarai, Asma, Banas, Bernhard, Bergler, Tobia, Ehrl, Yvonne, Putz, Franz, Schuster, Antonia, Kuhn, Stefanie, Schramm, Torsten, Degenhardt, Stefan, Schmidt, Gerhard, Weiland, Lea, Giebeln-Hudnell, Ulrike, Kielstein, Jan, Eden, Gabriele, Fuchs, Brigitte, Morig, Gina, Winkler, Manuela, Darius, Harald, Kriatselis, Charalampo, Roesch, Carl-Philipp, Maselli, Astrid, Alscher, Dominik, Ketteler, Marku, Schanz, Moritz, Schricker, Severin, Rettenmaier, Bianka, Schwab, Andrea, Pergola, Pablo, Leal, Irene, Cagle, Melissa, Romo, Anna, Torres, Anthony, Joshi, Sucharit, Barrett, Kulli, Africano, Alexi, Dodds, Vicki, Gowen, Dorleena, Morris, Ashlee, Fernandez, Juan, Jimenez, Guillermo, Viera, Ricardo, Bruce, Kendaling, Barrios, Ryan, Garcia, Maylin, Garcia, Kerelyn, Leal, Iradi, Tietjen, David, Bains, David, Castillo, Carlo, Brewer, Genielle, Davis, Justin, Freking, Natalie, Golson, Brittany, Ham, Sally, Roesch, Jesslyn, Suchinda, Pusadee, Beigh, Shameem, Lilavivat, Usah, Bilton, Joyce, Bocchicchia, Kim, Turner, Jeffrey, Dahl, Neera, Peixoto, Aldo, Kavak, Yasemin, Liberti, Lauren, Nair, Hari, Page, Nicola, Rosenberg, Stephanie, Simmons, Kathryn, Isakova, Tamara, Frazier, Rebecca, Mehta, Rupal, Srivastava, Anand, Fox, Patrick, Hecktman, Jonathan, Hodakowski, Alexander, Martinez, Carlo, Phillips, Rachel, Stevenson, Alexi, Mustafa, Reem, Jansson, Kyle, Kimber, Cassandra, Stubbs, Jason, Tuffaha, Ahmad, Yarlagadda, Sri, Griffin, Debbie, Laundy, Elisabeth, Tang, Zhuo, Alicic, Radica, Cooper, Ann, Davis, Lisa, Gore, Ashwini, Goldfaden, Rebecca, Harvill, Leslie, Hichkad, Lisa, Johns, Barry, Jones, Thoma, Merritt, Kayla, Sheldon, Jennifer, Stanfield, Jennifer, Alexander, Lindsay, Preston, Kaitlyn, Wood, Lindsey, Pradhan, Rajesh, Deraad, Roger, Mcintosh, Kelli, Raymond, Loui, Shepperd, Michael, Mclaughlin, Susan, Seifert, Mary, Shepherd, Andrew, Aiello, Joseph, Durham, William, Loudermilk, Laurie, Manley, John, Burnette, Sabrina, Evans, Stephanie, Johnson, Tara, Sloan, Lance, Ann Acosta, Judy, Gillham, Stacy, Sloan, Katia, Squyres, Sueann, Rocco, Michael, Hawfield, Amret, Bagwell, Ben, Richmond, Lauren, Soufer, Joseph, Clarke, Subha, Aliu, Amanda, Calabrese, Kristine, Davis, Amanda, Poma, Veronica, Spinola, Tracy, Magee, Jame, Silva, Ricardo, Choksi, Rushab, Dajani, Lorraine, Evans, John, George, Anil, Krish, Prasanth, Martins, Gerard, Sheikh-Ali, Mae, Sutton, David, Driver, Freda, Hanburry, Abraham, Hume, Laura, Hurst, Amber, Taddeo, Matthew, Turner, Marla, Yousif, Veronica, Beddhu, Srinivasan, Al-Rabadi, Laith, Abraham, Nikita, Caamano, Amalia, Carle, Judy, Gonce, Victoria, Staylor, Kaitlyn, Zhou, Na, Bansal, Shweta, Bhattarai, Manoj, Sharma, Kumar, Debnath, Subrata, Garza, Aliseiya, Velagapudi, Chakradhar, Rovner, Sergio, Almeida, Javier, Casares, Pablo, Stewart-Ray, Verlaine, Almaraz, Rene, Dayrell, Renata, Moncada, Ana, Pulido, Ricardo, Rodriquez, Roxana, Deeb, Wasim, Degoursey, Kathryn, Gloria, Rodel, Greene, Trevor, Miller, Robert, Pereira, Edward, Roura, Miguel, Domingo, Debbie, Dorestin, Sasha, Hodge, William, Jackson, Cathy, Lund, Deborah, Taylor, Katrina, Boren, Kenneth, Cleveland, Brittany, Gaiser, Sandra, Sahani, Mandeep, Aldrich, Logan, Edmerson, Exodu, Limon, Edmond, Valletta, Cole, Vasquez, Patricia, Provenzano, Christopher, Brar, Navkiranjot, Henderson, Heather, Keith, Bellovich, Khai, Qur, Khairullah, Quresh, Makos, Gail, Topf, Joel, Gasko, Sherry, Henschel, Rosemarie, Knapp, Kaitlin, Kozlowski, Teresa, Lafleur, Paula, Varughese, Ashwathy, Xue, Hui, Wu, Patricia, Arechiga, Olga, Darbeau, Shan, Fechter, Michael, Martinez, Stephanie, Hanson, Lenita, Cooper, Nyla, Madera, Areli, Cadorna, Jay, Sheridan, Rita, Sparks, Helen, Eilerman, Bradley, Bodine, Susanne, Eid, Wael, Flora, Rebecca, Avery, Amber, Hardy, Cashmere, Biscoveanu, Mihaela, Nagelberg, Steven, Cummins, Tracey, Rahbari-Oskoui, Frederic, Oommen, Anju, Forghani, Zohreh, Hitchcock, Stacie, Hosein, Darya, Watkins, Diane, Patel, Minesh, Lambert, Anthony, Newman, Elizabeth, Wood, Autumn, Ross, Tammy, Topping, Stephany, Mulhern, Jeffrey, Murphy, Lorna, Vasseur, Ann, Greenwood, Gregory, Hadley, Alexander, Laurienti, Denise, Marshall, Christopher, Mclean, Nichola, Satko, Scott, Caudill, Brandy, Maris, Jacob, Rogers, Janice, Vanhoy, Cindy, Thomas, George, Nakhoul, George, O'Toole, John, Taliercio, Jonathan, Cooperman, Leslie, Markovic, Marina, Tucky, Barbara, Dev, Devasmita, Hasan, Alia, Yalamanchili, Hima, Jain, Namita, Mcneil, Lesley, Wines, Eric, Park, Jean, Ghazi, Adline, Hamm, Mia, Patel, Teja, Mottl, Amy, Chang, Emily, Derebail, Vimal, Cole, Emmie, Froment, Anne, Kelley, Sara, Osmond Foster, Jordan, Mahabadi, Vahid, Jafari, Golriz, Kamarzarian, Anita, Arriaga, Wendy, Arteaga, Daisy, Machicado, Rosario, Naverrete, Genesi, Kumar, Prashant, Nazeer, Imran, Urquia, Karina, Glider, Tammi, Jones, Vickie, Rucker, Savannah, Wiley, Jennifer, Pandey, Rahul, Arroyo, Jesu, Pariani, Harish, Ahmad, Mohammad, Mozaffari, Shahin, Perez, Erika, Budoff, Matthew, Roy, Sion, Birudaraju, Divya, Ghanem, Ahmed, Hamal, Sajad, Aronoff, Stephen, Joye Petr, Elisa, Sachson, Richard, Wiebel, Jaime, Akram, Sana, Jones, Laurie, Knight, Curti, Tarlac, Maurie, Ahmed, Shahbaz, Szerlip, Harold, Akinfolarin, Akinwande, Mehta, Ankit, Camp, Shana, Castro, Cindy, Cooper, Zanaida, Terry, Jessica, Awad, Ahmed, Kothapalli, Bhavya, Lustig, Ryan, Alfaress, Serine, Jasim, Hyder, Parrigon, Mary, Karounos, Denni, Ahmed, Sadiq, Berry, Maggie, Oremus, Ruth, Hernandez-Cassis, Carlo, Ugwu, Elia, Junejo, Nazia, Suazo, Nancy, Segal, Mark, Kazory, Amir, Brown, Sherry, Daniels, Tristan, Dayi, Sofia, Hogan, Renee, Mccray, Kathy, Stickley, Jennifer, Rahman, Mahboob, Dobre, Mirela, Negrea, Lavinia, Padiyar, Aparna, Pradhan, Nishigandha, Rashidi, Arash, Sarabu, Nagaraju, Donley, Vicki, Young, Tricia, Oguchi, Godson, Onyema, Judepatrick, Damianik, Kahla, Dienes, Jack, Plummer-Morgan, Judith, Roman, Marilyn, Skipper, Mauver, Villaruel, Stacey-Ann, Williams, Krystle, Sugimoto, Danny, Dugas, Jeffrey, Ahmed, Ismeal, Bhairoo, Jamie, Rijos, Dolore, Salim, Huzaifa, Gavrila, Madita, Lafferty, Kathryn, Rabara, Ria, Ruse, Sally, Weetman, Maria, Bushnell, Jame, Power, Albert, Jenkins, Alison, Jones, Stefanie, Scott, Amanda, Byrne, Cath, Jesky, Mark, Cowley, Alison, Mchaffie, Emma, Waterfall, Holly, Taylor, Jo, Bough, Laura, Phillips, Thoma, Winter-Goodwin, Barbara, Phin Kon, Sui, Macdougall, Iain, Lioudaki, Eirini, Shah, Sapna, Sharpe, Claire, Aguilar, Francisco, Hernandez Pena, Abegail, Pugay, Conception, Te, Amelia, Finn, Hugh, Hanif, Wasim, Mostafa, Samiul, Aitken, Alice, Draxlbauer, Katharine, Grobovaite, Evelina, Kearney, Jennifer, Mccarthy, Theresa, Gentile, Giorgio, Browne, Duncan, Chellamuthu, Palanichamy, Dugal, Tabinda, Chant, Terri, Jones, Laura, Laity, Emily, Miners, Megan, Muir, Jame, Swanson, Elizabeth, Frankel, Andrew, Tomlinson, Jame, Alegata, Marlon, Almasarwah, Rashid, Apostolidi, Anthoula, Vourvou, Maria, Walters, Thoma, Taal, Maarten, Dukka, Hari, Kolhe, Nitin, Mcdonald, Carly, White, Kelly, Ugni, Shiva, Gunda, Smita, Oluyombo, Rotimi, Brindle, Vicki, Coutts, Ping, Fuller, Tracy, Nadar, Evelyn, Ramadoss, Suresh, Motherwell, Nichola, Pajak, Susannah, Tonks, Louise, Bhandari, Sunil, Bodington, Richard, Hazara, Adil, Fellowes, Dominic, Wong, Christopher, Goldsmith, Christopher, Barnes, Sherald, Bennett, Ann, Burston, Claire, Hope, Samantha, Hunt, Nicola, Kurian, Lini, Fish, Richard, Farrugia, Daniela, Lee, Judy, Sadler, Emma, Turner, Hannah, Hill, Christopher, Brown, Henry, Masengu, Agne, Maxwell, Peter, Bleakley, Nina, Murtagh, Hugh, Petchey, William, Yiu, Vivian, Kellett, Joanne, Williams, Angharad, Clarke, Helen, Carnall, Victoria, Benyon, Sarah, Blake, Caroline, Estcourt, Stephanie, Piper, Jane, Morgan, Neal, Hutchinson, Carolyn, Mckinley, Teresa, Woodman, Alastair, Graham, Judi, Leonard, Niall, Smyth, John, Adell, Vicki, Hagan, Samantha, Caplin, Ben, Oomatia, Amin, Damian, Eleanor, Sobande, Toluleyi, Doulton, Tim, Delaney, Michael, Montasser, Mahmoud, Hansen, Jenny, Loader, David, Moon, Angela, Morris, France, Sinha, Smeeta, Chukwu, Chukwuma, Hudson, Amy, Campbell, Diane, Kershaw, Melanie, Whittaker, Stephanie, Irtiza-Ali, Ayesha, Ghalli, Farid, Nosseir, Heba, Leslie, Allison, Trivedi, Kate, Fraser, Donald, Alhadj Ali, Mohammad, Griffin, Sian, Latif, Farah, Witczak, Justyna, Wonnacott, Alexa, Jeffers, Lynda, Webley, Yvette, Phelan, Paul, Miller-Hodges, Eve, Geddes, Ailsa, Glenwright, Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, Subash, Sood, Bhrigu, Swift, Pauline, Acheampong, Sarah, Ansu, Kwame, Augustin, Martia, Sampson, Anna, Vinall, Lynn, Wren, Kim, Wanninayake, Shamila, Wooding, Nichola, Edwards, Heather, Owen, Lydia, Bolton, Stephanie, Carson, Marion, Matthews, Michael, Brunskill, Nigel, Jesus-Silva, Jorge, Howson, Alex, Quashie-Akponeware, Mary, Tindall, Hilary, Nethaji, Chidambaram, Eldon, Helen, Patel, Rajan, Mark, Patrick, Rankin, Alastair, Sullivan, Michael, Forsyth, Kirsty, Mcdougall, Rowan, Dasgupta, Tanaji, Davies, Louisa, Ryder, Maggie, Grimmer, Philip, Macdonald, Clare, Webster, Mary, Newcastle, Newcastle, Ellam, Timothy, Wong, Edwin, Meshykhi, Christine, Webster, Andrea, Wilson, Peter, Vilar, Enric, Berdeprado, Jocelyn, Doctolero, Eunice, Wilkinson, Lily, Mccarroll, Frank, Ammar, Hesham, Kuan, Ying, Moran, Conor, Shivashankar, Girish, Campbell, Ryan, Glowski, Deborah, Mcdermott, Paula, Ali, Amar, Patel, Zuber, Bond, Christine, Whalley, Gillian, Zhang, Haitao, Yang, Liu, Zhang, Lihua, Kan, Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative
Subjects: chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract: Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.)
Published: 2023

30. Progress in Pathological Diagnosis after Kidney Transplantation: Current Trend and Future Perspective

Author: Kosuke Masutani
Subjects: Biochemistry (medical), Internal Medicine, Cardiology and Cardiovascular Medicine
Published: 2023

31. Focal segmental glomerulosclerosis and concurrent glomerular microangiopathy after long-term imatinib administration

Author: Soichiro Yokota, Naoko Himuro, Maho Watanabe, Katsuhisa Miyake, Kosuke Masutani, Aya Nawata, Tetsuhiko Yasuno, Toshiyuki Nakayama, Natsumi Morita, Kenji Ito, Hidenori Sasaki, Koji Takahashi, Noriko Uesugi, and Tomomi Ozaki
Subjects: Male, Nephrology, medicine.medical_specialty, Urology, Renal function, Case Report, Focal segmental glomerulosclerosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, Edema, medicine, Humans, Aged, Kidney, Proteinuria, Glomerulosclerosis, Focal Segmental, urogenital system, business.industry, Microangiopathy, Endothelial Cells, Imatinib, General Medicine, medicine.disease, medicine.anatomical_structure, Imatinib Mesylate, Female, Kidney Diseases, medicine.symptom, business, medicine.drug
Abstract: A 79-year-old Japanese man was admitted to our hospital because of proteinuria and kidney dysfunction. He was diagnosed with chronic myeloid leukemia 13 years before and was treated with imatinib. Deep molecular response was achieved but he developed 1+ proteinuria in the first year, which gradually worsened thereafter. Imatinib was discontinued 12 years later but proteinuria and kidney dysfunction were progressive. Percutaneous kidney biopsy revealed mild mesangial hyper-cellularity and matrix increase, swelling of endothelial cells, and partial double contours of glomerular tufts. Subendothelial edema in the interlobular artery was also noted. Immunofluorescence was not remarkable. Electron microscopy revealed endothelial injury with severe sub-endothelial edema. Since imatinib had already been discontinued, conservative therapy with maximal dose of azilsartan was administered. A second biopsy was performed 1 year later because of further deterioration of kidney function, which revealed markedly increased global glomerulosclerosis and severe interstitial fibrosis and tubular atrophy. Segmental glomerulosclerosis with podocyte hyperplasia was also observed. Electron microscopy revealed glomerulosclerotic changes and partially attenuated endothelial injury. Two and a half years later, proteinuria reduced, progression of kidney dysfunction slowed, and he was independent on dialysis therapy. Molecular response of chronic myeloid leukemia was also maintained. The clinical course suggested that endothelial and podocyte injuries were induced by imatinib, and that the nephrotoxic effects lasted for a few years after discontinuation.
Published: 2021

32. Comparison of Body Mass Index and Waist Circumference in the Prediction of Diabetes: A Retrospective Longitudinal Study

Author: Atsushi Satoh, Chikara Yoshimura, Hisatomi Arima, Soichiro Yokota, Toshiki Maeda, Tetsuhiko Yasuno, Shigeki Mukoubara, Shunsuke Funakoshi, Kazuhiro Tada, Kozaburo Akiyoshi, Makiko Abe, Takeshi Kuga, Toshitaka Yamanokuchi, Kenji Ito, Daiji Kawanami, Koji Takahashi, Miki Kawazoe, Kosuke Masutani, Ryosuke Mimata, and Hideyuki Fujii
Subjects: education.field_of_study, Waist, Diabetes risk, Proportional hazards model, business.industry, Endocrinology, Diabetes and Metabolism, Diabetes, Hazard ratio, Population, medicine.disease, Diabetes mellitus, Internal Medicine, medicine, Waist circumference, Mass index, Obesity, education, business, Body mass index, Original Research, Demography
Abstract: Introduction Both body mass index (BMI) and waist circumference (WC) are associated with diabetes risk, and the difference between them in predictive ability for diabetes is still contentious. We conducted a population-based study to investigate and compare the association of them with diabetes by sex. Methods This study included a total of 4754 subjects aged 40–80 years with no diabetes at baseline between 2008 and 2017. Using multivariate Cox proportional hazards models, we calculated hazard ratios for diabetes according to tertiles of BMI or WC. Harrell's C statistics was applied to assess and compare the predictive ability of the models using BMI and WC. Results Both BMI and WC showed the significant positive trends with diabetes risk. In men, the extreme tertiles (BMI > 25.1 kg/m2 and WC > 88.0 cm) provided 1.58-fold or 2.04-fold higher risk compared with the first tertiles ( 24.4 kg/m2 showed 3.28-fold higher risk than the first tertile (
Published: 2021

33. Correcting anemia and native vitamin D supplementation in kidney transplant recipients: a multicenter, 2 × 2 factorial, open‐label, randomized clinical trial

Author: Yoshitaka Isaka, Kazunari Yoshida, Takayuki Hamano, Shinichi Ito, Daisuke Ishii, Daiki Iwami, Yoshiharu Tsubakihara, Kazuhiro Iwadoh, Akinari Sekine, Yusuke Sakaguchi, Takamitsu Inoue, Ken Sakai, Tatsuo Yoneda, Katsunori Yoshida, Morikuni Nishihira, Yoshitsugu Obi, Naotake Akutsu, Candle-Kit Trial Investigators, Shiro Takahara, Shigeru Satoh, Kosuke Masutani, Naotsugu Ichimaru, Jun-ya Kaimori, Motoo Araki, Yoshifumi Ubara, Keiichi Sumida, and Hiroshi Harada
Subjects: medicine.medical_specialty, Anemia, Malignancy, Gastroenterology, vitamin D deficiency, law.invention, chemistry.chemical_compound, Japan, Randomized controlled trial, law, Internal medicine, medicine, Vitamin D and neurology, Humans, Vitamin D, Transplantation, business.industry, Cancer, medicine.disease, Kidney Transplantation, chemistry, Dietary Supplements, Cholecalciferol, business
Abstract: Anemia and vitamin D deficiency are associated with allograft failure, and hence, are potential therapeutic targets among kidney transplant recipients (KTRs). We conducted a multicenter, two-by-two factorial, open-label, randomized clinical trial to examine the effects of anemia correction and vitamin D supplementation on 2-year change in eGFR among KTRs (CANDLE-KIT). We enrolled 153 patients with anemia and >1-year history of transplantation across 23 facilities in Japan, and randomly assigned them to either a high or low hemoglobin target (>12.5 vs.
Published: 2021

34. Acute Kidney Injury and Remission of Proteinuria in Minimal Change Disease

Author: Ryohei Yamamoto, Enyu Imai, Shoichi Maruyama, Hitoshi Yokoyama, Hitoshi Sugiyama, Asami Takeda, Shunya Uchida, Tatsuo Tsukamoto, Kazuhiko Tsuruya, Yasuhiro Akai, Kosaku Nitta, Megumu Fukunaga, Hiroki Hayashi, Tatsuya Shoji, Kosuke Masutani, Tsuneo Konta, Ritsuko Katafuchi, Saori Nishio, Takashi Wada, Shunsuke Goto, Hirofumi Tamai, Arimasa Shirasaki, Kojiro Nagai, Tomoya Nishino, Kunihiro Yamagata, Junichiro J. Kazama, Keiju Hiromura, Hideo Yasuda, Tadashi Sofue, Shouichi Fujimoto, Makoto Mizutani, Tomohiko Naruse, Takeyuki Hiramatsu, Kunio Morozumi, Hiroshi Sobajima, Yosuke Saka, Eiji Ishimura, Takafumi Ito, Daisuke Ichikawa, Takashi Shigematsu, Hiroshi Sato, Ichiei Narita, and Isaka Yoshitaka
Subjects: Nephrology
Published: 2022

35. Effect of Low-Density Lipoprotein Apheresis on Quality of Life in Patients with Diabetes, Proteinuria, and Hypercholesterolemia

Author: Akinori, Hara, Takashi, Wada, Eri, Muso, Shoichi, Maruyama, Sawako, Kato, Kengo, Furuichi, Kenichi, Yoshimura, Tadashi, Toyama, Norihiko, Sakai, Hiroyuki, Suzuki, Tatsuo, Tsukamoto, Mariko, Miyazaki, Eiichi, Sato, Masanori, Abe, Yugo, Shibagaki, Ichiei, Narita, Shin, Goto, Yuichi, Sakamaki, Hitoshi, Yokoyama, Noriko, Mori, Satoshi, Tanaka, Yukio, Yuzawa, Midori, Hasegawa, Takeshi, Matsubara, Jun, Wada, Katsuyuki, Tanabe, Kosuke, Masutani, Yasuhiro, Abe, Kazuhiko, Tsuruya, Shouichi, Fujimoto, Shuji, Iwatsubo, Akihiro, Tsuda, Hitoshi, Suzuki, Kenji, Kasuno, Yoshio, Terada, Takeshi, Nakata, Noriaki, Iino, Tadashi, Sofue, Hitomi, Miyata, Toshiaki, Nakano, Takayasu, Ohtake, and Shuzo, Kobayashi
Subjects: Nephrology, Hematology, General Medicine
Abstract: Introduction: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients’ quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. Methods: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels Results: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (β coefficient −6.935, 95% confidence interval, 13.313 to−0.556, p = 0.034). Conclusion: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.
Published: 2022

36. Association between serum uric acid and new onset and progression of chronic kidney disease in a Japanese general population: Iki epidemiological study of atherosclerosis and chronic kidney disease

Author: Shunsuke Funakoshi, Hitoshi Nakashima, Chikara Yoshimura, Koji Takahashi, Miki Kawazoe, Shigeaki Mukoubara, Atsushi Satoh, Hisatomi Arima, Kenji Ito, Kazuhiro Tada, Kosuke Masutani, Toshiki Maeda, and Tetsuhiko Yasuno
Subjects: Male, Nephrology, medicine.medical_specialty, Physiology, Population, 030232 urology & nephrology, Renal function, 030204 cardiovascular system & hematology, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Asian People, Physiology (medical), Internal medicine, medicine, Humans, Hyperuricemia, Renal Insufficiency, Chronic, education, Aged, Retrospective Studies, education.field_of_study, Proportional hazards model, business.industry, Hazard ratio, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, Uric Acid, Proteinuria, Disease Progression, Female, business, Kidney disease, Cohort study
Abstract: Although several risk factors for chronic kidney disease (CKD) have been proposed, it remains unclear whether elevated serum uric acid (SUA) is negatively association with kidney function. The aim of this study was to elucidate the association between SUA and new onset and progression of CKD in a Japanese general population. This was a population-based retrospective cohort study using annual health checkup data of residents of Iki Island. A total of 5,507 adults (979 with CKD and 4,528 without) were included. The outcomes were new onset of CKD among participants without CKD at baseline, and progression of CKD among those with CKD. A Cox proportional hazards model was used to evaluate the association between SUA and new onset and progression of CKD. During mean follow-up of 4.6 years, 757 cases of new onset of CKD and 193 with progression of CKD were observed. SUA was significantly associated with new onset of CKD (adjusted hazard ratio 1.13, [95% confidence interval 1.03–1.24] per standard deviation [SD] increase in SUA). In contrast, SUA was not significantly associated with progression of CKD (hazard ratio 1.08, [0.92–1.27] per SD increase). Similar results were obtained when classifying uric acid as categorical. SUA was significantly associated with increased risk for new onset of CKD, but not with progression of CKD among a Japanese general population.
Published: 2021

37. Significance of revised criteria for chronic active T cell–mediated rejection in the 2017 Banff classification: Surveillance by 1-year protocol biopsies for kidney transplantation

Author: Kosuke Masutani, Akihiro Tsuchimoto, Kaneyasu Nakagawa, Toshiaki Nakano, Kohei Unagami, Takanari Kitazono, Masayoshi Okumi, Yasuhiro Okabe, Masafumi Nakamura, Kazunari Tanabe, Yuta Matsukuma, Yoichi Kakuta, and Kenji Ueki
Subjects: Graft Rejection, medicine.medical_specialty, Biopsy, T-Lymphocytes, Urology, 030230 surgery, Kidney, Nephropathy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Survival analysis, Kidney transplantation, Transplantation, Creatinine, medicine.diagnostic_test, business.industry, Graft Survival, Hazard ratio, Reproducibility of Results, medicine.disease, Kidney Transplantation, Confidence interval, Tacrolimus, chemistry, business
Abstract: Diagnostic criteria for chronic active T cell-mediated rejection (CA-TCMR) were revised in the Banff 2017 consensus, but it is unknown whether the new criteria predict graft prognosis of kidney transplantation. We enrolled 406 kidney allograft recipients who underwent a 1-year protocol biopsy (PB) and investigated the diagnostic significance of Banff 2017. Interobserver reproducibility of the 3 diagnosticians showed a substantial agreement rate of 0.68 in Fleiss's kappa coefficient. Thirty-three patients (8%) were classified as CA-TCMR according to Banff 2017, and 6 were previously diagnosed as normal, 12 as acute TCMR, 10 with borderline changes, and 5 as CA-TCMR according to Banff 2015 criteria. Determinant factors of CA-TCMR were cyclosporine use (vs tacrolimus), previous acute rejection, and BK polyomavirus-associated nephropathy. In survival analysis, the new diagnosis of CA-TCMR predicted a composite graft endpoint defined as doubling serum creatinine or death-censored graft loss (log-rank test, P < .001). In multivariate analysis, CA-TCMR was associated with the second highest risk of the composite endpoint (hazard ratio: 5.42; 95% confidence interval, 2.02-14.61; P < .001 vs normal) behind antibody-mediated rejection. In conclusion, diagnosis of CA-TCMR in Banff 2017 may facilitate detecting an unfavorable prognosis of kidney allograft recipients who undergo a 1-year PB.
Published: 2021

38. Impact of Multivascular Disease on Cardiovascular Mortality and Morbidity in Patients Receiving Hemodialysis: Ten-Year Outcomes of the Q-Cohort Study

Author: Hiroaki Ooboshi, Shigeru Tanaka, Kazuhiko Tsuruya, Hiroto Hiyamuta, Masanori Tokumoto, Toshiaki Nakano, Takanari Kitazono, Masatomo Taniguchi, and Kosuke Masutani
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Comorbidity, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Japan, Interquartile range, Renal Dialysis, Internal medicine, Outcome Assessment, Health Care, Internal Medicine, medicine, Humans, Risk factor, Mortality, Stroke, business.industry, Vascular disease, Biochemistry (medical), Hazard ratio, End-stage kidney disease, Middle Aged, medicine.disease, Cardiovascular disease, Atherosclerosis, Cardiovascular Diseases, Heart Disease Risk Factors, Cardiology, Kidney Failure, Chronic, Original Article, Female, Hemodialysis, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Cohort study, Follow-Up Studies
Abstract: Aim: Multivascular disease, indicating concurrent arteriosclerotic lesions in a number of different vascular beds, is an independent risk factor for recurrent ischemic events in the general population. However, the impact of multivascular disease on the risk of developing cardiovascular disease has not been fully evaluated in patients receiving hemodialysis. Methods: A total of 3,504 hemodialysis patients were prospectively followed for 10 years. In this study, multivascular disease was defined as the coexistence of coronary artery disease and stroke. We examined the relationship between multivascular disease and the occurrence of composite cardiovascular endpoint, consisting of cardiovascular death, nonfatal coronary artery disease, nonfatal stroke, and peripheral artery disease. Results: The proportion of participants with multivascular disease was 5.7% (n = 200) at baseline. During follow-up (median, 106.6 months; interquartile range, 50.1–121.8 months), 1,311 patients experienced the composite endpoint, which was defined as at least one of the following: cardiovascular death (n = 620), nonfatal coronary artery disease (n = 318), nonfatal stroke (n = 340), and peripheral artery disease (n = 257). Compared with the group with no history of cardiovascular disease, the risk of experiencing the composite endpoint increased significantly with higher numbers of injured vascular beds in patients with single vascular disease (hazard ratio, 1.68; 95% confidence interval, 1.49–1.89) and in those with multivascular disease (hazard ratio, 2.11; 95% confidence interval, 1.71–2.60). In a multivariable analysis, multivascular disease was an independent predictor of cardiovascular events, in addition to diabetes, aging, and hypertension. Conclusions: This study clearly demonstrated that multivascular disease was a powerful predictor for cardiovascular mortality and morbidity in patients receiving hemodialysis.
Published: 2021

39. PS-P10-2: NON-LINEAR RELATIONSHIP BETWEEN CKD PROGRESSION AND SYSTOLIC AND DIASTOLIC BLOOD PRESSURE; IKI EPIDEMIOLOGICAL STUDY OF ATHEROSCLEROSIS AND CKD (ISSA-CKD)

Author: Toshiki Maeda, Takumi Nishi, Yukiko Shinohara, Makiko Abe, Miki Kawazoe, Atsushi Satoh, Koji Takahashi, Kazuhiro Tada, Kenji Itoh, Tetsuhiko Yasuno, Chikara Yoshimura, Shigeaki Mukobara, Kosuke Masutani, and Hisatomi Arima
Subjects: Physiology, Internal Medicine, Cardiology and Cardiovascular Medicine
Published: 2023

40. Concurrent minimal change disease and retroperitoneal liposarcoma successfully treated by tumor resection and steroid therapy

Author: Natsumi Morita, Yasuhiro Abe, Ryoko Shibata, Yuki Yasui, Makoto Hamsaki, Katsuhisa Miyake, Aki Hamauchi, Tetsuhiko Yasuno, Naoko Himuro, Satoshi Hisano, Maho Watanabe, Kosuke Masutani, Kenji Ito, Hitoshi Nakashima, and Fumihiro Yoshimura
Subjects: Nephrology, medicine.medical_specialty, Nephrotic Syndrome, Thymoma, Biopsy, 030232 urology & nephrology, Case Report, 030204 cardiovascular system & hematology, Liposarcoma, Kidney, Gastroenterology, 03 medical and health sciences, Hypoproteinemia, Pancreatectomy, 0302 clinical medicine, Asian People, Internal medicine, medicine, Edema, Humans, Minimal change disease, Retroperitoneal Neoplasms, Hematuria, Leg, business.industry, Nephrosis, Lipoid, Remission Induction, Acute kidney injury, General Medicine, Acute Kidney Injury, Middle Aged, medicine.disease, Proteinuria, Treatment Outcome, Splenectomy, Prednisolone, Female, Steroids, Tomography, X-Ray Computed, business, Nephrotic syndrome, medicine.drug
Abstract: A 54-year-old Japanese woman developed simultaneous abdominal distension and bilateral leg edema. Her medical history and results of periodic medical check-up were unremarkable. Blood tests revealed severe hypoproteinemia and acute kidney injury, and urinalysis revealed 4+ proteinuria and 2+ hematuria. Abdominal computed tomography revealed a large intra-abdominal mass with fat tissue density. She underwent emergency tumor excision, splenectomy, and distal pancreatectomy. However, hypoproteinemia and acute kidney injury worsened. Therefore, she was transferred to the nephrology division for confirmation of diagnosis and for treatment of acute kidney injury and nephrotic syndrome. We conducted percutaneous kidney biopsy and diagnosed minimal change disease (MCD). Intravenous prednisolone was started, and heavy proteinuria and systemic edema were gradually alleviated. She achieved complete remission 2 months later, and oral prednisolone was tapered. Histopathological diagnosis of abdominal tumor was dedifferentiated liposarcoma of retroperitoneal origin. Immunohistochemical staining revealed strong expression of vascular endothelial growth factor in the tumor cells in the dedifferentiated component. Currently, her clinical course is stable without recurrence of liposarcoma and nephrotic syndrome. MCD develops in patients with Hodgkin’s lymphoma, solid organ cancers, hematological malignancies, and thymoma, whereas concurrent MCD and liposarcoma are rare. Remission of nephrotic syndrome and normalized kidney function induced by steroid therapy are important for better management of patients with malignancy.
Published: 2020

41. Estimated plasma osmolarity and risk of end-stage kidney disease in patients with IgA nephropathy

Author: Shigeru Tanaka, Kosuke Masutani, Hiroaki Ooboshi, Toshiaki Nakano, Masanori Tokumoto, Akihiro Tsuchimoto, and Takanari Kitazono
Subjects: Adult, Male, Nephrology, medicine.medical_specialty, Physiology, 030232 urology & nephrology, Urology, Renal function, 030204 cardiovascular system & hematology, Nephropathy, Plasma, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Physiology (medical), Internal medicine, Prevalence, medicine, Humans, Risk factor, Proportional Hazards Models, Kidney, business.industry, Incidence, Osmolar Concentration, Glomerulonephritis, IGA, Glomerulonephritis, Middle Aged, medicine.disease, medicine.anatomical_structure, Vasopressin secretion, Disease Progression, Kidney Failure, Chronic, Female, business, Follow-Up Studies, Glomerular Filtration Rate, Kidney disease
Abstract: Several experimental studies have indicated that increased plasma osmolarity caused by recurrent dehydration is involved in kidney injury via a mechanism, mediated by vasopressin secretion and activation of the aldose reductase pathway. Epidemiologic evidence linking increased plasma osmolarity and the onset of end-stage kidney disease (ESKD), in patients with primary glomerulonephritis, is lacking. We retrospectively examined 663 patients with IgA nephropathy (IgAN) diagnosed by kidney biopsy and evaluated the association between estimated plasma osmolarity and ESKD prevalence, using a Cox proportional hazards model. During follow-up (median 80.4 months; interquartile range 22.2–120.1), 73 patients developed ESKD. In a baseline survey, plasma osmolarity was correlated negatively with the mean value of the estimated glomerular filtration rate, but correlated positively with the mean value of urinary protein excretion, systolic blood pressure, and pathologic severity of extracapillary proliferation, in addition to tissue fibrosis and sclerosis. The incidence rate of ESKD increased linearly with increase in plasma osmolarity (P
Published: 2020

42. 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)

Author: 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
Subjects: 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.
Published: 2020

43. Uric Acid and Prevalence of Hypertension in a General Population of Japanese: ISSA-CKD Study

Author: Hisatomi Arima, Shigetomo Mori, Kenji Ito, Seiji Kondo, Ikuko Miyabayashi, Atsushi Satoh, Kazuhiro Tada, Miki Kawazoe, Kosuke Masutani, Hitoshi Nakashima, Chikara Yoshimura, Shintaro Ishida, Koji Takahashi, Shunsuke Funakoshi, Toshiki Maeda, and Tetsuhiko Yasuno
Subjects: medicine.medical_specialty, Population, Hypertension, Japanese, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, Serum uric acid, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, 030212 general & internal medicine, education, education.field_of_study, Proteinuria, business.industry, General Medicine, Odds ratio, medicine.disease, Obesity, Blood pressure, chemistry, Uric acid, Original Article, medicine.symptom, business, Dyslipidemia
Abstract: Background There is uncertainty surrounding the causal relationship between serum uric acid and hypertension. The aim was to investigate the association between serum uric acid and prevalence of hypertension in a general population of Japanese. Methods This was a population-based cross-sectional study using health check-up data of the residents of the Iki City, Nagasaki Prefecture, Japan. A total of 7,484 participants aged 30 years or older were included in this study. Serum uric acid was classified into four groups: group 1 (< 357 µmol/L (< 6 mg/dL)), group 2 (357 - 415 µmol/L (6 - 6.9 mg/dL)), group 3 (416 - 475 µmol/L (7 - 7.9 mg/dL)) and group 4 (≥ 476 µmol/L (≥ 8 mg/dL)). Hypertension was defined as blood pressure (BP) levels of ≥ 140/90 mm Hg or use of BP lowering medications. Results Hypertension was observed among 3,467 participants (prevalence 46.3%). The prevalence of hypertension increased with elevation of serum uric acid levels: 42.8% in group 1, 55.0% in group 2, 57.6% in group 3 and 59.8% in group 4 (P < 0.001 for trend). This association was significant even after adjustment for other risk factors including age, sex, current smoking, current alcohol intake, obesity, diabetes, dyslipidemia, estimated glomerular filtration rate and proteinuria: odds ratios (95% confidence intervals) were 1.50 (1.28 - 1.77) for group 2, 1.58 (1.25 - 1.99) for group 3 and 1.89 (1.36 - 2.64) for group 4 compared with the reference group of group 1 (P < 0.001 for trend). Conclusions Serum uric acid was clearly associated with prevalence of hypertension in a general population of Japanese.
Published: 2020

44. Effect of chronic kidney disease on the association between hyperuricemia and new-onset hypertension in the general Japanese population: ISSA-CKD study

Author: Hisatomi Arima, Shigeaki Mukobara, Shota Okutsu, Kazuhiro Tada, Chikara Yoshimura, Seiji Kondo, Soichiro Yokota, Miki Kawazoe, Kenji Ito, Koji Takahashi, Shigeki Nabeshima, Shintaro Ishida, Daiji Kawanami, Shunsuke Funakoshi, Masayoshi Tsuji, Hideyuki Fujii, Atsushi Satoh, Toshiki Maeda, Tetsuhiko Yasuno, and Kosuke Masutani
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, Hyperuricemia, Japan, Risk Factors, Internal medicine, Chronic Kidney Disease, Internal Medicine, medicine, Humans, Risk factor, Renal Insufficiency, Chronic, education, Retrospective Studies, education.field_of_study, business.industry, Hazard ratio, Retrospective cohort study, medicine.disease, Uric Acid, Blood pressure, Quartile, Hypertension, Commentary, Cardiology and Cardiovascular Medicine, business, Kidney disease, Glomerular Filtration Rate
Abstract: We aimed to investigate the association between serum uric acid (SUA) level and development of hypertension as well as the interaction effect of chronic kidney disease (CKD) on this relationship in the general Japanese population. We included 7895 participants aged ≥30 years from the ISSA-CKD study, a population-based retrospective cohort study that used annual health check-up data of residents from Iki Island, Japan. After the exclusion of 1881 with l < 1-year follow-up, 2812 with hypertension at baseline, and 165 with missing information on SUA, a total of 3037 participants were enrolled in this analysis. Participants were divided into four groups according to the quartiles of SUA level at baseline, and multivariable-adjusted hazard ratios for new-onset hypertension were calculated. Stratified analyses were performed for each subgroup (defined by sex, age, alcohol intake, and CKD) to assess the interaction effects. During a mean follow-up period of 4.4 years, 943 participants developed hypertension. The first quartile group was set as the reference group, and the multivariable-adjusted hazard ratios (95% confidence interval) for new-onset hypertension were 1.11 (0.90-1.36) in the second quartile, 1.25 (1.02-1.54) in the third quartile, and 1.35 (1.07-1.70) in the fourth quartile compared with those in the reference group (p = .007 for trend). The stratified analyses showed that the association between SUA and hypertension was significantly stronger in participants with CKD than in those without CKD (p = .035 for interaction). SUA level is an independent risk factor for new-onset hypertension. This tendency was significantly stronger in participants with CKD.
Published: 2021

45. Time to remission of proteinuria and incidence of relapse in patients with steroid-sensitive minimal change disease and focal segmental glomerulosclerosis: the Japan Nephrotic Syndrome Cohort Study

Author: Ryohei, Yamamoto, Enyu, Imai, Shoichi, Maruyama, Hitoshi, Yokoyama, Hitoshi, Sugiyama, Asami, Takeda, Tatsuo, Tsukamoto, Shunya, Uchida, Kazuhiko, Tsuruya, Tatsuya, Shoji, Hiroki, Hayashi, Yasuhiro, Akai, Megumu, Fukunaga, Tsuneo, Konta, Saori, Nishio, Shunsuke, Goto, Hirofumi, Tamai, Kojiro, Nagai, Ritsuko, Katafuchi, Kosuke, Masutani, Takashi, Wada, Tomoya, Nishino, Arimasa, Shirasaki, Hiroshi, Sobajima, Kosaku, Nitta, Kunihiro, Yamagata, Junichiro J, Kazama, Keiju, Hiromura, Hideo, Yasuda, Makoto, Mizutani, Toshiyuki, Akahori, Tomohiko, Naruse, Takeyuki, Hiramatsu, Kunio, Morozumi, Tetsushi, Mimura, Yosuke, Saka, Eiji, Ishimura, Hajime, Hasegawa, Daisuke, Ichikawa, Takashi, Shigematsu, Hiroshi, Sato, Ichiei, Narita, Yoshitaka, Isaka, and Hiroyuki, Komatsu
Subjects: Adult, Male, Nephrotic Syndrome, Glomerulosclerosis, Focal Segmental, Incidence, Nephrosis, Lipoid, Cohort Studies, Proteinuria, Japan, Recurrence, Humans, Female, Steroids, Prospective Studies, Immunosuppressive Agents
Abstract: Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse.This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors.Remission was observed at 3-7, 8-14, 15-21, 22-28, and 30-56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3-7, 8-14, 15-21, 22-28, 30-56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively).The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients.
Published: 2021

46. Eating Speed and Incidence of Diabetes in a Japanese General Population: ISSA-CKD

Author: Hitoshi Nakashima, Masaki Fujita, Shota Okutsu, Chikara Yoshimura, Miki Kawazoe, Hideyuki Fujii, Hisatomi Arima, Koji Takahashi, Shintaro Ishida, Atsushi Satoh, Kosuke Masutani, Daiji Kawanami, Kenji Ito, Kazuhiro Tada, Toshiki Maeda, Tetsuhiko Yasuno, Shigeaki Mukoubara, Shigeki Nabeshima, Shunsuke Funakoshi, Soichiro Yokota, and Seiji Kondo
Subjects: lifestyle, Population, primary prevention, 030209 endocrinology & metabolism, eating speed, Article, 03 medical and health sciences, 0302 clinical medicine, Primary prevention, Diabetes mellitus, medicine, 030212 general & internal medicine, education, education.field_of_study, diabetes, business.industry, Incidence (epidemiology), digestive, oral, and skin physiology, General Medicine, Japanese population, medicine.disease, Obesity, Medicine, Smoking status, business, Dyslipidemia, Demography
Abstract: Background: We investigated whether eating speed was associated with the incidence of diabetes in a Japanese general population. Methods: A total of 4853 Japanese individuals without diabetes at baseline were analyzed. Self-reported eating speed was categorized as slow, medium, and fast on the basis of questionnaire responses. The study outcome was the incidence of diabetes. Results: After an average follow-up period of 5.1 years, 234 individuals developed diabetes. The incidence of diabetes per 1000 person-years was 4.9 in the slow eating speed group, 8.8 in the medium eating speed group, and 12.5 in the fast eating speed group, respectively (*** p &lt, 0.001 for trend). The HRs were 1.69 (95%CI 0.94–3.06) for the medium eating speed and 2.08 (95%CI 1.13–3.84) for the fast eating speed, compared to the slow eating speed (* p = 0.014 for trend) after adjustment for age, gender, smoking status, drinking, exercise, obesity, hypertension, and dyslipidemia. Conclusion: Faster eating speed increased a risk for the incidence of diabetes in a general Japanese population.
Published: 2021

47. MO638ANEMIA IN DIABETIC PATIENTS REFLECTS SEVERE TUBULOINTERSTITIAL INJURY AND ASSISTS CLINICALLY IN PREDICTING DIAGNOSIS OF DIABETIC NEPHROPATHY

Author: Soichiro Yokota, Naoko Himuro, Koji Takahashi, Yori Inoue, Katsuhisa Miyake, Maho Watanabe, Kosuke Masutani, Noriko Uesugi, Kenji Ito, Hitoshi Nakashima, and Tetsuhiko Yasuno
Subjects: Transplantation, Kidney, medicine.medical_specialty, business.industry, Urology, Renal function, medicine.disease, Net reclassification improvement, Diabetic nephropathy, medicine.anatomical_structure, Nephrology, Erythropoietin, medicine, Glomerulonephritis iga, business, medicine.drug
Abstract: Background and Aims Diabetic nephropathy (DN) is currently a leading cause of end-stage kidney disease worldwide. Kidney biopsy is generally performed in diabetic patients to discriminate between DN and non-diabetic kidney disease (NDKD), and to provide more specific treatments. In addition to conventional predicting factors of DN, recent studies suggested the predictive value of anemia in the diagnosis of DN, however detailed pathophysiology and the significance of anemia in renal pathology are not fully understood. This study aimed to investigate the impact of anemia on renal pathology and clinical course in patients who underwent kidney biopsy. Method We reviewed 81 patients (60.4 ± 13.7 years, 54 men and 27 women) with type 2 diabetes who underwent percutaneous kidney biopsy in Fukuoka University Hospital from January 2001 through March 2020. DN was diagnosed by mesangial expansion or nodular glomerulosclerosis observed under a light microscope, and immunofluorescence assisted in differentiating NDKD from DN. Anemia was defined as hemoglobin level Results According to their pathological findings, patients were classified into two groups: isolated DN (DN group, n=30) and NDKD alone or concurrent DN (NDKD group, n=51). There were 11 types of NDKD. Of these, membranous nephropathy was the most common (23.5%), followed by IgA nephropathy (17.6%), and crescentic glomerulonephritis (13.7%). In multiple logistic regression analysis, absence of severe hematuria (odds ratio (OR) 11.66, 95% confidence interval (CI) 1.68 - 89.9) and presence of anemia (OR 11.38, 95% CI 2.51 - 51.52) were significantly related with the diagnosis of DN. Akaike’s information criterion (AIC) and net reclassification improvement (NRI) analyses revealed improved predictive performance by adding anemia to the conventional factors (AIC 100.152 to 91.844; NRI 27.0%). The tissues of patients in the DN group demonstrated more severe interstitial fibrosis and tubular atrophy (IF/TA) than the NDKD group (p Conclusion DN is associated with anemia because of severe IF/TA regardless of renal function, and anemia helps clinician discriminate clinically between isolated DN and NDKD.
Published: 2021

48. Predictive Value of the Combination of Peripheral Blood Lymphocyte Count and Urinary Cytology in BK Polyomavirus–associated Nephropathy

Author: Kei Kurihara, Hitoshi Nakashima, Kazuhiko Tsuruya, Yasuhiro Okabe, Shigeru Tanaka, Hiroshi Noguchi, Masafumi Nakamura, Keizo Kaku, Takanari Kitazono, Akihiro Tsuchimoto, Kosuke Masutani, Yuta Matsukuma, and Toshiaki Nakano
Subjects: Adult, Male, medicine.medical_specialty, Urinary system, Urology, Nephropathy, Postoperative Complications, Predictive Value of Tests, Cytology, Biopsy, medicine, Humans, Lymphocyte Count, Kidney transplantation, Polyomavirus Infections, Transplantation, medicine.diagnostic_test, business.industry, Gold standard (test), Middle Aged, medicine.disease, Kidney Transplantation, Tumor Virus Infections, Early Diagnosis, BK Virus, Predictive value of tests, Peripheral blood lymphocyte, Female, Kidney Diseases, Surgery, business
Abstract: Graft biopsy is the gold standard for diagnosis of BK polyomavirus-associated nephropathy (BKPyVAN), and polymerase chain reaction is the most specific screening technique. Development of a noninvasive, cost-effective marker for BKPyVAN is important.We reviewed 492 adult kidney transplant patients. We investigated peripheral blood lymphocyte (PBL) count and urinary cytology at graft biopsy in patients with BKVPyAN (n = 21), acute T-cell-mediated rejection (n = 79), and no evidence of acute rejection (n = 149). We performed univariate and multivariate logistic regression and receiver operating characteristics analyses to compare the test performance of PBL count, urinary cytology, and their combination for diagnosis of BKPyVAN.The PBL count at biopsy was significantly lower in the BKPyVAN group than the acute T-cell-mediated rejection and no acute rejection groups (959 ± 290/μL, 1433 ± 673/μL, and 1531 ± 549/μL, respectively; P .01). The PBL count was 959 ± 290/μL at diagnosis of BKPyVAN and increased to 1123 ± 377/μL, 1238 ± 419/μL, and 1292 ± 491/μL at 1, 2, and 3 months after treatment, respectively (P .05). On univariate analysis, the area under the curve was significantly higher for the combined model than for PBL and cytology alone (0.930, 0.797, and 0.875, respectively; P .01). The improved test performance in the combined model remained significant after multivariate adjustment (0.972, 0.844, and 0.928, respectively; P .01).Decreased PBL count was found in BKPyVAN, and the predictive performance of the combination of PBL count and urinary cytology was significantly enhanced for diagnosis of BKPyVAN.
Published: 2019

49. Kidney transplantation for treatment of end-stage kidney disease after haematopoietic stem cell transplantation: case series and literature review

Author: Akihiro, Tsuchimoto, Kosuke, Masutani, Kazuya, Omoto, Masayoshi, Okumi, Yasuhiro, Okabe, Takehiro, Nishiki, Morihito, Ota, Toshiaki, Nakano, Kazuhiko, Tsuruya, Takanari, Kitazono, Masafumi, Nakamura, Hideki, Ishida, Kazunari, Tanabe, and Ota, Morihito
Subjects: Adult, Male, Nephrology, medicine.medical_specialty, Adolescent, Physiology, medicine.medical_treatment, 030232 urology & nephrology, Graft vs Host Disease, 030204 cardiovascular system & hematology, Infections, Young Adult, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Physiology (medical), Internal medicine, medicine, Humans, Child, Kidney transplantation, Retrospective Studies, Immunosuppression Therapy, Umbilical Cord Blood Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Middle Aged, Allografts, medicine.disease, Hematologic Diseases, Kidney Transplantation, Survival Rate, Transplantation, Treatment Outcome, surgical procedures, operative, Kidney Failure, Chronic, Female, Rituximab, Plasmapheresis, Mantle cell lymphoma, business, Immunosuppressive Agents, medicine.drug, Kidney disease
Abstract: The safety of kidney transplantation (KT) for end-stage kidney disease (ESKD) after haematopoietic stem cell transplantation (HSCT) for haematological disease has not been investigated thoroughly. In this retrospective multicentre study, we investigated the clinical courses of six ESKD patients that received KT after HSCT for various haematological diseases. Data for six such patients were obtained from three institutions in our consortium. Two patients with chronic myeloid leukaemia, one with refractory aplastic anaemia and another one with acute lymphocytic leukaemia received bone marrow transplantation. One patients with acute lymphocytic leukaemia received umbilical cord blood transplantation, and one with mantle cell lymphoma received peripheral blood stem cell transplantation. The patients developed ESKD at a median of 133 months after HSCT. Two patients who received KT and HSCT from the same donor were temporarily treated with immunosuppressive drugs. The other patients received KT and HSCT from different donors and were treated with antibody induction using our standard regimens. For one patient with ABO-incompatible transplantation, we added rituximab, splenectomy, and plasmapheresis. In the observational period at a median of 51 months after KT, only one patient experienced acute T-cell-mediated rejection. Four patients underwent hospitalization because of infection and fully recovered. No patient experienced recurrence of their original haematological disease. All patients survived throughout the observational periods, and graft functions were preserved. Despite the high infection frequency, survival rates and graft functions were extremely good in patients compared with previous studies. Therefore, current management contributed to favourable outcomes of these patients.
Published: 2018

50. Preformed C1q-binding Donor-specific Anti-HLA Antibodies and Graft Function After Kidney Transplantation

Author: Akihiro Tsuchimoto, Masafumi Nakamura, Hideko Noguchi, Keizo Kaku, Kosuke Masutani, Kyoko Miyamoto, and Yasuhiro Okabe
Subjects: Adult, Graft Rejection, Male, medicine.medical_specialty, 030232 urology & nephrology, Urology, Delayed Graft Function, 030230 surgery, Graft function, 03 medical and health sciences, 0302 clinical medicine, HLA Antigens, Isoantibodies, Risk Factors, Biopsy, Humans, Medicine, Hla antibodies, Risk factor, Kidney transplantation, Retrospective Studies, Transplantation, Kidney, medicine.diagnostic_test, biology, business.industry, Complement C1q, Incidence, Incidence (epidemiology), Graft Survival, Middle Aged, medicine.disease, Kidney Transplantation, Tissue Donors, medicine.anatomical_structure, biology.protein, Female, Surgery, Antibody, business
Abstract: Background De novo complement-binding donor-specific anti-human leukocyte antigen antibodies (DSAs) are reportedly associated with an increased risk of kidney graft failure, but there is little information on preformed complement-binding DSAs. This study investigated the correlation between preformed C1q-binding DSAs and medium-term outcomes in kidney transplantation (KT). Methods We retrospectively studied 44 pretransplant DSA-positive patients, including 36 patients who underwent KT between April 2010 and October 2016. There were 17 patients with C1q-binding DSAs and 27 patients without C1q-binding DSAs. Clinical variables were examined in the 2 groups. Results Patients with C1q-binding DSAs had significantly higher blood transfusion history (53.0% vs 18.6%; P = .0174), complement-dependent cytotoxicity crossmatch (CDC-XM)-positivity (29.4% vs 0%; P = .0012), and DSA median fluorescence intensity (MFI) (10,974 vs 2764; P = .0009). Among patients who were not excluded for CDC-XM-positivity and underwent KT, there was no significant difference in cumulative biopsy-proven acute rejection rate (32.5% vs 33.5%; P = .8354), cumulative graft survival, and 3-month and 12-month protocol biopsy results between patients with and without C1q-binding DSAs. Although patients with C1q-binding DSAs showed a higher incidence of delayed graft function (54.6% vs 20.0%; P = .0419), multivariate logistic regression showed that DSA MFI (P = .0124), but not C1q-binding DSAs (P = .2377), was an independent risk factor for delayed graft function. Conclusions In patients with CDC-XM-negativity, preformed C1q-binding DSAs were not associated with incidence of antibody-mediated rejection and medium-term graft survival after KT. C1q-binding DSAs were highly correlated with DSA MFI and CDC-XM-positivity.
Published: 2018

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