16 results on '"Jun-Ya Kaimori"'
Search Results
2. Association of Time-Updated Anion Gap With Risk of Kidney Failure in Advanced CKD: A Cohort Study
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Yusuke Sakaguchi, Yoshitaka Isaka, Yohei Doi, Koki Hattori, Yuta Asahina, Tatsufumi Oka, Jun-ya Kaimori, and Sachio Kajimoto
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Acid-Base Equilibrium ,medicine.medical_specialty ,business.industry ,Confounding ,Anion gap ,Marginal structural model ,Renal function ,Retrospective cohort study ,Metabolic acidosis ,medicine.disease ,Cohort Studies ,Nephrology ,Internal medicine ,Disease Progression ,medicine ,Humans ,Renal Insufficiency ,Renal Insufficiency, Chronic ,business ,Glomerular Filtration Rate ,Retrospective Studies ,Cohort study ,Kidney disease - Abstract
Rationale & objective High anion gap acidosis frequently develops in patients with advanced chronic kidney disease (CKD) and might be involved in kidney injury. Its impact on kidney outcomes, however, has not been well studied. We sought to examine the association between time-updated anion gap and the risk of kidney failure with replacement therapy (KFRT) among patients with advanced CKD. Study design Retrospective cohort study. Setting & participants 1,168 patients with CKD glomerular filtration rate categories 3b-5 (G3b-G5) who had available data on anion gap. Exposure High time-updated anion gap defined as values ≥ 9.2 (top 25th percentile). Outcome KFRT and death. Analytical approach Marginal structural models were fit to characterize the association between anion gap and study outcomes while accounting for potential time-dependent confounding. Results The mean baseline estimated glomerular filtration rate (eGFR) of the study participants was 28 mL/min/1.73 m2. Over a median follow-up period of 3.1 years, 317 patients progressed to KFRT (7.5 per 100 patient-years), and 146 died (3.5 per 100 patient-years). In the marginal structural models, a high anion gap was associated with a higher rate of KFRT (HR, 3.04 [95% CI, 1.94-4.75]; P Limitations Observational study design and selection bias due clinical indications for measuring anion gap. Conclusions Among patients with advanced CKD, high anion gap was associated with an increased risk of progression to KFRT and death.
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- 2022
3. Quantitative Analyses of Foot Processes, Mitochondria, and Basement Membranes by Structured Illumination
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Jun-ya Kaimori, Tomoko Namba-Hamano, Karin Shimada, Yoshitaka Isaka, Ayumi Matsumoto, Kazunori Inoue, Yusuke Sakaguchi, Yoshitsugu Takabatake, Yusuke Katsuma, Seiichi Yasuda, and Isao Matsui
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Pathology ,medicine.medical_specialty ,business.industry ,030232 urology & nephrology ,Periodic acid–Schiff stain ,030204 cardiovascular system & hematology ,medicine.disease ,Acid fuchsin ,Staining ,law.invention ,Nephropathy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Membranous nephropathy ,Nephrology ,law ,Microscopy ,medicine ,Mitochondrial fission ,Electron microscope ,business - Abstract
Introduction Foot process effacement and mitochondrial fission associate with kidney disease pathogenesis. Electron microscopy is the gold-standard method for their visualization, but the observable area of electron microscopy is smaller than light microscopy. It is important to develop alternative ways to quantitatively evaluate these microstructural changes because the lesion site of renal diseases can be focal. Methods We analyzed elastica-Masson trichrome (EMT) and periodic acid-Schiff (PAS) stained kidney sections using structured illumination microscopy (SIM). Results EMT staining revealed three-dimensional (3D) structures of foot process, whereas ponceau xylidine acid fuchsin azophloxine solution induced fluorescence. Conversion of foot process images into their constituent frequencies by Fourier transform showed that the concentric square of (1/4)2-(1/16)2 in the power spectra (PS) included information for normal periodic structures of foot processes. Foot process integrity, assessed by PS, negatively correlated with proteinuria. EMT-stained sections revealed fragmented mitochondria in mice with mitochondrial injuries and patients with tubulointerstitial nephritis; Fourier transform quantified associated mitochondrial injury. Quantified mitochondrial damage in patients with immunoglobulin A (IgA) nephropathy predicted a decline in estimated glomerular filtration rate (eGFR) after kidney biopsy but did not correlate with eGFR at biopsy. PAS-stained sections, excited by a 640 nm laser, combined with the coefficient of variation values, quantified subtle changes in the basement membranes of patients with membranous nephropathy stage I. Conclusions Kidney microstructures are quantified from sections prepared in clinical practice using SIM.
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- 2021
4. Modulation of the Association of Hypobicarbonatemia and Incident Kidney Failure With Replacement Therapy by Venous pH: A Cohort Study
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Sachio Kajimoto, Yoshitaka Isaka, Yusuke Sakaguchi, Jun-ya Kaimori, and Yuta Asahina
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Bicarbonate ,Water-Electrolyte Imbalance ,030232 urology & nephrology ,Renal function ,Acid-Base Imbalance ,Gastroenterology ,Peritoneal dialysis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Japan ,Internal medicine ,medicine ,Humans ,Renal Insufficiency ,030212 general & internal medicine ,Kidney transplantation ,business.industry ,Retrospective cohort study ,Metabolic acidosis ,Hydrogen-Ion Concentration ,Middle Aged ,Prognosis ,medicine.disease ,Renal Replacement Therapy ,Bicarbonates ,Outcome and Process Assessment, Health Care ,chemistry ,Nephrology ,Disease Progression ,Kidney Failure, Chronic ,Female ,Hemodialysis ,business ,Glomerular Filtration Rate ,Kidney disease - Abstract
Studies showing an association between lower bicarbonate levels and worse kidney disease prognosis have not accounted for the influence of pH. It remains unknown whether this association is consistent across a wide range of blood pH values. This study sought to assess how pH modifies the relationship between hypobicarbonatemia and incident kidney failure requiring kidney replacement therapy (KFRT).Retrospective cohort study.1,058 Japanese patients with estimated glomerular filtration rates60mL/min/1.73mBaseline venous bicarbonate levels and venous pH.KFRT defined as initiation of kidney replacement therapy (hemodialysis, peritoneal dialysis, and kidney transplantation).Cox proportional hazards model assessing the interaction between baseline bicarbonate levels and venous pH on incident KFRT.In the lowest bicarbonate quartile (≤21.5 mEq/L), 59% of patients had acidemia (pH7.32), whereas 38% had venous pH within the normal range and 3% had alkalemia (pH7.42). During a median follow-up of 3.0 years, 374 patients developed KFRT. Venous pH modified the association between bicarbonate level and rate of KFRT (P for interaction=0.04). After adjustment for potential confounders, including capacity for respiratory compensation, the lowest (vs the highest) bicarbonate quartile was associated with a 2.29-fold (95% CI, 1.10-4.77; P=0.03) higher rate of KFRT among patients with acidemia (pH7.32). In contrast, among patients without acidemia (pH≥7.32), no significant association was found between bicarbonate level and KFRT. In an exploratory analysis, patients with higher respiratory compensation capacity had a lower rate of KFRT (HR per 0.1 increase in respiratory compensation capacity, 0.90; 95% CI, 0.87-0.94; P0.001).Observational study design; blood gas measurements were performed in a select patient population.Venous pH modified the association of hypobicarbonatemia with progression of chronic kidney disease to KFRT. Measurement of venous pH may be valuable for identifying patients with chronic kidney disease and hypobicarbonatemia and may inform treatment.
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- 2021
5. High-pressure carbon monoxide preserves rat kidney grafts from apoptosis and inflammation
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Naoyuki Hatayama, Masayuki Fujino, Naotsugu Ichimaru, Yoshitaka Isaka, Norio Nonomura, Shiro Takahara, Jun-ya Kaimori, Kunihiro Seki, Ryoichi Imamura, Koichi Tsutahara, Toyofumi Abe, Xiao-Kang Li, Yoichi Kakuta, Koji Yazawa, and Masayoshi Okumi
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Male ,0301 basic medicine ,Adenosine ,Gene Expression ,Apoptosis ,030230 surgery ,Kidney ,medicine.disease_cause ,p38 Mitogen-Activated Protein Kinases ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Insulin ,Phosphorylation ,Carbon Monoxide ,Reverse Transcriptase Polymerase Chain Reaction ,Chemistry ,Graft Survival ,Organ Preservation ,Glutathione ,Cold Temperature ,Kidney Tubules ,medicine.anatomical_structure ,Reperfusion Injury ,Cytokines ,Inflammation Mediators ,medicine.medical_specialty ,Allopurinol ,Partial Pressure ,p38 mitogen-activated protein kinases ,Blotting, Western ,Organ Preservation Solutions ,Pathology and Forensic Medicine ,Proinflammatory cytokine ,03 medical and health sciences ,Raffinose ,Internal medicine ,medicine ,Animals ,Viaspan ,Molecular Biology ,Protein kinase B ,Inflammation ,Kidney metabolism ,Cell Biology ,medicine.disease ,Kidney Transplantation ,Oxygen ,030104 developmental biology ,Endocrinology ,Rats, Inbred Lew ,Immunology ,Proto-Oncogene Proteins c-akt ,Reperfusion injury ,Oxidative stress - Abstract
Renal ischemia–reperfusion (I/R) injury is unavoidable in kidney transplantation (KTx) and frequently influences both short- and long-term allograft survival. Carbon monoxide (CO) has attracted attention as a medical gas with anti-inflammatory and anti-apoptotic effects. We investigated a new strategy for organ preservation using ex vivo application of high-pressure CO in an experimental rat KTx model. We preserved kidney grafts using a high-pressure chamber filled with mixed gases composed of CO and O2. We found that cold I/R injury resulted in progressive deterioration of renal graft function in University of Wisconsin solution, whereas CO significantly improved renal function. We confirmed that CO decreased oxidative stress and mRNA expression of proinflammatory cytokines and inhibited tubular apoptosis in the early phases. Western blot analysis demonstrated that CO increased phosphatidylinositol-3 kinase and phosphorylation of Akt and p38 mitogen-activated protein kinase. Furthermore, CO significantly alleviated tubular injury scores and suppressed the development of interstitial fibrosis at 100 days after KTx. Thus, high-pressure mixed CO and O2 gases successfully preserved rat kidney grafts for 24 h by protecting tubular epithelial cells from apoptosis and inhibiting inflammation.
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- 2017
6. Diffusion Tensor Imaging MRI With Spin-Echo Sequence and Long-Duration Measurement for Evaluation of Renal Fibrosis in a Rat Fibrosis Model
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Kagayaki Kuroda, Akira Fujimori, Naotsugu Ichimaru, Satoko Yamamoto, H. Shibata, Takashi Yokawa, Akihiko Fujikawa, Masaki Hatanaka, Yoshitaka Isaka, Toshiki Moriyama, Hiromi Rakugi, Jun-ya Kaimori, S. Takahara, and Sosuke Miyoshi
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Male ,030232 urology & nephrology ,urologic and male genital diseases ,030218 nuclear medicine & medical imaging ,Masson's trichrome stain ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Fractional anisotropy ,Renal fibrosis ,medicine ,Animals ,Sirius Red ,Transplantation ,Kidney ,business.industry ,medicine.disease ,Fibrosis ,Magnetic Resonance Imaging ,Rats ,Disease Models, Animal ,Diffusion Tensor Imaging ,medicine.anatomical_structure ,chemistry ,Disease Progression ,Kidney Diseases ,Surgery ,business ,Nuclear medicine ,Diffusion MRI ,Kidney disease - Abstract
Background Renal fibrosis (RF) is a well-known marker for chronic kidney disease (CKD) progression, including chronic renal injury after renal transplantation. However, invasive biopsy is an available examination for evaluation of RF. Diffusion MRI was once recognized as a promising option for RF. However, it is now controversial for RF evaluation in a unilateral ureteral obstruction (UUO) model. Methods To seek an optimal imaging method applicable for RF in UUO model kidneys, we attempted a series of MRI methods, including proton density–weighted imaging, T1-weighted imaging, T2-weighted imaging, T2*-weighted imaging, diffusion-weighted imaging, and diffusion tensor imaging (DTI). Results We identified DTI MRI by spin-echo sequence plus a special kidney attachment as the best option for evaluation of renal UUO fibrosis, compared with normal kidney on the opposite side. To confirm these results, we applied this technique to a rat UUO therapeutic model with the anti-fibrotic reagent Fasudil. Fractional anisotropy values calculated from DTI MRI showed statistically significant linear correlation with the RF area measured by use of Sirius red or Masson trichrome staining of the positive area [cortex ( r = 0.6397, P = .0283) and outer stripe of the outer medulla ( r = 0.7810, P = .0039)]. Conclusions By use of the DTI MRI with spin-echo sequence, it may be possible to accurately evaluate RF in CKD.
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- 2017
7. Comparison of Sensitivity of Immunocomplex Capture Fluorescence Analysis for Detecting Donor-specific Anti-HLA Class II Antibodies in Kidney Transplant Patients
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H. Hirase, Toyofumi Abe, Ryoichi Imamura, T. Takayama, Naotsugu Ichimaru, Taigo Kato, Masataka Kawamura, Y. Hisayama, Jun-ya Kaimori, Shigeaki Nakazawa, S. Takahara, and Norio Nonomura
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Adult ,Graft Rejection ,Male ,Hla class ii ,Fluorescent Antibody Technique ,Human leukocyte antigen ,Kidney transplant ,Antibodies ,Humans ,Immunoassay ,Transplantation ,biology ,HLA-DQ Antigen ,Chemistry ,Histocompatibility Testing ,Histocompatibility Antigens Class II ,Middle Aged ,Kidney Transplantation ,Fluorescence ,Molecular biology ,Tissue Donors ,biology.protein ,Female ,Surgery ,Surface expression ,Antibody - Abstract
Background Immunocomplex capture fluorescence analysis (ICFA) detects donor-specific antihuman leukocyte antigen (HLA) antibodies (DSA), but the detection sensitivity of HLA class II antibodies using conventional ICFA is as low as 57%. The aim of the study was to improve the detection sensitivity of HLA class II antibodies by ICFA, and compare the ICFA results with the Luminex single-antigen bead test. Methods Six DSA-negative kidney transplant donors and recipient pairs and 10 HLA class II DSA-positive pairs were included in the study. The detection sensitivity of modified ICFA was compared with conventional ICFA, and the ICFA results were compared with the Luminex single-antigen bead test. Results The index value of modified ICFA was higher than that of conventional ICFA. The cutoff value of conventional ICFA was 30,686 (MFI), which was improved to 19,405 using modified ICFA. Regarding the HLA-DQ antibody, 5 samples found to be positive by Luminex single-antigen bead testing were all negative using modified ICFA. The reason for this discrepancy could be related to: (1) the difference in detection sensitivity; (2) the difference in HLA antigen surface expression between naive lymphocytes and synthetic beads; or (3) the structure of synthetic HLA DQ antigen on the Luminex single-antigen beads. Conclusion The index value of the modified ICFA was higher than that of conventional ICFA, and the detection sensitivity of HLA class II antibodies was improved by modified ICFA. Further assessment is necessary to clarify the reasons for divergence between ICFA and Luminex single-antigen bead test results.
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- 2018
8. Post-Transplant Anemia Has Strong Influences on Renal and Patient Outcomes in Living Kidney Transplant Patients
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Naotsugu Ichimaru, Kazuaki Yamanaka, Shigeaki Nakazawa, Toyofumi Abe, Toshiki Moriyama, Yoshitsugu Obi, S. Takahara, Norio Nonomura, Jun-ya Kaimori, Ryoichi Imamura, and Yoichi Kakuta
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Adult ,Male ,medicine.medical_specialty ,Anemia ,030230 surgery ,Kidney transplant ,Hemoglobins ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Japan ,Risk Factors ,Internal medicine ,Living Donors ,medicine ,Humans ,Risk factor ,Survival rate ,Kidney transplantation ,Transplantation ,Creatinine ,Proteinuria ,business.industry ,Prognosis ,medicine.disease ,Kidney Transplantation ,Surgery ,Survival Rate ,chemistry ,Female ,030211 gastroenterology & hepatology ,Hemoglobin ,medicine.symptom ,business - Abstract
Post-transplant anemia (PTA) is a risk factor for mortality and graft loss in kidney transplant patients.In all, 172 patients were included in this study. PTA was defined as hemoglobin 13.0 g/dL in men and 12.0 g/dL in women. The primary outcome of interest was the renal outcome, defined as a 50% increase in serum levels of creatinine, a return to chronic dialysis, and subsequent kidney transplantation (KTx). The secondary outcome was a composite of the primary outcome and death.At baseline, 75 patients (43.6%) had PTA. During follow-up of a median of 7.3 years, 52 patients (30.2%) had 2-fold higher creatinine levels than at baseline, 24 patients (14.0%) had to return to chronic dialysis or subsequent KTx, and 11 patients (6.4%) died; 8 (4.7%) of the deceased patients had functioning allografts. Univariate regression analyses showed that a lower hemoglobin level and positive proteinuria were significantly associated with both outcomes. After adjusting for important clinical variables, a lower hemoglobin level remained a strong predictor for both outcomes. Restricted cubic splines showed an almost linear inverse association with a hemoglobin level ≥12 g/dL. The risk of the outcomes increased with decreasing tertiles of the baseline hemoglobin level for both men and women, but the associations in women were much weaker than those in men, suggesting a different prognostic value of the hemoglobin level between men and women.PTA strongly influenced the renal and patient outcomes in living kidney transplant patients.
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- 2016
9. Adherence to Dietary Recommendations in Maintenance Phase Kidney Transplant Patients
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Yoichi Kakuta, Kazuaki Yamanaka, Ryoichi Imamura, Toyofumi Abe, Naotsugu Ichimaru, Shigeaki Nakazawa, Norio Nonomura, Jun-ya Kaimori, and S. Takahara
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Male ,Nephrology ,medicine.medical_specialty ,Renal function ,030204 cardiovascular system & hematology ,Gastroenterology ,Excretion ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Renal Insufficiency, Chronic ,Salt intake ,Intensive care medicine ,Kidney transplantation ,Transplantation ,Kidney ,business.industry ,Sodium ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Diet ,medicine.anatomical_structure ,Female ,Surgery ,Guideline Adherence ,business ,Body mass index ,Glomerular Filtration Rate ,Kidney disease - Abstract
Current adherence to dietary recommendations for chronic kidney disease was evaluated in kidney transplant patients in the maintenance phase.A total of 268 maintenance phase kidney transplant patients were included in the study. Estimated daily intakes of oral protein and salt were calculated from 24-h urinary excretion of nitrogen and sodium, respectively. Dietary recommendations for chronic kidney disease, as issued in 2014 by the Japanese Society of Nephrology, were used as the basis for assessing diet.The study included 114 female patients and 154 male patients. The mean age, posttransplantation years, body mass index, estimated glomerular filtration rate, and 24-h urinary excretion of protein were 56.3 years, 11.2 years, 22.0 kg/m(2), 42.6 mL/min/1.73 m(2), and 321 mg/d, respectively. Estimated daily protein and salt intakes were 0.98 ± 0.26 g/kg/d and 9.3 ± 3.9 g/d. Only 47 patients (17.5%) in the case of salt intake and 105 patients (39.2%) in the case of protein intake were within reference values. The 24-h urinary protein excretion of the daily salt intake-adherent group (6 g) was significantly less than that of the nonadherent group (≥6 g) (P = .021).The adherence rate to dietary recommendations for chronic kidney disease in kidney transplant patients was low. The 24-h urinary protein excretion of the daily salt intake-adherent group was significantly less than that of the nonadherent group. Dietary therapy for these patients may have the potential to improve kidney graft function and survival.
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- 2016
10. Performance of the Japanese Glomerular Filtration Rate Equation Based on Standardized Serum Cystatin C in Potential Kidney Donors
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Yoshitaka Isaka, Naotsugu Ichimaru, Seiichi Matsuo, Masaru Horio, Shiro Takahara, Yoshinari Yasuda, Yoichi Kakuta, and Jun-ya Kaimori
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Male ,medicine.medical_specialty ,Urology ,Renal function ,urologic and male genital diseases ,chemistry.chemical_compound ,Japan ,Serum cystatin ,Internal medicine ,medicine ,Humans ,Cystatin C ,Aged ,Transplantation ,Inulin Clearance ,Creatinine ,Kidney ,urogenital system ,Chemistry ,Inulin renal clearance ,Middle Aged ,Kidney Transplantation ,Tissue Donors ,Confidence interval ,Endocrinology ,medicine.anatomical_structure ,Female ,Surgery ,Glomerular Filtration Rate - Abstract
Background It was reported that the glomerula filtration rate (GFR) equation based on serum creatinine underestimated the GFR in potential kidney donors. Recently, the Japanese GFR equation based on standardized serum cystatin C was reported. Therefore, we assessed the performance of the equation in potential kidney donors. Methods Forty-five potential kidney donors from 2 hospitals were included. GFR was measured (mGFR) using inulin renal clearance. Serum creatinine was measured using the enzymatic method. Serum cystatin C was measured using a nephelometric immunoassay (Siemens) and calibrated to the standardized value traceable to ERM-DA471/IFCC using an equation reported previously. The estimated GFR (eGFR) was calculated using the Japanese GFR equation based on serum creatinine (eGFRcreat) and the Japanese GFR equation based on serum cystatin C (eGFRcys). Bias (mGFR - eGFR) and accuracy (P30) of the equations were evaluated. Results Inulin clearance, eGFRcreat, and eGFRcys were 91.0 ± 18.2, 78.5 ± 18.8, and 93.3 ± 16.3 mL/min/1.73 m 2 , respectively. Bias of eGFRcreat was 12.4 ± 15.8 mL/min/1.73 m 2 and significantly different from zero, indicating underestimation of GFR. Bias of eGFRcys was −2.3 ± 16.3 mL/min/1.73 m 2 and was not significantly different from zero, suggesting better performance. But, the precision (standard deviation [SD] of bias) and accuracy (P30: Percentage of participants with eGFR within 30% of mGFR) of eGFRcys were not better compared with eGFRcreat. Accuracies (P30) of eGFRcreat and eGFRcys were 87% (95% confidence interval [CI], 74–94) and 82% (95% CI, 69–91), respectively. Conclusion Bias of eGFRcys was better compared with eGFRcreat. But, the precision (SD of bias) and accuracy of eGFRcys were not superior compared with eGFRcreat in potential kidney donors.
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- 2014
11. Febuxostat suppressed renal ischemia–reperfusion injury via reduced oxidative stress
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Toshiki Moriyama, Hiromi Rakugi, Shiro Takahara, Noritaka Kawada, Harumi Kitamura, Hidetoshi Tsuda, Jun-ya Kaimori, and Yoshitaka Isaka
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Male ,Xanthine Oxidase ,Xanthine Dehydrogenase ,Biophysics ,Renal function ,Apoptosis ,Hyperuricemia ,Pharmacology ,Kidney ,medicine.disease_cause ,Biochemistry ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Febuxostat ,TBARS ,medicine ,Animals ,Xanthine oxidase ,Molecular Biology ,Nitrotyrosine ,Cell Biology ,Endoplasmic Reticulum Stress ,Rats ,Oxidative Stress ,Thiazoles ,Kidney Tubules ,medicine.anatomical_structure ,chemistry ,Reperfusion Injury ,Uric acid ,Oxidative stress ,medicine.drug - Abstract
Febuxostat is a novel selective inhibitor of xanthine oxidase (XO), approved for treating hyperuricemia. XO inhibits the generation of uric acid (UA) as well as the resulting generation of superoxide. During renal ischemia-reperfusion (I/R) injury, the burst of reactive oxygen species (ROS) can trigger the inflammation and the tubular cell injury. As XO is a critical source of ROS, inhibition of XO could be a therapeutic target for I/R injury. Therefore, we performed this study to test the therapeutic effect of febuxostat on renal I/R injury. Sprague-Dawley rats, received vehicle or febuxostat, were subjected to right nephrectomy and left renal I/R injury. Febuxostat significantly suppressed XO activity, and thereby reduced oxidative stress, assessed by nitrotyrosine, thiobarbituric acid-reactive substances (TBARS) and urine 8-isoprostane. Furthermore, febuxostat reduced the induction of endoplasmic reticulum (ER) stress, assessed by GRP-78, ATF4, and CHOP. Vehicle-treated I/R injured rats exhibited elevated serum creatinine and UN, which were significantly suppressed in febuxostat-treated I/R-injured rats. Histological analysis revealed that fubuxostat-treated rats showed less tubular injury and interstitial fibrosis with reduction in ED1-positive macrophage infiltration, TUNEL positive apoptotic tubular cells, and interstitial smooth muscle α actin (SMαA) expression, compared to vehicle-treated rats. In conclusion; novel XO inhibitor, febuxostat, can protect kidney from renal I/R injury, and may contribute to preserve kidney function.
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- 2012
12. Autophagy Guards Against Cisplatin-Induced Acute Kidney Injury
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Taiji Matsusaka, Naonobu Fujita, Isao Matsui, Atsushi Takahashi, Yoshitsugu Takabatake, Yoshitaka Isaka, Tamotsu Yoshimori, Harumi Kitamura, Tomoko Namba, Hiromi Rakugi, Jun-ya Kaimori, Tomonori Kimura, and Fumio Niimura
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Male ,DNA damage ,Green Fluorescent Proteins ,Cellular homeostasis ,Antineoplastic Agents ,Apoptosis ,Mice, Transgenic ,Protein degradation ,Biology ,Pathology and Forensic Medicine ,Kidney Tubules, Proximal ,Mice ,Autophagy ,medicine ,Animals ,chemistry.chemical_classification ,Cisplatin ,Reactive oxygen species ,Kidney ,Ubiquitin ,Acute kidney injury ,Acute Kidney Injury ,medicine.disease ,Mitochondria ,Cell biology ,medicine.anatomical_structure ,chemistry ,Tumor Suppressor Protein p53 ,Reactive Oxygen Species ,Microtubule-Associated Proteins ,Transcription Factor TFIIH ,DNA Damage ,Transcription Factors ,medicine.drug - Abstract
Autophagy is a highly conserved bulk protein degradation pathway involved in cellular homeostasis. Although emerging evidence indicates involvement of autophagy in various conditions, efforts to clarify the role of autophagy in renal tubules are beginning to be elucidated. In the present study, we examined the hypothesis that autophagy guards against acute kidney injury (AKI) by modulating several deteriorative pathways that lead to tubular cell death using a cisplatin-induced model of AKI. Cisplatin treatment of GFP-LC3 (green fluorescent protein-microtubule-associated protein 1 light chain 3) transgenic mice induced autophagy in kidney proximal tubules in a time-dependent manner. Proximal tubule-specific autophagy-deficient mice exhibited more severe cisplatin-induced AKI than did control mice, as assessed via kidney function and morphologic findings. In addition, cisplatin induced more severe DNA damage and p53 activation, concomitant with an increase in apoptotic cell number, and a massive accumulation of protein aggregates in autophagy-deficient proximal tubules. Cisplatin treatment significantly increased reactive oxygen species-producing damaged mitochondria in immortalized autophagy-deficient proximal tubular cells when compared with autophagy-retrieved control cells. In conclusion, autophagy guards kidney proximal tubules against AKI, possibly by alleviating DNA damage and reactive oxygen species production and by eliminating toxic protein aggregates. Enhancing autophagy may provide a novel therapeutic option to minimize AKI.
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- 2012
13. Beneficial Effects of Tonsillectomy for Mesangial Immunoglobulin A (IgA) Deposition and Clinical Outcome in Five Kidney Transplant Patients With Recurrent IgA Nephropathy: Case Report
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Y. Fan, Naotsugu Ichimaru, Masayoshi Okumi, Y. Wang, Jun-ya Kaimori, Masahiro Kyo, S. Takahara, Norio Nonomura, and Yoichi Kakuta
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Adult ,Male ,Immunoglobulin A ,medicine.medical_specialty ,Pathology ,medicine.medical_treatment ,urologic and male genital diseases ,Gastroenterology ,Nephropathy ,chemistry.chemical_compound ,Internal medicine ,Biopsy ,medicine ,Humans ,Kidney transplantation ,Tonsillectomy ,Transplantation ,Creatinine ,Proteinuria ,medicine.diagnostic_test ,biology ,business.industry ,Glomerulonephritis, IGA ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Glomerular Mesangium ,Treatment Outcome ,chemistry ,biology.protein ,Female ,Surgery ,medicine.symptom ,Antibody ,business - Abstract
Introduction Tonsillectomy has been applied for recurrent immunoglobulin (Ig)A nephropathy (IgAN) in kidney transplantation recipients, but allograft histologic changes after this treatment remain unclear. Methods Five patients with recurrent IgAN underwent tonsillectomy for persistent proteinuria (average, 397.2 mg/d; >6 months). Six repeated biopsies were taken 33.8 ± 17.1 months after treatment. Glomerular IgA deposition was detected by immunofluorescence staining on frozen tissue. Histologic and clinical data have been collected. Results An average of 11.2 months (range, 6–20) after tonsillectomy, proteinuria decreased to 60.8 ± 49.3 mg/d. Serum creatinine (SCr) slightly decreased (1.33 ± 0.31 before vs 1.24 ± 0.29 after treatment; P > .05). In 5 of the 6 repeated biopsy samples month after tonsillectomy, there was decreased mesangial IgA deposition. Glomerular crescent and endothelial proliferation were no longer found, although there was increased focal sclerosis and adhesion. After tonsillectomy, there were increased interstitial fibrosis and tubular atrophy, with no significant differences in Banff scores. Conclusions Tonsillectomy can reverse not only persistent proteinuria, but also mesangial IgA deposition in patients with recurrent IgAN. Tonsillectomy may have both favorable clinical and histologic effects in recurrent IgAN after kidney transplantation.
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- 2014
14. Induction of Glia Maturation Factor-β in Proximal Tubular Cells Leads to Vulnerability to Oxidative Injury through the p38 Pathway and Changes in Antioxidant Enzyme Activities
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Takeshi Sugaya, Kousaku Okubo, Hideaki Nakajima, Masaru Horio, Enyu Imai, Masatsugu Hori, Takahito Ito, Masaru Takenaka, Takayuki Hamano, and Jun-ya Kaimori
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Time Factors ,Apoptosis ,Kidney ,medicine.disease_cause ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,Antioxidants ,Mice ,chemistry.chemical_compound ,Annexin A5 ,Coloring Agents ,In Situ Hybridization ,chemistry.chemical_classification ,Microscopy, Confocal ,Caspase 3 ,Angiotensin II ,Glutathione peroxidase ,Brain ,3T3 Cells ,Flow Cytometry ,Cell biology ,Kidney Tubules ,Caspases ,Tumor necrosis factor alpha ,Mitogen-Activated Protein Kinases ,Glia Maturation Factor ,Programmed cell death ,Cell Survival ,Glia maturation factor ,Biology ,Transfection ,Models, Biological ,medicine ,Animals ,Molecular Biology ,Glutathione Peroxidase ,L-Lactate Dehydrogenase ,Superoxide Dismutase ,Tumor Necrosis Factor-alpha ,Lasers ,Hydrogen Peroxide ,Cell Biology ,Glutathione ,Blotting, Northern ,Actins ,Mice, Inbred C57BL ,Oxygen ,Oxidative Stress ,chemistry ,Oxidative stress - Abstract
Proteinuria is an independent risk factor for progression of renal diseases. Glia maturation factor-beta (GMF-beta), a 17-kDa brain-specific protein originally purified as a neurotrophic factor from brain, was induced in renal proximal tubular (PT) cells by proteinuria. To examine the role of GMF-beta in PT cells, we constructed PT cell lines continuously expressing GMF-beta. The PT cells overexpressing GMF-beta acquired susceptibility to cell death upon stimulation with tumor necrosis factor-alpha and angiotensin II, both of which are reported to cause oxidative stress. GMF-beta overexpression also promoted oxidative insults by H2O2, leading to the reorganization of F-actin as well as apoptosis in non-brain cells (not only PT cells, but also NIH 3T3 cells). The measurement of intracellular reactive oxygen species in the GMF-beta-overexpressing cells showed a sustained increase in H2O2 in response to tumor necrosis factor-alpha, angiotensin II, and H2O2 stimuli. The sustained increase in H2O2 was caused by an increase in the activity of the H2O2-producing enzyme copper/zinc-superoxide dismutase, a decrease in the activities of the H2O2-reducing enzymes catalase and glutathione peroxidase, and a depletion of the content of the cellular glutathione peroxidase substrate GSH. The p38 pathway was significantly involved in the sustained oxidative stress to the cells. Taken together, the alteration of the antioxidant enzyme activities, in particular the peroxide-scavenging deficit, underlies the susceptibility to cell death in GMF-beta-overexpressing cells. In conclusion, we suggest that the proteinuria induction of GMF-beta in renal PT cells may play a critical role in the progression of renal diseases by enhancing oxidative injuries.
- Published
- 2003
15. Gene expression profile of renal proximal tubules regulated by proteinuria
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Yasuyuki Nagasawa, Kousaku Okubo, Masaru Takenaka, Atsushi Kosugi, Jun-ya Kaimori, Enyu Imai, Masatsugu Hori, Shouko Kawamoto, and Hideaki Nakajima
- Subjects
Male ,T-Lymphocytes ,Kidney Tubules, Proximal ,Mice ,Gene expression ,Antigens, Ly ,tubulointerstitial fibrosis ,Osteopontin ,Laser capture microdissection ,Kidney ,education.field_of_study ,Chromosome Mapping ,progressive renal disease ,Up-Regulation ,Proteinuria ,medicine.anatomical_structure ,thymic shared antigen-1 ,Nephrology ,laser microdissection ,Female ,Nephritis ,medicine.medical_specialty ,Lipoproteins ,Molecular Sequence Data ,Population ,Biology ,Avian Proteins ,proximal tubule ,Internal medicine ,medicine ,Extracellular ,Animals ,Humans ,Amino Acid Sequence ,RNA, Messenger ,education ,Base Sequence ,Gene Expression Profiling ,Membrane Proteins ,Proteins ,Ly-6 ,medicine.disease ,LR8 ,Molecular biology ,Mice, Inbred C57BL ,Gene expression profiling ,Disease Models, Animal ,Endocrinology ,gene expression ,biology.protein ,Nephritis, Interstitial - Abstract
population [8]. In experimental in vivo models of proMethod. Gene expression profiles were constructed by teinuria, repeated intravenous injections of albumin have means of direct sequencing procedures to identify genes in- been shown to increase permeability of the glomerular duced in the mouse kidney proximal tubules (PT) exposed to barrier and cause proteinuria [9, 10]. These events are proteinuria. followed by tubular changes accompanying infiltration Results. By comparing the gene expression of control PT to that of disease model PT, the abundantly expressed genes in of macrophages and T lymphocytes into the kidney [9]. control PT were down-regulated presumably because of poten- Consequently, interstitial inflammation could trigger fitially toxic effects of proteinuria. From the more than 1000 broblast proliferation and accumulation of extracellular up-regulated genes, an immunity related gene, thymic shared matrix proteins, which may facilitate the progression of antigen-1 (TSA-1), and a novel gene, GS188, were selected for further characterization. The increased expression of TSA-1, renal disease. Several factors, including osteopontin [11], a member of the Ly-6 family, and of GS188 in response to intercellular adhesion molecule-1 (ICAM-1), vascular proteinuria was confirmed by Northern analysis, immunohisto- cellular adhesion molecule-1 (VCAM-1), transforming chemistry, in situ hybridization and laser microdissection along growth factor-1 (TGF-1) [12] and monocyte chemoatwith real-time PCR analysis. Full length cloning of GS188 iden- tractant protein-1 (MCP-1) [13], have been shown to tified it as a family member of LR8 that was reported to express predominantly in fibroblasts. play important roles in causing renal damage. Conclusions. The gene expression profiles showed that the In vitro experiments, proximal tubular cells (PT) with expression patterns in PT were changed dramatically by pro- protein overload were found to activate the transcription teinuria. The profiles include novel genes that should be further of a number of genes encoding vasoactive and inflamcharacterized to aid the understanding of the pathophysiology matory molecules that have potentially toxic effects on of progressive kidney diseases.
- Published
- 2002
16. Effect of amygdala lesion on learning behavior in mice
- Author
-
Nobuyoshi Nishiyama, Jun-ya Kaimori, Yuriko Nomura, Akane Ishihara, Hiroshi Saito, and Ken Takashina
- Subjects
Pharmacology ,Lesion ,medicine.anatomical_structure ,business.industry ,Medicine ,medicine.symptom ,business ,Amygdala ,Neuroscience ,Learning behavior - Published
- 1992
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