Joichi Usui

University of Tsukuba, Tsukuba, Ibaraki, Japan

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Publications (46)126.97 Total impact

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    ABSTRACT: Pulmonary involvement is one of the hallmark lesions of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) as well as rapidly progressive glomerulonephritis (RPGN). However, the pulmonary involvement of AAV patients seems to differ between Europe and Japan, as does the ANCA serotype. This retrospective and prospective multicenter cohort study collected the clinical data of the features and outcomes of 1772 RPGN patients treated from 1989 to 2007 in Japan. Based on this nationwide RPGN survey, we analyzed the cases of 1147 AAV patients. We found that 52.3% of the AAV patients had pulmonary involvements: 15.4% of the AAV patients had alveolar hemorrhage (AH), 26.2% had interstitial lung disease (ILD), 2.8% had bronchial asthma, 2.4% had pulmonary granuloma and 12.8% had a chest X-ray abnormality without AH, ILD or pulmonary granuloma. Patient survival was significantly different among the following six groups: the 5-year survival rate was 41.5% in the patients with AH, 50.2% in those with ILD, 67.9% in those with bronchial asthma, 62.5% in those with pulmonary granuloma, 55.8% in those with chest X-ray abnormality and 73.3% in those without pulmonary involvement. AH was one of the predictors of 1- and 5-year mortality for patient survival in AAV, and ILD was added as one of the predictors of 5-year mortality. In these AAV patients, not only AH but also ILD was frequently observed. AH was associated with the prognosis, but ILD was associated with the long-term prognosis of AAV. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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    ABSTRACT: Capillary permeability is a tightly regulated feature of microcirculation in all organ beds; however, in sepsis this feature is fundamentally altered. Several molecules are investigated as associated factors with capillary permeability and vascular endothelial (VE)-cadherin internalization by vascular endothelial growth factor (VEGF)-induced signaling through VEGF receptors leads to increased vascular endothelial cell detachment and trans-endothelial permeability. We investigated serum soluble VE-cadherin levels in septic patients. An enzyme-linked immunoassay was used to measure serum soluble VE-cadherin levels in 47 septic patients treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX). The serum soluble VE-cadherin level of septic patients before PMX-DHP was 3424.1 ± 2033.0 ng/mL, which was significantly lower than that of the controls (5862.0 ± 1521.2 ng/mL; P < 0.0001). The time course of serum soluble VE-cadherin levels remained unchanged during PMX-DHP therapy. There was no significant difference in serum soluble VE-cadherin levels before PMX-DHP therapy between survivors and non-survivors, and there was no significant difference in those levels between the groups at any time after the initiation of PMX-DHP therapy. There was no correlation between soluble VE-cadherin levels and clinical data, except white blood cell count (r = −0.277, P = 0.0009). There was no correlation between soluble VE-cadherin levels and the levels of angiopoietin 1 and 2. In summary, the relationship between VE-cadherin and capillary permeability in sepsis could not be demonstrated. Soluble VE-cadherins are not reflected in the balance between intercellular junction plasticity and integrity, but VE-cadherin stabilization by its phosphorylation or internalization may be associated with capillary permeability.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 06/2014; 18(3). DOI:10.1111/1744-9987.12215 · 1.53 Impact Factor
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    ABSTRACT: Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis characterized by the deposition of IgA immune complexes in the glomerular region. The cause of IgAN is unknown, but multiple mechanisms have been suggested. We previously reported a rare case of mesangioproliferative glomerulonephritis in a patient with monoclonal immunoglobulin deposition disease associated with monoclonal IgA1. In this study, we performed the detailed analyses of serum IgA1 from this patient in comparison with those from patients with mIgA plasma cell disorder without renal involvement and healthy volunteers. We found unusual polymerization of IgA1 with additional N-glycosylation distinctive in this patient, which was different from known etiologies. Glycan profiling of IgA1 by the lectin microarray revealed an intense signal for Wisteria floribunda agglutinin (WFA). This signal was reduced by disrupting the native conformation of IgA1, suggesting that the distinct glycan profile was reflecting the conformational alteration of IgA1, including the glycan conformation detected as additional N-glycans on both the heavy and light chains. This unusually polymerized state of IgA1 would cause an increase of the binding avidity for lectins. WFA specifically recognized highly polymerized and glycosylated IgA1. Our results of analysis in the rare case of a patient with monoclonal immunoglobulin deposition disease suggest that the formation of unusually polymerized IgA1 is caused by divergent mechanisms including multiple structural alterations of glycans, which contributes to IgA1 deposition and mesangium proliferation.
    PLoS ONE 03/2014; 9(3):e91079. DOI:10.1371/journal.pone.0091079 · 3.53 Impact Factor
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    ABSTRACT: Chronic kidney disease (CKD) is a major global problem and is also associated with a decreased health-related quality of life (HRQOL). The aim of this study was to evaluate measured HRQOL based on the new CKD classification including proteinuria stage, and the effect of measured HRQOL on CKD progression and clinical outcomes over a 3-year period. EuroQol (EQ-5D), a generic preference-based questionnaire, was administered to 537 CKD outpatients at the University of Tsukuba Hospital between November and December 2008. We evaluated disease progression in CKD patients including the incidence of end-stage kidney disease (ESKD), cardiovascular disease (CVD) and all-cause mortality over a 3-year follow-up period. The proportions progressing to the higher stages were 32.6, 20.0, 36.6, 39.5, and 45.8 % from glomerular filtration rate (GFR) stages (G) 1-4, respectively. The proportion progressing to ESKD (G5D) was 0.7 % from G2, 3.9 % from G3b, 20.8 % from G4 and 63.4 % from G5. The incidence of CVD and/or death was 1.2, 4.6, 4.9, 5.3, 8.3 and 21.1 % from G1-G5, respectively. The quality-adjustment weights at G4-5 were significantly lower than at G1-2 and the weights at proteinuria stage (A) 3 were significantly lower than at A1-2. The quality-adjustment weights of patients with events such as 50 % estimated GFR decline, dialysis, CVD, and/or death were significantly lower than those without events. We showed CKD progression and clinical outcomes over a 3-year period. Quality-adjustment weights in CKD patients were associated with not only disease progression such as initiation of dialysis treatment and incidence of CVD events and all-cause death, but also the level of proteinuria at baseline.
    Clinical and Experimental Nephrology 11/2013; 18(5). DOI:10.1007/s10157-013-0901-x · 1.71 Impact Factor
  • Joichi Usui, Kunihiro Yamagata
    Nihon Naika Gakkai Zasshi 05/2013; 102(5):1128-35.
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    ABSTRACT: Objective Some angiotensin receptor blockers (ARBs), including irbesartan, increase the peroxisome proliferator-activated receptor (PPAR)-g activity in vitro. The aim of this study was to evaluate the interactions between obesity and the effects of irbesartan on inflammatory cytokines in chronic glomerulonephritis patients without diabetes. Methods The anti-inflammatory effects of irbesartan were evaluated in 29 hypertensive chronic glomerulonephritis patients without diabetes in a prospective, single-arm study. Results Following treatment with irbesartan for 26 weeks, blood pressure and proteinuria significantly decreased, as previously reported (blood pressure decreased from 142±1/87±1 to 131±1/81±1 mmHg and the urine protein/creatinine ratio decreased from 1,030±143 to 779±121 mg/g Cr). BMI did not significantly change after the study. Among the inflammatory parameters, the concentrations of adiponectin and high-sensitivity C-reactive protein (hsCRP) significantly improved after treatment; however, the changes in the concentrations of interleukin-6 (IL-6), tumor necrosis factor (TNF)-a and leptin did not reach statistical significance. Moreover, the changes in these five parameters following treatment were moderately correlated with the BMI values obtained at the initiation of the study, and the improvements were particularly prominent in those with a BMI greater than 25. Improvements in proteinuria were significantly correlated with increases in the adiponectin concentration, but not with BMI. There was also a moderate correlation between the changes in the adiponectin and insulin concentrations. Conclusion Irbesartan improves metabolic parameters in nondiabetic hypertensive chronic glomerulonephritis patients, especially those with a high BMI. Improving the adiponectin concentration may be important for reducing proteinuria.
    Internal Medicine 01/2013; 52(3):303-308. DOI:10.2169/internalmedicine.52.9066 · 0.97 Impact Factor
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    ABSTRACT: Renal involvement with significant organ damage is common in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). As a result, it is independently referred to ANCA-associated renal vasculitis. Clinically, ANCA-associated renal vasculitis is characterized by rapidly progressive glomerulonephritis. Pathologically, it is defined by pauci-immune type necrotizing and crescentic glomerulonephritis. According to previous reports from all over the world, the etiology, prevalence, and prognosis of RPGN including ANCA-associated renal vasculitis varies among races and periods. To elucidate the clinical characteristics of Japanese RPGN patients, a registry derived from a questionnaire survey was established in 1999 and maintained until 2006. As a result, 1,772 cases were collected, analyzed, and reported previously. In this mini-review, we outline the characteristic clinical findings of Japanese patients (Asian) with ANCA-associated renal vasculitis, based on the registry data.
    Clinical and Experimental Nephrology 12/2012; DOI:10.1007/s10157-012-0740-1 · 1.71 Impact Factor
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    ABSTRACT: Dysfunction of mitochondria in podocytes is believed to be a trigger of injury and contributes to progressive glomerular sclerosis; however, the mechanisms had not been fully understood. Yuan et al. report involvement of SIRT1 (a homolog of the life-extending gene sir2 in mammals) and PPAR-γ coactivator 1α, a major regulator of oxidative metabolism, in mitochondria during podocyte injury. This information will be important in exploration of the mechanisms and future treatment of glomerular sclerosis.
    Kidney International 10/2012; 82(7):735-6. DOI:10.1038/ki.2012.182 · 8.52 Impact Factor
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    ABSTRACT: BACKGROUND: A prolonged change in the rate of primary membranoproliferative glomerulonephritis (MPGN) was identified using a Japanese database of renal biopsies. METHODS: We retrospectively investigated 6,369 renal biopsies that were performed between 1976 and 2009. Primary MPGN patients were selected, and the clinical and pathological findings were examined. We also statistically analyzed the changing rate of the onset of primary MPGN according to each decade. RESULTS: Seventy-nine cases with primary MPGN (1.2 % of total biopsies) were diagnosed. The age of the patients ranged from 6-79 years (average 34.6 years). There were 24 children and 55 adults, including 37 male and 42 female patients. Thirty-six cases of primary MPGN (45.6 %) showed nephrotic syndrome-8 childhood and 28 adult cases. In the pathological classification of 44 samples using electron microscopy, 29 cases were MPGN type I, 1 case was MPGN type II, and 14 cases were MPGN type III. The secular change of the rate of primary MPGN onset showed a statistically significant reduction from the 1970s to the 2000s. The rate of primary MPGN onset in the child population also significantly decreased, but not in the adult population. Among the clinical parameters, disease severity and prognosis remained unchanged. Regarding treatment in recent years, steroid pulse therapy became more available but the administration of warfarin and anti-platelet drugs significantly decreased. CONCLUSION: We concluded that the rate of total primary MPGN and that of pediatric patients with primary MPGN decreased.
    Clinical and Experimental Nephrology 09/2012; DOI:10.1007/s10157-012-0690-7 · 1.71 Impact Factor
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    ABSTRACT: This study was conducted to standardize treatment and determine patient and renal outcome in Japanese anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis/rapidly progressive glomerulonephritis (AAV/RPGN) patients, because the prognosis of AAV/RPGN patients in Japan had been poor compared with that of other countries. The participants in this retrospective cohort study were 824 ANCA-positive RPGN patients, 705 of whom were only myeloperoxidase (MPO)-ANCA positive. Among the early-years cohort (group A; cases diagnosed between 1988 and 1998), patients frequently died due to opportunistic infection. Therefore, we recommended a reduced dose of prednisolone (oral prednisolone dose <0.8 mg/kg/day) with or without cyclophosphamide for initial treatment of Japanese RPGN patients. After this recommendation, 1-year survival of the patients improved: 75% in group A, 79% in group B (between 1999 and 2002), and 81% in group C (after 2003). During the entire observation period, average serum creatinine level at the start of treatment decreased, and improvement of 1-year renal survival was also found (72% in group A, 83% in group B, and 83% in group C), while the recurrence rate was significantly increased in group C (0.05/patient-year in group A, 0.07/patient-year in group B, and 0.13/patient-year in group C). Oral prednisolone dose <0.8 mg/kg/day with or without cyclophosphamide as an initial treatment could improve patient survival in older Japanese AAV/RPGN patients. However, maintenance treatment avoiding relapse should be established to improve renal outcomes.
    Clinical and Experimental Nephrology 02/2012; 16(4):580-8. DOI:10.1007/s10157-012-0598-2 · 1.71 Impact Factor
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    ABSTRACT: Renal involvement is a significant complication of multicentric Castleman's disease (MCD) and various glomerular involvements have been reported. A 45-year-old Japanese man presented with persistent proteinuria, with lymphadenopathy and hypergammaglobulinemia. He had been diagnosed 4 years previously with MCD. As his renal impairment had progressed to renal failure, he underwent a renal biopsy. Histology revealed diffuse and global membranous lesions with large and heterogeneous epimembranous deposits. In addition, mesangial cell proliferation and focal extracapillary lesions were found. Under immunofluorescence, granular staining for anti-IgG, IgG1, IgG2 and IgA was strongly positive in the capillary loop, and weakly positive in the mesangium. As such, there was a diversity of histological features. Our perspective with regard to pathogenesis is that the formation of the immune-complex contributed to the membranoproliferative glomerulonephritis type 3-like lesion. This histological multiform with MCD is valuable for increasing our understanding of the mechanism for onset of immune-complex glomerular deposition and cellular proliferation of glomerulonephritis.
    Pathology International 11/2011; 61(11):686-90. DOI:10.1111/j.1440-1827.2011.02727.x · 1.59 Impact Factor
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    ABSTRACT: Acute lung injury (ALI) in sepsis is characterized by an increase in microvascular permeability, resulting in pulmonary edema. Several studies have suggested that angiopoietin-1 and -2 play a contributory role in the pathogenesis of ALI. Polymyxin B-immobilized fiber column hemoperfusion is effective for sepsis-induced ALI. We investigated the angiopoietin levels before and after direct hemoperfusion with polymyxin B-immobilized fiber column (PMX) therapy. Enzyme-linked immunoassay was used to measure the serum angiopoietin-1 and -2 levels in 25 patients with septic shock treated with PMX. Eleven of the 25 patients were diagnosed with ALI. There was a significant positive correlation between the angiopoietin-1 level and the PaO(2) /FiO(2) ratio, but there was a significant inverse correlation between the angiopoietin-2 level and the PaO(2) /FiO(2) ratio. The mean angiopoietin-1 level before PMX therapy in the ALI group was significantly lower and the mean angiopoietin-2 level was significantly higher than in the non-ALI group. The mean angiopoietin-1 level of the ALI patients in response to PMX therapy was increased during PMX therapy, but that of the non-ALI patients with newly occurring ALI showed a decreased angiopoietin-1 level. On the other hand, the mean angiopoietin-2 level of the responders was decreased during PMX therapy, but that of patients with newly occurring ALI showed an increased angiopoietin-2 level. This result suggested that each angiopoietin-1 and -2 level may play a role in the pathogenesis of ALI and that PMX therapy ameliorates the angiopoietin balance in patients with ALI in sepsis.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 08/2011; 15(4):349-54. DOI:10.1111/j.1744-9987.2011.00963.x · 1.53 Impact Factor
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    ABSTRACT: We believe that bacterial-infection-associated glomerulonephritis (GN), so-called methicillin-resistant Staphylococcus aureus (MRSA)-GN, was exterminated in Japan. The control of bacterial infection is the most important part of infection-associated GN. In 1990s Japan, hospital-associated MRSA (HA-MRSA) caused MRSA-GN outbreaks. On the other hand, MRSA-GN incidence has been quite limited since 2000. This epidemiological transition suggests that antibacterial therapies and health programs for HA-MRSA infection in Japan were effective against MRSA-GN. Moreover, it appears that staphylococcal superantigens act in the pathogenesis of GN. The change of superantigen production might have influenced to the disappearance of MRSA-GN. If HA-MRSA-producing superantigen outbreaks occur in developing countries, our experience in Japan can provide guiding principles for preventing and eradicating GN.
    Clinical and Experimental Nephrology 11/2010; 15(1):184-6. DOI:10.1007/s10157-010-0369-x · 1.71 Impact Factor
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    ABSTRACT: Human hepatitis B virus (HBV) is well known as a cause of membranous nephropathy (MN). While the association of HBV infection with MN is strong, data regarding its association with other glomerular diseases are conflicting. Here, we report a case of focal segmental glomerulosclerosis (FSGS) with HBV infection. In this case, we have found HBV-DNA in urinary podocytes by real-time PCR methods. After the administration of anti-viral therapy, FSGS improved, paralleling the decreased level of HBV-DNA in podocytes. The refractory FSGS induced by HBV could be effectively treated with appropriate anti-viral agents.
    Nephrology Dialysis Transplantation 10/2010; 26(1):371-3. DOI:10.1093/ndt/gfq600 · 3.37 Impact Factor
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    ABSTRACT: A 38-year-old man was admitted to the hospital for the evaluation of proteinuria, microscopic hematuria, and monoclonal IgA-kappa gammopathy. The initial renal pathological findings showed mesangial proliferative glomerulonephritis with endocapillary proliferation, a necrotizing lesion, and cellular crescent formation accompanied by IgA1-kappa deposition in the mesangium. Neither typical immune-complex deposits nor organized-structure deposits were detected. We diagnosed the patient with monoclonal immunoglobulin deposition disease (MIDD) associated with monoclonal IgA (mIgA). After the initiation of a monthly treatment with melphalan and predonisolone (MP therapy), the patient's serum IgA levels declined, and clinical remission was ultimately achieved. The follow-up renal biopsy showed reduced IgA-kappa staining, and both the endocapillary proliferation and the necrotizing lesion had disappeared. To elucidate the mechanism of IgA deposition, we investigated the glycan profile of the patient's serum mIgA using a mass spectrometry technique. The results revealed an unusual N-glycan profile compared to that of another patient with circulating mIgA lacking renal involvement and that of a healthy control. mIgA deposition in the mesangial area is a rare disease, and the glycan profiling of MIDD with renal involvement has not been reported previously. Thus, the present case suggests that any variation in Ig glycosylation may be a step in the pathogenesis of MIDD with renal involvement and/or contribute to some cases of IgA nephropathy.
    Clinical and Experimental Nephrology 05/2010; 14(4):389-95. DOI:10.1007/s10157-010-0285-0 · 1.71 Impact Factor
  • NDT Plus 01/2010; 3(1):91-92. DOI:10.1093/ndtplus/sfp130
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    ABSTRACT: Capillary permeability is a tightly regulated feature of microcirculation in all organ beds; however, in sepsis this feature is fundamentally altered. We previously reported elevated levels of vascular endothelial growth factor and its receptor (fms-like tyrosine kinase-1) in patients with septic shock, then investigated two kinds of angiopoietins in those patients. An enzyme-linked immunoassay was used to measure serum angiopoietin-1 and -2 levels in 12 patients with septic shock who were treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX). The angiopoietin-1 level was lower in patients with septic shock (7.01 +/- 10.08 ng/mL) than in controls (28.24 +/- 11.61 ng/mL, P < 0.001), but the angiopoietin-2 level was higher in septic shock patients (40.83 +/- 30.13 ng/mL vs. 2.47 +/- 1.78 ng/mL, P < 0.001). Between seven survivors and five non-survivors there was no significant difference in angiopoietin-1 levels before DHP-PMX therapy. During DHP-PMX therapy, however, the angiopoietin-2 level was significantly decreased in survivors (31.52 +/- 26.15 ng/mL vs. 17.32 +/- 22.46 ng/mL, P = 0.035). Moreover, at the end of the therapy, the angiopoietin-1 level was significantly lower in non-survivors (1.14 +/- 1.30 ng/mL vs. 10.43 +/- 13.56 ng/mL, P = 0.042), but the angiopoietin-2 level in non-survivors was significantly higher (70.79 +/- 40.47 ng/mL vs. 17.32 +/- 22.46 ng/mL, P = 0.019). The angiopoietin-2 level may be associated with vascular permeability in septic patients, and angiopoietins may be suitable markers of disease severity and mortality.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 12/2009; 13(6):520-7. DOI:10.1111/j.1744-9987.2009.00777.x · 1.53 Impact Factor
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    ABSTRACT: To determine the cytokine balance in patients with lupus nephritis (LN), we analysed kidney-infiltrating T cells. Renal biopsy samples from 15 systemic lupus erythematosus (SLE) patients were used. In accordance with the classification of International Society of Nephrology/Renal Pathology Society, they were categorized into Class III, Class III+V (Class III-predominant group, n = 4), Class IV, Class IV+V (Class IV-predominant group, n = 7) and Class V (n = 4) groups. The single-cell samples of both the glomelular and interstitial infiltrating cells were captured by laser-microdissection. The glomerular and interstitial infiltrating T cells produced interleukin (IL)-2, IL-4, IL-10, IL-13 and IL-17 cytokines in the Class III-predominant, Class IV-predominant and Class V groups. Interferon-gamma was detected only in the glomeruli of the Class III-predominant and Class V group samples. The expression level of IL-17 was correlated closely with clinical parameters such as haematuria, blood urea nitrogen level, SLE Disease Activity Index scores in both glomeruli and interstitium, urine protein level in glomeruli and serum creatinine and creatinine clearance levels in interstitium. This suggests that the glomerular infiltrating T cells might act as T helper type 1 (Th1), Th2 and Th17 cells while the interstitial infiltrating T cells, act as Th2 and Th17 cells in the Class III-predominant and Class V groups. In contrast, both the glomerular and interstitial infiltrating T cells might act as Th2 and Th17 cells in the Class IV-predominant group. The cytokine balances may be dependent upon the classification of renal pathology, and IL-17 might play a critical role in SLE development.
    Clinical & Experimental Immunology 10/2009; 159(1):1-10. DOI:10.1111/j.1365-2249.2009.04031.x · 3.28 Impact Factor
  • Joichi Usui, Kunihiro Yamagata
    Nippon Jinzo Gakkai shi 02/2009; 51(2):78-83.
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    ABSTRACT: A 29-year-old man with malignant lymphoma developed membranous nephropathy (MN) after allogeneic bone-marrow transplantation (BMT). There had been no obvious findings of graft versus host diseases (GVHD) after BMT, and the dosage of immunosuppressant drugs had not been reduced during this period. At the onset of MN, a few lymphoma cells still remained in the bone marrow; the patient achieved complete remission of MN after the disappearance of the lymphoma cells. In this case it is suggested that immune complexes including antigens expressed by lymphoma cells might induce MN. Therefore, this is a significant case that may reveal an alternative mechanism of the onset of MN related to BMT.
    Clinical and Experimental Nephrology 01/2009; 13(2):174-8. DOI:10.1007/s10157-008-0120-z · 1.71 Impact Factor

Publication Stats

446 Citations
126.97 Total Impact Points


  • 1999–2015
    • University of Tsukuba
      • • Department of Neurology
      • • Institute of Clinical Medicine
      • • Institute of Basic Medical Sciences
      Tsukuba, Ibaraki, Japan
  • 2006–2008
    • The University of Tokyo
      • • Institute of Medical Science
      • • International Medical Center
      Tokyo, Tokyo-to, Japan