Mitsuyo Itabashi

Tokyo Women's Medical University, Edo, Tōkyō, Japan

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Publications (62)84.96 Total impact

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    ABSTRACT: Atypical hemolytic uremic syndrome (aHUS) in allograft kidney transplantation is caused by various factors including rejection, infection, and immunosuppressive drugs. We present a case of a 32 year old woman with aHUS four years after an ABO-incompatible kidney transplantation from a living relative. The primary cause of end-stage renal disease was unknown; however, IgA nephropathy (IgAN) was suspected from her clinical course. She underwent pre-emptive kidney transplantation from her 60 year old mother. The allograft preserved good renal function [serum creatinine (sCr) level 110-130 μmol/L] until a sudden attack of abdominal pain four years after transplant, with acute renal failure (sCr level, 385.3 μmol/L), decreasing platelet count, and hemolytic anemia with schizocytes. On allograft biopsy, there was thrombotic microangiopathy in the glomeruli, with a cellular crescent formation and mesangial IgA and C3 deposition. Microvascular inflammation, such as glomerulitis, peritubular capillaritis, and arteriole endarteritis were also detected. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) did not decrease and Shiga toxin was not detected. Donor-specific antibodies or autoantibodies, including anti-neutrophil cytoplasmic antibody and anti-glomerular basement membrane (anti-GBM) antibody, were negative. The patient was diagnosed with aHUS and received three sessions of plasmapheresis and methylprednisolone pulse therapy, followed by oral methylprednisolone (0.25-0.5 mg/kg) instead of tacrolimus. She temporarily required hemodialysis (sCr level, 658.3 μmol/L). Thereafter, her sCr level improved to 284.5 μmol/L without dialysis therapy. This case is clinically considered as aHUS after kidney transplantation, associated with various factors, including rejection, glomerulonephritis, and toxicity from drugs such as tacrolimus. © 2015 Asian Pacific Society of Nephrology.
    Nephrology 07/2015; 20 Suppl 2(S2):61-5. DOI:10.1111/nep.12465 · 1.86 Impact Factor
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    ABSTRACT: Endothelial dysfunction is often found in both hyperuricemia and hemodialysis patients. Recent studies have shown that treating hyperuricemia with allopurinol improves endothelial dysfunction. This study is performed to assess the effect of febuxostat on endothelial dysfunction in hemodialysis patients with hyperuricemia. We randomly assigned 53 hemodialysis patients with hyperuricemia to a febuxostat (10 mg daily) group and a control group and measured flow-mediated dilation, serum uric acid (UA) levels, systolic and diastolic blood pressure, malondialdehyde-modified low-density lipoprotein (MDA-LDL), and highly sensitive C-reactive protein (hsCRP) at baseline and at the end of a 4-week study period. Flow-mediated dilation increased from 5.3% ± 2.4% to 8.9% ± 3.6% in the febuxostat group but did not change significantly in the control group. Treatment with febuxostat resulted in a significant decrease in serum UA level and a significant decrease in MDA-LDL compared with baseline, but no significant difference was observed in hsCRP level or blood pressure. No significant differences were observed in the control group. Febuxostat improved endothelial dysfunction and reduced serum UA levels and oxidative stress in hemodialysis patients with hyperuricemia. © 2015 International Society for Hemodialysis.
    Hemodialysis International 06/2015; DOI:10.1111/hdi.12313 · 1.36 Impact Factor
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    ABSTRACT: Caveolae on human renal glomerular endothelial cells (HRGECs) are increased in glomerular disease and correlate with the degree of albuminuria. To assess the mechanism by which caveolae contribute to albuminuria, we investigated whether albumin enters into HRGECs through caveolae. HRGECs were incubated with Alexa Fluor 488 labeled BSA or transferrin, followed by immunofluorescence localization with antibody to caveolin-1 (Cav-1), the main structural protein of caveolae, or clathrin, the major structural protein of clathrin coated pits, to assess whether BSA colocalized with Cav-1. HRGECs were also incubated with albumin and caveolae disrupting agents, including methyl beta cyclodextrin (MBCD) and nystatin, to determine whether disrupting caveolae interfered with albumin endocytosis into HRGECs. HRGECs were also incubated with albumin after transfection with Cav-1 small interfering RNAs (siRNAs). Labeled BSA colocalized with Cav-1, but not with clathrin. In contrast, labeled transferrin colocalized with clathrin, but not with Cav-1. Incubation of HRGECs with MBCD or nystatin, or transfection with Cav-1 siRNA, significantly reduced the intracellular amounts of albumin and Cav-1, relative to normal HRGECs, as shown by western blotting and immunofluorescence. These findings indicate that albumin enters HRGECs through the caveolae, suggesting that caveolae play an important role in the pathogenesis of albuminuria by providing a pathway through which albumin can enter glomerular endothelial cells. This article is protected by copyright. All rights reserved
    Journal of Cellular Biochemistry 01/2015; 116(6). DOI:10.1002/jcb.25061 · 3.37 Impact Factor
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    ABSTRACT: A 48-year-old male was admitted to our hospital with nephrotic syndrome. Light-microscopic examination of a renal biopsy specimen showed almost normal glomerular appearance, however, immunofluorescence examination revealed linear and granular IgG deposits on the glomerular basement membrane (GBM), accompanied by slight IgG deposition in the tubular basement membrane (TBM). Further investigation of the IgG subclass and light chain staining revealed that the glomerular deposits were composed of IgG1 and IgG4, with both κ and λ light chains, while the tubular deposits were composed of only IgG4 and κ light chains. The electron-microscopic findings of small granular deposits in the GBM and TBM closely resembled those of light and heavy chain deposition disease (LHCDD). Immunoelectron microscopy confirmed the presence of κ and λ chains in the GBM and TBM, however, only significant κ chain deposition was found in the TBM. There was no evidence of monoclonal gammopathy. Clinically, the patient subsequently developed neutropenia and thrombocytopenia associated with the presence of anti-neutrophil antibody and anti-GPIIb/IIIa antibody-producing B cells in the blood. Oral steroid administration was initiated, which led to amelioration of the neutropenia, thrombocytopenia and proteinuria. This may be a very rare case of combined IgG4κ and IgG1λ deposition disease accompanied by autoimmune neutropenia (AIN) and immune thrombocytopenia (ITP) suggestive of biclonal immunoglobulin deposition disease (BIDD). Investigation of the IgG subclass and of the light chains was useful for recognizing the clonality of the immunoglobulin deposits in the kidney.
    01/2015; DOI:10.1007/s13730-015-0170-5
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    ABSTRACT: This study was to evaluate the long-term efficacy and safety of a single-dose rituximab regimen rituximab treatment in adult patients with steroid-dependent minimal change nephrotic syndrome (MCNS).We conducted a prospective cohort study with historical controls to evaluate the effect of single-dose infusions of rituximab at 375 mg/m BSA per dose administered at intervals of 6 months for a period of 24 months. At the end of the 24-month period, the patients were divided into the treatment continuation (n = 20) and treatment discontinuation (n = 5) groups according to their intention to continue/discontinue the treatment.A significant reduction in the total number of relapses was observed during the 24-month period after the first rituximab infusion as compared with that during the 24-month period before the first rituximab infusion (108 vs. 8, P < 0.001). Complete remission was induced/maintained in all patients from 12 to 24 months after the first rituximab infusion. In regard to the clinical course after 24 months, 4 of the 20 patients in the treatment continuation group discontinued the rituximab treatment after the fifth infusion and 2 patients discontinued the treatment after the sixth infusion. However, complete remission was maintained in all the 20 patients of this group during the 12-month observation period after the first four single-dose rituximab infusions. On the other hand, 1 of the 5 patients in the treatment discontinuation group developed relapse during the observation period after the first four rituximab infusions, and the rituximab treatment was resumed.In our trial, rituximab therapy was associated with maintenance of complete remission. Complete remission was maintained even in most of the patients who showed B-cell repletion after discontinuation of rituximab therapy. Thus, rituximab may be considered as a radical therapeutic agent for patients with steroid-dependent MCNS.
    Medicine 12/2014; 93(29):e300. DOI:10.1097/MD.0000000000000300 · 4.87 Impact Factor
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    ABSTRACT: The susceptible age for IgA nephropathy (IgAN) is < 30 years. However, IgAN sometimes develops in people aged > 60 years, and its characteristics remain unknown. We divided 600 IgAN patients into three groups: advanced-age group (AAG, n = 31, a parts per thousand yen60 years); middle-aged group (MAG, n = 162, 40-59 years); and young-aged group (YAG, n = 407, 20-39 years). We analyzed clinical and histological background, renal outcome, and risk of progression. In the AAG, mean arterial pressure (MAP) and the number of hypertensive patients were significantly higher than in the YAG. Total protein, serum albumin, and estimated glomerular filtration rate were significantly lower, and blood urea nitrogen, proteinuria, and N-acetyl-beta-d-glucosaminidase were significantly higher in the AAG than in MAG and YAG. In histological findings, interstitial fibrosis/tubular atrophy by Oxford classification and arteriosclerosis were more severe in the AAG than the in YAG. Renal survival rate analyzed by Kaplan-Meier method was significantly lower in the AAG (22.9 %/19 years in the AAG vs. 69.2 and 84.9 %/20 years in the MAG and YAG, p < 0.0001). The patients who progressed to end-stage renal disease (ESRD) in the AAG had higher MAP and more severe proteinuria compared with the patients who did not progress to ESRD in the AAG. The characteristics of IgAN in advanced-age were lower renal function, high levels of proteinuria, severe interstitial change, and arteriolosclerosis caused by glomerulopathy and concomitant diseases, such as hypertension, dyslipidemia, and hyperuricemia. Prognosis was poor, and > 70 % developed ESRD within 20 years.
    International Urology and Nephrology 11/2014; 47(1). DOI:10.1007/s11255-014-0872-1 · 1.29 Impact Factor
  • Orie Hirose, Mitsuyo Itabashi, Takashi Takei, Kosaku Nitta
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    ABSTRACT: Background. Myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (ANCA) represents the serological hallmark of ANCA-associated vasculitis (AAV). We evaluated the analytical and diagnostic accuracy of chemiluminescence enzyme immunoassay (CLEIA) versus enzyme-linked immunosorbent assay (ELISA) for the detection of MPO-ANCA. Methods. A total of 242 sera obtained from 51 patients with AAV and 103 patients without AAV were tested for MPO-ANCA by ELISA (NephroScholor MPOANC II) and CLEIA (the STACIA MEBLux test). Disease activity in the patients with AAV was determined based on the Birmingham Vasculitis Activity Score. We analyzed the correlations between the MPO-ANCA titers determined by the CLEIA and those determined by the ELISA, and also between the MPO-ANCA titers and the disease activity. Results. The MPO-ANCA titers determined by the CLEIA (x) were strongly correlated with those determined by the ELISA (y). The correlation could be expressed by the following equation in this study: y = 1.8x + 7.7 (r = 0.96; p < 0.0001). At the cutoff value of 3.5 U/ml, the CLEIA yielded positive test results for MPO-ANCA in 73 of the 242 sera (30.2%), while at the cutoff value of 20 U/ml, ELISA yielded positive test results in 57 of the 242 sera (23.6%). The CLEIA yielded false-positive test results in 4 of the 120 sera obtained from the non-AAV patients (3.3%), whereas the ELISA yielded a false-positive result in only 1 of the 120 sera obtained from the non-AAV patients (0.8%). The sensitivity and specificity of the CLEIA for the diagnosis of AAV were 100% and 96.7%, respectively, while those of the ELISA were 94.3% and 99.2%, respectively. The sensitivity and specificity of the CLEIA for the prediction of active disease were 100% and 64.4%, respectively, while those of the ELISA were 94.3% and 73.6%, respectively. Conclusion. The false positivity rate of the CLEIA for MPO-ANCA tended to be high as compared with that of the ELISA. Also, according to the correlation coefficient between the results of the CLEIA and the ELISA calculated in this study, it is necessary to pay attention to the differences in the sensitivity and specificity between CLEIA and ELISA.
    Modern Rheumatology 11/2014; 25(2):1-5. DOI:10.3109/14397595.2014.951113 · 2.21 Impact Factor
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    ABSTRACT: High uric acid level is a known risk factor for deterioration of renal function in chronic kidney disease (CKD), but its influence on the progression of IgA nephropathy (IgAN) remains unclear.
    Journal of nephrology 10/2014; DOI:10.1007/s40620-014-0154-0 · 2.00 Impact Factor
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    ABSTRACT: Hyperuricemia is a frequent complication of chronic kidney disease (CKD). Febuxostat is a novel xanthine oxidase inhibitor that is metabolized by many metabolic pathways in the kidney and the liver. We performed a 1-year cohort study of 73 hyperuricemic patients who had an estimated glomerular filtration rate (eGFR) below 45 ml/min and were being treated with urate-lowering therapy. In 51 patients, treatment was changed from allopurinol to febuxostat, and the other 22 patients were continued on allopurinol. The serum levels of uric acid (UA) level, creatinine, and other biochemical parameters were measured at baseline and after 3, 6, 9, and 12 months of treatment. The serum UA levels significantly decreased from 6.1 ± 1.0 to 5.7 ± 1.2 mg/dl in the febuxostat group and significantly increased from 6.2 ± 1.1 to 6.6 ± 1.1 mg/dl in the allopurinol group. The eGFR decreased 27.3 to 25.7 ml/min in the febuxostat group and from 26.1 to 19.9 ml/min in the allopurinol group. The switch from allopurinol to febuxostat was significantly associated with the changes in eGFR according to a multiple regression analysis (β = -0.22145, P < 0.05). Febuxostat reduced the serum UA levels and slowed the progression of renal disease in our CKD cohort in comparison with allopurinol.
    Clinical Rheumatology 07/2014; 33(11). DOI:10.1007/s10067-014-2745-5 · 1.77 Impact Factor
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    ABSTRACT: Little is known about the long-term prognosis of patients with IgA nephropathy (IgAN). This retrospective cohort analysis evaluated clinical and histological findings at the time of renal biopsy, initial treatment, patient outcomes over 30 years, and risk factors associated with progression in 1,012 patients diagnosed with IgAN at our center since 1974. Of the 1,012 patients, 40.5% were male. Mean patient age was 33±12 years and mean blood pressure was 122±17/75±13 mmHg. Mean serum creatinine concentration was 0.89±0.42 mg/dL, and mean estimated glomerular filtration rate (eGFR) was 78.5±26.2 ml/min/1.73 m2. Mean proteinuria was 1.19±1.61 g/day, and mean urinary red blood cells were 36.6±35.3/high-powered field. Histologically, mesangial hypercellularity was present in 47.6% of patients, endothelial hypercellularity in 44.3%, segmental sclerosis in 74.6%, and tubular atrophy/interstitial fibrosis in 28.8% by Oxford classification. Initial treatment consisted of corticosteroids in 26.9% of patients, renin-angiotensin-aldosterone system inhibitor in 28.9%, and tonsillectomy plus steroids in 11.7%. The 10-, 20-, and 30-year renal survival rates were 84.3, 66.6, and 50.3%, respectively. Tonsillectomy plus steroids dramatically improved renal outcome. Cox multivariate regression analysis showed that higher proteinuria, lower eGFR, and higher uric acid at the time of renal biopsy were independent risk factors for the development of end stage renal disease (ESRD). IgAN is not a benign disease, with about 50% of patients progressing to ESRD within 30 years despite treatment.
    PLoS ONE 03/2014; 9(3):e91756. DOI:10.1371/journal.pone.0091756 · 3.53 Impact Factor
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    ABSTRACT: Abstract Background: The renoprotective pleiotropic effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has recently been reported by several investigators. However, the effect of statins on IgA nephropathy (IgAN) is still unknown. Methods: We selected 24 IgAN patients who had newly started statin therapy and were not treated with steroids and immunosuppressive agents during the observation period. We analyzed and compared clinical findings 1 year before and after treatment. Results: Mean age was 50.5 ± 9.91 years and mean blood pressure was 90.9 ± 10.8 mmHg. Renal function was slightly deteriorated, serum creatinine was 1.03 (0.71-1.24) mg/dL and estimated glomerular filtration rate (eGFR) was 55.8 ± 22.8 mL/min. Lipid metabolism was poorly controlled [total cholesterol 247.7 ± 35.7 mg/dL, low-density lipoprotein cholesterol 151.5 (140.8-172.8) mg/dL, and triglyceride 163.0 (126.3-243.8) mg/dL]. Mild urinary abnormality was observed [proteinuria: 0.50 (0.22-1.29) g/g creatinine, urinary red blood cells 1.0 (0.2-5.0) per high power field]. After 1 year of statin treatment, lipid control was significantly better than at baseline. Proteinuria was not significantly decreased but renal function was improved. eGFR changed from a -5.9% decrease to a 2.4% increase (p = 0.0098). Conclusion: Our results indicated that statins stabilized the renal function of IgAN patients independent of their reduction of proteinuria.
    Renal Failure 12/2013; 36(3). DOI:10.3109/0886022X.2013.866512 · 0.78 Impact Factor
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    ABSTRACT: Antineutrophil cytoplasmic autoantibody (ANCA) directed against myeloperoxidase (MPO), a diagnostic criterion in MPO-ANCA-associated vasculitis (MPO-AAV), does not always correlate with disease activity. Here, we detected autoantibodies against moesin, which was located on the surface of stimulated endothelial cells, in the serum of patients. The anti-moesin autoantibody titer was evaluated by ELISA. Seventeen kinds of cytokines/chemokines were measured by a Bio-Plex system. Serum creatinine in the anti-moesin autoantibody-positive group was higher than that in the negative group. Additionally, interferon (IFN)-γ, macrophage chemotactic peptide-1 (MCP-1), interleukin (IL)-2, IL-7, IL-12p70, IL-13, granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor were significantly higher in the positive group. Furthermore, IL-7 and IL-12p70 levels correlated with the anti-moesin autoantibody titer. Based on these findings and the binding of anti-moesin IgG to neutrophils and monocytes, we detected the secretion of cytokines/chemokines such as IFN-γ, MCP-1 and GM-CSF from these cells. The anti-moesin autoantibody existed in the serum of patients with MPO-AAV and was associated with the production of inflammatory cytokines/chemokines targeting neutrophils with a cytoplasmic profile, which suggests that the anti-moesin autoantibody has the possibility to be a novel autoantibody developing vasculitis via neutrophil and endothelial cell activation.
    Nephrology Dialysis Transplantation 12/2013; DOI:10.1093/ndt/gft469 · 3.49 Impact Factor
  • La Presse Médicale 04/2013; 42(4):667. DOI:10.1016/j.lpm.2013.02.040 · 1.17 Impact Factor
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    ABSTRACT: OBJECTIVES: The Vasculitis Damage Index (VDI) is used to define the degree of damage occurring in patients with systemic vasculitis. We conducted a retrospective study of 30 patients with microscopic polyangiitis (MPA) and renal-limited vasculitis (RLV). METHODS: The clinical data and VDI of the 30 patients enrolled in the study were collected and assessed for a period of 5 years. RESULT: The VDI score, which was 2.5 at 1 year after the initial diagnosis, increased gradually to 4.3 at 5 years post-diagnosis. The degrees of musculoskeletal and ocular damage significantly increased during the 5-year period (p = 0.001 and p = 0.002, respectively). The most frequent damage items in the VDI were cataract (13 %), hypertension (12 %), diabetes mellitus (9 %), and osteoporosis (6 %). The VDI score was significantly higher in the groups of patients who showed relapse or MPA than in the groups of patients who did not show relapse or RLV at 5 years (p = 0.02 and p = 0.03, respectively). In addition, a significant correlation was found between the VDI score at 5 years and the Birmingham Vasculitis Activity Score at diagnosis (p = 0.04, r = 0.4). CONCLUSION: The VDI was found to be a useful tool for determining the severity of damage caused by disease and the effects of treatment. The individual contributions of the VDI items may also be applied to treatment decisions.
    Modern Rheumatology 01/2013; 24(1). DOI:10.1007/s10165-012-0829-0 · 2.21 Impact Factor
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    ABSTRACT: Objective The beneficial effects of renin-angiotensin-aldosterone system inhibitors (RASI) and the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on IgA nephropathy (IgAN) have been reported. However, it is unknown whether these agents have any synergistic interactions. Methods We divided 38 IgAN patients into two groups: an EPA group (n=18) treated with RASI plus EPA and a DILAZEP group (n=20) treated with RASI plus dilazep dihydrochloride. We analyzed the clinical and histological background of each patient, any relevant clinical findings obtained one year after treatment and any factors significantly related to decreases in proteinuria. Results The clinical findings were largely similar between the groups, except for body mass index (24.9±4.5 in the EPA group vs. 21.4±2.1 in the DILAZEP group, p=0.0041) and total cholesterol (median: 206.0 vs. 177.5 mg/dL, p=0.0493). The histological findings, evaluated according to the Oxford classification, were also similar between the groups. At one year after treatment, the EPA group demonstrated a significantly decreased mean blood pressure (from 94.7±9.0 to 86.4±7.2 mmHg, p=0.0007) and a significantly decreased median level of proteinuria (from 0.80 to 0.41 g/g creatinine, p<0.001). In the DILAZEP group, the mean blood pressure significantly decreased (from 95.2±13.2 to 88.1±7.7 mmHg, p<0.001) without any significant decrease in the median level of proteinuria (from 0.88 to 0.60 g/g creatinine). According to a multivariate logistic analysis, EPA was found to be the only independent factor related to decreases in proteinuria (odds ratio = 5.073, 95% CI: 1.18-26.7, p=0.0285). Conclusion We conclude that EPA accelerates the effects of RASI and thus decreases the proteinuria observed in patients with IgAN.
    Internal Medicine 01/2013; 52(2):193-9. DOI:10.2169/internalmedicine.52.8323 · 0.97 Impact Factor
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    ABSTRACT: Objective IgA nephropathy (IgAN) is widely regarded as a slowly progressive disease. However, a minor population of patients present with a rapidly progressive form of glomerulonephritis (RPGN). Methods We studied 25 cases of IgAN who presented with RPGN. The laboratory data, histology, and five-year prognosis after diagnostic renal biopsy were evaluated. We compared the data of these patients with those of 495 patients with the non-RPGN type. In addition, we divided the patients with the RPGN type of IgAN into a group with reduced renal function and a group with maintained renal function, and compared the data between the two groups. Results In the 'RPGN type', the serum creatinine levels and a 24-hour urinary protein excretion were significantly higher than in the non-RPGN type. Histological examinations showed that the rates of endocapillary hypercellularity and tubular atrophy/interstitial fibrosis were significantly higher in the patients with the RPGN type. In the comparison between the groups with reduced and maintained renal functions, the former group exhibited higher levels of proteinuria, serum creatinine and crescent formation than the latter group. Conclusion The RPGN type of IgAN was significantly worse in terms of the renal survival rate at five years than the non-RPGN type. Intensive and active treatments are necessary for this minor population, according to the guideline for the management of RPGN.
    Internal Medicine 01/2013; 52(22):2489-94. DOI:10.2169/internalmedicine.52.0420 · 0.97 Impact Factor
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    ABSTRACT: The prognostic value of renal biopsy in anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis is widely recognized; however, there is no consensus regarding its pathological classification. Berden et al. proposed a new classification of glomerulonephritis in ANCA-associated vasculitis (AAV) categorized into focal, crescentic, mixed, and sclerotic classes and showed its prognostic value in 100 international multicenter cohorts for 1- and 5-year renal outcomes. In order to evaluate whether this new classification has predictive value and reproducibility in Japanese AAV cases, 87 cohorts with only microscopic polyangiitis in 3 limited centers in Japan were analyzed. In addition, those from Japan, Europe (Berden's cohorts) and China were compared in a recent report.
    Clinical and Experimental Nephrology 12/2012; 17(5). DOI:10.1007/s10157-012-0755-7 · 1.71 Impact Factor
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    ABSTRACT: Background Steroid-dependent minimal-change nephrotic syndrome (MCNS) requires administration of prolonged courses of prednisolone (PSL); therefore, a paradigm shift from such toxic 'non-specific' therapies to selective immunomodulating regimens is necessary for these cases.Methods To assess the therapeutic effects of rituximab (an anti-CD20 antibody) in adult patients with steroid-dependent MCNS, we performed a prospective trial of the effects of a single dose of rituximab administered twice at an interval of 6 months in 25 MCNS patients. We evaluated the biochemical parameters and compared the clinical findings between the 12-month period before and 12-month period after the first rituximab infusion.ResultsA significant reduction in the number of relapses and the total dose and the maintenance dose of PSL administered was observed during the 12-month period after the first rituximab infusion when compared with the findings during the 12-month period before the first rituximab infusion [25 (100%) versus 4 (16%), P < 0.001; 8.2 versus 3.3 g, P < 0.001; 26.4 mg/day at baseline versus 1.1 mg/day at 12-month, P < 0.0001]. Complete remission was achieved/maintained in all patients undergoing B-cell depletion. Four of 17 patients with B-cell repletion developed relapse.Conclusions Our results revealed that rituximab therapy was associated with a reduction in the number of relapses and in the total dose of PSL needed. Therefore, rituximab appears to be a useful therapeutic agent for adult patients with steroid-dependent MCNS. These results suggest that this treatment is rational and should be considered as an important option in the management of adult patients with steroid-dependent MCNS.
    Nephrology Dialysis Transplantation 12/2012; DOI:10.1093/ndt/gfs515 · 3.49 Impact Factor
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    ABSTRACT: BACKGROUND: Pathogenesis and clinical prognosis of membranoproliferative glomerulonephritis (MPGN) has not yet been established. METHODS: We conducted a retrospective study of 41 patients with MPGN (type I and III) and examined the renal survival. In addition, factors contributing to survival time were analyzed. RESULTS: Fourteen patients (34 %) were classified into the renal death group. Patients with nephrotic syndrome and positive C1q staining of glomerular deposits showed a particularly poor prognosis. Significantly higher frequency of nephrotic syndrome and higher urinary protein excretion were observed in the renal death group (p = 0.0002, p = 0.0002) than in the renal survival group. The intensity of C1q staining was positively correlated with the severity of the proteinuria (p = 0.004). Factors that influenced the survival time were positive C1q staining of glomerular deposits (p = 0.003), presence of nephrotic syndrome (p = 0.004), serum albumin (p = 0.02), and proteinuria (p = 0.04). CONCLUSIONS: C1q staining in glomerular deposits and nephrotic syndrome were important factors influencing the prognosis and outcome in MPGN patients. C1q deposition may play a key role in the pathogenesis of MPGN, as evidenced by numerous observations, such as induction of proteinuria.
    Clinical and Experimental Nephrology 07/2012; 17(1). DOI:10.1007/s10157-012-0667-6 · 1.71 Impact Factor
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    ABSTRACT: IgA nephropathy with nephrotic syndrome (nephrotic IgAN) is a rare form of IgAN. Its prognosis and response to steroid therapy are still controversial because the differential diagnosis between nephrotic IgAN and minimal change nephrotic syndrome with IgA depositions is sometimes confused. In this retrospective cohort analysis, we accurately diagnosed 42 cases of nephrotic IgAN (4.4%) from 954 IgAN patients, according to the Oxford classification. We analyzed the clinical and histological data, prognosis, and response to steroid therapy. In nephrotic IgAN, mean estimated glomerular filtration rate (eGFR) was 51.1 ± 24.6 ml/min, proteinuria was 5.71 ± 2.56 g/day, and urinary red blood cells were 51.0 ± 37.8 high power field. Both active and chronic histological lesions were observed. Cumulative renal survival rate was significantly lower in nephrotic IgAN than in non-nephrotic IgAN (the control group consisted of 47 non-nephrotic IgAN patients diagnosed between 1995 and 1996) (log-rank test: P < 0.0001). The cases with steroid therapy significantly improved their prognosis, though their male-to-female ratio and blood pressure level measured at renal biopsy were significantly lower than in the cases without steroid therapy. Steroid therapy was particularly effective in cases with low-grade tubular atrophy and interstitial fibrosis (T-grade in Oxford classification). Without steroid therapy, lower eGFR and higher T-grade were independent risk factors for severe outcome by multivariate Cox regression. Nephrotic IgAN is a very severe form of IgAN, with renal dysfunction, massive hematuria, and active and chronic histopathological lesions. Renal outcome is severe; however, steroid therapy can improve prognosis in cases with higher eGFR and lower T-grade, according to the Oxford classification.
    International Urology and Nephrology 01/2012; 44(4):1177-84. DOI:10.1007/s11255-011-0109-5 · 1.29 Impact Factor