Mitsuyo Itabashi

Chiba University, Tiba, Chiba, Japan

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Publications (52)61.7 Total impact

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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;
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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 01/2014; 9(3):e91756. · 3.73 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; · 0.94 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; · 3.37 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; · 1.72 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. · 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. · 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; · 1.25 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; · 3.37 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; · 1.25 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. · 1.33 Impact Factor
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    ABSTRACT: We present two cases with steroid-resistant nephrotic syndrome (SRNS) and two cases with steroid-dependent nephrotic syndrome (SDNS) due to focal segmental glomerulonephritis (FSGS) who were treated with a single dose of rituximab (375 mg/m(2)). Although the two cases with SRNS showed no response, the two cases with SDNS achieved complete remission. The patients in whom the peripheral B-cell counts subsequently increased after the administration of rituximab demonstrated a relapse. Rituximab may be an effective treatment agent for SDNS with FSGS and the peripheral B-cell count may be a useful marker in such patients for preventing disease relapse.
    Internal Medicine 01/2012; 51(7):759-62. · 0.97 Impact Factor
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    ABSTRACT: Familial renal hypouricemia is a hereditary disease characterized by extraordinary high renal uric acid (UA) clearance and is associated with acute renal failure (ARF). A 17-year-old Japanese male developed ARF after anerobic exercise. Renal function improved completely after approximately 2 weeks of hydration treatment. After remission, hypouricemia became evident (1.0 mg/dL) from the initial level of UA (4.8 mg/dL) and fractional excretion of uric acid (FEUA) was >50%. His parents showed normal levels of UA and FEUA. Polymerase chain reaction of a urate anion exchanger known to regulate UA level [SLC22A12 gene: UA transporter 1 (URAT1)] demonstrated compound heterozygous mutations (Q297X and R90H). Thus, we describe a Japanese male with hypouricemia complicated by anerobic exercise-induced ARF, with definite demonstration of a genetic abnormality in the responsible gene, URAT1.
    Clinical and Experimental Nephrology 11/2011; 16(2):316-9. · 1.25 Impact Factor
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    ABSTRACT: The adaptation of steroid therapy and the effect of renin-angiotensin-aldosterone system inhibitors (RASIs) for advanced immunoglobulin A nephropathy (IgAN) patients with impaired renal function are still controversial. We divided 63 IgAN patients with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m(2) and proteinuria ≥ 0.5 g/day into two groups: the RASI group (RASI, n = 33), treated with RASIs alone; and the combination group (COMBI, n = 30), treated with corticosteroids and RASIs. We analyzed the clinical and histological background, renal survival rate, and the risk factors for progression. Renal function (mean eGFR: COMBI 46.4 vs. RASI 47.0 ml/min/1.73 m(2)), the amount of proteinuria (median: COMBI 1.39 vs. RASI 1.17 g/g creatinine) and histological backgrounds were not significantly different between the groups, but urinary red blood cells (U-RBCs) were significantly higher in the COMBI group than in the RASI group (median: COMBI 30.0 vs. RASI 10.0 counts/high-power field, P = 0.0171). The serial change in proteinuria did not differ until 5 years after treatment, but U-RBCs were significantly decreased in both groups (P < 0.0001), and eGFR was significantly decreased in the RASI group (P < 0.001) but not in the COMBI group. The results for each year after treatment did not differ significantly between both groups. The renal survival rate was not significantly different between the groups. There was no independent risk factor for progression by Cox regression analysis. Combination therapy with steroids and RASIs was not superior to monotherapy with RASIs for advanced IgAN with impaired renal function.
    Clinical and Experimental Nephrology 10/2011; 16(2):231-7. · 1.25 Impact Factor
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    ABSTRACT: The validity of the Birmingham Vasculitis Activity Score (BVAS) as an index of disease activity and a predictor of the prognosis and outcome in patients with MPA has not yet been established in Japan. We conducted a retrospective study of the data of 73 patients with MPA who were followed up for at least 2 years. We divided the patients into two groups according to the BVAS, namely, the high-BVAS group (≥16) and the low-BVAS group (<16), and compared the clinical characteristics. In addition, the distribution of the BVAS items in the patients and the items contributing to the total score in MPA patients were analyzed. Remission was achieved in 85% of patients at 1 month. There were no significant differences in the serum CRP, creatinine (Cre), or MPO-ANCA between the high- and low-BVAS group; however, the survival time was significantly shorter (p = 0.048) and the mortality rate significantly higher in the high-BVAS group (p = 0.04). The items of the BVAS contributing to the total score were motor neuropathy, sensory neuropathy, pulmonary infiltrate, hematuria, proteinuria, Cre ≥5.6 mg/dL, hypertension, scleritis, rise in Cre by ≥30%, and myalgia. BVAS was found to be a useful tool for determining the disease activity and outcome in patients with MPA in Japan. The initial BVAS was also predictive of the mortality and survival time and can also be used as a prognostic tool; therefore, use of the tool may facilitate the selection of appropriate treatment.
    Clinical Rheumatology 09/2011; 30(11):1499-505. · 2.04 Impact Factor
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    ABSTRACT: Treatment with a single dose of rituximab alone induced remission in a patient with relapsed minimal change nephrotic syndrome (MCNS). A 27-year-old man was given corticosteroid (prednisolone; PSL) and cyclosporine (CyA) therapy combined with rituximab for his fifth relapse in 2008. Thereafter, complete remission was achieved and maintained despite eventual discontinuation of the PSL and CyA. In 2010, we treated his sixth relapse with a single dose of rituximab. Complete remission was obtained 32 days later. This is the first report of rituximab monotherapy in the treatment of MCNS.
    Clinical and Experimental Nephrology 08/2011; 15(6):933-6. · 1.25 Impact Factor
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    ABSTRACT: The therapeutic strategy for advanced IgA nephropathy patients with impaired renal function is still controversial. We divided 44 IgA nephropathy patients with an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.76 m(2) and proteinuria greater than 0.5 g/g · creatinine into two groups: the angiotensin receptor blocker (ARB) group (n = 22), treated with ARBs, and the steroid group (n = 22), treated with corticosteroid. We analyzed the clinical and histological background, renal survival rate until progression to end-stage renal disease (ESRD), and the risk factors for progression. The clinical and histological backgrounds were not significantly different between the groups. At 1 and 2 years after treatment, proteinuria tended to be decreased from baseline in both groups, but not significantly, and urinary red blood cells were significantly decreased in the steroid groups (p < 0.001), but not in the ARB group. The eGFR tended to be increased in the steroid group and decreased in the ARB group. However, the renal survival rate until ESRD was not significantly different between the groups. There were no significant independent risk factors for progression. The beneficial effect of ARBs on renal survival of advanced IgA nephropathy with impaired renal function is equal to that with steroids.
    American Journal of Nephrology 07/2011; 34(3):233-40. · 2.62 Impact Factor
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    ABSTRACT: There are few reports analyzing the effects of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) on the long-term renal survival of advanced immunoglobulin A nephropathy (IgAN) patients. In this retrospective cohort analysis, we divided 66 IgAN patients with an estimated glomerular filtration rate (eGFR) <60 ml/min into three groups: ACEI group (n = 20, treated with ACEIs), ARB group (n = 23, treated with ARBs), and control group (n = 23, treated with antiplatelet agents), and analyzed the clinical and histological background, renal survival rate until the primary endpoint of 50% decrease of eGFR from baseline, and the secondary endpoint of progression to end-stage renal disease, and the risk factors for progression. The clinical and histological background without serum IgA and C3 were not significantly different among the three groups. The renal survival rate until the primary and secondary endpoints was significantly higher in the ACEI and ARB groups than in the control group. The independent risk factors for progression were higher mean blood pressure (hazard ratio [HR] 1.76, P = 0.04), higher histological grade (HR 2.54, P = 0.0184) at baseline, and without ACEIs or ARBs (HR 7.09, P = 0.001), but decreased proteinuria and blood pressure. The risk factors with resistance to ACEIs or ARBs were higher blood pressure and lower eGFR at baseline. There was no difference regarding the survival rate and the risk for progression between ACEI s and ARBs. ACEIs or ARBs were effective for long-term renal survival of advanced IgAN, although proteinuria and blood pressure did not decrease.
    Clinical and Experimental Nephrology 05/2011; 15(5):700-7. · 1.25 Impact Factor
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    ABSTRACT: Blockade of the renin-angiotensin-aldosterone system is a therapeutic mainstay in patients with chronic kidney disease (CKD). However, the renoprotective effect of the novel direct renin inhibitor aliskiren is unknown. We performed a prospective study in 10 CKD patients. All 10 patients with persistent proteinuria (urinary protein-to-creatinin ratio 0.3-3.5 g/g), despite good blood pressure control (<130/80 mmHg) with olmesartan, were started on 150 mg/day aliskiren. Clinical parameters were examined before and after 4, 8, 12, and 16 weeks of treatment. Urinary protein-to-creatinine ratio significantly decreased by about 40% at 16 weeks from baseline (P = 0.0002), although estimated glomerular filtration rate and blood pressure did not change throughout the study period. Plasma renin activity also decreased significantly from baseline (P = 0.019), although plasma aldosterone concentration did not change. Aliskiren combined with olmesartan reduces proteinuria in CKD patients.
    International Urology and Nephrology 05/2011; 44(3):841-5. · 1.33 Impact Factor
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    ABSTRACT: The aim of this study was to demonstrate expression of cell membrane invagination 'caveolae' in glomeruli and to correlate this with functional and structural characteristics of the human glomerular diseases. The expression of caveolin-1 (Cav-1), which is the main component of caveolae, was examined in the glomeruli, and the relationship between Cav-1 expression and pathological and clinical findings was determined in 99 patients with glomerular disease and in 50 renal transplantation donors as controls. Cav-1 was expressed very weakly in the controls, and the area of Cav-1 expression relative to the total glomerular area was 0.57±0.65%. However, the area of Cav-1 expression was significantly larger in each glomerular disease (IgA nephropathy, 1.05±1.36%, p<0.05; crescent glomerulonephritis, 1.86±1.19%, p<0.001; minimal change disease, 2.38±1.24%, p<0.001; focal segmental glomerulosclerosis, 2.88±2.05%, p<0.01; membranous nephritis, 4.27±2.95%, p<0.001; membranoproliferative glomerulonephritis, 4.49±3.15%, p<0.001; and diabetic nephropathy, 2.45±1.52%, p<0.001; compared with the controls. Cav-1 expression was significantly decreased in glomerular disease treated with steroids. Co-localisation of Cav-1 and the endothelial marker 'pathologische anatomie leiden-endothelium' was prominent in an immunofluorescence study, and caveolae on the glomerular endothelial cells were observed in electron microscopy. The expression of Cav-1 was significantly increased in the glomeruli of patients with glomerular disease, and it was related to urinary albumin excretion. Cav-1 expression and caveolae were observed in glomerular endothelial cells. It is hypothesised that they play a role in the recovery phase of capillary injury or endocytosis of albumin into endothelial cells. Basic research should be performed to elucidate the role played by Cav-1 and caveolae.
    Journal of clinical pathology 03/2011; 64(6):504-9. · 2.43 Impact Factor

Publication Stats

176 Citations
61.70 Total Impact Points

Institutions

  • 2013
    • Chiba University
      • Graduate School of Medicine
      Tiba, Chiba, Japan
  • 2002–2013
    • Tokyo Women's Medical University
      • Kidney Center
      Edo, Tōkyō, Japan
  • 2012
    • Tazuke Kofukai Medical Research Institute, Kitano Hospital
      Ōsaka, Ōsaka, Japan
    • Tokyo Junshin Women's College
      • Department of Internal Medicine
      Edo, Tōkyō, Japan