Misao Tsukada

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

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Publications (30)19.62 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The effects of novel biocompatible peritoneal dialysis (PD) solutions on human peritoneal membrane pathology have yet to be determined. Quantitative evaluation of human peritoneal biopsy specimens may reveal the effects of the new solutions on peritoneal membrane pathology. METHODS: Peritoneal specimens from 24 PD patients being treated with either acidic solution containing high-glucose degradation products [GDPs (n = 12)] or neutral solution with low GDPs (n = 12) were investigated at the end of PD. As controls, pre-PD peritoneal specimens, obtained from 13 patients at PD catheter insertion, were also investigated. The extent of peritoneal fibrosis, vascular sclerosis, and advanced glycation end-product (AGE) accumulation were evaluated by quantitative or semi-quantitative methods. The average densities of CD31-positive vessels and podoplanin-positive lymphatic vessels were also determined. RESULTS: Peritoneal membrane fibrosis, vascular sclerosis, and AGE accumulation were significantly suppressed in the neutral group compared with the acidic group. The neutral group also showed lower peritoneal equilibration test scores and preserved ultrafiltration volume. The density of blood capillaries, but not of lymphatic capillaries, was significantly increased in the neutral group compared with the acidic and pre-PD groups. CONCLUSIONS: Neutral solutions with low GDPs are associated with less peritoneal membrane fibrosis and vascular sclerosis through suppression of AGE accumulation. However, contrary to expectation, blood capillary density was increased in the neutral group. The altered contents of the new PD solutions modified peritoneal membrane morphology and function in patients undergoing PD.
    Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 11/2012;
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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. · 1.29 Impact Factor
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    ABSTRACT: Hepcidin is the key mediator of renal anemia, and reliable measurement of serum hepcidin levels has been made possible by the ProteinChip system. We therefore investigated the iron status and serum hepcidin levels of peritoneal dialysis (PD) patients who had not received frequent doses of an erythrocytosis-stimulating agent (ESA) and had not received iron therapy. In addition to the usual iron parameters, the iron status of erythrocytes can be determined by measuring reticulocyte hemoglobin (RET-He). The mean serum hepcidin level of the PD patients (n = 52) was 80.7 ng/mL. Their serum hepcidin levels were significantly positively correlated with their serum ferritin levels and transferrin saturation (TSAT) levels, but no correlations were found between their serum hepcidin levels and RET-He levels, thereby suggesting that hepcidin has no effect on the iron dynamics of reticulocytes. Since low serum levels of CRP and IL-6, biomarkers of inflammation, were not correlated with the serum hepcidin levels, there is likely to be a threshold for induction of hepcidin expression by inflammation.
    International journal of nephrology. 01/2012; 2012:239476.
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    ABSTRACT: A paradigm shift from such toxic 'nonspecific' therapies to selective immunomodulating regimens is necessary for glomerular diseases. Rituximab, which acts by inhibiting CD20-mediated B cell proliferation and differentiation, could be effective in the treatment of nephrotic syndrome as shown in recent reports. To assess the effects of rituximab in patients with primary glomerular diseases, including minimal-change disease, immunoglobulin A (IgA) nephropathy, focal segmental glomerulonephritis, membranous nephropathy and membranoproliferative glomerulonephritis, we performed a prospective trial of the effects of single-dose rituximab therapy in 24 patients. We prospectively evaluated the serum and urinary biochemical parameters before and after 6 months of therapy. In all of the patients studied, depletion of CD19 and CD20 cells was noted, with significant reduction in the degree of proteinuria from 3.7 ± 3.4 g/day at baseline to 1.3 ± 2.0 g/day at 6 months after the drug administration (p = 0.002). However, no significant changes of the serum creatinine, urinary RBC sediment, serum CD4/8 or serum IL-4 levels were observed at 6 months after the drug administration. In subjects with IgA nephropathy, while depletion of CD19 and CD20 cells was noted, no significant change in the severity of proteinuria was observed at 6 months after the drug administration as compared with the level at the baseline. For the treatment of primary glomerular diseases, the use of a single dose of rituximab is demonstrated with no serious adverse events. Further study of the mechanism of action of rituximab in successfully treated patients could encourage new perspectives in the treatment of primary glomerular diseases.
    Nephron Clinical Practice 01/2011; 117(2):c98-105. · 1.65 Impact Factor
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    ABSTRACT: Frequently, focal segmental glomerulosclerosis (FSGS) recurs after renal transplantation, resulting in poor graft survival. Pathological mechanisms of the recurrence are still unknown, but both B and T cell disorders are suspected based on much evidence. This supports theoretical benefits using plasma exchange (PE) and lymphocytapheresis (LCAP). A renal transplant was performed for a 35-year-old woman, who suffered steroid-resistant FSGS and developed to chronic kidney disease stage 5D at 31 years old. We treated the patient with recurrent FSGS by LACP and examined whether peripheral neutrophils were dynamically changed after the therapy. Further, we performed flowcytometric analysis to examine lymphocyte fractions before and after LCAP. The decrease of helper (CD4 positive) and memory (CD4 and CD45RO positive) T cells was prominent after LCAP. Although B cells were at the nadir because of rituximab treatment, LCAP also decreased peripheral B cells. These suggest that LCAP has the potential to suppress the activities of recurrent FSGS after renal transplant.
    Internal Medicine 01/2011; 50(24):3009-12. · 0.97 Impact Factor
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    ABSTRACT: Oligomeganephronia is classified as a subgroup of renal hypoplasia, characterized by histopathologic abnormalities which progress to end-stage renal disease (ESRD) by school age. We describe three adult cases of oligomeganephronia who have not yet developed ESRD. We performed a renal biopsy in all of them. The pathological features, consisting of a reduced number of enlarged glomeruli, were diagnostic of oligomeganephronia. It was assumed that the condition had not progressed to ESRD in the patients because the degree of loss of glomeruli may have been milder than that in typical cases of oligomeganephronia.
    NDT Plus 10/2010;
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    ABSTRACT: Renal involvement is very common in AL amyloidosis. Our aim was to investigate associations between the clinical characteristics and renal pathology of patients with AL amyloidosis. The data of 11 adult Japanese patients with AL amyloidosis and renal involvement were analyzed retrospectively. To assess the difference based on the pattern of distribution of amyloid deposition, we divided the patients into a group with the capillary form and a group with the small vessel form, and compared the clinical characteristics of the two groups. Concerning AL amyloidosis, the small vessel form group was associated with cardiac involvement and left ventricular thickening compared with the capillary form group (p = 0.03). There were no significant differences between the groups in the rates of patient survival and renal survival. There was a negative correlation between grade of amyloid deposition and renal survival duration (p = 0.04, r² = 0.66). The degree of amyloid deposition was not correlated with the extent of proteinuria or renal function. These findings suggest that the vascular deposition pattern of amyloid in the kidney is important for determining patient survival and renal outcome.
    Heart and Vessels 10/2010; 25(6):543-8. · 2.13 Impact Factor
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    ABSTRACT: Evaluation of the iron status of patients with renal anemia provides information essential to prescribing adequate rHuEPO therapy. Cellular iron status can be determined by the recently available method of measuring the reticulocyte hemoglobin equivalent (RET-He). We previously showed that RET-He values were correlated with conventional parameters and with a direct marker of the reticulocyte hemoglobin (CHr) content of hemodialysis patients. We attempted to utilize the measurements of RET-He levels of non-dialyzed patients and the iron status of peritoneal dialysis (PD) patients. Iron deficiency was defined on the basis of the TSAT (< 20 %) and ferritin (< 100 ng/mL) levels. RET-He levels and conventional red blood cell parameters were measured with a Sysmex XE-2100 automated blood cell counter. CHr was measured with an ADVIA120 autoanalyzer. The serum hepcidin levels of PD patients were measured by mass-spectrometry. The mean RET-He value was 32.0 pg in the non-dialysis group and 32.5 pg in the PD group, and a correlation was found between the RET-He and TSAT values, but not the ferritin values in both groups. The serum hepcidin level was 49.8 pg in the PD group and there was a positive correlation between their hepcidin and ferritin values. Receiver operating characteristic analysis yielded a cut-off value of RET-He in the non-dialysis group (31.0 pg) and the PD group (32.7 pg). The RET-He values of PD patients who were switched from epoetin beta to darbepoetin alfa responded more rapidly than TSAT or ferritin values. RET-He is a new parameter, whose values are equivalent to CHr, and can be easily measured with a widely available and popular blood cell counter. Reticulocyte hemoglobin is an indispensable marker of iron status for chronic kidney disease patients. Moreover, reticulocyte hemoglobin is likely to provide useful information regarding the need for iron supplementation in patients being treated with an ESA.
    Nippon Jinzo Gakkai shi 01/2010; 52(2):132-40.
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    ABSTRACT: We report the case of a 58-year-old male patient who visited our hospital for the management of edema and proteinuria. He was diagnosed as having nephrotic syndrome, with serum total protein and albumin levels of 4.6 g/dL and 2.1 g/dL, respectively, and a urinary protein excretion level of 6.0 g/day. A percutaneous renal biopsy showed features of membranous glomerulonephritis, with capillary-wall granular deposits of IgG and C3 on immunofluorescence and subepithelial immune complex deposits on electron microscopy. No other secondary cause of membranous glomerulopathy was found even after extensive investigations. The patient was started on mycophenolate mofetil (MMF) monotherapy (1,500 mg/day), and 18 months after the start of this therapy, the proteinuria decreased to 0.5 g/day, with return to a normal serum albumin level. No digestive symptoms, kidney function worsening or increase in blood pressure were noted during treatment. These findings suggest that MMF monotherapy is effective and safe for the treatment of membranous nephropathy.
    Nippon Jinzo Gakkai shi 01/2010; 52(5):572-7.
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    ABSTRACT: The pharmacokinetics of orally administered tacrolimus were examined in six female lupus nephritis patients (mean age 43 years, range 24-55 years). Tacrolimus (3 mg) was administered after supper, and blood tacrolimus concentrations were measured just prior to dosing and 1, 2, 4, 6, 8, 12 and 24 h after administration. The maximum blood concentration (C(max)) was observed 4-8 h (mean: 6.7 h) after administration. The mean C(max) and area under the tacrolimus concentrationti-me curve (AUC(0-24 h)) were 12.7 ng/ml and 163.1 ng x h/ml, respectively. Although there was a weak correlation between AUC(0-24 h) values and tacrolimus concentrations 2, 4, and 6 h after administration, concentrations at 12 h and 24 h were highly correlated with AUC(0-24 h) values, suggesting that the trough concentration (C(24 h)) and C(12 h) are valid markers for therapeutic tacrolimus monitoring. Enzyme-linked immunoabsorbent assay (ELISA) and microparticle enzyme immunoassay (MEIA) measurements of blood tacrolimus concentrations were similar. We recommend that monitoring should be carried out by C(12 h) in lupus nephritis outpatients.
    Yakugaku zasshi journal of the Pharmaceutical Society of Japan 01/2010; 130(1):113-8. · 0.31 Impact Factor
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    ABSTRACT: We examined the data of 24 patients with Henoch-Schönlein purpura nephritis (HSPN) over a 5-year follow-up period. Proteinuria, sediment RBC and CRP significantly decreased between the time of diagnosis and the end of the 5-year period. In the steroid usage group (n = 16), proteinuria was significantly higher, and crescent formation was significant higher at the time of diagnosis than in the non-steroid usage group (n = 8). However, there was no significant difference in the decrease in eGFR from the baseline at the end of the 5-year period between the two groups. Furthermore, to clarify the factors influencing the risk of renal function deterioration, we divided the patients into two groups, the (delta eGFR/pre eGFR) <0.25 group (n = 13) and (delta eGFR/pre eGFR) >0.25 group (n = 11), and compared the clinico-pathophysiological characteristics between the two groups. In the (delta eGFR/pre eGFR) >0.25 group, the ratio of glomerular obsolescence at the time of diagnosis was significantly higher than in the (delta eGFR/pre eGFR) <0.25 group. Glomerular obsolescence was identified as an independent risk factor for renal function deterioration. In this study, the prognosis of HSPN was related to glomerular obsolescence rather than to the disease activity. It may be necessary to consider the decrease in nephrons, in accordance with non-immunological glomerular obsolescence, in addition to immunological treatment to clarify the prognosis.
    Nippon Jinzo Gakkai shi 01/2010; 52(1):51-7.
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    ABSTRACT: Evaluating the frequency of renal disease according to sex, age, time period and ethnicity is of considerable importance. Disease frequency was evaluated in a total of 2,404 cases that had undergone a renal biopsy at Tokyo Women's Medical University between 1979 and 2008. The overall frequencies of primary glomerulonephritis (GN) and secondary GN were 77.8 and 14.4%, respectively. Primary GN and nephrosclerosis occurred more frequently among men, while secondary GN was more frequent among women. Primary GN decreased and secondary GN increased with advancing age. Immunoglobulin A nephropathy was the most common form of primary GN during each time period and also gradually increased over time (44.4-57.4%). The most common form of secondary GN was lupus nephritis (59.0%); this disease was commonly observed in women (79.3%) but not as frequently among men (27.9%). Our data regarding the frequencies of each form of primary GN were almost the same as data from other regions of Japan and East Asia but were quite different from data originating in West Asia and South America. Our epidemiological results may be useful for analyzing the morbidity of renal disease.
    Nephron Clinical Practice 01/2010; 115(3):c227-36. · 1.65 Impact Factor
  • Nihon Toseki Igakkai Zasshi 01/2010; 43(1):71-76.
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    ABSTRACT: Minimal-change nephrotic syndrome (MCNS) is treated by the administration of prednisolone (PSL) at high doses. Steroid-induced osteoporosis is a serious adverse effect of this drug. Patients with MCNS were randomly assigned to two groups, the risedronate (2.5 mg/day) + alfacalcidol (0.25 µg/day) group (n=20) and the alfacalcidol (0.25 µg/day)-alone group (n=20). All the patients had received PSL and the clinical characteristics were compared between the two groups at baseline and at 12 months. A significant decrease of the mean bone mineral density (BMD) of the lumbar spine from 0.710±0.162 (g/cm(2)) to 0.588±0.125 was observed in the alfacalcidol-alone group (p=0.02), while no such decrease of the bone mineral density was found in the risedronate + alfacalcidol group (0.663±0.169 at baseline and 0.626±0.129 at 12 months). No significant differences in the results of other biochemical tests performed at the baseline and at 12 months were observed between the two groups. The likelihood of development of steroid-induced osteoporosis was influenced by the cumulative dose of PSL, the mean BMD at the baseline, occurrence of disease relapse, and risedronate therapy. Risedronate appears to be effective in preventing steroid-induced osteoporosis. It is necessary to use bisphosphonates to maintain the BMD in patients with MCNS receiving prolonged steroid therapy.
    Internal Medicine 01/2010; 49(19):2065-70. · 0.97 Impact Factor
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    ABSTRACT: Minimal change nephrotic syndrome (MCNS) usually is considered to have a good renal prognosis, but the frequency of relapses is a therapeutic challenge to physicians. The treatment of patients with multiple relapses remains a matter of controversy, because few controlled studies are available. We report the case of a 25-year-old man who experienced relapses of MCNS. Single-dose rituximab therapy (total dose 500 mg) was given during the fourth relapse. Complete remission occurred 10 days later, when no CD19/20-positive B cells were detected in the blood. This the first report of efficacy of single-dose rituximab therapy to treat multi-relapsing MCNS in an adult patient.
    Clinical nephrology 08/2009; 72(1):69-72. · 1.23 Impact Factor
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    ABSTRACT: We present the case of a 23-year-old man with steroid-resistant nephrotic syndrome due to minimal change disease who was treated with rituximab. The patient was resistant to conventional therapy. We therefore treated him with a single dose of rituximab (375 mg/m(2)). One month after the administration of rituximab, complete remission was achieved. However, six months later, the patient was administered a second dose of rituximab as the peripheral B cell counts began to recover. Thereafter, at present, that is, one year after the first rituximab administration, complete remission has been maintained. We conclude that rituximab may be an effective treatment agent for resistant nephrotic syndrome and the peripheral B cell count may be a useful marker in such patients for preventing disease relapse.
    Internal Medicine 01/2009; 48(21):1901-4. · 0.97 Impact Factor
  • Nephrology 09/2008; 7. · 1.86 Impact Factor
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    ABSTRACT: The pathological and clinical findings, therapies and prognoses of MPO-ANCA-associated vasculitis, were investigated in cases who showed rapidly progressive nephritic syndrome and received renal biopsy. Vasculitis activity was evaluated by BVAS(Birmingham Vasculitis Activity Score). The renal biopsy findings were evaluated by scoring glomeruli, interstitial and vascular lesions. The renal prognoses were studied by dividing the cases into a dialysis group, which went onto maintenance dialysis in one year and another group without dialysis, which maintained renal functions. The average age was 58.6 +/- 13.9 years, and the 60s age bracket was the largest. Vasculitis activity was 14.8 +/- 3.2 on the average by BVAS. CRP was 1.2 +/- 1.4 for the kidney-located type group, and 12.6 +/- 10.5 for the multiorgan-damaged group respectively, which shows the former to be significantly lower (p = 0.0079). Serum creatinine at renal biopsy was 3.57 +/- 2.31 mg/dL in the dialysis-independent group, and this was significantly lower than the serum creatinine level of 9.10 +/- 2.6 mg/dL of the dialysis group (p = 0.000259). As for the renal pathological findings, the percentage of global sclerosis among all the glomeruli was 24.7 +/- 19.9% in the dialysis-independent group vs. 68.5 +/- 19.7% in the dialysis group, which shows the latter to be significantly higher (p = 0.002). CRP was significantly higher in the multi-organ-damaged group relative to the kidney-located type group. The percentage of global sclerosis determined by renal biopsy and the amount of serum creatinine at the renal biopsy were key factors in determining the renal prognosis. The absence of a significant correlation between the percentage of crescentic formation and the renal prognosis suggests the possibility of suppressing progress to global sclerosis.
    Nippon Jinzo Gakkai shi 02/2008; 50(7):927-33.
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    ABSTRACT: Chronic kidney disease (CKD) is an important worldwide health problem. The incidence of end-stage renal disease (ESRD) is increasing steadily around the world, however few studies have discussed the risk factors for progression in patients with early-stage CKD. Therefore, we designed a retrospective cohort study of patients with early-stage CKD to identify the risk factors influencing the annualized slope of the estimated glomerular filtration rate (eGFR). In this longitudinal cohort study, baseline examination was conducted in 2012 outpatients treated at the Kidney Center, Tokyo Women's Medical University. Follow-up examinations were completed in 485 patients with stage 1 and stage 2 CKD within the study period (2002-2007). The conventional risk factors for CKD progression, such as proteinuria, blood pressure, serum triglyceride, serum HDL, fasting plasma glucose, smoking habit, hypertension or treatment with antihypertensive medication and body mass index, were examined. The annualized eGFR slope was calculated at the start and end of the study period. Multivariate analysis was performed to determine the associations of the eGFR slope with the predisposing risk factors. The mean annualized eGFR slope was -1.64 mL/min/1.73 m(2)/year. Concerning the relationship between etiology and the GFR decreasing slope, IgA nephropathy was defined as the worst (-1.80 mL/min/year) due to the high ratio of proteinuria. Proteinuria (-2.13 mL/min/1.73 m(2)/year, p=0.005), smoking habit (-2.06 mL/min/1.73 m(2)/year, p=0.014), low serum HDL (-1.95 mL/min/1.73 m(2)/year, p=0.035), and hypertension (-1.73 mL/min/1.73 m(2)/year, p=0.045) were all significantly related to the eGFR slope. The estimated GFR for the highest BMI quartile was significantly higher than that of the eGFR for the lowest BMI. Proteinuria, smoking habit, hypertension and low HDL were clearly related to accelerated disease progression in patients with early-stage CKD. Therefore, aggressive treatment of these risk factors is essential in the early stages of CKD.
    Internal Medicine 02/2008; 47(21):1859-64. · 0.97 Impact Factor
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    ABSTRACT: Although membranous nephropathy is a common cause of nephrotic syndrome in adults, its treatment remains under debate. To clarify the effects of steroid therapy, the data of 51 Japanese adult patients with idiopathic membranous nephropathy who received treatment at our department were analyzed retrospectively. We divided the patients with nephrotic syndrome and a serum creatinine level <1.7 mg/dL, into two groups: the steroid therapy group (n=20) and the non-steroid therapy group (n=7), and compared the clinical characteristics between the two groups. Significantly decreased proteinuria levels (p<0.05) after 2 and 5 years were observed in the steroid therapy group as compared to the non-steroid therapy group. There was no significant difference in the serum creatinine levels after 2 and 5 years between the steroid therapy group and the non-steroid therapy group. Steroid therapy in idiopathic membranous nephropathy showed good efficacy in patients with nephrotic syndrome.
    Nippon Jinzo Gakkai shi 01/2008; 50(5):597-601.