Successful treatment with rituximab in a patient with TTP secondary to severe ANCA-associated vasculitis.

We report a case of thrombotic thrombocytopenic purpura (TTP) secondary to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis treated by rituximab. TTP secondary to ANCA-associated vasculitis is very rare and has a high mortality rate. We employed rituximab and successfully treated TTP secondary to ANCA-associated vasculitis, because standard therapies, such as steroid therapy, intravenous pulse cyclophosphamide, and repeated plasma exchange (PE), did not suppress her disease activity. This is the first report to suggest that rituximab can achieve complete remission of TTP secondary to ANCA-associated vasculitis.

Pharmacokinetics of orally administered tacrolimus in lupus nephritis patients.

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.

Phosphorylation status of nephrin in human membranous nephropathy.

BACKGROUND: We recently reported that nephrin, a major slit-diaphragm protein, is phosphorylated at Y1204 and Y1228 in normal human glomeruli and that phosphorylation decreased significantly in minimal-change nephrosis. These results indicate that phosphorylation of nephrin is important for maintenance of normal podocyte morphology and function. On the other hand, phosphorylation of nephrin was reportedly increased in certain animal models of glomerular injury. METHODS: We performed immunofluorescent and immunoelectron staining of phosphorylated nephrin in human kidney biopsy specimens of membranous nephropathy (MN) to investigate whether phosphorylation of nephrin was altered in human MN and whether it correlated with MN staging. RESULTS: Although aberrant localization of phosphorylated nephrin was detected using immunoelectron microscopy in stage I MN, a decrease in the immunofluorescent intensity of phosphorylated nephrin was not observed in stage I, and only a slight decrease was seen in stages II, III, and IV compared with controls. No significant correlation between nephrin phosphorylation and proteinuria was observed. CONCLUSION: Nephrin phosphorylation was not significantly decreased in the early stage of MN.

Successful use of single-dose rituximab for the maintenance of remission in a patient with steroid-resistant nephrotic syndrome.

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.

Clinical assessment of tacrolimus therapy in lupus nephritis: one-year follow-up study in a single center.

BACKGROUND/AIMS: The purpose of this study was to examine whether tacrolimus is effective and safe, and to determine the optimal dose of tacrolimus for maintenance treatment in patients with lupus nephritis (LN). METHODS: A total of 17 adult patients (1 man and 16 women) with LN were enrolled. Tacrolimus was initiated at a dose of 3 mg/day which was administered once per day after the evening meal. Prospective data on renal response and serologic lupus activity were collected and followed for a year. RESULTS: Mean age at baseline was 48.8 +/- 12.6 years (range 31-72 years). The mean urinary protein/creatinine ratio significantly decreased from 1.14 +/- 1.74 at baseline to 0.23 +/- 0.47 at 1 year (p < 0.05). Mean serum C3 significantly increased from 73.0 +/- 12.3 mg/dl at baseline to 84.7 +/- 12.2 mg/dl at 1 year (p < 0.01). Mean serum creatinine levels were unchanged after tacrolimus treatment. The mean blood concentration of tacrolimus was 3.9 +/- 2.1 ng/ml. There was no relationship between the incidence of adverse effects and blood tacrolimus level. CONCLUSION: Our results suggest tacrolimus to be potentially effective and safe for maintenance treatment in patients with LN.

The importance of low blood urea nitrogen levels in pregnant patients undergoing hemodialysis to optimize birth weight and gestational age.

Most published reports indicate that intensified hemodialysis results in better pregnancy outcomes. Here we studied clinical characteristics and the outcomes of 28 pregnant women receiving hemodialysis. We found an association between maternal blood data and birth weight, and gestational age and outcomes. There were 18 surviving infants who were followed up for one year. In the others there were 4 spontaneous abortions, 1 stillbirth, 3 neonatal deaths and 2 deaths after birth. Analysis of blood chemistry for 20 pregnancies from 12 weeks of gestation until delivery showed that the average hemoglobin level was significantly higher in the group that successfully delivered than in the unsuccessful group. There were significant negative relationships between the blood urea nitrogen (BUN) level and the birth weight or gestational age in the latter cohort. A birth weight equal to or greater than 1500 g or a gestational age equal to or exceeding 32 weeks corresponded to BUN levels of 48-49 mg/dl or less. Whether the low BUN is the direct cause of the improved outcome remains to be examined.

[Effects of steroid therapy on membranous nephropathy].

BACKGROUND: Although membranous nephropathy is a common cause of nephrotic syndrome in adults, its treatment remains under debate. METHODS: 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. RESULTS: 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. CONCLUSION: Steroid therapy in idiopathic membranous nephropathy showed good efficacy in patients with nephrotic syndrome.

Patterns in the prevalence of hepatitis C virus infection at the start of hemodialysis in Japan.

BACKGROUND: Although hepatitis C virus (HCV) infection is a persistent public health concern in hemodialysis patients, there seem to have been only a few reports on the prevalence of HCV at the start of hemodialysis. In this study we investigated whether patients starting on hemodialysis therapy are positive for anti-HCV antibody or not. METHODS: The 400 patients who began regular hemodialysis between February 2003 and June 2007 were enrolled in this study. Clinical data such as age, anti-HCV antibody and primary cause of end-stage kidney disease (ESKD) were examined. As healthy controls we used 70,717 healthy blood donors in 2005 whose data were obtained from Tokyo Metropolitan Red Cross Blood Center. Anti-HCV antibody was used as an indicator of HCV infection. Since the prevalence of HCV infection is affected by age in Japan, we classified the patients by age group. RESULTS: The anti-HCV antibody prevalence rate among the patients who were new to hemodialysis was 7.3%, as opposed to 0.15% in the healthy volunteers. The prevalence of HCV in the 31-45-, 46-60-, and 61-year-old groups was significantly higher among the hemodialysis patients than among the healthy volunteers (P = 0.0209, <0.0001, and <0.0001, respectively). The prevalence rate of anti-HCV antibody was higher among men (10.0%) than among women (1.5%, P < 0.0001) in the hemodialysis patients. The anti-HCV-antibody-positive patients were significantly older than the anti-HCV-antibody-negative patients (66.4 +/- 14.3 years versus 58.6+/-16.6 years; P = 0.0152). Diabetic nephropathy was a more frequent cause of ESKD among the anti-HCV-antibody-positive patients (30.4%) than among the anti-HCV-antibody-negative patients (19.9%, P = 0.0122). Among the anti-HCV-antibody-positive patients, 55.2% had received a blood transfusion. The rate was significantly higher than that among the anti-HCV-antibody-negative patients (19.4%, P < 0.0001). CONCLUSION: The results showed a much higher rate of anti-HCV antibody positivity in patients new to hemodialysis than in healthy volunteers. Older age, blood transfusion, male gender, and diabetic nephropathy seemed to be risk factors for anti-HCV antibody positivity in Japan.

Achievement of the Japanese Society for Dialysis Therapy guideline targets for mineral metabolism measures: one Japanese university center result.

A consensus conference for the Guidelines for the Management of Secondary Hyperparathyroidism in Chronic Dialysis Patients was conducted in the general meeting of the Japanese Society for Dialysis Therapy (JSDT) in June 2006, and the guidelines were proposed in the Journal of JSDT in 4 months later. The aim of this study was performed on the status of observance with the data, based on 6 months later proposal of the guidelines. Only 48.9% stayed within the range specified by the calcium and phosphorus guideline. Moreover, only 12% of patients were able to remain within the ranges specified by all three guidelines (calcium, phosphorus, and PTH), 6 months later proposal of the guidelines. In our institution, compliance with the JSDT guidelines was inadequate. Major reasons were the special characteristics of the medical care system and patients in our institution as a university hospital. Further improvement in the contents and method of the use of the guidelines is necessary alongside observation of the present situation in Japan.