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/m2 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.
Objective We conducted a cohort study to investigate whether diastolic function could predict cardiovascular (CV) events in 161 HD patients with preserved systolic function. Materials and MethodsThe ratio of early transmitral flow velocity to early mitral annular velocity (E/E') was measured by tissue Doppler imaging. Patients were stratified into two groups based on whether they experienced a CV event.Results During a 4-year follow-up period, 64 patients experienced a CV event. The E/E' values (15.18 ± 5.78) in the CV-event group were significantly higher than in the group who had not experienced a CV event (12.32 ± 4.23). Kaplan-Meier analysis indicated that the incidence of CV events was significantly higher in the group of patients whose E/E' was >15 than in the group whose E/E' was !15 (log-rank p=0.0016). Multivariate Cox proportional hazards regression analysis revealed the E/E' ratio to be a significant predictor of CV events in HD patients with preserved LV systolic function. Conclusion The results of this study showed that elevated E/E' ratio in chronic HD patients predicts CV events better than other echocardiographic parameters.
Rituximab treatment was effective and safe in patients with steroid-dependent nephrotic syndrome, allowed reduction of the PRED dose, and ameliorated the adverse effects of PRED. It may be preferentially used in patients at a risk of the adverse effect of PRED.
Rituximab has been approved in Japan for the treatment of intractable nephrotic syndrome, but in cases of childhood-onset disease only; its efficacy and safety in adult-onset disease has yet to be established. This study was undertaken to evaluate the efficacy of rituximab and adverse effects in patients with adult-onset minimal change nephrotic syndrome (MCNS).The study involved 32 childhood-onset cases (mean age at onset: 8.6 years) and 19 adult-onset cases (mean age at onset: 30.6 years) of frequently relapsing steroid-dependent MCNS, all of whom received intravenous rituximab drip infusion (375 mg/m2 body surface area per dose) at 4 time points at 6-month intervals. Relapse frequency, oral dose of immunosuppressants, and adverse effects were compared between the 2 groups.Remission was maintained in all cases in the childhood-onset and adult-onset groups; a significant reduction in relapse frequency was noted during the first 24 months of rituximab therapy (0.3 ± 0.7 times and 0.3 ± 0.6 times in the childhood-onset and adult-onset groups, respectively; P < .001). Oral corticosteroid therapy could be discontinued in 81.3% of cases of the childhood-onset group (26/32 cases) and in 70.6% of cases of the adult-onset group (12/17 cases); the oral corticosteroid dose was reduced significantly to 0.9 ± 2.5 mg/day in the childhood-onset group and to 0.8 ± 1.6 mg/day in the adult-onset group (P < .001). Cyclosporin treatment was also discontinued in 87.5% of cases in the childhood-onset group (21/24 cases) and in 80.0% of cases of the adult-onset group (15/21 cases); the oral cyclosporin dose was reduced significantly to 8.6 ± 27.4 mg/day and 9.2 ± 22.0 mg/day, respectively (P < .001). Regarding adverse reactions, infusion reactions developed at a frequency of 21.1% and 19.7% in both groups, respectively, with no significant inter-group difference (P = .72).Rituximab showed significant efficacy in adult-onset MCNS, with a comparable incidence of adverse reactions to that in childhood-onset cases, suggesting that this drug can also be used safely in adult-onset MCNS.
The Oxford classification for IgA nephropathy (IgAN) was updated in 2017. We have validated the revised Oxford classification considering treatment with corticosteroids/immunosuppressors. In this retrospective analysis, 871 IgAN patients were enrolled. Patients were divided into two groups, those treated with or without corticosteroids/immunosuppressors. The 20-year renal prognosis up to end-stage renal disease was assessed using the Oxford classification. In all patients, the renal survival rate was 87.5% at 10 years and 72.6% at 20 years. The T score alone was significantly related to renal prognosis in the Kaplan-Meier analysis and multivariate Cox regression analysis. In the non-treatment group (n = 445), E, S, T, and C scores were significantly related to renal survival rates, however, in the treatment group (n = 426), T score alone was significantly related to renal prognosis on Kaplan-Meier analysis, indicating that corticosteroids/immunosuppressors improved renal prognosis in E1, S1, and C1. In patients with E1, S1, or C1, the treatment group showed significantly better renal prognosis than the non-treatment group in univariate and multivariate analysis. The Oxford classification and T score were used to determine renal prognosis in IgAN patients. Corticosteroids/immunosuppressors improved renal prognosis, especially E1, S1, and C1 scores. IgA nephropathy (IgAN) was first reported 50 years ago by Berger 1. IgAN was initially labelled as a benign disease; however, it was later shown to have a poor long-term prognosis 2-5. Although the prognostic risk factors of IgAN have not been clearly defined, hypertension, deterioration of renal function, and increased levels of proteinuria are known prognostic factors 2-5. Histological findings may also inform prognosis 6-9 , although these factors have not achieved worldwide acceptance. In 2009, the Oxford classification was reported by the International IgAN Network and International Renal Pathology Society 10,11. In the Oxford classification, mesangial hypercellularity (M), segmental glomerulosclerosis (S), tubular atrophy/interstitial fibrosis (T), were selected as prognostic factors and endothelial hypercellularity (E) were selected as reactive factors against corticosteroids/immunosuppressors (MEST score). After this report of the Oxford classification, several validation studies were performed, with different results among those studies 12-25. Using a multivariate analysis, it was determined that the T score was the most valuable marker of progression; however, other factors differed according to the clinical background (race, age), inclusion criteria (estimated glomerular filtration rate [eGFR] > 30 mL/min/1.73 m 2 , proteinuria > 0.5 g/day, minimum followup > 1 year), duration of follow-up, treatment, and endpoint of each study (eGFR slope, 50% reduction of eGFR, or end-stage renal disease [ESRD]). Interestingly, several reports validated not only the MEST score but also the crescent formation (as the C score), and multivariate analysis indicated that the C s...
H-UA induced global glomerular sclerosis and accelerated the progression of IgAN in CKD stage G3a.
The Oxford classification of IgA nephropathy (IgAN) can evaluate each MEST-C score individually. We analysed a new grading system that utilised the total MEST-C score in predicting renal prognosis. Altogether, 871 IgAN patients were classified into three groups using the new Oxford classification system (O-grade) that utilised the total MEST-C score (O-grade I: 0–1, II: 2–4, and III: 5–7 points), and the 10-year renal prognosis was analysed. The clinical findings became significantly severer with increasing O-grades, and the renal survival rate by the Kaplan–Meier method was 94.1%, 86.9%, and 74.1% for O-grades I, II, and III, respectively. The hazard ratios (HRs) for O-grades II and III with reference to O-grade I were 2.8 (95% confidence interval [CI] 1.3–6.0) and 6.3 (95% CI 2.7–14.5), respectively. In the multivariate analysis, mean arterial pressure and eGFR, proteinuria at the time of biopsy, treatment of corticosteroids/immunosuppressors, and O-grade (HR 1.63; 95% CI 1.11–2.38) were the independent factors predicting renal prognosis. Among the nine groups classified using the O-grade and Japanese clinical-grade, the renal prognosis had an HR of 15.2 (95% CI 3.5–67) in the severest group. The O-grade classified by the total score of the Oxford classification was associated with renal prognosis.
Left ventricular (LV) function is impaired in most hemodialysis (HD) patients. We conducted an observational cohort study to investigate whether LV end-diastolic diameter (LVDd) could predict all-cause mortality in a cohort of 166 HD patients. The LVDd values (5.06 ± 0.64 cm) of the non-survivor group were significantly greater than in the survivor group (4.78 ± 0.71 cm). The area under the receiver operating characteristic curve for an LVDd cut-off value of 5.01 cm was 0.6145 (P = 0.0234). The sensitivity and specificity of the LVDd threshold of 5.01 cm were 75.7% and 50.4%, respectively. The 4-year survival rate was significantly lower in the group with LVDd ≥ 5.01 cm than in the group with LVDd < 5.01 cm (log-rank test, P = 0.0047). Multivariate analysis with adjustments for clinical and echocardiographic parameters showed that increased LVDd was an independent predictor of all-cause mortality (hazard ratio 2.363, 95% CI 1.320-4.228, P = 0.0013). The results of the present study showed that increased LVDd predicts the all-cause mortality of chronic HD patients better than other echocardiographic parameters. Our findings suggest that LVDd measurements may be helpful for risk stratification and providing therapeutic direction for the management of HD patients.
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