Background and Objectives: Rituximab, given in four weekly doses, is a promising treatment for idiopathic membranous nephropathy and other immune-mediated diseases and lymphoproliferative disorders. This multidose regimen, however, may cause hypersensitivity reactions and is extremely expensive. This study was aimed at evaluating whether titrating rituximab to circulating CD20 B cells may improve safety and limit costs of treatment.Design, Setting, Participants, & Measurements: In a matched-cohort, single-center, controlled study, the outcome of 12 new incident patients who had idiopathic membranous nephropathy and nephrotic syndrome and received a B cell-driven treatment was compared with that of 24 historical reference patients who were given the standard protocol of four weekly doses of 375 mg/m 2 . Results: Only one patient needed a second dose to achieve full CD20 cell depletion. At 1 yr, time course of the components of nephrotic syndrome and the proportion of patients who achieved disease remission (25%) was identical in both groups. Persistent CD20 cell depletion was achieved in all patients. Costs for rituximab treatment and hospitalizations totalled €3770.90 ($4902.20) and €13,977.60 ($18,170.80) with the B cell-driven and the four-dose protocol, respectively. One patient on standard protocol had a severe adverse reaction at second rituximab dose. Thus, B cell titrated as effectively as standard rituximab treatment achieves B cell depletion and idiopathic membranous nephropathy remission but is fourfold less expensive, allowing for more than €10,000, approximately $13,000 in savings per patient.Conclusions: Avoiding unnecessary reexposure to rituximab is extremely cost-saving and may limit the production of antichimeric antibodies that may increase the risk for adverse reactions and prevent re-treatment of disease recurrences.Clin J Am Soc Nephrol 2: 932-937, 2007.

Background/Aims: First-line immunosuppression with the B-cell depleting antibody rituximab reduced proteinuria and induced remission of the disease in patients with nephrotic syndrome (NS) secondary to idiopathic membranous nephropathy (IMN). Here we evaluated whether rituximab is equally effective in patients who failed to respond to previous immunosuppressive treatment. Methods: This academic, matched-cohort study, compared 2-year outcomes of 11 consecutive IMN patients who received second-line rituximab therapy for NS persisting or relapsing after previous treatment with steroids alone or combined with alkylating agents, cyclosporine, or immunoglobulin G, with those of 11 age- (±5 years), gender- and proteinuria- (±1 g/24h) matched reference patients given first-line rituximab therapy. Results: Patients’ and reference patients’ baseline characteristics were similar. Compared to baseline, 24-hour proteinuria similarly declined at 1 and 2 years post-rituximab (by 50.5 ± 25.1% and 60.9 ± 17.4% in patients and by 52.7 ± 31.5% and 69.4 ± 40.4% in reference patients, respectively; p < 0.01 for all comparisons vs. baseline). 8 patients and 7 reference patients achieved full (3 vs. 2) or partial (5 per cohort) proteinuria remission. Hypoalbuminemia and hyperlipidemia normalized in both groups. Self-limited infusion-related reactions occurred in 1 subject per cohort. Conclusion: Rituximab reduced proteinuria in IMN patients with no or only transientresponse to unselective immunosuppression as effectively and safely as in patients without previous immunosuppression.

In human IMN, treatment-induced NS remission is associated with restoration of sodium homeostasis and kidney hemodynamics, and regression of the glomerular changes underlying proteinuria. These effects are likely to translate into long-term renoprotection.

Objectives Daily nocturnal hemodialysis (NHD) has been proposed as a valuable strategy to improve outcomes for patients on conventional hemodialysis (CHD), but it is burdened by high costs and logistic issues. Thrice NHD might represent a more affordable approach to improve hemodialysis patient outcome. Methods Here we retrospectively analyzed the data on blood pressure, body weight, and hematochemical parameters in a cohort of 7 patients (mean age 50.4 ± 11.0 years, duration of CHD 14.3 ± 11.5 years) who registered in the NHD program at the dialysis unit of Ospedali Riuniti, Bergamo, Italy. Data for the 2 first years of NHD were compared with those of the last year on CHD. Results At 2 years after start of NHD, we found a significant decrease in systolic (149.4 ± 16.6 vs. 128.4 ± 26.0 mm Hg, p<0.001) and diastolic (87.7 ± 11.1 vs. 79.6 ± 16.7 mm Hg, p<0.05) blood pressure, along with a significant reduction in the use of per-patient antihypertensive agents (1.17 ± 1.19 vs. 0.47 ± 0.89, p<0.05) and an increase in dry body weight (61.4 ± 21.8 vs. 67.1 ± 16.4 kg, p<0.001). Moreover, patients had a significant reduction in phosphate levels (6.2 ± 2.4 vs. 5.4 ± 3.0 mg/dL, p<0.01). The procedure was safe and well tolerated and did not require extra cost for ad hoc facilities. Conclusion NHD is an effective approach to optimize chronic dialysis therapy.