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Background The optimal dosing and the efficacy of rituximab for primary membranous nephropathy (PMN) has not been established. This multicentric prospective study evaluates the efficacy and safety of low-dose rituximab (RTX) therapy in patients with PMN in clinical practice. Methods Thirty-four consecutive patients with PMN and nephrotic syndrome were included and received RTX (375 mg/m 2) once (18 patients) or twice (16 patients). RTX was the first-line therapy for 19 (56%) and the second line for 15 (44%) patients. All patients were followed for 12 months after RTX and 24 for at least 18 months (mean 23.9 ± 18.6 months). Results At 12 months, 5 patients (14.7%) achieved complete response, 10 (29.4%) partial and 19 (55.8%) no response. Response occurred '1/46 months after RTX. At 24 months, the clinical situation was unchanged: two non-responders achieved partial response and two responders relapsed. Responders had significantly higher baseline GFR and lower anti-PLA2R antibodies compared with non-responders. Outcome was similar between one or two doses of RTX (non-responders 55.5 versus 56%, respectively) and between patients who had received previous therapy versus those receiving RTX as first-line therapy (non-responders 40 versus 68%, respectively). In the 15 patients already treated, the response to RTX was comparable to that of previous therapies. Conclusion Low-dose RTX obtains remission in

Objectives The objective of this study was to evaluate the clinical features, course, outcome, and prognostic indicators in lupus membranous nephritis (LMN) and to compare data of "pure" LMN vs "mixed" forms. Methods We retrospectively examined medical records and kidney biopsies of 103 patients with a diagnosis of LMN. Results Sixty-seven patients had "pure" LMN and 36 had "mixed" forms. Patients with mixed LMN had more frequent nephrotic syndrome (66.6 vs 44.7%, P = 0.05), low C3 (83.3 vs 62.6%, P = 0.05) and C4 (80.5 vs 52.2%, P = 0.005), anti-DNA positivity (86.0 vs 62.6%, P = 0.03), and a tendency toward a lower creatinine clearance (93 ± 29 vs 112 ± 50 mL/min, P = 0.07). Moreover, mixed membranous nephritis had a higher activity and chronicity index (6.5 ± 2.1 vs 1.4 ± 2.03, P = 0.005 and 2.4 ± 1.7 vs 1.4 ± 1.8, P = 0.0001, respectively). Methylprednisolone pulses and immunosuppressive therapy were more often used in patients with mixed forms (86.1 vs 60.6%, P = 0.016 and 83.3 vs 57.5%, P = 0.008, respectively). After a mean follow-up of 156.5 ± 104.5 months, there was no difference in the 2 subgroups concerning the number of patients achieving remission and patient/renal survival (94.5 vs 94.0% and 85.8 vs 86% at 10 years). At multivariate analysis, serum creatinine at presentation ( P = 0.0013), chronicity index ( P = 0.007), failure of achieving remission ( P = 0.000001), and occurrence of nephritic flares ( P = 0.00167) were independent predictors of chronic renal insufficiency. Conclusions Despite the differences in clinical and histological presentation, a therapy tailored on the grounds of clinical and histological features may reduce the differences in the outcome of white patients with mixed and pure membranous nephritis.

The clinical course of lupus nephritis is characterised by alternation of quiescences and exacerbations. The potential treatment strategies for renal flares are an important issue considering the potential toxicity and the incomplete efficacy of available drugs.1,–,4 Among the new agents for induction of remission, rituximab (RTX), an anti-CD20 monoclonal antibody, has emerged as a potential therapeutic alternative.5,–,8 In this prospective study, we report the first comparison between RTX and cyclophosphamide (CY) in the treatment of relapses of proliferative lupus nephritis (PLN). From April 2006 to January 2010, 24 patients with established PLN and a new renal relapse discontinued all immunosuppressive drugs and received one intravenous methylprednisolone pulse (MPP) (0.5–1 g each) for 3 days and, based on the patients' choice …

Objectives:To evaluate the role of immunological tests for monitoring lupus nephritis (LN) activity.Methods:C3, C4, anti-dsDNA and anti-C1q antibodies were prospectively performed over 6 years in 228 patients with LN.Results:In membranous LN only anti-C1q antibodies differentiated proteinuric flares from quiescent disease (p = 0.02). However, in this group 46% of flares occurred with a normal value of anti-C1q antibodies versus 20% in proliferative LN (p = 0.02). In patients with antiphospholipid antibodies (APL), 33% of flares occurred with normal levels of anti-C1q antibodies versus 14.5% in patients that were APL-negative (p = 0.02). In proliferative LN, anti-C1q antibodies showed a slightly better sensitivity and specificity (80.5 and 71% respectively) than other tests for the diagnosis of renal flares. All four tests had good negative predictive value (NPV). At univariate analysis anti-C1q was the best renal flare predictor (pConclusions:Anti-C1q is slightly better than the other tests to confirm the clinical activity of LN, particularly in patients with proliferative LN and in the absence of APL. All four “specific” tests had a good NPV, suggesting that, in the presence of normal values of each, active LN is unlikely.

Anti-C1q antibodies are found in a variety of diseases, in addition to systemic lupus erythematosus (SLE), and in 3-5% of normal individuals. In particular, anti-C1q antibodies are detected at a high titer in 100% of patients with hypocomplementemic urticarial vasculitis and in 30-48% of SLE patients. Their titer correlates with active renal disease with a sensitivity of 44-100% and a specificity of 70-92%. An increase in anti-C1q antibody titer has been suggested to be able to predict renal flares in lupus nephritis so that monitoring anti-C1q might be valuable for the clinical management of SLE patients as a noninvasive biological marker. Recently our group studied 228 patients affected by lupus nephritis and found that the association of anti-C1q, C3, and C4, in a multivariate analysis, provided the best prediction of renal flares, particularly in patients with focal and diffuse proliferative lupus nephritis and in the absence of antiphospholipid antibodies. © 2009 New York Academy of Sciences.