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Background and Objectives: Resistant lupus nephritis (LN) has been associated with the persistence of long-lived plasma cells. Preliminary studies identified bortezomib as a potential treatment option for patients with refractory LN. The aim of this study was to analyze the efficacy and safety of bortezomib in the treatment of severe refractory LN., Methods: This retrospective study included 12 female patients diagnosed for the first time with class IV or IV/V LN with acute or rapidly progressive kidney injury ( n  = 11) and/or severe nephrotic syndrome ( n  = 1) who showed resistance to induction therapy with cyclophosphamide, steroids, mycophenolate, and rituximab, and were treated with either intravenous or subcutaneous bortezomib plus intravenous dexamethasone., Results: All patients with acute or rapidly progressive kidney injury showed a significant reduction in both biochemical and immunological activity after a mean of 6 (minimum 5, maximum 7) weekly cycles of bortezomib regimen, with a significant increase in C3 levels and a significant decrease of anti-ds DNA antibody titers, Systemic Lupus Erythematosus Disease Activity Index score, serum creatinine, and proteinuria. One patient (8.3%) achieved a complete response, and 10 patients (83.4%) achieved a partial response. During follow-up, all these patients maintained partial responses under treatment with mycophenolate and low-dose glucocorticoids. The patient with refractory nephrotic syndrome showed a partial response but relapsed 11 months after the end of bortezomib treatment and was resistant to treatment. A significant decrease in serum IgG levels after initiation of bortezomib treatment was observed in all patients, five of them (41.6%) showed hypogammaglobulinemia (<500 mg/dl), but no patient suffered from opportunistic infections; in only two patients (16.6%) hypogammaglobulinemia persisted at the end of follow-up. Two patients (16.6%) suffered from sensory neuropathy, which led to bortezomib treatment discontinuation., Conclusions: Bortezomib may be an effective option for refractory LN, but close monitoring must be performed for possible adverse events such as peripheral neuropathy and hypogammaglobulinemia.

Background and Objectives: The prognostic value of mesangial C4d deposits in IgA nephropathy has been analyzed in patients with reduced GFR but has not been analyzed in those with normal kidney function. The main objective of the study was to analyze the prognostic value of C4d deposits and association with response to treatment in patients with IgA nephropathy and normal GFR., Design, Setting, Participants, & Measurements: This retrospective cohort study included 190 patients with idiopathic IgA nephropathy diagnosed by kidney biopsy between 1988 and 2005. The patients had GFR≥80 ml/min per 1.73 m 2 at the time of diagnosis, and they had a paraffin-embedded kidney biopsy with eight glomeruli available., Results: In total, 170 (89%) and 20 (11%) patients were >18 and <18 years old, respectively; median (interquartile range) follow-up was 15 (12-22) years. Mesangial C4d deposit prevalence was 20% (38 of 190). At diagnosis, C4d-positive versus -negative patients had higher protein-to-creatinine ratio (median [interquartile range]: 1.94 g/g [0.9-3.1] versus 1.45 g/g [0.9-2.2]; P =0.04). During follow-up, C4d-positive patients showed a higher number of nephritic flares (median [range]: 1.4 [0-5] versus 0.9 [0-2]; P =0.04), had a higher protein-to-creatinine ratio (median [interquartile range]: 1.32 g/g [0.7-1.7] versus 0.89 g/g [0.1-1.3]; P <0.01), were more prone to receive repeated treatment with corticosteroids (45% versus 24%; P <0.01), and showed a larger reduction in eGFR (-1.6 versus -0.8 ml/min per 1.73 m 2 per year; P =0.04). Furthermore, the presence of mesangial C4d deposits was an independent predictor of long-term kidney survival., Conclusions: C4d deposits may be one of the earliest poor prognostic variables available for patients with idiopathic IgA nephropathy and normal kidney function at the time of diagnosis. However, Cd4 deposits alone are not associated with the response to angiotensin blockers or corticosteroid treatment., (Copyright © 2018 by the American Society of Nephrology.)

Context: The dynamics of anti-phospholipase A2 antibody titers during treatment could predict clinical responses in patients with membranous nephropathy., Objectives: We analyzed the predictive value of the dynamics of these antibodies on clinical responses., Materials and Methods: The serum antibody levels were measured before and during treatment in 79 patients with anti-phospholipase A2 receptor antibody membranous nephropathy treated with two different immunosuppression regimens, Results: In both groups of patients, the relative reduction in antibody titers at 3 and 6 months preceded and predicted the clinical responses., Conclusions: Antibody titer dynamics was useful for predicting clinical responses.

Introduction and Objectives: The level of circulating antibodies against M-type phospolipase A2 receptor has been reported as having a significant correlation with clinical activity in idiopathic membranous nephropathy. However, the usefulness of monitoring antibody titre as a predictor of clinical response following the onset of treatment has not been formally analysed. The predictive value of the evolution of anti-PLA2R antibody titre on the clinical response of idiopathic membranous nephropathy patients treated with tacrolimus is analysed in the following study., Patients and Method: 36 patients with nephrotic syndrome secondary to idiopathic membranous nephropathy with immunosuppressive treatment indication criteria were treated with tacrolimus in monotherapy. The level of anti-PLA2R antibodies was determined before treatment and at 3, 6, 9 and 12 months after the onset of treatment. The study analysed the predictive value of the reduction in antibody titre and the relative and absolute reduction in antibody titre at 3 and 6 months over the period until remission and on the probability of remission at 6, 9 and 12 months., Results: The relative reduction in the anti-PLA2R antibody titre was significantly greater in those patients with remission and it preceded the clinical response. No association was observed between the antibody titre prior to treatment and the mean response time or the response at 12 months. Reduction in antibody titre is significantly associated with the time until signs of remission. Relative reduction in anti-PLA2R antibody titre at 3 months had a high sensitivity and specificity to predict the response at 6 and 9 months, but not at 12 months; however the relative reduction in the antibody titre at 6 months had a high sensitivity and specificity for predicting the response at 12 months., Conclusion: In patients with IMN associated with anti-PLA2R antibodies, the monitoring of antibody titre following the onset of treatment is useful for estimating the time period until remission and predicting the probability of remission at 12 months.