Updates on the Treatment of Lupus Nephritis

Department of Medicine, Division of Nephrology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Journal of the American Society of Nephrology (Impact Factor: 9.34). 11/2010; 21(12):2028-35. DOI: 10.1681/ASN.2010050472
Source: PubMed


Purpose of review:
Lupus nephritis occurs in as many as half of patients presenting with systemic lupus erythematosus and is a major predictor of morbidity and mortality in this patient population. Prior to the last decade, the treatment of lupus nephritis was largely limited to corticosteroids, high-dose alkylating agents, and azathioprine, and this therapy was broadly prescribed regardless of patient demographics, clinical presentation, or prior toxicities.

Recent findings:
Over the last decade, new immunomodulatory agents have emerged as effective induction and maintenance therapies in lupus nephritis. With these options, physicians are able to individualize the treatment regimens in an attempt to maximize clinical benefit and minimize adverse events. Moreover, the influence of patient demographics on disease severity and response to treatment has come to the forefront.

Here, we review the recent progress made in the therapy of lupus nephritis with a focus on the randomized controlled trials which have demonstrated the efficacy of these new treatment regimens.

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    • "Lupus nephritis (LN) is a severe manifestation in patients with systemic lupus erythematosus (SLE), and is an important cause of renal failure in some racial groups such as Asians [1], . The treatments to date are based on non-selective immunosuppression. "
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    ABSTRACT: In vitro data showed that immunoglobulin G (IgG) from patients with lupus nephritis (LN) could bind to cultured human mesangial cells (HMC). The clinical relevance of such binding was unknown. Binding of IgG and subclasses was measured in 189 serial serum samples from 23 patients with Class III/IV±V LN (48 during renal flares, 141 during low level disease activity (LLDA)). 64 patients with non-lupus glomerular diseases (NLGD) and 23 healthy individuals were used as controls. HMC-binding was measured with cellular ELISA and expressed as OD index. HMC-binding index of total IgG was 0.12±0.09, 0.36±0.25, 0.59±0.37 and 0.74±0.42 in healthy subjects, NLGD, LN patients during LLDA, and LN flares respectively (P = 0.046, LN flare vs. LLDA; P<0.001, for healthy controls or NLGD vs. LN during flare or LLDA). Binding of serum IgG1 to HMC was 0.05±0.05, 0.15±0.11, 0.41±0.38 and 0.55±0.40 for the corresponding groups respectively (P = 0.007, LN flare vs. remission; P<0.001, for healthy controls or NLGD vs. LN during flare or remission). IgG2, IgG3 and IgG4 from patients and controls did not show significant binding to HMC. Total IgG and IgG1 HMC-binding index correlated with anti-dsDNA level (r = 0.26 and 0.39 respectively, P<0.001 for both), and inversely with C3 (r = -0.17 and -0.45, P<0.05 for both). Sensitivity/specificity of total IgG or IgG1 binding to HMC in predicting renal flares were 81.3%/39.7% (ROC AUC 0.61, P = 0.03) and 83.8%/41.8% (AUC 0.63, P = 0.009) respectively. HMC-binding by IgG1, but not total IgG, correlated with mesangial immune deposition in LN renal biopsies under electron microscopy. Our results showed that binding of serum total IgG and IgG1 in LN patients correlates with disease activity. The correlation between IgG1 HMC-binding and mesangial immune deposition suggests a potential pathogenic significance.
    Full-text · Article · Jul 2014 · PLoS ONE
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    • "Patients with lupus MN present with proteinuria and hematuria up to NS. Patients are frequently treated with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), and often with a low-salt diet or thiazide diuretics. Other protocols have been proposed including short steroid therapy, more potent immunosuppressive drugs like cyclophosphamide, mycophenolic acid, calcineurin inhibitors, and B-cell depleting agents, but controlled studies are rare [10, 11, 12, 13, 14, 15, 16, 17] despite existing guidelines from the KDIGO [18], ERA/EDTA [19] and ACR [20]. Specific pediatric recommendations do not exist. "
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    ABSTRACT: We report the case of an 11-year-old previously healthy girl who presented for microscopic hematuria and nephrotic proteinuria with normal renal function, which persisted after 6 months of steroids, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers, hydroxychloroquine, mycophenolic acid and a low-salt diet. A serum investigation suggested lupus nephritis and a renal biopsy, performed 2 weeks after the first proteinuria detection, revealed membranous lupus nephritis. We decided to perform ten sessions of daily immunoadsorption. Proteinuria decreased significantly over these ten sessions from 8 to 0.12 g/l. After the tenth immunoadsorption session, the patient received the first rituximab (RTX) infusion leading to complete B-cell depletion. The patient was maintained on ACEi associated with mycophenolic acid and hydroxychloroquine. Three RTX reinjections were performed when CD19-positive cells reappeared in peripheral blood. Despite complete B-cell recovery and positive anti-dsDNA-Ab, the patient remained in complete remission 18 months after the initial diagnosis with negative proteinuria and a normal renal function.
    Full-text · Article · Mar 2014
    • "End-stage renal disease (ESRD) is one of the most serious complication of systemic lupus erythematosus (SLE) and caries significant short- and long-term morbidity.[1234] Approximately, 50% of SLE patients have clinical evidence of lupus nephritis (LN) at the time of diagnosis, with an even greater incidence of ESRD among children and adolescents.[45] "
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    ABSTRACT: Chronic kidney disease is one of the most common complication of systemic lupus erythematosus, which if untreated can lead to the end-stage renal disease (ESRD). Early diagnosis and adequate treatment of lupus nephritis (LN) is critical to prevent the chronic kidney disease incidence and to reduce the development of ESRD. The treatment of LN has changed significantly over the past decade. In patients with active proliferative LN (Classes III and IV) intravenous methylprednisolone 1 g/m2/day for 1-3 days then prednisone 0.5-1.0 mg/kg/day, tapered to <0.5 mg/kg/day after 10-12 weeks of treatment plus mycophenolate mofetile (MMF) 1.2 g/m2/day for 6 months followed by maintenance lower doses of MMF 1-2 g/day or azathioprine (AZA) 2 mg/kg/day for 3 years have proven to be efficacy and less toxic than cyclophosphamide (CYC) therapy. Patients with membranous LN (Class V) plus diffuse or local proliferative LN (Class III and Class IV) should receive either the standard 6 monthly pulses of CYC (0.5-1 g/m2/month) then every 3(rd) month or to a shorter treatment course consisting of 0.5 g/m2 IV CYC every 2 weeks for six doses (total dose 3 g) followed by maintenance therapy with daily AZA (2 mg/kg/day) or MMF (0.6 g/m2/day) for 3 years. Combination of MMF plus rituximab or MMF plus calcineurin inhibitors may be an effective co-therapy for those refractory to induction or maintenance therapies. This report introduces a new treatment algorithm to prevent the development of ESRD in children with LN.
    No preview · Article · Mar 2014 · International journal of preventive medicine
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