Active clinical trials for "Lupus Nephritis"

B-cell activating factor (BAFF), also known as B lymphocyte stimulator (BLyS) serves as a vital survival and differentiation factor for normal B-cell development. There is an inverse relationship between BAFF circulating levels and the percentage and number of circulating B cells. BAFF levels have been associated with the clinical activity of SLE in humans. BAFF plays a pathogenic role in SLE in part through T cell-dependent B cell autoantibody production. BAFF, has a role in the maintenance of memory B cells and promotes plasma cell survival. Treatment strategies involving BAFF blockade haven been studied in patients with SLE inducing overall improvement in disease activity, mainly in musculoskeletal and mucocutaneous domains leading to the approval of Belimumab for the treatment of patients with systemic lupus erythematosus without severe renal or neurological involvement. Antibodies against CD20 molecule, anti-CD20 antibodies (Rituximab), cyclophosphamide (CYC), and mycophenolate (MMF) have all been used for the treatment of different manifestations of systemic lupus erythematosus and both moderate and severe activity. Baseline C4 level, early normalization of complement, and reduction in proteinuria have been shown to predict renal response to therapy with MMF or CYC in lupus nephritis. With Rituximab (RTX), B cell depletion has been associated with response to treatment and relapse prediction. The elevation of serum BAFF levels after B cell depletion with RTX in SLE are associated with anti-double-stranded DNA antibody levels and disease flare. The rise of BAFF is probably due to the decrease in its receptors leading to a release of BAFF and a delayed regulation of BAFF mRNA transcription, both of which could favor the re-emergence of autoreactive B cells. It has been suggested that the rise in BAFF levels after anti-CD20 therapy might be related to flares of the disease. Additionally, the combination of anti-CD20 with anti-BAFF or antibodies against CD4, anti-CD4 antibody greatly reduces the number of splenic plasma cells in mouse models and anti-CD20 plus anti-BAFF has been proven to have a lasting benefit both in lupus-prone mice and in mice with established disease. Currently, there is a lack of information regarding MMF or CYC and BAFF levels without the use of concomitant RTX (for CYC) and in monotherapy (for MMF). We consider that it is fundamental to know the behavior of BAFF in patients with SLE after treatment with MMF or CYC bearing in mind the proposal of multiple experts of the possible use of sequential therapy of BAFF inhibition after B-cell depletion. Knowledge of the behavior of BAFF will allow me to better understand its implications in SLE and its therapy. If our hypothesis is true maybe, we can postulate the use of sequence therapy with Belimumab after CYC o MF induction with the proposal to reduce the flares.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease affecting many organ systems. SLE includes a wide spectrum of severity, ranging from relatively mild manifestations (e.g. skin rash or non-erosive arthritis) to seriously disabling or even life threatening complications, such as lupus nephritis (LN) and neuropsychiatric disorders . LN is one of the most serious SLE complications since it is the major predictor of poor prognosis . Lupus nephritis is a common major organ manifestation and main cause of morbidity and mortality of the disease . It is occurred in 30-50% of SLE patients at initial diagnosis and more prevalent in Asians and Blacks than other races . Approximately, 10-30% of LN patients will develop the end-stage renal disease (ESRD) within 15 years after diagnosis. The 5-year survival rate of a patient with severe LN is less than70-80%. Therefore, an involvement of renal disease activity is one of the most important prognostic factors for patients with SLE, and the diagnosis of SLE patients with LN has an important clinical implication in guiding the treatment of SLE in clinical settings.

The purpose of this study is to clarify the mechanisms involved in the formation and glomerular deposition of immune complexes in lupus nephritis. The determination of an antibody pattern specific for systemic lupus erythematosus and lupus nephritis may also have a role in predicting disease progression in patients with systemic lupus erythematosus without renal impairment. As for the patients enrolled in the study, the determination of their antibody patterns may contribute to a more targeted and personalized treatment, allowing a prediction of disease progression and the introduction of early targeted treatments, in order to block the onset and/or progression of renal damage.

During 1993 and 2006, a total of 987 patients older than 20 years underwent native kidney biopsy at the Renal Division of this hospital. 404 patients with membranoproliferative glomerulonephritis and mesangioproliferative glomerulonephritis, and patients with secondary glomerulonephritis or other renal pathologies, such as diabetic nephropathy, lupus nephritis, rapid progress glomerulonephritis, acute tubular necrosis, and tubulointerstitial nephritis will be analyzed. The demographic characteristics and laboratory data of these patients at presentation or before renal biopsy will be recorded. These data included parameters such as age, sex, diabetes, hypertension, immunosuppressants treatment, BUN, serum creatinine, albumin, hemoglobin, total cholesterol, triglycerides, and urine protein. All subjects will be followed until 2015 for occurrence of primary endpoints, including all-cause death or ESRD requiring long-term dialysis or renal transplantation. A total of 433 patients who had been followed for 3 years during 2003 and 2007 will receive regular clinic follow-up. GFR will be estimated according to the Modification of Diet in Renal Disease (MDRD) abbreviated formula: 186 x Scr -1.154 x age -0.203 x 0.742 (if female). CKD stage will be determined as described by the National Kidney Foundation of the United States. At the time of entry, GFRs of 30-59, 29-15 and < 15 ml/min/1.73 m2 for more than 3 months will be classified as CKD stages 3, 4 and 5, respectively. Baseline Data of the 433 patients are used as recorded at the beginning during 2003 and 2007. The observation period of each patient is defined to start immediately after the registered measurement of serum creatinine satisfying the above criteria (designated as the index date) and lasted until ESRD or end of 2015. ESRD is defined as initiation of RRT, i.e. chronic dialysis or renal transplantation.

At this moment, the duration of the treatment in Proliferative Lupus Nephritis has not been determined. Almost 30 percent of patients in total remission during or after a treatment, will relapse in the first 5 years. The factors associated to Renal relapses are not completly known. The investigators think that an histological control study performed to patient with complete remission for a year at the end of a 3 years treatment could help us to know which patients are going to relapse.

Systemic lupus erythematosus (SLE) is an autoimmune disease which may give rise to multiple organ involvement because of immune complex deposits. Lupus nephritis (LN) is one of the severe manifestations of systemic lupus erythematous (SLE) and a common cause for end-stage renal disease, significantly affecting the survival of SLE patients Immunosuppressive treatment is the major therapy for active LN. Generally, at least six months are needed to assess treatment responses Failure to respond to immunosuppressive therapy can lead to a worsening of renal function