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Persistent and isolated serum low C3 and lupus nephritis








Persistent and isolated serum low C3 and lupus nephritis


Lucio Manenti


Azienda Sanitaria Liguria 5- La Spezia (Italy)






07 November 2023


Lupus nephritis (LN) is a type of kidney disease caused by systemic lupus erythematosus (SLE). SLE is an autoimmune disease —a disorder in which the body's immune system attacks the body's own cells and organs. LN occurs when SLE autoantibodies affect structures in the kidney that filter out waste.This cause kidney inflammation and may lead to blood in the urine, protein in the urine, high blood pressure, impaired kidney function or even kidney failure. LN would lead to end stage renale disease (ESRD)in about a 20% of cases at 5 years. ESRD is the final, permanent stage of chronic renal failure, where kidney function has declined to the point that the kidneys can no longer function on their own.A number of clinical and laboratory data have been identified as biomarkers of disease activity in LN but only few of them are reliable predictors of renal outcome. The complement system (also known as complement cascade) is a group of nearly 60 proteins that are in blood plasma or on the surface of some cells.The complement system is a part of the immune system that enhances (complements) the ability of antibodies and cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane. Three biochemical pathways activate the complement cascade: the classical complement pathway, the alternative complement pathway, and the lectin pathway.Circulating serum C3 (sC3) and serum C4 (sC4) are important proteins of the complement system. Both are regularly tested and a reduction under the normal laboratory values of sC3 or sC4 indicates an activation of the complement cascade. In LN both sC3 and sC4 values are usually low and mark renal activity. However their prognostic significance is still unclear.One of the main limitations of the studies on prognostic biomarker in LN, and on sC3 and sC4 values in particular,is that they often consider only baseline variables (i.e taken at diagnosis or at the beginning of therapy) or variables taken at the time of relapse. Conversely, assessing their dynamic behaviour over time can be even more important since persistent abnormalities may reflect refractoriness to treatment and thus portend a poor prognosis.This would be consistent with data regarding other immune-mediated renal disease, such as atypical forms of post-infectious glomerulonephritis, a kidney inflammation resulting from immunological events triggered by a variety of bacterial, viral, and protozoal infections, where persistent low sC3 values causes a more severe and chronic disease.We would explore if persitently reduced sC3 is a marker of renal prognosis and of treatment failure in patients affected by LN. The proposed post-hoc analysis will be performed on data from the BLISS-LN (Belimumab in Subjects with Systemic Lupus Erythematosus- Lupus Nephritis) study, that evaluated efficacy and safety of Belimumab in a randomized double blind placebo controlled Phase III trial in patients with LN treated concomitantly with standard of care (Mycophenolate Mofetil or Cyclophosphamide+ steroids). The trial evaluated as secondary end points changes from baseline to week 104 in sC3 levels. The regularly repeated doses of sC3 and sC4 levels associated to renal outcome would offer an answer to our research question.



[{ "PostingID": 21074, "Title": "GSK-114054", "Description": "A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Belimumab plus Standard of Care versus Placebo plus Standard of Care in Adult Subjects with Active Lupus Nephritis" }]

Statistical Analysis Plan