Abstract
BackgroundNew non-invasive biomarkers are demanded to identify renal damage in various autoimmune-associated kidney diseases. Glomerular podocyte damage mediated by systemic lupus erythematosus (SLE) plays an important role in the pathogenesis and progression of lupus nephritis (LN). This study evaluated whether the podocyte-derived microparticles (MPs) were novel biomarkers of clinical and histological features in SLE patients with LN.MethodsA cross-sectional study, including 34 SLE patients and 16 healthy controls, was designed. Urinary annexin V+ podocalyxin+ MPs of all participants were quantified by flow cytometry. The correlation of podocyte-derived MPs with clinical and histological parameters of SLE patients was analysed.ResultsThe number of annexin V+ podocalyxin+ MPs from urine samples were markly increased in patients with SLE. Furthermore, the level of urinary podocyte-derived MPs was positively correlated with the SLE Disease Activity Index (SLEDAI) score, anti-dsDNA antibody titre, erythrocyte sedimentation rate, and proteinuria. Conversely, it was negatively correlated with the level of complement C3 and serum albumin. The number of urinary podocyte-derived MPs was significantly increased in SLE patients with high activity indices. Receiver operating characteristic (ROC) curves were calculated to assess the power for podocyte-derived MP levels in differentiating between SLE patients with and without LN. Podocyte-derived MP levels were able to differentiate between SLE patients with mild disease activity, as well as those with moderate and above disease activity. SLE patients showed increased podocyte-derived MP excretion into the urine.ConclusionsThese findings suggest that the change in urinary podocyte-derived MP levels could be useful for evaluating and monitoring SLE disease activity.
Highlights
New non-invasive biomarkers are demanded to identify renal damage in various autoimmune-associated kidney diseases
We found that there were a variety of morphological podocyte lesions among different pathological types of lupus nephritis (LN)
There were extensive effaced podocyte foot processes in LN with Type III/V, Type IV/V, and Type V. These findings suggest that the urinary levels of podocyte-derived microparticles are closely correlated with the active indices and the ultrastructure change of podocytes
Summary
New non-invasive biomarkers are demanded to identify renal damage in various autoimmune-associated kidney diseases. Glomerular podocyte damage mediated by systemic lupus erythematosus (SLE) plays an important role in the pathogenesis and progression of lupus nephritis (LN). This study evaluated whether the podocyte-derived microparticles (MPs) were novel biomarkers of clinical and histological features in SLE patients with LN. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiple organ injuries. Lupus nephritis (LN) is recognized as one of the most severe organ manifestations of SLE and is characterized by proteinuria, haematuria and progressive renal dysfunction. The pathogenesis of LN involves the glomerular deposition of autoantibodies related to self-antigens, the activation of complement system, the infiltration of inflammatory cells, Microparticles (MPs), a subtype of extracellular vesicles (EVs), are released by outward blebbing of the plasma membrane after the externalization of phosphatidylserine (PS) during cell activation and apoptosis [1].
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