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Identifying new markers of disease flares in lupus nephritis (LN) that facilitate patient stratification and prognosis is important. Therefore, the aim of the present study was to analyze whether urinary SIRT1 expression was altered in LN and whether SIRT1 values in urine could be valuable biomarker of disease activity. In a cohort study, urinary pellets from 40 patients diagnosed with systemic lupus erythematosus (SLE) were analyzed. Clinical measures of lupus activity were assessed. The expression of SIRT1 was quantified by quantitative PCR (qRT-PCR) and immunoblot, then compared between patients with active lupus nephritis, in remission and healthy controls. Association with lupus activity and renal histological features was also analyzed. A significant increase in SIRT1 mRNA levels in patients with active LN was observed compared with those in remission (P=0.02) or healthy controls (P=0.009). In addition, SIRT-1 protein levels were also augmented in LN group than remission (P=0.029) and controls (P=0.001). A strong association was found between SIRT1 expression with anti-dsDNA in SLE and in patients with LN. In addition, histological features in LN biopsies were related with SIRT1, increasing its expression in proliferative forms. Finally, SIRT1 expression values showed a strong discriminatory power of renal injury in SLE. Our study demonstrated an altered urinary expression of SIRT1 and a strong association with disease activity in LN patients, being a valuable marker of renal injury. These results showed the role of the SIRT1 pathway in the SLE pathogenesis. [ABSTRACT FROM AUTHOR]

Despite considerable progress in our understanding of systemic lupus erythematosus (SLE) pathophysiology, patient diagnosis is often deficient and late, and this has an impact on disease progression. The aim of this study was to analyze non-coding RNA (ncRNA) packaged into exosomes by next-generation sequencing to assess the molecular profile associated with renal damage, one of the most serious complications of SLE, to identify new potential targets to improve disease diagnosis and management using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The plasma exosomes had a specific ncRNA profile associated with lupus nephritis (LN). The three ncRNA types with the highest number of differentially expressed transcripts were microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and piwi-interacting RNAs (piRNAs). We identified an exosomal 29-ncRNA molecular signature, of which 15 were associated only with LN presence; piRNAs were the most representative, followed by lncRNAs and miRNAs. The transcriptional regulatory network showed a significant role for four lncRNAs (LINC01015, LINC01986, AC087257.1 and AC022596.1) and two miRNAs (miR-16-5p and miR-101-3p) in network organization, targeting critical pathways implicated in inflammation, fibrosis, epithelial–mesenchymal transition and actin cytoskeleton. From these, a handful of potential targets, such as transforming growth factor-β (TGF-β) superfamily binding proteins (activin-A, TGFB receptors, etc.), WNT/β-catenin and fibroblast growth factors (FGFs) have been identified for use as therapeutic targets of renal damage in SLE. [ABSTRACT FROM AUTHOR]

Background. Currently, renal biopsy remains the gold standard for the diagnosis and prognosis of lupus nephritis (LN). However, it is an invasive method, and new non-invasive laboratory tests are needed to identify renal involvement without renal biopsy. Podocyte damage plays an important role in the pathogenesis and progression of systemic lupus erythematosus (SLE). We characterize whether the phenotype of urinary podocytes (viability, apoptosis, mRNA and protein levels of the podocyteassociated molecules) is a novel marker of clinical and histological features in SLE patients with or without LN. Methods. We quantified in urinary sediments of 32 SLE patients and 20 controls, mRNA and protein levels of podocalyxin, synapotopodin, podocin, nephrin andWT-1 by quantitative real-time polymerase chain reaction and western blot analysis and correlated thesewith clinical and histological parameters. The viability of detached urine podocytes was analysed by flow cytometry with podocalyxin and annexin V/7-AAD double staining and immunofluorescence of urine podocyte cultures. Results. The degree of a poptotic podocytes from urine samples was significantly decreased in patients with LN, especially in the active state (33% compared with 75% in controls, P < 0.001), and the majority of the detached podocytes in the urine of patients with active LN were viable (70% grew in culture). Furthermore, urinary mRNA of podocyte-associated molecules was significantly lower in patients with active LN (P < 0.05) compared with healthy controls, and protein levels of podocyte markers were significantly increased in SLE patients, especially with LN compared with SLE without LN (P < 0.05) and the healthy control group (P < 0.01). Finally, urinary protein levels of podocyte-related markers were associated with proteinuria and histological features (P < 0.05 and P < 0.01), and receiver operating characteristics curves of protein levels discriminate between LN and healthy controls with an area under the curve (AUC) between 0.91 and 0.77 (P < 0.001). Conclusions. Urinary dedifferentiated podocytes were shown in active LN, and their protein levels correlated with proteinuria and histological features in LN. These preliminary results suggest that it could be a potentially useful non-invasive marker for evaluating the progression of glomerular disease in SLE. [ABSTRACT FROM AUTHOR]