Analysis of urinary TGF-β1, MCP-1, NGAL, and IL-17 as biomarkers for lupus nephritis

Susianti, Hani; Iriane, Vincentia M.; Dharmanata, Suriya; Handono, Kusworini; Widijanti, Anik; Gunawan, Atma; Kalim, Handono

doi:10.1016/j.pathophys.2014.12.003

Cited by 40 publications

(37 citation statements)

References 19 publications

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“…Additionally, the urine sediment, glomerular filtration rate (GFR), and complement components (like C3 and C4) are considered to be too inaccurate to differentiate the acute inflammatory and the chronic degenerative changes (4). Thus, alternative accurate biomarkers have been required for LN diagnosis or monitoring (5). Presently, numerous studies have been carried out to discover potential biomarkers including urinary monocyte chemoattractant protein-1 (uMCP-1)(6), transforming growth factor beta 1 (uTGF-β1), clusterin (7), and interleukin-17 (uIL-17).…”

Section: Introductionmentioning

confidence: 99%

“…In a mouse model of LN, NGAL level in the kidney, urine, and serum is elevated in connection with disease severity (20). Likewise, human studies have displayed that urinary NGAL (uNGAL) levels can reflect the decline of renal function and the disease activity in LN (5,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Furthermore, it may predict poor response after induction therapy (31).…”

Section: Introductionmentioning

confidence: 99%

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The importance of serum neutrophil gelatinase-associated lipocalin level in patients with lupus nephritis

et al. 2019

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Introduction: The neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a biomarker of renal damage. Objectives: The aim of this study was to assess the serum levels of NGAL (sNGAL) as a marker of disease activity in individuals with lupus nephritis (LN). Patients and Methods: This study contained 50 systemic lupus erythematosus (SLE) individuals with (n = 25) and without (n = 25) nephritis, and 39 healthy controls. The sNGAL levels were measured by ELISA. Renal function test, urinary parameters, lupus serology activity, and also calculated SLE disease activity index (SLEDAI) were analyzed to determine their associations with sNGAL. Results: The results revealed that the SLE individuals with or without nephritis had a raised serum NGAL levels as compared to control subjects (P<0.001). Additionally, sNGAL levels in LN individuals were meaningfully higher compared to those in non-LN patients (P<0.001). Serum NGAL showed a significant correlation with the SLEDAI, serum creatinine, and 24-h urinary protein (P<0.05). More importantly, sNGAL had a significant positive correlation with the activity index of LN (r = 0.616, P=0.001). In the ROC curve analysis, the measurement of sNGAL level showed a good diagnostic performance for distinguishing individuals with LN from SLE patients without renal involvement with AUC=0.902 (P<0.001), 72% sensitivity, and 99% specificity. Moreover, sNGAL could identify all of SLE patients from controls with high accuracy, AUC= 0.99, P<0.001, with 99% sensitivity, and 97% specificity. Conclusion: Serum NGAL had an association with clinical parameters and could discriminate LN from SLE patients without renal involvement. Our result suggests that serum NGAL can be used for early diagnosis of LN and identifying active LN.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The importance of serum neutrophil gelatinase-associated lipocalin level in patients with lupus nephritis

et al. 2019

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“…TGF-β is a multifunctional polypeptide growth factor that regulates cell proliferation, differentiation and apoptosis by complex receptor signaling pathways in the cell surface (19). TGF-β inhibits proliferation of glomerular epithelial cells and endothelial cells; however, it has a dual role on MCs: It stimulates proliferation at a low concentration, and inhibits proliferation at a high concentration (20). MCs have been revealed to secrete TGF-β, and TGF-β regulates the proliferation rate and synthesis of ECM components by binding to the corresponding receptors on MCs (21).…”

Section: Discussionmentioning

confidence: 99%

Effects of Artesunate prevent nephritis via the Toll-like receptor 4/nuclear factor-κB signaling pathway in rats

Wan

2017

Molecular Medicine Reports

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The active ingredient in Artemisia carvifolia, artemisinin, may alleviate inflammation and toxicity. Artemisinin and its derivatives are first‑line anti‑malarial drugs currently, which have rapid effects on fever caused by malaria parasites with fewer side effects. The present study investigated the effects of Artesunate in a mouse nephritis model. Mice were injected intraperitoneally with 500 µl pristine to induce nephritis, and were treated with 28.8 mg/kg Artesunate. Subsequently, proteinuria, renal function, and tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 levels were assessed to evaluate the effects of Artesunate on nephritis. Western blot analysis was used to measure the protein expression levels of α‑smooth muscle actin (SMA), TLR4, myeloid differentiation primary response gene 88 (MyD88), NF‑κB p65 and transforming growth factor (TGF)‑β1 to investigate the underlying mechanisms of Artesunate on nephritis. The results demonstrated that Artesunate reduced proteinuria and preserved renal function in nephritis mice. Artesunate attenuated TNF‑α and IL‑6 levels, suppressed α‑SMA, TLR4, MyD88, NF‑κB p65 and TGF‑β1 protein expression, and decreased caspase‑3 activity in nephritis mice. These results indicated that the effects of Artesunate may prevent nephritis and inhibit inflammation via the TLR4/NF‑κB signaling pathway in mice. Therefore, Artesunate may be a potential therapeutic agent to prevent nephritis.

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“…Table 6 lists the comparison of sensitivity and specificity of different published serum80,111–113 and urine19,114–117 biomarkers related to LN. However, only serum anti-dsDNA antibodies fulfill the aforementioned criteria as a useful disease biomarker in patients with LN.…”

Section: Comparison Of Sensitivity and Specificity Of Part Of The Potmentioning

confidence: 99%

Potential serum and urine biomarkers in patients with lupus nephritis and the unsolved problems

Hsieh¹,

Tsai²,

Yu³

2016

OARRR

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Lupus nephritis (LN) is one of the most frequent and serious complications in the patients with systemic lupus erythematosus. Autoimmune-mediated inflammation in both renal glomerular and tubulointerstitial tissues is the major pathological finding of LN. In clinical practice, the elevated anti-dsDNA antibody titer concomitant with reduced complement C3 and C4 levels has become the predictive and disease-activity surrogate biomarkers in LN. However, more and more evidences suggest that autoantibodies other than anti-dsDNA antibodies, such as anti-nucleosome, anti-C1q, anti-C3b, anti-cardiolipin, anti-endothelial cell, anti-ribonuclear proteins, and anti-glomerular matrix (anti-actinin) antibodies, may also involve in LN. Researchers have demonstrated that the circulating preformed and in situ-formed immune complexes as well as the direct cytotoxic effects by those cross-reactive autoantibodies mediated kidney damage. On the other hand, many efforts had been made to find useful urine biomarkers for LN activity via measurement of immune-related mediators, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry proteomic signature, and assessment of mRNA and exosomal-derived microRNA from urine sediment cell. Our group had also devoted to this field with some novel findings. In this review, we briefly discuss the possible mechanisms of LN and try to figure out the potential serum and urine biomarkers in LN. Finally, some of the unsolved problems in this field are discussed.

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Analysis of urinary TGF-β1, MCP-1, NGAL, and IL-17 as biomarkers for lupus nephritis

Cited by 40 publications

References 19 publications

The importance of serum neutrophil gelatinase-associated lipocalin level in patients with lupus nephritis

The importance of serum neutrophil gelatinase-associated lipocalin level in patients with lupus nephritis

Effects of Artesunate prevent nephritis via the Toll-like receptor 4/nuclear factor-κB signaling pathway in rats

Potential serum and urine biomarkers in patients with lupus nephritis and the unsolved problems

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