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

2019 ◽  
Vol 8 (2) ◽  
pp. 133-139
Author(s):  
Mohammad Reza Jafari Nakhjavani ◽  
Sima Abediazar ◽  
Amir Ghorbanihaghjo ◽  
Behnaz Hanafizadeh ◽  
Sepideh Zununi Vahed ◽  
...  

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.

2015 ◽  
Vol 10 ◽  
pp. BMI.S27625 ◽  
Author(s):  
Hani Susianti ◽  
Jullyanny W. Wijaya ◽  
Ati Rastini ◽  
Kusworini Handono ◽  
Atma Gunawan ◽  
...  

Background This study was conducted to determine whether there is an association between urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary transforming growth factor-β1 (uTGF-β1) with lupus nephritis (LN) disease activity. Methods Urine samples from 18 LN patients were collected every month for six months then examined for uNGAL, uTGF-β1, and renal domain Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. Results The uNGAL levels were significantly different between active and inactive LN (P < 0.05). uTGF-β1 levels were not different between active and inactive LN (P > 0.05). There was a significant correlation between uNGAL levels and renal domain SLEDAI score (r= 0.417, P < 0.05). There was no correlation between uTGF-β1 levels and renal domain SLEDAI score (r = 0.031, P > 0.05). Conclusion uNGAL is better than uTGF-β1 for differentiation of active and inactive LN. uNGAL can be considered as a biomarker to monitor LN disease activity.


2017 ◽  
Author(s):  
Άρτεμις-Ωραιάνθη Κουτσονικολή

Εισαγωγή. Η νεφρίτιδα αποτελεί τον καθοριστικότερο παράγοντα της συνολικής βαρύτητας και πρόγνωσης του παιδιατρικού Συστηματικού Ερυθηματώδους Λύκου (πΣΕΛ). Η ανεύρεση νέων βιολογικών δεικτών, ειδικών για τη νεφρίτιδα του πΣΕΛ, θα επιτρέψει τη μη επεμβατική εκτίμηση της πορείας της και τη στοχευμένη θεραπεία. Τα επιστημονικά δεδομένα για τους παιδιατρικούς ασθενείς, ιδιαιτέρως για ομοιογενείς καυκάσιους πληθυσμούς, είναι ακόμη ελλειπή. Σκοπός. Να διερευνηθεί η σχέση των αντισωμάτων έναντι των νουκλεοσωμάτων (αντι-NCS) ορού, των αντισωμάτων έναντι της βασικής μεμβράνης του σπειράματος (αντι-GBM) ορού, των αντισωμάτων έναντι του παράγοντα C1q του συμπληρώματος (αντι-C1q) ορού, της πρωτεΐνης High-Mobility Group Box-1 (HMGB1) ορού και ούρων και της Neutrophil Gelatinase-Associated Lipocalin (NGAL) ούρων με: (α) την παρουσία νεφρίτιδας στον πΣΕΛ και (β) με την ενεργότητα του πΣΕΛ και της νεφρίτιδας ειδικότερα, σε έναν αμιγώς καυκάσιο πληθυσμό ασθενών από τη βόρεια Ελλάδα. Υλικό-Μέθοδοι. Ελήφθησαν δείγματα ορού και ούρων από 22 ασθενείς με πΣΕΛ και νεφρίτιδα, 20 ασθενείς με πΣΕΛ χωρίς νεφρίτιδα, 15 ασθενείς με νεφρίτιδα άλλης αυτοάνοσης αιτιολογίας (IgA νεφροπάθεια, νεφρίτιδα πορφύρας Henoch-Schönlein, μεταλοιμώδη νεφρίτιδα ή μεμβρανώδη σπειραματονεφρίτιδα) και 26 υγιείς μάρτυρες. Ο προσδιορισμός των βιολογικών δεικτών έγινε με τη μέθοδο ELISA. Η ενεργότητα του πΣΕΛ και της νεφρίτιδας του πΣΕΛ εκτιμήθηκε με το εργαλείο SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index-2000). Αποτελέσματα. Α. Βιολογικοί δείκτες ορού. Τα επίπεδα των αντι-NCS, των αντι-GBM, των αντι-C1q και της HMGB1 βρέθηκαν στατιστικώς σημαντικά υψηλότερα στους ασθενείς με νεφρίτιδα του πΣΕΛ συγκριτικά με τους υγιείς μάρτυρες αλλά και συγκριτικά με τους ασθενείς με νεφρίτιδα άλλης αυτοάνοσης αιτιολογίας. Κατά τη σύγκριση των επιπέδων των βιολογικών δεικτών ορού μεταξύ των ασθενών με νεφρίτιδα του πΣΕΛ και των ασθενών με πΣΕΛ χωρίς νεφρίτιδα, τα αντι-NCS, τα αντι-GBM και η HMGB1 παρουσίαζαν στατιστικώς σημαντικά υψηλότερες τιμές στους ασθενείς με νεφρίτιδα, ενώ για τα αντι-C1q δεν παρατηρήθηκαν στατιστικώς σημαντικές διαφορές. Τα επίπεδα της HMGB1 παρουσίασαν υψηλή θετική συσχέτιση με την ενεργότητα της νεφρίτιδας του πΣΕΛ. Τα επίπεδα της HMGB1 και των αντι-C1q παρουσίασαν μέτρια θετική συσχέτιση με την ενεργότητα του πΣΕΛ συνολικά. Β. Βιολογικοί δείκτες ούρων. Τα επίπεδα της NGAL και της HMGB1 ήταν στατιστικώς σημαντικά υψηλότερα στους ασθενείς με νεφρίτιδα του πΣΕΛ συγκριτικά με τους ασθενείς με πΣΕΛ χωρίς νεφρίτιδα. Επιπλέον, τα επίπεδα της NGAL παρουσίασαν μέτρια θετική συσχέτιση και τα επίπεδα της HMGB1 υψηλή θετική συσχέτιση με την ενεργότητα της νεφρίτιδας του πΣΕΛ. Συμπεράσματα. Σε αυτόν τον ομοιογενή πληθυσμό Καυκάσιων ασθενών με πΣΕΛ, τα αντι-NCS, τα αντι-GBM, η HMGB1 ορού και ούρων και η NGAL ούρων προέκυψαν ως πιθανοί χρήσιμοι βιολογικοί δείκτες, ενδεικτικοί της νεφρικής προσβολής. Επιπλέον, τα αντι-NCS, τα αντι-GBM και η HMGB1 ορού δεν φαίνεται να παρουσιάζουν αύξηση σε νεφρίτιδες άλλης αυτοάνοσης αιτιολογίας. Η HMGB1 ορού και ούρων και η NGAL ούρων προέκυψαν ως πιθανοί χρήσιμοι βιολογικοί δείκτες παρακολούθησης της ενεργότητας της νεφρίτιδας του πΣΕΛ. Τα αντι-C1q και η HMGB1 ορού προέκυψαν ως πιθανοί χρήσιμοι βιολογικοί δείκτες παρακολούθησης της ενεργότητας του πΣΕΛ συνολικά.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Christopher Sjӧwall ◽  
Chelsea Bentow ◽  
Mary Ann Aure ◽  
Michael Mahler

Objective. Anti-double-stranded (ds) DNA and anti-C1q autoantibodies are useful tools in the assessment of disease activity and nephritis in systemic lupus erythematosus (SLE) patients. This study aimed to explore the utility of these antibodies along with anti-Ku antibodies in an oligoparametric model approach for the assessment of disease activity and lupus nephritis. Methods. Samples from 261 well-characterized SLE patients were tested using chemiluminescent immunoassays (CIA) for anti-dsDNA and anti-Ku antibodies as well as by anti-C1q antibody ELISA (Inova Diagnostics, USA). Of these SLE patients, 26.4% had lupus nephritis (LN) at the time of blood draw or had a history of LN, and modified SLE disease activity index-2K (SLEDAI) scores were used to assess disease activity. Results. All three antibodies demonstrated higher prevalence and higher antibody levels in active versus inactive SLE patients and in LN versus non-LN patients. When oligoparametric analysis was performed, the likelihood of LN and patients with active disease increased with dual and triple positivity. Conclusions. Anti-dsDNA and anti-C1q antibodies are useful tools to identify disease activity and/or renal involvement in SLE patients. In addition, the combination of those antibodies in a two-parametric score might improve the clinical utility of those markers.


Lupus ◽  
2020 ◽  
Vol 29 (4) ◽  
pp. 379-388 ◽  
Author(s):  
S Mirioglu ◽  
S Cinar ◽  
H Yazici ◽  
Y Ozluk ◽  
I Kilicaslan ◽  
...  

Objectives TNF-like weak inducer of apoptosis (TWEAK), monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) are proinflammatory cytokines/chemokines that are considered as potential biomarkers reflecting disease activity in systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of serum (s) and urine (u) levels of TWEAK, MCP-1 and NGAL with disease activity in both renal and extra-renal SLE. Methods Thirty active patients with SLE (15 renal and 15 extra-renal) were recruited. Thirty-one inactive patients with SLE (16 renal and 15 extra-renal), 14 patients with ANCA-associated vasculitis (AAV) all of whom had active renal involvement and 20 healthy volunteers were selected as control groups. Serum and urine levels of TWEAK, MCP-1 and NGAL were tested using ELISA. Results Serum and urine levels of TWEAK and NGAL were significantly higher in the active SLE group compared to the inactive SLE group (sTWEAK p = 0.005; uTWEAK p = 0.026; sNGAL p < 0.001; uNGAL p = 0.002), whilst no significant differences regarding serum and urine MCP-1 levels were observed ( p = 0.189 and p = 0.106, respectively). uTWEAK ( p = 0.237), sMCP-1 ( p = 0.141), uMCP-1 ( p = 0.206), sNGAL ( p = 0.419) and uNGAL ( p = 0.443) levels did not differ between patients with active renal and extra-renal SLE. Serum TWEAK was higher in patients with active renal SLE ( p = 0.006). There were no differences between active renal SLE and active renal AAV. Levels of all biomarkers were correlated with the SLE Disease Activity Index. Conclusion sTWEAK, uTWEAK, sNGAL and uNGAL are biomarkers showing disease activity in SLE. However, our results implicate that these biomarkers may not be specific for SLE, and can be elevated in patients with active renal involvement of AAV.


Author(s):  
Sonia L La’ulu ◽  
Brenda B Suh-Lailam ◽  
K Wayne Davis ◽  
Joely A Straseski ◽  
Anne E Tebo

Background Lupus nephritis is one of the most serious complications of systemic lupus erythematosus. This study evaluates the prevalence and correlation between neutrophil gelatinase-associated lipocalin and other biomarkers associated with renal involvement in systemic lupus erythematosus. Methods Paired serum and urine specimens from 50 suspected systemic lupus erythematosus patients, characterized by antinuclear antibodies detected by indirect immunofluorescence assay and varying positive concentrations of anti-double stranded DNA antibodies by Crithidia luciliae immunofluorescence assay, were investigated. Of these 50 patients, 18 were identified with renal involvement based upon laboratory serology. Patients and healthy control serum samples ( n = 50) were also evaluated for high avidity double stranded DNA IgG antibodies, anti-C1q IgG antibodies, and serum creatinine. The prevalence and relationship between biomarkers were evaluated using statistical methods. Results Serum and urine neutrophil gelatinase-associated lipocalin concentrations were significantly elevated in patients compared to controls, with a prevalence of 24% and 36%, respectively. These concentrations were also more markedly increased in systemic lupus erythematosus patients with renal involvement than those without. Spearman’s correlations between neutrophil gelatinase-associated lipocalin and other biomarkers tested ranged from 0.06 to 0.66 in all patients. Combined concordance as determined by Cronbach alpha coefficient between biomarkers was reduced from 0.71 to 0.58 (serum) and 0.62 (urine) when neutrophil gelatinase-associated lipocalin was removed. Conclusions Neutrophil gelatinase-associated lipocalin concentrations are elevated and demonstrate variable associated with other laboratory markers for renal involvement in systemic lupus erythematosus. Prospective longitudinal studies are needed to determine the optimal biomarker combinations for use in routine management of systemic lupus erythematosus patients at-risk for lupus nephritis.


Lupus ◽  
2020 ◽  
Vol 29 (6) ◽  
pp. 607-616
Author(s):  
Asmaa SM Abdel-Rehim ◽  
Nesrine A Mohamed ◽  
Marwa M Shakweer

Background Lupus nephritis (LN) is an ominous manifestation of systemic lupus erythematosus (SLE). Clinical renal affection is present in about 70% of lupus patients, and more patients have histological evidence of renal involvement without clinical manifestations. This study aimed to investigate the potential role of serum interleukin-34 (IL-34) as an early marker for the detection of silent LN. Methods Thirty-three lupus patients with silent LN (group I), 37 patients with clinical LN (group II) and 20 controls were included. The SLE Disease Activity Index (SLEDAI), IL-34, anti-dsDNA antibodies and renal biopsy were assessed in all patients. Results Serum IL-34 levels were significantly higher in all lupus patients compared to healthy controls ( p < 0.001) and showed a significant positive correlation with SLEDAI score. SLE patients with positive anti-dsDNA antibodies had more active disease according to SLEDAI and higher levels of IL-34 than those with negative anti-dsDNA antibodies. In both studied groups, serum IL-34 levels were significantly higher in patients with proliferative LN (class III and class IV) than those with non-proliferative lupus (class II and class V) and controls. Yet, in both groups, IL-34 was not useful in differentiating active from chronic renal affection. Conclusion In lupus patients with insignificant proteinuria, serum levels of IL-34 distinguished the different histological classes of subclinical LN. Serum IL-34 may be used as a surrogate marker for early renal affection in silent LN, especially the proliferative type.


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Azita Sohrabian ◽  
Ioannis Parodis ◽  
Nellie Carlströmer-Berthén ◽  
Martina Frodlund ◽  
Andreas Jönsen ◽  
...  

Abstract Introduction Immune complexes are of importance in systemic lupus erythematosus pathogenesis, and autoantibodies are believed to participate in immune complex formation. Quantification of autoantibody levels in circulating IC might be of prognostic value. Methods A C1q-binding-eluting technique was applied to purify immune complexes from 55 belimumab-treated systemic lupus erythematosus patients during a 24-month follow-up. Autoantibodies in serum and in solubilized immune complexes were quantified using addressable laser bead immunoassay. We investigated whether levels of autoantibodies in immune complexes associate with disease activity and response to belimumab treatment. Results High baseline anti-double-stranded DNA and anti-histone levels in immune complexes associated with attainment of zero scores in clinical systemic lupus erythematosus disease activity index 2000 during the 24-month follow-up (p = 0.003 and p = 0.048, respectively). Low complement levels associated with high serum anti-double-stranded DNA and anti-ribosomal P levels (p = 0.003 and p = 0.008, respectively) and high anti-double-stranded DNA (p = 0.002) but not anti-ribosomal P levels in immune complexes. Anti-SSA/SSB serum levels were lower in patients attaining lupus low disease activity state at month 6; these associations were stronger for corresponding immune complex levels. Serum levels of most autoantibodies had declined at month 3, whereas autoantibody levels in immune complexes, except for anti-double-stranded DNA, showed a more gradual decline over 1–2 years. Serum anti-double-stranded DNA levels decreased in all patients irrespective of systemic lupus erythematosus disease activity index 2000=0 attainment, whereas immune complex levels decreased only in achievers. Conclusion Immune complex levels of autoantibodies against double-stranded DNA and the SSA/SSB complex show more specific associations with treatment outcome compared with serum levels in belimumab-treated systemic lupus erythematosus patients. Characterization of autoantibody content in circulating immune complexes could prove useful in treatment evaluation in systemic lupus erythematosus and other immune complex-associated diseases.


2005 ◽  
Vol 12 (1) ◽  
pp. 56-59 ◽  
Author(s):  
Krisztina Sallai ◽  
Eszter Nagy ◽  
Beata Derfalvy ◽  
Györgyi Müzes ◽  
Peter Gergely

ABSTRACT Nucleosomes are the dominant autoantigens in patients with systemic lupus erythematosus (SLE), and immune complexes involving nucleosomes are the major cause of tissue damage. The activity of DNase I, the enzyme responsible for nucleosome degradation, has been found to be decreased in patients with SLE. However, it is not known whether DNase activity is a clinically useful parameter. The aim of our study was to assess DNase activity in a prospective study of 113 patients with SLE in relation to disease activity and organ involvement. We included two control groups: 9 patients with undifferentiated connective tissue disease (UCTD) and 14 healthy individuals. DNase activity was found to be lower in patients with SLE (63.75% ± 12.1%) than in the controls (81.3% ± 9.25%) (P < 0.001). DNase activity in patients with UCTD (64.9% ± 18.2%; P = 0.854) did not differ from that in patients with SLE. Patients with SLE had higher antinucleosome antibody titers (356.3 ± 851) than the controls (1.44 ± 2.77; P < 0.01) or UCTD patients (39.9 ± 57.7; P < 0.01). In addition, samples positive for antinucleosome antibodies displayed low levels of DNase activity. Within the SLE group, the presence of renal disease had no impact on DNase activity or antinucleosome antibody titers. Also, the SLE disease activity index showed no correlation with DNase activity. In a longitudinal study of six SLE patients, DNase activity did not follow disease activity or autoantibody titers. Our results confirm that serum DNase activity is decreased in patients with SLE, but we conclude that it is not a clinically useful parameter for the prediction of flare-ups of disease or renal involvement.


Lupus ◽  
2020 ◽  
Vol 29 (6) ◽  
pp. 560-568 ◽  
Author(s):  
Tatiana N Pedrosa ◽  
Sandra G Pasoto ◽  
Nadia E Aikawa ◽  
Emily FN Yuki ◽  
Eduardo F Borba ◽  
...  

Objectives It is unknown if hydroxychloroquine blood level dynamics impact flare rates in lupus nephritis patients. We prospectively evaluated hydroxychloroquine levels to determine which blood-based patterns are more associated with disease activity. Methods In total, 82 lupus nephritis patients under a prescribed hydroxychloroquine dose of 4–5.5 mg/kg actual body weight (maximum 400 mg/day) for ≥3 months were evaluated at baseline and 7 months. Hydroxychloroquine blood levels were determined by liquid chromatography-tandem mass spectrometry. Flare was defined as increase ≥3 in the Systemic Lupus Erythematosus Disease Activity Index 2000 score and/or a change or increase in therapy. Results Overall, 9/82(11%) patients had flares during follow-up and had lower baseline hydroxychloroquine blood levels than those without flares (220.4 (53.5–1471.1) vs. 1006.3 (53.5–2137.8) ng/ml, p = 0.013). The hydroxychloroquine blood level cut-off that best predicted flares was 613.5 ng/ml (odds ratio = 8.67, 95% confidence interval: 1.66–45.18, p = 0.006). For 77 (94%) patients, the 7-month hydroxychloroquine level dynamics was evaluated and revealed: 59/77 (77%) had a persistent pattern of adequate (41/77(53%)) or fluctuating (18/77 (23%)) levels, with a low and comparable risk of flares (2/41 (5%) vs. 1/18 (5%), p = 1.000). The remaining group had persistent low levels (18/77 (23%)) and their flare frequency was significantly higher than the adequate group (5/18 (28%) vs. 2/41 (5%), p = 0.023). The frequencies of adequate/inadequate hydroxychloroquine blood levels in patients were comparable at baseline and 7 months (McNemar’s test, p = 0.480). Conclusion We provide novel evidence that hydroxychloroquine blood-level patterns (persistently low, adequate, or intermittent) have distinct impacts on flare rates in lupus nephritis patients. These findings reinforce the need of routine hydroxychloroquine measurements to maintain the appropriate blood levels.


2020 ◽  
Vol 47 (1) ◽  
Author(s):  
Sahar A. Elsayed ◽  
Omar M M. Mohafez

Abstract Background Specific autoantibodies are considered as an important marker in autoimmune rheumatic diseases and are of great value for the diagnosis and prognosis of systemic lupus erythematosus (SLE) patients. A total of eighteen autoantibodies were analyzed for their positivity in SLE patients and we evaluated the clinical relevance of the five most frequent autoantibodies: anti-dsDNA, anti-nucleosome, anti-histone, anti-Ro60, and anti-Ro52 on disease activity and renal affection in SLE Egyptian patients. Results Immunological profile and correlation of the five autoantibodies with disease activity and histopathological pattern of renal involvement were analyzed for 190 SLE patients. Lupus nephritis (LN) patients showed much worse constitutional and mucocutaneous manifestations than patients without nephritis. Autoantibody profile showed a significant increased frequency of anti-dsDNA, anti-nucleosome, anti-histone, anti-Ro-60, and anti-Ro52 antibodies in LN patients. The impact of the co-positivity of the autoantibodies on the renal function was obvious. Moreover, the disease activity increased by the increased frequency of autoantibodies positivity in LN patients. ROC curve analysis showed that anti-nucleosome had the highest sensitivity; 93% followed by anti-dsDNA 83.3% then anti-histone 73.8%, but anti-Ro60 and anti-Ro52 showed a humble sensitivity. Furthermore, the highest frequency of positivity for the five autoantibodies was found in class-III and class-IV LN patients. Conclusion Detection of anti-dsDNA, anti-nucleosome, anti-histone, and anti-Ro60 in SLE patients may be important for predicting disease progression and kidney affection. Moreover, anti-nucleosome and anti-dsDNA show high sensitivity and specificity for lupus nephritis, thus patients with four to five positive autoantibody panels should be kept under close monitoring as they may warrant considering aggressive therapy to control their disease and prevent renal damage.


Sign in / Sign up

Export Citation Format

Share Document