Urinary Neutrophil Gelatinase-Associated Lipocalin as a Novel Predictor in Treatment of Active Lupus Nephritis

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Gamal E Mady ◽  
Sahar M Shawky ◽  
Walid A Bichari ◽  
Mohamed S Hassan ◽  
Ahmed M Tawfik ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Disease ◽  
Induction Therapy ◽  
Lupus Erythematosus ◽  
Complete Response ◽  
Response To Treatment ◽  
Class Iii ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Response Groups ◽  
Neutrophil Gelatinase

Abstract Introduction Lupus nephritis (LN) affects almost two-thirds of Systemic lupus erythematosus (SLE) patients. Despite initial aggressive therapy, up to 25% of patients with LN will progress to end stage renal disease (ESRD). Conventional serum markers for LN lack the sensitivity of an ideal biomarker. Urinary Neutrophil gelatinase-associated lipocalin (UNGAL) is an excellent biomarker for early diagnosis of acute kidney injury and predicting renal outcomes. Objectives To measure UNGAL among LN patients correlating its levels with renal disease activity to investigate its predictive performance in response to induction therapy. Patients and Methods 40 SLE patients with biopsy-proven LN, class III, IV, or V were randomly selected. The study was conducted in internal medicine department and Outpatient clinic in Ain Shams University Hospitals on and completed after six months. UNGAL was measured at baseline and after complete induction therapy. Results In LN patients at baseline; mean UNGAL levels of complete response, partial response, and no response groups were 14.48 ±2.99 ng/ml, 34.49 ±4.09, and 62.07 ±14.44 ng/ml respectively. Based on ROC curve, we found better performance of baseline UNGAL to discriminate complete response group from partial and non-response groups to predict response to induction, outperforming conventional biomarkers. The area under the curve was 0.943 (92.31% sensitivity, 88.89% specificity), and the best cut-off level was 26.5 ng/ml. Conclusion UNGAL performed better than conventional biomarkers in predicting response to treatment of active LN.

scholarly journals Value of Urinary Neutrophil Gelatinase-Associated Lipocalin versus Conventional Biomarkers in Predicting Response to Treatment of Active Lupus Nephritis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Mohamed Abd El-Mohsen ◽  
Ahmed Tawfik ◽  
Walid Bichari ◽  
Sahar Shawky ◽  
Gamal Mady ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Induction Therapy ◽  
Lupus Erythematosus ◽  
Complete Response ◽  
Response To Treatment ◽  
Class Iii ◽  
University Hospitals ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
The Mean ◽  
Neutrophil Gelatinase

Introduction. Lupus nephritis (LN) affects almost two-thirds of systemic lupus erythematosus (SLE) patients. Despite initial aggressive therapy, up to 25% of patients with LN will progress to permanent renal damage. Conventional serum markers for LN lack the sensitivity of an ideal biomarker. Urinary neutrophil gelatinase-associated lipocalin (UNGAL) is an excellent biomarker for early diagnosis of acute kidney injury and predicting renal outcomes. Objective. To measure UNGAL among LN patients to correlate its levels with renal disease activity and to investigate its predictive performance in response to induction therapy. Patients and Methods. 40 SLE patients with biopsy-proven LN class III, IV, or V were randomly selected. The study was conducted in the internal medicine department and outpatient clinic in Ain Shams University Hospitals and completed after six months. UNGAL was measured at baseline, three-month follow-up, and after complete induction therapy. Results. In LN patients at baseline, the mean serum creatinine was 2.57 ± 0.96 mg/dL and the mean UNGAL was 33.50 ± 18.34 ng/dL. Mean UNGAL levels of complete response, partial response, and nonresponse groups were 14.48 ± 2.99 ng/mL, 34.49 ± 4.09 ng/mL, and 62.07 ± 14.44 ng/mL, respectively. Based on the ROC curve, we found a better performance of baseline UNGAL to discriminate the complete response group from partial and nonresponse groups to predict response to induction, outperforming conventional biomarkers. The area under the curve was 0.943, and the best cutoff level was 26.5 ng/mL (92.31% sensitivity and 88.89% specificity). Conclusion. UNGAL performed better than conventional biomarkers in predicting response to treatment of active LN.

scholarly journals Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study

2019 ◽  
Vol 6 (1) ◽  
pp. e000298 ◽  
Author(s):  
Thitima Benjachat Suttichet ◽  
Wonngarm Kittanamongkolchai ◽  
Chutipha Phromjeen ◽  
Sirirat Anutrakulchai ◽  
Thanachai Panaput ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Treatment Response ◽  
Induction Therapy ◽  
Characteristic Curve ◽  
Predictive Performance ◽  
Complete Response ◽  
Early Response ◽  
Response To Treatment ◽  
Urine Protein ◽  
Spot Urine

BackgroundTNF-like weak inducer of apoptosis (TWEAK) is a proinflammatory molecule that plays a key role in active inflammation of lupus nephritis (LN). Urine TWEAK (uTWEAK) levels were found to be associated with renal disease activity among patients with LN. Here, we determined whether serial measurements of uTWEAK during induction therapy could predict treatment response or not.MethodsSpot urine samples were collected from patients with biopsy-proven active LN at time of flare, and 3 and 6 months after flare to assess the uTWEAK levels. All patients received standard immunosuppressive therapy and treatment response was evaluated at 6 months. The performance of uTWEAK as a predictor for treatment response was compared with clinically used biomarkers for patients with LN.ResultsAmong 110 patients with LN, there were 29% complete responders (CR), 34% partial responders (PR) and 37% non-responders (NR). On average, uTWEAK level was consistently low in CR, trended down by 3 months in PR and persistently elevated in NR. uTWEAK levels at month 3 were able to predict complete response at month 6 (OR adjusted for age, sex and creatinine=0.34 [95% CI 0.15 to 0.80], the area under the receiver operating characteristic curve [ROC-AUC]=0.68, p=0.02). The optimal threshold for uTWEAK level at month 3 was 0.46 pg/mgCr, discriminating complete response with 70% sensitivity and 63% specificity. Combining uTWEAK and urine protein at month 3 improved predictive performance for complete response at 6 months (ROC-AUC 0.83, p<0.001).ConclusionsIn addition to urine protein, uTWEAK level at 3 months after flare can improve the accuracy in predicting complete response at 6 months of induction therapy.

scholarly journals Comparative analysis of neutrophil gelatinase-associated lipocalin and other laboratory markers for lupus nephritis: a cross-sectional investigation

2016 ◽  
Vol 54 (2) ◽  
pp. 240-245 ◽  
Author(s):  
Sonia L La’ulu ◽  
Brenda B Suh-Lailam ◽  
K Wayne Davis ◽  
Joely A Straseski ◽  
Anne E Tebo
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Immunofluorescence Assay ◽  
Igg Antibodies ◽  
Systemic Lupus ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Double Stranded Dna ◽  
Neutrophil Gelatinase

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.

scholarly journals Urinary Neutrophil Gelatinase-Associated Lipocalin to Monitor Lupus Nephritis Disease Activity

2015 ◽  
Vol 10 ◽  
pp. BMI.S27625 ◽  
Author(s):  
Hani Susianti ◽  
Jullyanny W. Wijaya ◽  
Ati Rastini ◽  
Kusworini Handono ◽  
Atma Gunawan ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Transforming Growth Factor ◽  
Activity Index ◽  
Disease Activity Index ◽  
Transforming Growth Factor Β1 ◽  
Sledai Score ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Neutrophil Gelatinase

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.

CD62L on blood basophils: a first pre-treatment predictor of remission in severe lupus nephritis

2020 ◽  
Author(s):  
Matthieu Halfon ◽  
Delphine Bachelet ◽  
Guillaume Hanouna ◽  
Barbara Dema ◽  
Christophe Pellefigues ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Induction Therapy ◽  
Response To Treatment ◽  
Induction Treatment ◽  
Diagnostic Study ◽  
Class Iii ◽  
Activation Markers ◽  
Class V ◽  
Fluorescent Intensity ◽  
Pre Treatment

Abstract Background Basophils were recently shown to contribute to lupus nephritis (LN). This study assessed blood basophil activation markers (BAMs) for the diagnosis of LN severity and as pre-treatment prognostic markers of the response to treatment in patients with severe LN. Method The diagnostic study included all the patients of a monocentric prospective observational cohort built with consecutive patients diagnosed with LN on the basis of a renal biopsy. The prognostic study selected patients of this cohort according to the following inclusion criteria: ≥18 years old, Class III or IV A ± C ± Class V or pure Class V LN at the time of inclusion and treated with an induction treatment for LN. Clinical data and BAMs were obtained at the time of the kidney biopsy. LN remission status was recorded 12 months after induction therapy initiation. Associations between baseline data and histological severity of LN or LN remission were assessed using logistic regression. Results No significant association was found between BAMs and the histological severity of LN in 101 patients. Among the 83 patients included in the prognostic study, 64 reached renal remission. CD62L expression on blood basophils at baseline was independently negatively associated with remission at 12 months [odds ratio = 0.26, 95% confidence interval 0.08–0.82, P = 0.02 for quantitative CD62L expression &gt;105 (geometric fluorescent intensity) gMFI]. CD62L &lt;105 gMFI was associated with a probability of 0.87 of LN remission in the next 12 months after the start of induction therapy. Conclusion Pre-treatment CD62L expression on blood basophils could be a first predictive biomarker of renal response to induction therapy at 12 months in patients with severe LN.

scholarly journals POS0184 URINE-GALECTINE 3 BINDING PROTEIN (U-GAL3BP) IS A SENSITIVE MARKER OF KIDNEY INFLAMMATION AND RESPONSE TO TREATMENT IN LUPUS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 305.2-306
Author(s):  
F. Faustini ◽  
H. Idborg ◽  
E. Svenungsson ◽  
S. Poetzsch ◽  
S. Okitsu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Binding Protein ◽  
Response To Treatment ◽  
Induction Treatment ◽  
High Dose ◽  
Class Iii ◽  
Systemic Lupus ◽  
Galectin 3

Background:Lupus nephritis (LN) represents a serious manifestation of systemic lupus erythematosus (SLE) which requires timely diagnosis, treatment and monitoring. Kidney biopsy is the gold standard of diagnosis and is instrumental to treatment decisions, however it is not generally performed for monitoring and evaluation of response to treatment. To such purposes, accessible biomarkers, for instance urinary, might be highly advantageous.Objectives:To evaluate urine-Galectin 3 binding protein (uGAL3BP) as a novel biomarker in biopsy-proven active lupus nephritis (A-LN) in comparison to active non-renal SLE (ANR-SLE), inactive SLE (I-SLE), and in population-based controls (HC). Furthermore, we compared uGAL3BP with known markers of renal pathology including neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), kidney injury molecule 1 (KIM-1), and galectin 3 (GAL3).Methods:Urine samples from A-LN (n=86), ANR-SLE (n=63), I-SLE (n=73) and HC (n=48) were included. uGAL3BP was measured using a commercial ELISA kit and values, adjusted for u-creatinine levels, were expressed as ng/mmol. Other markers analyzed according to clinical routine at the Department of Clinical Chemistry at Uppsala University Hospital were also adjusted for u-creatinine levels. Renal biopsies were graded according to the ISN/RPS classification(1) and evaluated for activity and chronicity index. Ten A-LN patients were evaluated before and after induction treatment.Results:In the A-LN group, median (IQR) levels of u-GAL3BP were 15.8 (6.8-24.6) ng/mmol, while in ANR-SLE, I-SLE, HC were significantly lower 4.4 (2.0-9.0), 2.8 (1.7-4.7), 2.0 (0.9-4.8) respectively (Kruskal-Wallis p<0.0001). Similarly, u-NGAL was found at higher levels in A-LN patients, 3.3 (2.0-5.7) μg/mmol, with respect to the ANR-SLE 2.0 (0.9-4.5), I-SLE 1.6 (0.8-3.2), and HC 2.4 (1.2-5.3), (p=0.008). The highest levels of OPN were found in the group of I-SLE (190.6 (85.1-299.9) μg/mmol, compared to A-LN 72.98 (37.6-118.1), ANR-SLE 92.3 (58.5-129.7) and HC 76.5 (58.2-120.3), (p<0.0001). KIM-1 levels differed among groups with higher levels in the A-LN group (188.9 (113.7-309.7) ng/mmol), in comparison to ANR-SLE 131.4 (92.2-186.1), I-SLE 123.8 (70.3-200.2), and HC 78.2 (68.8-115.1), (p<0.0001). GAL3 showed comparable levels across groups.When exploring the biomarkers across histologic subgroups of LN, u-GAL3BP could discriminate between proliferative and mesangial forms (17.7(9.6-32.5) vs 6.7(5.1-16.1) ng/mmol, p=0.027), while it did not discriminate against membranous LN. U-NGAL was higher in proliferative LN 3.7(2.4-5.8) µg/mmol with respect to membranous 2.4 (1.1-3.8) (p=0.01), while mesangial LN showed comparable levels. OPN, KIM-1 and GAL3 were comparable across groups.In the ten patients with available samples after induction therapy (mycophenolate mofetil (MMF) in 4, rituximab (RTX) in one, cyclophosphamide in 5 (one combined with MMF and one with RTX), u-GAL3BP showed a significant decrease of median levels from 218.8 to 41.5 ng/mmol (Wilcoxon p=0.03). u-GAL3BP associated with renal activity in class III/IV LN (R=0.42, p=0.004).Conclusion:Among the tested markers, high uGal3BP adjusted for creatinine was found to be a promising marker of renal involvement in SLE patients and associated with renal activity in patients with proliferative forms (class III/IV) of LN. A decrease was further seen following therapy, suggesting that u GAL3-BP could be used to monitor renal activity.References:[1]Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol. 2004;15(2):241-50.[2]Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, Garrido Ed Ede R, Danieli MG, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 2002;46(8):2121-31.Disclosure of Interests:Francesca Faustini Speakers bureau: I have received speaking fees, last time more than two years ago, Helena Idborg: None declared, Elisabet Svenungsson: None declared, Sven Poetzsch Employee of: Merck Serono, Shinji Okitsu Employee of: Merck Serono, Anders Larsson: None declared, Iva Gunnarsson: None declared

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 ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Renal Involvement ◽  
Disease Activity Index ◽  
Serum Levels ◽  
Roc Curve Analysis ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Neutrophil Gelatinase

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.

scholarly journals Elevated Urinary Neutrophil Gelatinase-Associated Lipocalin Is a Biomarker for Lupus Nephritis: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-18 ◽  
Author(s):  
Yueming Gao ◽  
Bin Wang ◽  
Jingyuan Cao ◽  
Songtao Feng ◽  
Bicheng Liu
Keyword(s):  
Lupus Nephritis ◽  
Publication Bias ◽  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Summary Receiver Operating Characteristic ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Renal Flare ◽  
Auc Value ◽  
Neutrophil Gelatinase

Objective. Lupus nephritis (LN) is a major and severe complication of systemic lupus erythematosus (SLE). Neutrophil gelatinase-associated lipocalin (NGAL), as a promising next-generation biomarker in clinical nephrology, has received extensive attention. However, its diagnostic performance in LN has high variability. Therefore, we performed an updated meta-analysis to further evaluate the diagnostic accuracy of urinary NGAL (uNGAL). Materials and Methods. PubMed, Embase, and Cochrane Library were searched from inception to October 27, 2019. Meta-analysis was performed with a bivariate random effects model. Additionally, the summary receiver operating characteristic (SROC) curves were established. The sources of heterogeneity were explored by meta-regression, subgroup analysis, and sensitivity analysis. Publication bias was assessed using the Deeks test. Results. 19 articles consisting of 21 eligible studies were included. In diagnosing LN, the estimates (95% confidence interval (CI)) were as follows: sensitivity, 0.84 (0.71-0.91); specificity, 0.91 (0.70-0.98); and the SROC-AUC value, 0.92 (0.90-0.94). In identifying active LN, the estimates were as follows: sensitivity, 0.72 (0.56-0.84); specificity, 0.71 (0.51-0.84); and the AUC value, 0.77 (0.74-0.81). With respect to predicting renal flare, the estimates were as follows: sensitivity, 0.80 (0.57-0.92); specificity, 0.67 (0.58-0.75); and the AUC value, 0.74 (0.70-0.78). For the studies to distinguish proliferative LN, the estimates were as follows: sensitivity, 0.87 (0.66-0.97), and specificity, 0.69 (0.39-0.91). Deeks’ funnel plot suggested that there was no significant publication bias. Conclusions. Our meta-analysis indicates that uNGAL was a useful biomarker for diagnosis, estimation of activity, and prediction of renal flare of LN. In addition, the usefulness of uNGAL to distinguish pathological types of LN needs to be further investigated.

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