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 Urinary MCP-1 and TWEAK as non-invasive markers of disease activity and treatment response in patients with lupus nephritis in South Africa

2020 ◽  
Author(s):  
Mothusi W Moloi ◽  
Jody A Rusch ◽  
Fierdoz Omar ◽  
Udeme Ekrikpo ◽  
Collet Dandara ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Induction Therapy ◽  
Response To Treatment ◽  
Response Monitoring ◽  
Mixed Ancestry ◽  
Monocyte Chemoattractant Protein 1 ◽  
Spot Urine ◽  
Novel Biomarkers

Abstract Background: Treatment of patients with lupus nephritis (LN) requires judicious use of immunosuppression. Novel biomarkers may be useful for monitoring disease activity and treatment response. We assessed the utility of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary tumour necrosis factor-like weak inducer of apoptosis (uTWEAK) for disease activity and treatment response monitoring in South Africans with LN.Methods: We recruited consenting patients with active LN confirmed on kidney biopsy. Urinary levels of MCP-1 and TWEAK were assayed at baseline and after completion of induction therapy using ELISA methods. We also collected relevant demographic, clinical and biochemical data for patients included in this study.Results: The mean age of patients in this study was 29.8 ± 10.7 years, 60% were patients of mixed ancestry, 70% had proliferative LN and mean spot urine proteinuria at baseline was 0.37 (0.18-0.59) g/mmolCr. At completion of induction therapy, the level of uMCP-1 had reduced to 314.5 (IQR: 197.0 – 622) pg/mgCr from a baseline of 1092.7 (IQR: 578.6-1848) pg/mgCr (P=0.06) while uTWEAK had reduced to 36.0 (IQR: 17.0-88.0) pg/mgCr from 159.0 (IQR: 88.5-295.5) pg/mgCr (P=0.03). For patients reaching early complete or partial remission (n=17), both biomarkers had significantly declined in their urine: uMCP-1 (p=0.018) and uTWEAK (p=0.015). There was no reduction of both biomarkers in patients not achieving remission and no association between uMCP-1 or uTWEAK with renal histological features.Conclusion: Our study shows that uMCP-1 and uTWEAK are elevated in patients with active LN, correlated with the remission status (response to treatment) at the end of induction therapy and can therefore be useful for monitoring disease activity and treatment response.

scholarly journals Urinary MCP-1 and TWEAK as non-invasive markers of disease activity and treatment response in patients with lupus nephritis in South Africa

2020 ◽  
Author(s):  
Mothusi W Moloi ◽  
Jody A Rusch ◽  
Fierdoz Omar ◽  
Udeme Ekrikpo ◽  
Collet Dandara ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Induction Therapy ◽  
Response To Treatment ◽  
Response Monitoring ◽  
Mixed Ancestry ◽  
Monocyte Chemoattractant Protein 1 ◽  
Spot Urine ◽  
Study Results

Abstract Background: Treatment of patients with lupus nephritis (LN) requires judicious use of immunosuppression. Novel biomarkers may be useful for monitoring disease activity and treatment response. We assessed the utility of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary tumour necrosis factor-like weak inducer of apoptosis (uTWEAK) for disease activity and treatment response monitoring in South Africans with LN. Methods: We recruited consenting patients with active LN confirmed on kidney biopsy. Urinary levels of MCP-1 and TWEAK were assayed at baseline and after completion of induction therapy using ELISA methods. We also collected relevant demographic, clinical and biochemical data for patients included in this study. Results: The mean age of patients in this study was 29.8 ± 10.7 years, 60% were patients of mixed ancestry, 70% had proliferative LN and mean spot urine proteinuria at baseline was 0.37 (0.18-0.59) g/mmolCr. At completion of induction therapy, the level of uMCP-1 had reduced to 314.5 (IQR: 197.0 – 622) pg/mgCr from a baseline of 1092.7 (IQR: 578.6-1848) pg/mgCr (P=0.06) while uTWEAK had reduced to 36.0 (IQR: 17.0-88.0) pg/mgCr from 159.0 (IQR: 88.5-295.5) pg/mgCr (P=0.03). For patients reaching early complete or partial remission, both biomarkers had significantly declined in their urine: uMCP-1 (p=0.018) and uTWEAK (p=0.015). There was no reduction of both biomarkers in patients not achieving remission and no association between uMCP-1 or uTWEAK with renal histological features. Conclusion: Our study shows that uMCP-1 and uTWEAK are elevated in patients with active LN, correlated with the remission status (response to treatment) at the end of induction therapy and can therefore be useful for monitoring disease activity and treatment response.

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 Differences in rituximab use between pediatric rheumatologists and nephrologists for the treatment of refractory lupus nephritis and renal flare in childhood-onset SLE

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mileka Gilbert ◽  
Beatrice Goilav ◽  
Joyce J. Hsu ◽  
Paul J. Nietert ◽  
Esra Meidan ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Induction Therapy ◽  
Pediatric Nephrology ◽  
Response To Treatment ◽  
Individual Treatment ◽  
Induction Treatment ◽  
Childhood Onset ◽  
Renal Flare ◽  
Treatment Plans

Abstract Background Consensus treatment plans have been developed for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in childhood-onset systemic lupus erythematosus. However, patients who do not respond to initial therapy, or who develop renal flare after remission, warrant escalation of treatment. Our objective was to assess current practices of pediatric nephrologists and rheumatologists in North America in treatment of refractory proliferative LN and flare. Methods Members of Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the American Society for Pediatric Nephrology (ASPN) were surveyed in November 2015 to assess therapy choices (other than modifying steroid dosing) and level of agreement between rheumatologists and nephrologists for proliferative LN patients. Two cases were presented: (1) refractory disease after induction treatment with corticosteroid and cyclophosphamide (CYC) and (2) nephritis flare after initial response to treatment. Survey respondents chose treatments for three follow up scenarios for each case that varied by severity of presentation. Treatment options included CYC, mycophenolate mofetil (MMF), rituximab (RTX), and others, alone or in combination. Results Seventy-six respondents from ASPN and foty-one respondents from CARRA represented approximately 15 % of the eligible members from each organization. Treatment choices between nephrologists and rheumatologists were highly variable and received greater than 50 % agreement for an individual treatment choice in only the following 2 of 6 follow up scenarios: 59 % of nephrologists, but only 38 % of rheumatologists, chose increasing dose of MMF in the case of LN refractory to induction therapy with proteinuria, hematuria, and improved serum creatinine. In a follow up scenario showing severe renal flare after achieving remission with induction therapy, 58 % of rheumatologists chose CYC and RTX combination therapy, whereas the top choice for nephrologists (43 %) was CYC alone. Rheumatologists in comparison to nephrologists chose more therapy options that contained RTX in all follow up scenarios except one (p < 0.05). Conclusions Therapy choices for pediatric rheumatologists and nephrologists in the treatment of refractory LN or LN flare were highly variable with rheumatologists more often choosing rituximab. Further investigation is necessary to delineate the reasons behind this finding. This study highlights the importance of collaborative efforts in developing consensus treatment plans for pediatric LN.

scholarly journals Urine Biomarkers to Predict Response to Lupus Nephritis Therapy in Children and Young Adults

2017 ◽  
Vol 44 (8) ◽  
pp. 1239-1248 ◽  
Author(s):  
Hermine I. Brunner ◽  
Michael R. Bennett ◽  
Gaurav Gulati ◽  
Khalid Abulaban ◽  
Marisa S. Klein-Gitelman ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Transforming Growth Factor ◽  
Kidney Biopsy ◽  
Characteristic Curve ◽  
Kidney Injury ◽  
Transforming Growth Factor Β ◽  
Response To Therapy ◽  
Spot Urine ◽  
Urine Biomarkers

Objective.To delineate urine biomarkers that forecast response to therapy of lupus nephritis (LN).Methods.Starting from the time of kidney biopsy, patients with childhood-onset systemic lupus erythematosus who were diagnosed with LN were studied serially. Levels of 15 biomarkers were measured in random spot urine samples, including adiponectin, α-1-acid glycoprotein (AGP), ceruloplasmin, hemopexin, hepcidin, kidney injury molecule 1, monocyte chemotactic protein-1, lipocalin-like prostaglandin D synthase (LPGDS), transforming growth factor-β (TGF-β), transferrin, and vitamin D binding protein (VDBP).Results.Among 87 patients (mean age 15.6 yrs) with LN, there were 37 treatment responders and 50 nonresponders based on the American College of Rheumatology criteria. At the time of kidney biopsy, levels of TGF-β (p < 0.0001) and ceruloplasmin (p = 0.006) were significantly lower among responders than nonresponders; less pronounced differences were present for AGP, hepcidin, LPGDS, transferrin, and VDBP (all p < 0.05). By Month 3, responders experienced marked decreases of adiponectin, AGP, transferrin, and VDBP (all p < 0.01) and mean levels of these biomarkers were all outstanding (area under the receiver-operating characteristic curve ≥ 0.9) for discriminating responders from nonresponders. Patient demographics and extrarenal disease did not influence differences in biomarker levels between response groups.Conclusion.Low urine levels of TGF-β and ceruloplasmin at baseline and marked reduction of AGP, LPGDS, transferrin, or VDBP and combinations of other select biomarkers by Month 3 are outstanding predictors for achieving remission of LN. If confirmed, these results can be used to help personalize LN therapy.

scholarly journals Analysis of HLA-G expression in renal tissue in lupus nephritis: a pilot study

Lupus ◽  
2019 ◽  
Vol 28 (9) ◽  
pp. 1091-1100
Author(s):  
V Foschi ◽  
D Bortolotti ◽  
A F Doyle ◽  
V Stratigou ◽  
L Stephens ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Juxtaglomerular Apparatus ◽  
Complete Response ◽  
Renal Tissue ◽  
Response To Treatment ◽  
Induction Phase ◽  
Glomerular Epithelial Cells ◽  
Number Of Patients ◽  
Renal Biopsies ◽  
Infiltrating Cells

Background The study aimed to investigate whether HLA-G antigen is expressed in the kidneys of patients affected by lupus nephritis (LN) and whether its detection in renal biopsies could be adopted as a marker of treatment response and prognosis. Methods Thirty renal biopsies from patients with LN were selected and analyzed through immunohistochemistry. Laboratory and clinical data were retrospectively collected at baseline, 6 and 12 months and at the latest clinical appointment. A number of patients (63.3%) were treated with rituximab (RTX) +/− methylprednisolone in the induction phase. The expression of HLA-G in glomeruli, tubules and infiltrating cells was examined and compared between lupus patients who achieved either complete or partial renal response and those who did not respond to treatment. Results HLA-G staining was observed in the glomeruli of 20 of 30 samples from patients with LN. The expression of the antigen was detected in podocytes, along glomerular capillary walls, on parietal glomerular epithelial cells and within the juxtaglomerular apparatus. Seventy per cent of patients whose glomeruli expressed HLA-G achieved partial or complete response at 6 months and 75% at the latest available follow up compared with 30% and 40%, respectively, of those who did not show any expression. The pattern of staining in tubules and infiltrating cells was highly variable precluding any clinical correlation. Conclusion This study demonstrates that HLA-G is expressed in renal tissue in LN. Our retrospective data suggest that its expression could correlate with response to treatment.

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.

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