Identification of a urinary proteomic signature for lupus nephritis in children

Suzuki, Michiko; Ross, Gary F.; Wiers, Kristina; Nelson, Shannen; Bennett, Michael; Passo, Murray H.; Devarajan, Prasad; Brunner, Hermine I.

doi:10.1007/s00467-007-0608-x

Cited by 66 publications

(54 citation statements)

References 20 publications

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“…Further analysis with serial urine samples of six patients with biopsy-confirmed lupus nephritis showed that these proteins could predict renal flares and remission earlier than conventional markers for nephritis. Subsequently, Suzuki and colleagues used a similar technique to investigate the urinary protein profile ('signature') in pediatric patients with lupus nephritis [Suzuki et al 2007]. They identified 8 candidate peptides/proteins with molecular masses from 2700 to 133,000, including TF, AGP, CP, and L-PGDS.…”

Section: Sle Biomarker Panelsmentioning

confidence: 99%

Biomarkers in systemic lupus erythematosus: challenges and prospects for the future

Liu

Kao

Manzi

et al. 2013

Therapeutic Advances in Musculoskeletal

106

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Abstract:The search for lupus biomarkers to diagnose, monitor, stratify, and predict individual response to therapy is currently more intense than ever before. This effort is essential for several reasons. First, epidemic overdiagnosis and underdiagnosis of lupus, even by certified rheumatologists, leads to errors in therapy with concomitant side effects which may be more serious than the disease itself. Second, identification of lupus flares remains as much an art as it is a science. Third, the capacity to stratify patients so as to predict those who will develop specific patterns of organ involvement is not currently possible but would potentially lead to preventive therapeutic strategies. Fourth, only one new drug for the treatment of lupus has been approved by the US Food and Drug Administration in over 50 years. A major obstacle in this pipeline is the dearth of biomarkers available to prove a patient has responded to an experimental therapeutic intervention. This review will summarize the challenges faced in the discovery and validation of lupus biomarkers, the most promising lupus biomarkers identified to date, and the promise of future directions.

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Section: Sle Biomarker Panelsmentioning

confidence: 99%

Biomarkers in systemic lupus erythematosus: challenges and prospects for the future

Liu

Kao

Manzi

et al. 2013

Therapeutic Advances in Musculoskeletal

106

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“…Application of the proteomic discovery technique surfaceenhanced laser desorption/ionization time-of-flight mass spectrometry to the urine of pediatric SLE patients yielded a protein signature for active lupus nephritis that consisted of eight proteins/peptides ranging in molecular mass from 2.7 to 133 kD (31). Four of these were albumin fragments and the other four were transferrin (TF), ␣1-acid-glycoprotein (AGP), ceruloplasmin (CP), and lipocalin-type prostaglandin d-synthetase (L-PGDS) (32).…”

Section: Neutrophil Gelatinase-associated Lipocalinmentioning

confidence: 99%

Biomarkers for Lupus Nephritis

Rovin¹,

Zhang²

2009

Clinical Journal of the American Society of Nephrology

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Current treatment of severe lupus nephritis is unsatisfactory in terms of both outcome and toxicity. To improve the efficacy and decrease the adverse effects of immunosuppression, it would be ideal to be able to predict the course and pathology of lupus nephritis and adjust therapy appropriately. This will require biomarkers that reflect disease activity. Recently, significant effort has been put into identifying biomarkers that can anticipate impending lupus renal flare, forecast development of chronic kidney disease, or reflect kidney histology at the time of flare. Although these biomarkers are potentially useful, to date none has been clinically validated in a large, prospective cohort of patients with SLE. This article reviews the current status of lupus nephritis biomarker investigation and articulates a perspective of how future efforts should be focused.

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“…Proteomic analysis of urine from patients with lupus nephritis identified AGP as a potential biomarker. Subsequent work showed that urinary AGP can be used to predict renal flares in lupus nephritis 13,33 .…”

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confidence: 99%

Urinary Biomarkers in Relapsing Antineutrophil Cytoplasmic Antibody-associated Vasculitis

Lieberthal

Cuthbertson²,

Carette³

et al. 2013

J Rheumatol

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Objective Glomerulonephritis (GN) is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but tools for early detection of renal involvement are imperfect. We investigated 4 urinary proteins as markers of active renal AAV: alpha-1 acid glycoprotein (AGP), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), and neutrophil gelatinase-associated lipocalin (NGAL). Methods Patients with active renal AAV (n = 20), active nonrenal AAV (n = 16), and AAV in longterm remission (n = 14) were identified within a longitudinal cohort. Urinary biomarker concentrations (by ELISA) were normalized for urine creatinine. Marker levels during active AAV were compared to baseline remission levels (from 1–4 visits) for each patient. Areas under receiver-operating characteristic curves (AUC), sensitivities, specificities, and likelihood ratios (LR) comparing disease states were calculated. Results Baseline biomarker levels varied among patients. All 4 markers increased during renal flares (p < 0.05). MCP-1 discriminated best between active renal disease and remission: a 1.3-fold increase in MCP-1 had 94% sensitivity and 89% specificity for active renal disease (AUC = 0.93, positive LR 8.5, negative LR 0.07). Increased MCP-1 also characterized 50% of apparently nonrenal flares. Change in AGP, KIM-1, or NGAL showed more modest ability to distinguish active renal disease from remission (AUC 0.71–0.75). Hematuria was noted in 83% of active renal episodes, but also 43% of nonrenal flares and 25% of remission samples. Conclusion Either urinary MCP-1 is not specific for GN in AAV, or it identifies early GN not detected by standard assessment and thus has potential to improve care. A followup study with kidney biopsy as the gold standard is needed.

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Identification of a urinary proteomic signature for lupus nephritis in children

Cited by 66 publications

References 20 publications

Biomarkers in systemic lupus erythematosus: challenges and prospects for the future

Biomarkers in systemic lupus erythematosus: challenges and prospects for the future

Biomarkers for Lupus Nephritis

Urinary Biomarkers in Relapsing Antineutrophil Cytoplasmic Antibody-associated Vasculitis

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