Urinary Proteome of Steroid-Sensitive and Steroid-Resistant Idiopathic Nephrotic Syndrome of Childhood

Woroniecki, Robert P.; Orlova, Tetiana; Mendelev, Natalia; Shatat, Ibrahim F.; Hailpern, Susan M.; Kaskel, Frederick J.; Goligorsky, Michael S.; O’Riordan, Edmond

doi:10.1159/000093814

Cited by 58 publications

(32 citation statements)

References 33 publications

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“…Unfortunately, this results in unnecessary exposure of SRNS patients to the toxic effects of steroids without therapeutic benefits. Recently, urine protein analysis by surface-enhanced laser desorption ionization mass spectrometry revealed a differential expression of β 2 -microglobulin and an unidentified protein of 4,144-Da mass as the classifier in distinguishing SSNS from SRNS of childhood [12,13]. The two studies performed proteomic profiling of urine samples from a cross-sectional cohort of pediatric patients with SSNS and SRNS and have only identified biomarkers associated with, but not predictive of, steroid resistance.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling Identifies Haptoglobin as a Potential Serum Biomarker for Steroid-Resistant Nephrotic Syndrome

Wen¹,

Huang²,

Luo³

et al. 2012

Am J Nephrol

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Background: Long-term outcomes for patients with adult idiopathic nephrotic syndrome correlate closely with steroid responsiveness. The aim of this prospective study was to evaluate the difference in serum proteomes between steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) patients and identify potential biomarkers for the prediction of SRNS. Methods: We performed a gel-based proteomic study of serum obtained from SRNS and SSNS patients and healthy controls at the time of presentation (n = 6 for each group). Proteins from the serum samples were separated using 2-D electrophoresis, digested in-gel and subjected to MALDI-TOF-MS/MS analysis. Further validation was performed utilizing Western blot and ELISA. The sensitivities and specificities of the candidate proteins for predicting SRNS were determined using receiver operating characteristic curves. Results: Thirteen differentially expressed proteins were identified as haptoglobin (Hp) with different isoelectric points and molecular weights. Western blot and ELISA analysis of samples from 146 subjects (healthy controls = 52, SSNS = 54, SRNS = 40) showed a markedly increased level of Hp in the serum, but not urine, of SRNS compared to SSNS patients. The optimal serum cutoff level of Hp was set at ≥1,279 µg/ml using the receiver operating characteristic curve. The sensitivity and specificity for predicting SRNS were 85.0 and 96.3%, respectively. Conclusions: This study provides a novel overview of the difference in serum proteomes of SSNS and SRNS patients. Serum Hp may be a useful predictive biomarker for steroid therapy efficacy in the treatment of idiopathic nephrotic syndrome.

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Section: Discussionmentioning

confidence: 99%

Proteomic Profiling Identifies Haptoglobin as a Potential Serum Biomarker for Steroid-Resistant Nephrotic Syndrome

Wen¹,

Huang²,

Luo³

et al. 2012

Am J Nephrol

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“…A study using urine protein profiles on capillary electrophoresis mass spectrometry (urinary proteomics) suggested that these biomarkers could predict steroid sensitivity or resistance before embarking on steroid therapy [67]. These data however require confirmation in large prospective studies.…”

Section: Factors Predicting Steroid Sensitivity and Relapsesmentioning

confidence: 99%

Steroid Sensitive Nephrotic Syndrome in Children

Bhimma¹

2014

J Nephrol Ther

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Nephrotic Syndrome (NS) is one of the most frequent glomerular diseases seen in children. Children who go into complete remissin following treatment with corticosteroids are classified as having "steroid sensitive" NS. In developed countries over 80% of children with idiopathic NS have steroid sensitive disease although response to steroids is somewhat tempered in developing countries, especially in black children, the majority of whom have steroid resistant disease.The exact pathogenesis of this condition remains elusive. Podocyte injury and proteinuria are the two main issues in the pathogenesis. Recent studies suggest alterations in both innate and adaptive immune responses. There is release of cytokines by T-cells as well as a strong contribution of B-cell immunity. Genetic studies have reported human leucocyte antigen (HLA) class II antigens DR and DQ associations linked to steroid sensitive NS and in small case studies, single gene mutations e.g. PLCE1 although to date no homozygous mutations in NPHS1 or NPHS2 and WT-1 genes have been reported.Most children with steroid sensitive NS have multiple relapses and a significant percentage also develop steroid dependent NS. These children receive multiples courses of steroids and are at high risk of developing steroid toxicity. Patient with frequent relapses who develop steroid dependency thus require alternative treatment. Steroids sparing agents used include levamisole, cyclophosphamide, mycophenolate mofetil (MMF), calcineurin inhibitors (cyclosporine and tacrolimus), rituximab and vincristine. The steroid-sparing effects of these agents have greatly reduced the adverse effects seen with long-term use of steroids.Despite the wide arsenal of agents available, therapy needs to be individualised to achieve optimal care of each child. More randomised controlled trials are required to evaluate the therapeutic and economic efficacy of this agent, define criteria for selection of patients for use of particular agents and to determine the safety profile of these drugs in children.This article reviews the epidemiology, pathogenesis, clinical presentation, diagnosis, complications, management and long term outcome of children with steroid sensitive NS.

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“…Advantages of SELDI include its capacity to analyze multiple samples in a short time. SELDI has been used in numerous attempts to define biomarkers for a variety of diseases (32,35,36). Although the technology is easy to use, it is also prone to generating artifacts (37,38).…”

Section: Seldi-msmentioning

confidence: 99%

Advances in Urinary Proteome Analysis and Biomarker Discovery

Fliser¹,

Novák²,

Thongboonkerd³

et al. 2007

Journal of the American Society of Nephrology

255

206

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Noninvasive diagnosis of kidney diseases and assessment of the prognosis are still challenges in clinical nephrology. Definition of biomarkers on the basis of proteome analysis, especially of the urine, has advanced recently and may provide new tools to solve those challenges. This article highlights the most promising technological approaches toward deciphering the human proteome and applications of the knowledge in clinical nephrology, with emphasis on the urinary proteome. The data in the current literature indicate that although a thorough investigation of the entire urinary proteome is still a distant goal, clinical applications are already available. Progress in the analysis of human proteome in health and disease will depend more on the standardization of data and availability of suitable bioinformatics and software solutions than on new technological advances. It is predicted that proteomics will play an important role in clinical nephrology in the very near future and that this progress will require interactive dialogue and collaboration between clinicians and analytical specialists.

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Urinary Proteome of Steroid-Sensitive and Steroid-Resistant Idiopathic Nephrotic Syndrome of Childhood

Cited by 58 publications

References 33 publications

Proteomic Profiling Identifies Haptoglobin as a Potential Serum Biomarker for Steroid-Resistant Nephrotic Syndrome

Proteomic Profiling Identifies Haptoglobin as a Potential Serum Biomarker for Steroid-Resistant Nephrotic Syndrome

Steroid Sensitive Nephrotic Syndrome in Children

Advances in Urinary Proteome Analysis and Biomarker Discovery

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