Dataset Information

Predictive urinary biomarkers for steroid-resistant and steroid-sensitive focal segmental glomerulosclerosis using high resolution mass spectrometry and multivariate statistical analysis.

ABSTRACT:

Background

Focal segmental glomerulosclerosis (FSGS) is a glomerular scarring disease diagnosed mostly by kidney biopsy. Since there is currently no diagnostic test that can accurately predict steroid responsiveness in FSGS, prediction of the responsiveness of patients to steroid therapy with noninvasive means has become a critical issue. In the present study urinary proteomics was used as a noninvasive tool to discover potential predictive biomarkers.

Methods

Urinary proteome of 10 patients (n = 6 steroid-sensitive, n = 4 steroid-resistant) with biopsy proven FSGS was analyzed using nano-LC-MS/MS and supervised multivariate statistical analysis was performed.

Results

Twenty one proteins were identified as discriminating species among which apolipoprotein A-1 and Matrix-remodeling protein 8 had the most drastic fold changes being over- and underrepresented, respectively, in steroid sensitive compared to steroid resistant urine samples. Gene ontology enrichment analysis revealed acute inflammatory response as the dominant biological process.

Conclusion

The obtained results suggest a panel of predictive biomarkers for FSGS. Proteins involved in the inflammatory response are shown to be implicated in the responsiveness. As a tool for biomarker discovery, urinary proteomics is especially fruitful in the area of prediction of responsiveness to drugs. Further validation of these biomarkers is however needed.

SUBMITTER: Kalantari S

PROVIDER: S-EPMC4236676 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Publications

Predictive urinary biomarkers for steroid-resistant and steroid-sensitive focal segmental glomerulosclerosis using high resolution mass spectrometry and multivariate statistical analysis.

Kalantari Shiva S Nafar Mohsen M Rutishauser Dorothea D Samavat Shiva S Rezaei-Tavirani Mostafa M Yang Hongqian H Zubarev Roman A RA

BMC nephrology 20140902

<h4>Background</h4>Focal segmental glomerulosclerosis (FSGS) is a glomerular scarring disease diagnosed mostly by kidney biopsy. Since there is currently no diagnostic test that can accurately predict steroid responsiveness in FSGS, prediction of the responsiveness of patients to steroid therapy with noninvasive means has become a critical issue. In the present study urinary proteomics was used as a noninvasive tool to discover potential predictive biomarkers.<h4>Methods</h4>Urinary proteome of ...[more]

PMID: 25182141

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Project description:Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant-important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies are now recognized as drivers of FSGS: high-penetrance genetic FSGS due to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele-associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g, glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunofluorescence (e.g, to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.

Dataset Information

Predictive urinary biomarkers for steroid-resistant and steroid-sensitive focal segmental glomerulosclerosis using high resolution mass spectrometry and multivariate statistical analysis.

Background

Methods

Results

Conclusion

Publications

Predictive urinary biomarkers for steroid-resistant and steroid-sensitive focal segmental glomerulosclerosis using high resolution mass spectrometry and multivariate statistical analysis.

Similar Datasets

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