Dataset Information

Comparative differential proteomic analysis of minimal change disease and focal segmental glomerulosclerosis.

ABSTRACT: Minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS) are glomerular diseases characterized by nephrotic syndrome. Their diagnosis requires a renal biopsy, but it is an invasive procedure with potential complications. In a small biopsy sample, where only normal glomeruli are observed, FSGS cannot be differentiated from MCD. The correct diagnosis is crucial to an effective treatment, as MCD is normally responsive to steroid therapy, whereas FSGS is usually resistant. The purpose of our study was to discover and validate novel early urinary biomarkers capable to differentiate between MCD and FSGS.Forty-nine patients biopsy-diagnosed of MCD and primary FSGS were randomly subdivided into a training set (10 MCD, 11 FSGS) and a validation set (14 MCD, 14 FSGS). The urinary proteome of the training set was analyzed by two-dimensional differential gel electrophoresis coupled with mass spectrometry. The proteins identified were quantified by enzyme-linked immunosorbent assay in urine samples from the validation set.Urinary concentration of alpha-1 antitrypsin, transferrin, histatin-3 and 39S ribosomal protein L17 was decreased and calretinin was increased in FSGS compared to MCD. These proteins were used to build a decision tree capable to predict patient's pathology.This preliminary study suggests a group of urinary proteins as possible non-invasive biomarkers with potential value in the differential diagnosis of MCD and FSGS. These biomarkers would reduce the number of misdiagnoses, avoiding unnecessary or inadequate treatments.

SUBMITTER: Perez V

PROVIDER: S-EPMC5291957 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparative differential proteomic analysis of minimal change disease and focal segmental glomerulosclerosis.

Pérez Vanessa V López Dolores D Boixadera Ester E Ibernón Meritxell M Espinal Anna A Bonet Josep J Romero Ramón R

BMC nephrology 20170203 1

<h4>Background</h4>Minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS) are glomerular diseases characterized by nephrotic syndrome. Their diagnosis requires a renal biopsy, but it is an invasive procedure with potential complications. In a small biopsy sample, where only normal glomeruli are observed, FSGS cannot be differentiated from MCD. The correct diagnosis is crucial to an effective treatment, as MCD is normally responsive to steroid therapy, whereas FSGS is ...[more]

PMID: 28158993

Similar Datasets

Project description:Primary focal segmental glomerulosclerosis (FSGS), along with minimal change disease (MCD), are diseases with primary podocyte damage that are clinically manifested by the nephrotic syndrome. The pathogenesis of these podocytopathies is still unknown, and therefore, the search for biomarkers of these diseases is ongoing. Our aim was to determine of the proteomic profile of urine from patients with FSGS and MCD. Patients with a confirmed diagnosis of FSGS (n = 30) and MCD (n = 9) were recruited for the study. For a comprehensive assessment of the severity of FSGS a special index was introduced, which was calculated as follows: the first score was assigned depending on the level of eGFR, the second score-depending on the proteinuria level, the third score-resistance to steroid therapy. Patients with the sum of these scores of less than 3 were included in group 1, with 3 or more-in group 2. The urinary proteome was analyzed using liquid chromatography/mass spectrometry. The proteome profiles of patients with severe progressive FSGS from group 2, mild FSGS from group 1 and MCD were compared. Results of the label free analysis were validated using targeted LC-MS based on multiple reaction monitoring (MRM) with stable isotope labelled peptide standards (SIS) available for 47 of the 76 proteins identified as differentiating between at least one pair of groups. Quantitative MRM SIS validation measurements for these 47 proteins revealed 22 proteins with significant differences between at least one of the two group pairs and 14 proteins were validated for both comparisons. In addition, all of the 22 proteins validated by MRM SIS analysis showed the same direction of change as at the discovery stage with label-free LC-MS analysis, i.e., up or down regulation in MCD and FSGS1 against FSGS2. Patients from the FSGS group 2 showed a significantly different profile from both FSGS group 1 and MCD. Among the 47 significantly differentiating proteins, the most significant were apolipoprotein A-IV, hemopexin, vitronectin, gelsolin, components of the complement system (C4b, factors B and I), retinol- and vitamin D-binding proteins. Patients with mild form of FSGS and MCD showed lower levels of Cystatin C, gelsolin and complement factor I.

Dataset Information

Comparative differential proteomic analysis of minimal change disease and focal segmental glomerulosclerosis.

Publications

Comparative differential proteomic analysis of minimal change disease and focal segmental glomerulosclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets