Comparative differential proteomic analysis of minimal change disease and focal segmental glomerulosclerosis.
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.
Laboratory of Experimental Nephrology, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. vperez.igtp@gmail.es.|Department of Nephrology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Carretera del Canyet s/n, ES-08916, Badalona, Barcelona, Spain. vperez.igtp@gmail.es.
Vanessa
V
Pérez
Department of Pathology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
Dolores
D
López
Applied Statistics Service, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Ester
E
Boixadera
Department of Nephrology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Carretera del Canyet s/n, ES-08916, Badalona, Barcelona, Spain.
Meritxell
M
Ibernón
Applied Statistics Service, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Anna
A
Espinal
Department of Nephrology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Carretera del Canyet s/n, ES-08916, Badalona, Barcelona, Spain.
Josep
J
Bonet
Laboratory of Experimental Nephrology, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.|Department of Nephrology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Carretera del Canyet s/n, ES-08916, Badalona, Barcelona, Spain.|Department of Medicine, Universitat Autònoma de Barcelona, Badalona, Spain.
Ramón
R
Romero
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D064032:Calbindin 2 / Q000652:urine; D003663:Decision Trees; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis / Q000473:pathology / Q000652:urine*; D054808:Histatins / Q000652:urine; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000175:diagnosis / Q000473:pathology / Q000652:urine*; D040901:Proteomics; D015203:Reproducibility of Results; D012269:Ribosomal Proteins / Q000652:urine; D014168:Transferrin / Q000652:urine; D000515:alpha 1-Antitrypsin / Q000652:urine
D015415:Biomarkers; C576764:CALB2 protein, human; D064032:Calbindin 2; C068075:HTN3 protein, human; D054808:Histatins; D012269:Ribosomal Proteins; D014168:Transferrin; D000515:alpha 1-Antitrypsin; C032493:ribosomal protein L17
2D-DIGE; Focal segmental glomerulosclerosis; Glomerular disease; Mass spectrometry; Minimal change disease; Proteomics; Urine