Very Low-Molecular-Mass Fragments of Albumin in the Plasma of Patients With Focal Segmental Glomerulosclerosis

Background

Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that frequently does not respond to treatment and progresses to kidney failure. FSGS can be of either genetic origin, caused by mutations in slit diaphragm proteins, such as podocin, or idiopathic origin of unknown cause.

Study Design

Case series.

Setting & Participants

Children with FSGS (aged 3-18 years); 15 with idiopathic and 11 with genetic forms of FSGS.

Predictor

Genetic versus idiopathic forms.

Outcomes & Measurements

Differentially expressed proteins in the plasma proteome, detected using 2-dimensional electrophoresis and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Western blot, and liquid chromatography electron spray ionization tandem mass spectrometry for fragmentation and identification of the peptides.

Results

We found 3 very low-molecular-mass (9.2, 6.9, and 4.7 kDa; isoelectric point, 5.7) spots that were present in pooled samples from patients with genetic FSGS, but missing in patients with idiopathic FSGS and healthy individuals. Spots were identified using mass spectrometry as fragments of albumin, 2 of them apparently containing peptides from both C- and N-terminal parts of the whole protein. Proteomic analyses were carried out on all genetic patients individually; of these, 10 of 11 patients had ≥1 albumin fragment detected in the pool. We did not find an evident relationship between type of mutation or clinical status of patients and albumin fragments observed.

Limitations

Very low-molecular-weight albumin fragments also can be produced by other diseases.

Conclusions

We describe for the first time the presence of very low-molecular-mass albumin fragments in plasma of patients with FSGS with podocyte protein mutations that are absent in patients with idiopathic FSGS or healthy individuals. Additional studies are necessary to determine whether these fragments could be potential biomarkers to distinguish between genetic and idiopathic forms of FSGS.

Index Words: Focal segmental glomerulosclerosis, nephrotic syndrome, proteomics, albumin fragments