Urinary fetuin-A peptides as new markers for kidney damage in type-2 diabetes patients

Fragestellung:

The hepatokine fetuin-A, which is released by fatty liver, promotes the proinflammatory effects of perivascular fat. The involvement of inflammation in type-2 diabetes can affect the kidney and cause diabetic nephropathy. Therefore, we examined the association of urinary fetuin-A protein fragments with renal damage in diabetes type-2 patients.

Methodik:

The urinary proteome of 1494 diabetes type-2 patients was analysed by capillary-electrophoresis coupled to mass-spectrometry, to investigate the correlation of fetuin-A peptides with the estimated glomerular filtration rate (eGFR) to assess the severity of kidney damage. The correlation coefficient was estimated with non-parametric Spearman's rank correlation analysis.

Ergebnisse:

We identified 11 different protein fragments, which belong to 2 different motifs of the total fetuin-A protein (motif A: amino acid (AA) 302 – 319; motif B: AA 322 – 340). The corresponding peptides of each motif were combined (sum of amplitudes) and correlated to eGFR. Both fetuin-A motifs displayed significant correlations with eGFR (A: rho =-0.207, p = 0.0037; B: rho =-0.243, p < 0.0001). To investigate that urinary fetuin-A does not reflect proteinuria, we also used multiple regression analysis with adjustment for urinary albumin. This regression, as well as the adjustment for age and gender, resulted in a significant correlation of the fetuin-A peptides with eGFR.

Schlussfolgerungen:

The urinary proteome analysis demonstrated the association of fetuin-A peptides with kidney damage in diabetes type-2 patients. Therefore, fetuin-A peptides could be markers for early inflammatory processes in the kidney as a result of diabetes type-2 and therefore a possible new marker for kidney dysfunction.