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2017 ; 18
(1
): 112
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Early urinary biomarkers of diabetic nephropathy in type 1 diabetes mellitus show
involvement of kallikrein-kinin system
#MMPMID28359252
Vitova L
; Tuma Z
; Moravec J
; Kvapil M
; Matejovic M
; Mares J
BMC Nephrol
2017[Mar]; 18
(1
): 112
PMID28359252
show ga
BACKGROUND: Additional urinary biomarkers for diabetic nephropathy (DN) are
needed, providing early and reliable diagnosis and new insights into its
mechanisms. Rigorous selection criteria and homogeneous study population may
improve reproducibility of the proteomic approach. METHODS: Long-term type 1
diabetes patients without metabolic comorbidities were included, 11 with
sustained microalbuminuria (MA) and 14 without MA (nMA). Morning urine proteins
were precipitated and resolved by 2D electrophoresis. Principal component
analysis (PCA) and Projection to latent structures discriminatory analysis
(PLS-DA) were adopted to assess general data validity, to pick protein fractions
for identification with mass spectrometry (MS), and to test predictive value of
the resulting model. RESULTS: Proteins (n?=?113) detected in more than 90%
patients were considered representative. Unsupervised PCA showed excellent
natural data clustering without outliers. Protein spots reaching Variable
Importance in Projection score above 1 in PLS (n?=?42) were subjected to MS,
yielding 33 positive identifications. The PLS model rebuilt with these proteins
achieved accurate classification of all patients (R2X?=?0.553, R2Y?=?0.953,
Q2?=?0.947). Thus, multiple earlier recognized biomarkers of DN were confirmed
and several putative new biomarkers suggested. Among them, the highest
significance was met in kininogen-1. Its activation products detected in nMA
patients exceeded by an order of magnitude the amount found in MA patients.
CONCLUSIONS: Reducing metabolic complexity of the diseased and control groups by
meticulous patients' selection allows to focus the biomarker search in DN.
Suggested new biomarkers, particularly kininogen fragments, exhibit the highest
degree of correlation with MA and substantiate validation in larger and more
varied cohorts.