Early urinary biomarkers of diabetic nephropathy in type 1 diabetes mellitus show involvement of kallikrein-kinin system

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10360631" target="_blank" >RIV/00216208:11130/17:10360631 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11140/17:10360631 RIV/00064203:_____/17:10360631

Result on the web

<a href="https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-017-0519-4" target="_blank" >https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-017-0519-4</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12882-017-0519-4" target="_blank" >10.1186/s12882-017-0519-4</a>

Result language

angličtina

Original language name

Early urinary biomarkers of diabetic nephropathy in type 1 diabetes mellitus show involvement of kallikrein-kinin system

Original language description

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&apos; 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

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Continuities

Z - Vyzkumny zamer (s odkazem do CEZ)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

BMC Nephrology

ISSN

1471-2369

e-ISSN

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Volume of the periodical

18

Issue of the periodical within the volume

March

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

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UT code for WoS article

000397685100003

EID of the result in the Scopus database

2-s2.0-85016397250