Language

English

Publication Date

12-1-2024

Journal

Clinical Journal of the American Society of Nephrology

DOI

10.2215/CJN.0000000000000559

PMID

39432369

PMCID

PMC11637700

PubMedCentral® Posted Date

10-21-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background: The onset of diabetic kidney disease (DKD) in youth with type 2 diabetes (T2D) mellitus often occurs early, leading to complications in young adulthood. Risk biomarkers associated with the early onset of DKD are urgently needed in youth with T2D.

Methods: We conducted an in-depth analysis of 6596 proteins (SomaScan 7K) in 374 baseline plasma samples from the Treatment Options for Type 2 Diabetes in Adolescents and Youth study to identify multiprotein signatures associated with the onset of albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g), a rapid decline in eGFR (annual eGFR decline >3 ml/min per 1.73 m2 and/or ≥3.3% at two consecutive visits), and hyperfiltration (≥135 ml/min per 1.73 m2 at two consecutive visits). Elastic net Cox regression with ten-fold cross-validation was applied to the top 100 proteins (ranked by P value) to identify multiprotein signatures of time to development of DKD outcomes.

Results: Participants in the Treatment Options for Type 2 Diabetes in Adolescents and Youth study (14±2 years, 63% female, 7±6 months diabetes duration) experienced high rates of early DKD: 43% developed albuminuria, 48% hyperfiltration, and 16% rapid eGFR decline. Increased levels of seven and three proteins were predictive of shorter time to develop albuminuria and rapid eGFR decline, respectively; 118 proteins predicted time to development of hyperfiltration. Elastic net Cox proportional hazards models identified multiprotein signatures of time to incident early DKD with concordance for models with clinical covariates and selected proteins between 0.81 and 0.96, whereas the concordance for models with clinical covariates only was between 0.56 and 0.63.

Conclusions: Our research sheds new light on proteomic changes early in the course of youth-onset T2D that associate with DKD. Proteomic analyses identified promising risk factors that predict DKD risk in youth with T2D and could deepen our understanding of DKD mechanisms and potential interventions.

Comments

Clinical Trial registry name and registration number:: NCT00081328.

Published Open-Access

yes

Additional Files
cjasn-19-1603-g001.jpg (122 kB)
Visual Abstract
Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.