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Integrative analysis of prognostic biomarkers derived from multiomics panels helps discrimination of chronic kidney disease trajectories in people with type 2 diabetes
- Source :
- Kidney International, Kidney International, 96(6), 1381-1388. ELSEVIER SCIENCE INC
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Clinical risk factors explain only a fraction of the variability of estimated glomerular filtration rate (eGFR) decline in people with type 2 diabetes. Cross-omics technologies by virtue of a wide spectrum screening of plasma samples have the potential to identify biomarkers for the refinement of prognosis in addition to clinical variables. Here we utilized proteomics, metabolomics and lipidomics panel assay measurements in baseline plasma samples from the multinational PROVALID study (PROspective cohort study in patients with type 2 diabetes mellitus for VALIDation of biomarkers) of patients with incident or early chronic kidney disease (median follow-up 35 months, median baseline eGFR 84 mL/min/1.73 m(2), urine albumin-to-creatinine ratio 8.1 mg/g). In an accelerated case-control study, 258 individuals with a stable eGFR course (median eGFR change 0.1 mL/min/year) were compared to 223 individuals with a rapid eGFR decline (median eGFR decline -6.75 mL/min/year) using Bayesian multivariable logistic regression models to assess the discrimination of eGFR trajectories. The analysis included 402 candidate predictors and showed two protein markers (KIM-1, NTproBNP) to be relevant predictors of the eGFR trajectory with baseline eGFR being an important clinical covariate. The inclusion of metabolomic and lipidomic platforms did not improve discrimination substantially. Predictions using all available variables were statistically indistinguishable from predictions using only KIM-1 and baseline eGFR (area under the receiver operating characteristic curve 0.63). Thus, the discrimination of eGFR trajectories in patients with incident or early diabetic kidney disease and maintained baseline eGFR was modest and the protein marker KIM-1 was the most important predictor.
- Subjects :
- Male
0301 basic medicine
Oncology
medicine.medical_specialty
FUNCTION DECLINE
030232 urology & nephrology
Renal function
PROGRESSION
Type 2 diabetes
Disease
HIGH-THROUGHPUT
Logistic regression
LIPIDOMICS
03 medical and health sciences
0302 clinical medicine
Internal medicine
Natriuretic Peptide, Brain
Humans
Medicine
Hepatitis A Virus Cellular Receptor 1
INCIDENT CKD
Renal Insufficiency, Chronic
Prospective cohort study
Aged
OUTCOMES
Receiver operating characteristic
business.industry
Type 2 Diabetes Mellitus
Bayes Theorem
ASSOCIATION
Middle Aged
medicine.disease
Peptide Fragments
MODEL
030104 developmental biology
Diabetes Mellitus, Type 2
Nephrology
Case-Control Studies
Female
prognosis
type 2 diabetes
business
chronic kidney disease
multiomics
Biomarkers
integrative analysis
Glomerular Filtration Rate
Kidney disease
Subjects
Details
- ISSN :
- 00852538
- Volume :
- 96
- Database :
- OpenAIRE
- Journal :
- Kidney International
- Accession number :
- edsair.doi.dedup.....89c48b69c31961b691cfb8dd3d56a5a3