1. Serum kidney injury molecule 1 and β
- Author
-
Marco, Colombo, Helen C, Looker, Bassam, Farran, Sibylle, Hess, Leif, Groop, Colin N A, Palmer, Mary Julia, Brosnan, R Neil, Dalton, Max, Wong, Charles, Turner, Emma, Ahlqvist, David, Dunger, Felix, Agakov, Paul, Durrington, Shona, Livingstone, John, Betteridge, Paul M, McKeigue, and Helen M, Colhoun
- Subjects
Male ,Epidemiology ,Enzyme-Linked Immunosorbent Assay ,Middle Aged ,Kidney ,Mass Spectrometry ,Article ,Nephropathy ,Clinical science ,Diabetes Mellitus, Type 2 ,Proteomics/metabolomics ,Disease Progression ,Odds Ratio ,Humans ,Diabetic Nephropathies ,Female ,Hepatitis A Virus Cellular Receptor 1 ,beta 2-Microglobulin ,Biomarkers ,Aged ,Glomerular Filtration Rate - Abstract
Aims/hypothesis As part of the Surrogate Markers for Micro- and Macrovascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) programme we previously reported that large panels of biomarkers derived from three analytical platforms maximised prediction of progression of renal decline in type 2 diabetes. Here, we hypothesised that smaller (n ≤ 5), platform-specific combinations of biomarkers selected from these larger panels might achieve similar prediction performance when tested in three additional type 2 diabetes cohorts. Methods We used 657 serum samples, held under differing storage conditions, from the Scania Diabetes Registry (SDR) and Genetics of Diabetes Audit and Research Tayside (GoDARTS), and a further 183 nested case–control sample set from the Collaborative Atorvastatin in Diabetes Study (CARDS). We analysed 42 biomarkers measured on the SDR and GoDARTS samples by a variety of methods including standard ELISA, multiplexed ELISA (Luminex) and mass spectrometry. The subset of 21 Luminex biomarkers was also measured on the CARDS samples. We used the event definition of loss of >20% of baseline eGFR during follow-up from a baseline eGFR of 30–75 ml min−1 [1.73 m]−2. A total of 403 individuals experienced an event during a median follow-up of 7 years. We used discrete-time logistic regression models with tenfold cross-validation to assess association of biomarker panels with loss of kidney function. Results Twelve biomarkers showed significant association with eGFR decline adjusted for covariates in one or more of the sample sets when evaluated singly. Kidney injury molecule 1 (KIM-1) and β2-microglobulin (B2M) showed the most consistent effects, with standardised odds ratios for progression of at least 1.4 (p
- Published
- 2018