| Title: | Blood biomarkers improve the prediction of prevalent and incident severe chronic kidney disease |
| Journal: | Journal of Nephrology |
| Published: | 3 Feb 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38308753/ |
| DOI: | https://doi.org/10.1007/s40620-023-01872-w |
Publication 8791
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Abstract
BackgroundThe prevalence of chronic kidney disease (CKD) is high. Identification of cases with CKD or at high risk of developing it is important to tailor early interventions. The objective of this study was to identify blood metabolites associated with prevalent and incident severe CKD, and to quantify the corresponding improvement in CKD detection and prediction.MethodsData from four cohorts were analyzed: Singapore Epidemiology of Eye Diseases (SEED) (n = 8802), Copenhagen Chronic Kidney Disease (CPH) (n = 916), Singapore Diabetic Nephropathy (n = 714), and UK Biobank (UKBB) (n = 103,051). Prevalent CKD (stages 3-5) was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2; incident severe CKD as CKD-related mortality or kidney failure occurring within 10 years. We used multivariable regressions to identify, among 146 blood metabolites, those associated with CKD, and quantify the corresponding increase in performance.ResultsChronic kidney disease prevalence (stages 3-5) and severe incidence were 11.4% and 2.2% in SEED, and 2.3% and 0.2% in UKBB. Firstly, phenylalanine (Odds Ratio [OR] 1-SD increase = 1.83 [1.73, 1.93]), tyrosine (OR = 0.75 [0.71, 0.79]), docosahexaenoic acid (OR = 0.90 [0.85, 0.95]), citrate (OR = 1.41 [1.34, 1.47]) and triglycerides in medium high density lipoprotein (OR = 1.07 [1.02, 1.13]) were associated with prevalent stages 3-5 CKD. Mendelian randomization analyses suggested causal relationships. Adding these metabolites beyond traditional risk factors increased the area under the curve (AUC) by 3% and the sensitivity by 7%. Secondly, lactate (HR = 1.33 [1.08, 1.64]) and tyrosine (HR = 0.74 [0.58, 0.95]) were associated with incident severe CKD among individuals with eGFR < 90 mL/min/1.73 m2 at baseline. These metabolites increased the c-index by 2% and sensitivity by 5% when added to traditional risk factors.ConclusionThe performance improvements of CKD detection and prediction achieved by adding metabolites to traditional risk factors are modest and further research is necessary to fully understand the clinical implications of these findings.Graphical Abstract</p>
15 Authors
- Simon Nusinovici
- Hengtong Li
- Crystal Chong
- Marco Yu
- Ida Maria Hjelm Sørensen
- Line Stattau Bisgaard
- Christina Christoffersen
- Susanne Bro
- Sylvia Liu
- Jian-Jun Liu
- Lim Su Chi
- Tien-Yin Wong
- Gavin S. W. Tan
- Ching-Yu Cheng
- Charumathi Sabanayagam
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