Blood biomarkers improve the prediction of prevalent and incident severe chronic kidney disease

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Simon Nusinovici
  • Hengtong Li
  • Crystal Chong
  • Marco Yu
  • Ida Maria Hjelm Sørensen
  • Bisgaard, Line
  • Christoffersen, Christina
  • Susanne Bro
  • Sylvia Liu
  • Jian Jun Liu
  • Lim Su Chi
  • Tien Yin Wong
  • Gavin S.W. Tan
  • Ching Yu Cheng
  • Charumathi Sabanayagam

Background: The 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. Methods: Data 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. Results: Chronic 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. Conclusion: The 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: [Figure not available: see fulltext.]

TidsskriftJournal of Nephrology
StatusE-pub ahead of print - 2024

Bibliografisk note

Funding Information:
This study was funded by: Singapore Epidemiology of Eye Diseases: National Medical Research Council (NMRC): NMRC/CIRG/1371/2013, NMRC/CIRG/1488/2018, NMRC/STaR/016/2013 and NMRC/OFLCG/001/2017 . Singapore Diabetic Nephropathy cohort: Singapore Alexandra Health Fund Research Program and STAR grant 20201, National Medical Research Council NMRC/MOH-000066, NMRC/MOH-0000714 and OFLCG/001/2017. The Augustinus Foundation, the Danish Kidney Foundation, the Danish Society of Nephrology Foundation, the Helen and Ejnar Bjørnow Foundation, the Research Fund at Rigshospitalet, the Advokat Bent Thorbergs Foundation, and the Danish Diabetes Academy.

Publisher Copyright:
© 2024, The Author(s) under exclusive licence to Italian Society of Nephrology.

ID: 384423207