Associations of proteomics with kidney function and blood pressure in the general population

Lin, Jiesheng (2024): Associations of proteomics with kidney function and blood pressure in the general population. Dissertation, LMU München: Medizinische Fakultät

Abstract

Aims: Given the global burden of both chronic kidney disease (CKD) and hypertension, there is a pressing need to address challenges related to early diagnosis, treatment targets, and enhancing assessment for CKD and hypertension. Proteomics, with its ability to analyze a wide array of proteins, offers promising opportunities to address these challenges. Considering the interplay among cardiovascular disease (CVD), CKD, and hypertension, this cumulative thesis aims to identify and validate biomarkers for CKD and hypertension from a pool of 233 CVD- and inflammation-related proteins, measured by the Olink platform. Methods and Results: The study included participants from the Monitoring of Trends and Determinants in Cardiovascular Diseases (MONICA) / Cooperative Health Research in the Region of Augsburg (KORA) cohort study and Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium. Three papers are included in this cumulative thesis. In Paper I, 21 proteins were identified and confirmed as being associated with kidney function decline and incident CKD, with tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) further showing a potential causal relationship with kidney function decline. In Paper II, 27 proteins associated with hypertension and/or systolic blood pressure (SBP) were discovered and validated, with robust associations observed for kidney injury molecule 1 (KIM1), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and osteoprotegerin (OPG). Mendelian randomization analysis identified 5 proteins showing potential causal associations with SBP, including NT-proBNP and OPG. Notably, 5 proteins showed consistent associations with both kidney function and BP outcomes, including adrenomedullin (ADM), KIM1, NT-proBNP, programmed cell death 1 ligand 1 (PD-L1), and thrombomodulin (TM). Paper III further validated longitudinal (NT-proBNP only) and cross-sectional associations of mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), and NT-proBNP with kidney function and CKD. Conclusions: This thesis provides insight into the complex interplay between kidney function and BP from a proteomic perspective. Our findings illuminate potential biomarkers and pathways underlying the pathophysiology of CKD and hypertension, providing valuable insights for risk stratification, early diagnosis, and personalized management strategies.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: proteomics, kidney function, blood pressure, Mendelian randomization, cohort study
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 13. November 2024
• 1. Bericht­erstatter:in: Thorand, Barbara