From measurement to management of kidney function: population-based insights into biomarker discordance, risk factors, and outcomes

Liu, Qiaoling (2026) From measurement to management of kidney function: population-based insights into biomarker discordance, risk factors, and outcomes. PhD thesis, University of Glasgow.

Abstract

Chronic kidney disease is a major risk factor for cardiovascular diseases and mortality, yet both the measurement of kidney function and the management of kidney-related risk in the general population require further exploration. This thesis aims to move from measurement to management of kidney function by examining modifiable behaviours, identifying patterns of kidney function and their associations with adverse outcomes, and evaluating treatment strategies and their potential cardiorenal benefits.

A total of five published manuscripts were included in this thesis to achieve the above aims. These studies utilized data from the UK Biobank and several Swedish national registers.

The first study in Chapter 4 presents a systematic review and meta-analysis of intervention studies in generally healthy populations, examining how changes in physical activity influence kidney-related biomarkers. Higher physical activity was consistently associated with higher serum creatinine, while other biomarkers showed little or no change. The second study in Chapter 5 uses UK Biobank data to examine how changes in physical activity relate to changes in kidney function in more than 11,000 participants free of chronic kidney disease at baseline. The findings differed by biomarker. When rapid decline was defined using creatinine-based estimated glomerular filtration rate (eGFR), lower physical activity appeared protective, whereas cystatin C-based eGFR showed the opposite pattern, with higher activity associated with lower risk. The creatinine-cystatin C based eGFR showed no clear association.

The following two studies in Chapters 6 and 7 focus on discordance between creatinine-based and cystatin C-based eGFR. Chapter 6 synthesises evidence from 18 studies and shows that individuals with lower cystatin C-based eGFR relative to creatinine-based eGFR have substantially higher risks of mortality and cardiorenal events, while those with higher cystatin C-based eGFR tend to have lower risks. Chapter 7 extends this work in a large UK Biobank cohort, showing that 15.5% of the study population has discordantly lower cystatin C-based eGFR and that this discordance is strongly associated with all-cause mortality, particularly in older (65 years and above) and obese (BMI≥30 kg/m2) people, independent of established risk factors.

The last study in Chapter 8 shifts to pharmacological management in type 2 diabetes, comparing oral fixed-dose combination therapy with loose-dose combinations using Swedish national registers. In a propensity score matched cohort of 27,766 people, fixed-dose combinations were associated with a lower risk of heart failure, especially in older adults (65 years and above), with 47% of this benefit being mediated by improved medication adherence. No clear differences were observed for other cardiovascular or kidney outcomes.

In conclusion, this thesis provides population-based evidence that selection of kidney function biomarkers may play an important role in evaluating health outcomes, while intraindividual discrepancies in kidney function may reveal distinct physiological or pathological processes. In addition, pharmacological strategies may affect cardiorenal risk. Key limitations include reliance on estimated rather than measured GFR, potential residual confounding, the inability to establish causality inherent to observational analyses, and limited generalisability to more diverse populations.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: R Medicine > R Medicine (General); R Medicine > RC Internal medicine
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Supervisor's Name: Welsh, Professor Paul, Celis, Dr Carlos and Mark, Professor Patrick
• Date of Award: 2026
• Depositing User: Theses Team
• Unique ID: glathesis:2026-85771
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 20 Feb 2026 10:15
• Last Modified: 21 Feb 2026 12:56
• Thesis DOI: 10.5525/gla.thesis.85771
• URI: https://theses.gla.ac.uk/id/eprint/85771

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