Navigating the complexities of end-stage kidney disease (ESKD) from risk factors to outcome: insights from the UK Biobank cohort

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BACKGROUND: The global prevalence of end-stage kidney disease (ESKD) is increasing despite optimal management of traditional risk factors such as hyperglycaemia, hypertension, and dyslipidaemia. This study examines the influence of cardiorenal risk factors, socioeconomic status, and ethnic and cardiovascular comorbidities on ESKD outcomes in the general population. METHODS: This cross-sectional study analysed data from 502,408 UK Biobank study participants recruited between 2006 and 2010. Multivariable logistic regression models were fitted to assess risk factors for ESKD, with results presented as adjusted odds ratio (aOR) and 95% confidence intervals (95% CI). RESULTS: A total of 1191 (0.2%) of the study participants reported ESKD. Diabetes increased ESKD risk by 62% [1.62 (1.36-1.93)], with early-onset diabetes (before age 40) conferring higher odds compared to later-onset (after age 40) [2.26 (1.57-3.24)]. Similarly, early-onset hypertension (before age 40), compared to later onset (after age 40), increased ESKD odds by 73% [1.73 (1.21-2.44)]. Cardiovascular comorbidities, including stroke, hypertension, myocardial infarction and angina, were strongly associated with ESKD [5.97 (3.99-8.72), 5.35 (4.38-6.56), 4.94 (3.56-6.78), and 4.89 (3.47-6.81)], respectively. Males were at 22% higher risk of ESKD than females [1.22 (1.04-1.43)]. Each additional year of diabetes duration increased ESKD odds by 2% [1.02 (1.01-1.03)]. Non-white ethnicity, compared to white and socioeconomically most deprived, compared to the least deprived quintiles, were at 70% and 83% higher odds of ESKD. Each unit of HbA1c rise increased the odds of ESKD by 2%. Compared to microalbuminuria, macroalbuminuria increased the odds of ESKD by almost 10-fold [9.47 (7.95-11.27)] while normoalbuminuria reduced the odds by 73% [0.27 (0.22-0.32)]. CONCLUSIONS: Early onset of diabetes and hypertension, male sex, non-white ethnicity, deprivation, poor glycaemic control, and prolonged hyperglycaemia are significant risk factors for ESKD. These findings highlight the complexity of ESKD and the need for multifactorial targeted interventions in high-risk populations. CLINICAL TRIAL NUMBER: Not applicable.

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