Effect of Hypertension on Incident ESKD Across Various Diabetes Stages: A Nationwide Population-Based Cohort Study

Background: Diabetes and hypertension are recognized risk factors for the progression to end-stage kidney disease (ESKD). However, limited studies have investigated the interaction between these two conditions, particularly how pre-diabetes and pre-hypertension influence ESKD incidence. This study aims to assess the hazard ratios (HRs) for ESKD development based on diabetes and hypertension status, including pre-disease states, with further analyses stratified by sex and age. Methods: This retrospective cohort study involved 4,595,974 adults aged ≥20 years who participated in national health screenings in 2012, with follow-up until 2019. Participants were divided into five diabetes groups (normal, impaired fasting glucose (IFG), newly diagnosed, <5 years, and ≥5 years duration) and five hypertension groups (normal, prehypertension, newly diagnosed, controlled, and uncontrolled hypertension). HRs for ESKD development were calculated for each group, with additional analyses based on sex, age, chronic kidney disease, and proteinuria status. Results: The risk of ESKD increased progressively with worsening stages of hypertension in all diabetes groups, with the highest risk observed in those with diabetes for more than 5 years and uncontrolled hypertension (HR, 73.581; 95% CI [65.346, 82.855]) when compared to the normoglycemic and normotensive groups. Hypertension had a smaller impact on ESKD risk in the IFG group compared to both the diabetes and normoglycemic groups. Subgroup analyses revealed that hypertension posed a greater risk for ESKD in patients younger than 65 years, regardless of diabetes status. The presence of chronic kidney disease further amplified the ESKD risk associated with hypertension, though no significant differences were found based on sex or proteinuria status. Conclusion: ESKD risk increases with longer diabetes duration and uncontrolled hypertension, though this effect is less pronounced in individuals with IFG. In patients under 65, hypertension notably elevates ESKD risk, independent of diabetes status, emphasizing the importance of stringent blood pressure control, even in non-diabetic individuals.