(C-021) Age-Specific Associations and Attributable Burden of Risk Factors for All-cause and Cause-specific Mortality in Patients with Chronic Kidney Disease

Background: Chronic kidney disease (CKD) is a leading cause of mortality globally, with a rising prevalence across all adult age groups. However, the age-specific associations of risk factors with mortality and the attributable mortality burden of these risk factors across different ages remain unclear.

Objectives: We hypothesized that the significance and magnitude of risk factors attributable to deaths differ by age. This study aims to investigate the age-specific relationships and attributable burden of modifiable risk factors and comorbidities for all-cause and cause-specific mortality in CKD patients.

Methods: Using Hong Kong Hospital Authority’s electronic medical records, we identified a territory-wide retrospective cohort of 576,677 adults (mean age: 73.5 ± 13.8 years) first diagnosed with CKD between January 2008 and December 2020. Baseline was defined as the earliest date of CKD diagnosis or an estimated glomerular filtration rate less than 60 mL/min/1.73m². Risk factors included six modifiable risk factors (smoking and suboptimal control of blood pressure, fasting blood glucose, hemoglobin A1c [HbA1c], low-density lipoprotein cholesterol [LDL-C], and body mass index) and four primary comorbidities (diabetes mellitus, cardiovascular disease, heart failure, and cancer). Hazard ratios (HR) and population-attributable fractions (PAFs) of risk factors for mortality were estimated across five age groups (18-54, 55-64, 65-74, 75-84, and ≥85 years) with mutual adjustment.

Results: During a median follow-up of 4.8 years, 329,098 (57.1%) patients died. Primary causes of death were cardiovascular diseases (9.9%), cancer (9.9%), and renal diseases (4.7%). Although the five-year mortality rate was higher in older (81.6%) than younger patients (25.3%), the relative risk of mortality associated with most risk factors declined with age (e.g., HRs of suboptimal HbA1c decreased from 1.21 [95% confidence interval (CI) 1.14, 1.28] to 1.04 [1.01, 1.07]). All risk factors collectively accounted for a higher proportion of deaths in the youngest (PAF: 44.3% [95% CI 35.3%, 52.0%]) than in the oldest age group (22.6% [14.6%, 29.7%]). Leading risk factors for all-cause mortality were comorbid cancer (13.4% [13.3%, 13.5%]) and suboptimal LDL-C (12.0% [8.0%, 15.8%]) in the youngest group, while comorbid CVD (12.6% [12.1%, 13.1%]) was the most influential risk factor in the oldest age group.

Conclusions: The assessed risk factors were associated with a higher relative risk for mortality in younger compared to older CKD patients, with considerable variation in the leading risk factors across age groups. These findings underscore the importance of early management of modifiable risk factors and suggest the need for age-targeted clinical strategies to mitigate mortality risk in CKD patients.