Acute Kidney Injury and Subsequent Kidney Failure With Replacement Therapy Incidence in Older Adults With Advanced CKD: A Cohort Study of US Veterans

Abstract

Rationale & Objective: Advanced age is a major risk factor for chronic kidney disease (CKD) development, which has high heterogeneity in disease progression. Acute kidney injury (AKI) hospitalization rates are increasing, especially among older adults. Previous AKI epidemiologic analyses have focused on hospitalized populations, which may bias results toward sicker populations. This study examined the association between AKI and incident kidney failure with replacement therapy (KFRT) while evaluating age as an effect modifier of this relationship. Study Design: Retrospective cohort study. Setting & Participants: 24,133 Veterans at least 65 years old with incident CKD stage 4 from 2011 to 2013. Exposures: AKI, AKI severity, and age. Outcomes: KFRT and death. Analytical Approach: The Fine-Gray competing risk regression was used to model AKI and incident KFRT with death as a competing risk. A Cox regression was used to model AKI severity and death. Results: Despite a nonsignificant age interaction between AKI and KFRT, a clinically relevant combined effect of AKI and age on incident KFRT was observed. Compared with our oldest age group without AKI, those aged 65-74 years with AKI had the highest risk of KFRT (subdistribution HR [sHR], 14.9; 95% CI, 12.7-17.4), whereas those at least 85 years old with AKI had the lowest (sHR, 1.71; 95% CI, 1.22-2.39). Once Veterans underwent KFRT, their risk of death increased by 44%. A 2-fold increased risk of KFRT was observed across all AKI severity stages. However, the risk of death increased with worsening AKI severity. Limitations: Our study lacked generalizability, was restricted to ever use of medications, and used inpatient serum creatinine laboratory results to define AKI and AKI severity. Conclusions: In this national cohort, advanced age was protective against incident KFRT but not death. This is likely explained by the high frequency of deaths observed in this population (51.1%). Nonetheless, AKI and younger age are substantial risk factors for incident KFRT. Plain Language Summary: Older adults are at risk of acute kidney injury (AKI) and subsequent nonrecovery from AKI, resulting in long-term dialysis. Hospitalized patients have often been used in the past to study AKI. This could lead to biased conclusions when inferring from sicker populations. That is why we created a national cohort of 24,133 Veterans at least 65 years old with incident chronic kidney disease (CKD) stage 4 to examine the relationship between AKI and age and subsequent kidney failure with replacement therapy (KFRT). The data have showed that AKI and younger age are substantial risk factors for incident KFRT. As for older age, it appears to be protective against KFRT but not death. This is likely explained by the high frequency of deaths observed in our cohort.

Keywords

• Acute kidney injury
• chronic kidney disease
• kidney failure with replacement therapy
• Veterans