Accounting for Age in the Definition of Chronic Kidney Disease

Abstract

Importance: Using the same level of estimated glomerular filtration rate (eGFR) to define chronic kidney disease (CKD) regardless of patient age may classify many elderly people with a normal physiological age-related eGFR decline as having a disease.

Objective: To compare the outcomes associated with CKD as defined by a fixed vs an age-adapted eGFR threshold.

Design, setting, and participants: This population-based cohort study was conducted in Alberta, Canada and used linked administrative and laboratory data from adults with incident CKD from April 1, 2009, to March 31, 2017, defined by a sustained reduction in eGFR for longer than 3 months below a fixed or an age-adapted eGFR threshold. Non-CKD controls were defined as being 65 years or older with a sustained eGFR of 60 to 89 mL/min/1.73 m2 for longer than 3 months and normal/mild albuminuria. The follow-up ended on March 31, 2019. The data were analyzed from February to April 2020.

Exposures: A fixed eGFR threshold of 60 vs thresholds of 75, 60, and 45 mL/min/1.73 m2 for age younger than 40, 40 to 64, and 65 years or older, respectively.

Main outcomes and measures: Competing risks of kidney failure (kidney replacement initiation or sustained eGFR <15 mL/min/1.73 m2 for >3 months) and death without kidney failure.

Results: The fixed and age-adapted CKD cohorts included 127 132 (69 546 women [54.7%], 57 586 men [45.3%]) and 81 209 adults (44 582 women [54.9%], 36 627 men [45.1%]), respectively (537 vs 343 new cases per 100 000 person-years). The fixed-threshold cohort had lower risks of kidney failure (1.7% vs 3.0% at 5 years) and death (21.9% vs 25.4%) than the age-adapted cohort. A total of 53 906 adults were included in both cohorts. Of the individuals included in the fixed-threshold cohort only (n = 72 703), 54 342 (75%) were 65 years or older and had baseline eGFR of 45 to 59 mL/min/1.73 m2 with normal/mild albuminuria. The 5-year risks of kidney failure and death among these elderly people were similar to those of non-CKD controls, with a risk of kidney failure of 0.12% or less in both groups across all age categories and a risk of death at 69, 122, 279, and 935 times higher than the risk of kidney failure for 65 to 69, 70 to 74, 75 to 79, and 80 years or older, respectively.

Conclusions and relevance: This cohort study of adults with CKD suggests that the current criteria for CKD that use the same eGFR threshold for all ages may result in overestimation of the CKD burden in an aging population, overdiagnosis, and unnecessary interventions in many elderly people who have age-related loss of eGFR.

Figure 1.. Incidence of Chronic Kidney Disease (CKD)

Incident CKD cases per 100 000 person-years identified using estimated glomerular filtration rate algorithms by fiscal years (A) and age (B) during the accrual period from April 1, 2009, to March 31, 2017.

Figure 2.. Baseline Albuminuria by Age

Albuminuria was categorized as normal/mild, moderate, severe, or unmeasured based on the most recent outpatient values before cohort entry, with the following types of measurement in descending order of preference: albumin-to-creatinine ratio (<30, 30 to 300, or >300 mg/g), protein-to-creatinine ratio (<150, 150 to 500, or >500 mg/g), and urine dipstick protein (negative or trace, 1+, or ≥2+).

Figure 3.. Risks of Kidney Failure and Death From Time of Initial Chronic Kidney Disease (CKD) Diagnosis

Areas represent risks, which were estimated using cumulative incidence functions over time. Risks of kidney failure at 5 years were 1.67% (95% CI, 1.60%-1.75%) for the fixed-threshold cohort and 3.01% (95% CI, 2.89%-3.14%) for the age-adapted cohort; risks of death at 5 years were 21.9% (95% CI, 21.6%-22.1%) and 25.4% (95% CI, 25.1%-25.7%), respectively.

Figure 4.. Risks of Kidney Failure (KF) and Death at 5 Years by Index Estimated Glomerular Filtration Rate (eGFR) and Age in Elderly People With Normal/Mild Albuminuria

Analyses were restricted to people 65 years or older with normal/mild albuminuria. Chronic kidney disease (CKD) was defined using the fixed-threshold approach; individuals were assigned to eGFR categories based on the index eGFR when they first met the eGFR criteria for CKD. The absence of CKD was defined using a sustained eGFR of 60 to 89 mL/min/1.73 m² for more than 3 months. C, Values for 15 to 29 index eGFR for ages 65 to 69, 70 to 74, and 75 to 70, respectively: 179, 226, and 227.