An Age-Calibrated Definition of Chronic Kidney Disease: Rationale and Benefits

Abstract

Defining chronic kidney disease (CKD) is the subject of intense debate in the current nephrology literature. The debate concerns the threshold value of estimated glomerular filtration rate (eGFR) used to make the diagnosis of CKD. Current recommendations argue that a universal threshold of 60 mL/min/1.73m(2) should be used. This threshold has been defended by epidemiological studies showing that the risk of mortality or end-stage renal disease increases with an eGFR below 60 mL/min/1.73m(2). However, a universal threshold does not take into account the physiologic decline in GFR with ageing nor does it account for the risk of mortality and end-stage renal disease being trivial with isolated eGFR levels just below 60 mL/min/1.73m(2) in older subjects and significantly increased with eGFR levels just above 60 mL/min/1.73m(2) among younger patients. Overestimation of the CKD prevalence in the elderly (medicalisation of senescence) and underestimation of CKD (potentially from treatable primary nephrologic diseases) in younger patients is of primary concern. An age-calibrated definition of CKD has been proposed to distinguish age-related from disease-related changes in eGFR. For patients younger than 40 years, CKD is defined by eGFR below 75 mL/min/1.73m(2). For patients with ages between 40 and 65 years, CKD is defined by 60 mL/min/1.73m(2). For subjects older than 65 years without albuminuria or proteinuria, CKD is defined by eGFR below 45 mL/min/1.73m(2).

Figure 1.

Percentile (P) values (97.5^th, 50^th and 2.5^th) for estimated GFR (eGFR; in mL/min/1.73m²) by the CKD-EPI equation for healthy community living (Caucasian) adult Males and Females according to age between 18 and 85+ years (adapted with permission from van den Brand et al, 201132) . For comparison, the KDIGO threshold for defining CKD is given as a bold horizontal line (60 mL/min/1.73m²). Note the substantial numbers of individuals >60 years of age in the 2.5^th to approximately the 40^th percentile of eGFR that fall below the 60mL/min/1.73m² threshold.

Figure 2.

Prevalence of CKD in USA based on ACR and eGFR with the KDIGO classification system. Reprinted with permission from KDIGO.

Figure 3.

Proportion of CKD based on eGFR (yellow), ACR (green) or both (red) in different age categories (adapted from reference 42).

Figure 4.

HR for mortality when the reference group is the one with the lowest risk. eGFR ranges into the brackets (low risk) are not significantly different from the reference group.