CKD: A Call for an Age-Adapted Definition

Abstract

Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m² This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m², whereas in elderly people it is increased at levels <45 ml/min per 1.73 m² Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.

Keywords: chronic kidney disease; epidemiology and outcomes; glomerular filtration rate.

Graphical abstract

Figure 1.

The association between eGFR and all-cause mortality depends on the age group. Hazard ratio for mortality when the reference group is the one with the lowest risk. eGFR ranges are within the brackets (low risk) and are not significantly different from the reference group (from Denic et al.).

Figure 2.

The interpretation of GFR results depends on age. Examples of interpretation of GFR (here GFR estimated using the FAS equation but the same can be applied to measured GFR or eGFR using other estimating equations) according to age and normal percentiles: abnormal (bottom) and normal (below) GFR result. The red circle corresponds to FAS=48 ml/min per 1.73 m² (serum creatinine [SCr]=1.3 mg/dl corresponds to SCr/Q=1.3/0.9=1.44>1.33) and the green circle corresponds to FAS=58 ml/min per 1.73 m² (SCr=1.1 mg/dl corresponds to SCr/Q=1.22<1.33). These results are abnormally low and normal predicted eGFR-FAS results with the age-adapted staging, respectively. Dark green shaded area corresponds to reference intervals for mGFR±SD and symmetrical limits for FAS based on SCr/Q=1 (middle line) and SCr/Q=1.33 (lower limit) (14). Light green area corresponds to the upper limit for FAS, based on SCr/Q=0.67. The interval (0.67 to 1.33) is considered the reference interval for SCr/Q. FAS, full age spectrum. Q, median SCr from healthy populations to account for age and sex.

Figure 3.

Age-specific thresholds in relation to age-specific GFR percentiles. GFR cut-off values and percentiles according to age (here percentiles of eGFR are calculated using the FAS equation). The bold line represents an age-adapted threshold for CKD: 75 ml/min per 1.73 m² for age below 40 years, 60 ml/min per 1.73 m² for age between 40 and 65 years, and 45 ml/min per 1.73 m² for age above 65 years. The dashed line represents the median (50th percentile) and the thin solid lines represent the 97.5th and 2.5th percentiles. The shaded zone is considered as below the normal reference intervals for GFR (<2.5th percentile).