Dubourg, Laurence

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 m 2 . 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 m 2 , whereas in elderly people it is increased at levels <45 ml/min per 1.73 m 2 . 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.

Abstract Background. We recently published and validated the new serum creatinine (Scr)-based full-age-spectrum equation (FAScrea) for estimating the glomerular filtration rate (GFR) for healthy and kidney–diseased subjects of all ages. The equation was based on the concept of normalized Scr and shows equivalent to superior prediction performance to the currently recommended equations for children, adolescents, adults and older adults. Methods. Based on an evaluation of the serum cystatin C (ScysC) distribution, we defined normalization constants for ScysC (QcysC = 0.82 mg/L for ages &lt;70 years and QcysC = 0.95 mg/L for ages ≥70 years). By replacing Scr/Qcrea in the FAScrea equation with ScysC/QcysC, or with the average of both normalized biomarkers, we obtained new ScysC-based (FAScysC) and combined Scr-/ScysC-based FAS equations (FAScombi). To validate the new FAScysC and FAScombi we collected data on measured GFR, Scr, ScysC, age, gender, height and weight from 11 different cohorts including n = 6132 unique white subjects (368 children, aged ≤18 years, 4295 adults and 1469 older adults, aged ≥70 years). Results. In children and adolescents, the new FAScysC equation showed significantly better performance [percentage of patients within 30% of mGFR (P30) = 86.1%] than the Caucasian Asian Paediatric Adult Cohort equation (P30 = 76.6%; P &lt; 0.0001), or the ScysC-based Schwartz equation (P30 = 68.8%; P &lt; 0.0001) and the FAScombi equation outperformed all equations with P30 = 92.1% (P &lt; 0.0001). In adults, the FAScysC equation (P30 = 82.6%) performed equally as well as the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPIcysC) (P30 = 80.4%) and the FAScombi equation (P30 = 89.9%) was also equal to the combined CKD-EPI equation (P30 = 88.2%). In older adults, FAScysC was superior (P30 = 88.2%) to CKD-EPIcysC (P30 = 84.4%; P &lt; 0.0001) and the FAScombi equation (P30 = 91.2%) showed significantly higher performance than the combined CKD-EPI equation (P30 = 85.6%) (P &lt; 0.0001). Conclusion. The FAS equation is not only applicable to all ages, but also for all recommended renal biomarkers and their combinations.