Estimating glomerular filtration rate for the full age spectrum from serum creatinine and cystatin C

Abstract

Background: We recently published and validated the new serum creatinine (Scr)-based full-age-spectrum equation (FAS crea ) 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 ( Q cysC = 0.82 mg/L for ages <70 years and Q cysC = 0.95 mg/L for ages ≥70 years). By replacing Scr/ Q crea in the FAS crea equation with ScysC/ Q cysC , or with the average of both normalized biomarkers, we obtained new ScysC-based (FAS cysC ) and combined Scr-/ScysC-based FAS equations (FAS combi ). To validate the new FAS cysC and FAS combi 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 FAS cysC 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 < 0.0001), or the ScysC-based Schwartz equation (P30 = 68.8%; P < 0.0001) and the FAS combi equation outperformed all equations with P30 = 92.1% (P < 0.0001). In adults, the FAS cysC equation (P30 = 82.6%) performed equally as well as the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI cysC ) (P30 = 80.4%) and the FAS combi equation (P30 = 89.9%) was also equal to the combined CKD-EPI equation (P30 = 88.2%). In older adults, FAS cysC was superior (P30 = 88.2%) to CKD-EPI cysC (P30 = 84.4%; P < 0.0001) and the FAS combi equation (P30 = 91.2%) showed significantly higher performance than the combined CKD-EPI equation (P30 = 85.6%) (P < 0.0001).

Conclusion: The FAS equation is not only applicable to all ages, but also for all recommended renal biomarkers and their combinations.

Keywords: all ages; all renal biomarkers; combined FAS equation; cystatin C; serum creatinine.

FIGURE 1

(a) The linear relationship between median (solid black circles) ScysC and age for the n = 1333 apparently healthy Berlin Initiative Study participants (grey circles). (b) Histogram for ScysC measurements of n = 1333 apparently healthy older adults.

FIGURE 2

RMSE as a function of the weighting factor α for children [based on Q(height)], adults and older adults. The total RMSE for all n = 6132 measurements is also shown. For children the FAS_cysC equation has smaller RMSE than the FAS_crea equation. For adults there is a slightly smaller RMSE for the single biomarker FAS_crea equation compared with the single marker FAS_cysC equation. For older adults there is no real preference for the value of α. For all age groups the RMSE is minimal for α  ≈ 0.5 (= combined FAS equation).

FIGURE 3

P30 as a function of the weighting factor α for the different age groups.