Kidney age - chronological age difference (KCD) score provides an age-adapted measure of kidney function

Abstract

Background: Given the age-related decline in glomerular filtration rate (GFR) in healthy individuals, we examined the association of all-cause death or cardiovascular event with the Kidney age - Chronological age Difference (KCD) score, whereby an individual's kidney age is estimated from their estimated GFR (eGFR) and the age-dependent eGFR decline reported for healthy living potential kidney donors.

Methods: We examined the association between death or cardiovascular event and KCD score, age-dependent stepped eGFR criteria (eGFRstep), and eGFR < 60 ml/min/1.73 m2 (eGFR60) in a community-based high cardiovascular risk cohort of 3837 individuals aged ≥60 (median 70, interquartile range 65, 75) years, followed for a median of 5.6 years.

Results: In proportional hazards analysis, KCD score ≥ 20 years (KCD20) was associated with increased risk of death or cardiovascular event in unadjusted analysis and after adjustment for age, sex and cardiovascular risk factors. Addition of KCD20, eGFRstep or eGFR60 to a cardiovascular risk factor model did not improve area under the curve for identification of individuals who experienced death or cardiovascular event in receiver operating characteristic curve analysis. However, addition of KCD20 or eGFR60, but not eGFRstep, to a cardiovascular risk factor model improved net reclassification and integrated discrimination. KCD20 identified individuals who experienced death or cardiovascular event with greater sensitivity than eGFRstep for all participants, and with greater sensitivity than eGFR60 for participants aged 60-69 years, with similar sensitivities for men and women.

Conclusions: In this high cardiovascular risk cohort aged ≥60 years, the KCD score provided an age-adapted measure of kidney function that may assist patient education, and KCD20 provided an age-adapted criterion of eGFR-related increased risk of death or cardiovascular event. Further studies that include the full age spectrum are required to examine the optimal KCD score cut point that identifies increased risk of death or cardiovascular event, and kidney events, associated with impaired kidney function, and whether the optimal KCD score cut point is similar for men and women.

Trial registration: ClinicalTrials.gov NCT00400257 , NCT00604006 , and NCT01581827 .

Keywords: All-cause mortality; Cardiovascular disease; Chronic kidney disease; eGFR.

Conflict of interest statement

Bupa Australia was involved in study design, recruitment of participants, and funding, but was not involved in data collection, analysis or interpretation, or writing of the article. Bupa Australia had no control or influence over the decision to submit the final manuscript for publication.

U.B. was an employee of Bupa Australia. D.L. has received honoraria from Pfizer, Sanofi, Astra-Zeneca, Abbott, Bayer, MSD, GSK, Novartis and Nycomed. S.S. has received unrestricted educational grants from Schering Plough and Boehringer Ingelheim, and was Principal Investigator of the Novartis-sponsored Valsartan Intensified Primary Care Reduction of Blood Pressure (VIPER-BP) Study. H.K. received support from Novartis, Bristol-Myers Squibb, and Ardian/Medtronic. D.L.P. received payment from Johnson & Johnson, Bayer and Novartis for lectures. The remaining authors have no disclosures to report.

Figures

Fig. 1

Scattergram plot of eGFR in relation to age for 3837 SCREEN-HF participants. The black line represents the age-related decline in eGFR from 105 ml/min/1.73 m2 at age 40 years to 60 ml/min/1.73 m2 at age 90 years in healthy living potential kidney donors [3]. eGFR values below the black line represent eGFR values below that of a healthy living potential kidney donor of the same age, and correspond to a kidney age that exceeds the chronological age. A 70-year old individual with an eGFR of 60 ml/min/1.73 m2 has an eGFR of a healthy 90-year-old; thus, the kidney age is 20 years older than the chronological age, and the Kidney age - Chronological age Difference (KCD) score is 90–70 = 20 years. Whereas CKD may be defined by eGFR < 60 ml/min/1.73 m2 (green line), age-dependent stepped eGFR criteria of Delanaye et al. [10] define CKD as eGFR < 75 ml/min/1.73 m2 for age < 40 years, < 60 ml/min/1.73 m2 for individuals between 40 and 65 years, and < 45 ml/min/1.73 m2 for age > 65 years (purple line) The red line corresponds to a KCD score of 20 years

Fig. 2

Histograms of the numbers of participants according to eGFR (a) and KCD score (b)

Fig. 3

Hazard ratios for death or CV event according to KCD score. Hazard ratios (95% confidence interval, CI) for KCD score alone (a) or adjusted (b) for age, sex, and CV risk factors (previous myocardial infarction, coronary revascularisation, stroke or transient ischaemic attack, peripheral vascular disease, diabetes, atrial fibrillation, log2(BMI), systolic blood pressure, antihypertensive medication, and smoking status on enrolment). Hazard ratios from proportional hazards analysis of all events during follow-up (n = 782)

Fig. 4

Sensitivity (a) and specificity (b) for the identification of individuals who experienced death or CV event during 5-year follow-up. Sensitivity and specificity for either Kidney age - Chronological age Difference score ≥ 20 years (KCD20), age-dependent stepped eGFR criteria of Delanaye et al. [10] (eGFRstep), or eGFR < 60 ml/min/1.73 m2 (eGFR60), for all participants, and for participants aged 60- < 70 years, 70- < 80 years, and ≥ 80 years. Among all participants, and each age category, sensitivities and specificities, compared using McNemar’s test with Yates correction, were statistically significantly different between KCD20, eGFRstep and eGFR60 (P < 0.05)