Relevance of correction for drift and day-to-day variation in cystatin C measurement: a post-hoc analysis of the PREVEND cohort, with independent replication in the ESTHER cohort.

BACKGROUND: Despite standard laboratory quality control, drift and day-to-day variability in cystatin C measurements can be observed. We investigated whether correction for drift and day-to-day variation in cystatin C measurements improves the association of estimated glomerular filtration rate (eGFR) with chronic kidney disease (CKD) risk factors and prognosis.
METHODS: Plasma samples of the PREVEND study (Dutch cohort study, n=8592) were used to measure cystatin C (Gentian assay) on 243 random days. A correction factor was calculated for each measurement day. GFR was estimated with CKD-EPI equation using routinely measured cystatin C (eGFRcysC) and corrected cystatin C (eGFRcysC corr). Participants were categorized in six categories of eGFRcysC and eGFRcysC corr: ≥120, 90-119, 75-89, 60-74, 45-59 and <45 mL/min/1.73m2. Independent replication was performed in the ESTHER study (German cohort study, n=9949).
RESULTS: Compared to non-reclassified participants, participants re-classified upward had significantly lower age, body mass index, blood pressure, cholesterol, glucose and albuminuria, whereas the opposite was true for participants reclassified downward. CKD risk factors explained more variance in eGFRcysC corr than in eGFRcysC (p<0.001). Compared to non-reclassified participants, risk of incident cardiovascular events (n=789, follow-up 9.3±2.7 years) tended to be higher in downward reclassified and lower in upward reclassified participants. Net reclassification improvement for incident cardiovascular events using eGFRcysC corr was positive (0.102, p=0.019). The ESTHER study showed similar results.
CONCLUSIONS: Correction for drift and day-to-day variation in cystatin C measurement improves eGFR using cystatin C for its association with CKD risk factors and incident cardiovascular events.