Biological Variability of Estimated GFR and Albuminuria in CKD

Determining whether a change in estimated glomerular filtration rate (eGFR) or albuminuria is clinically significant requires knowledge of short-term within-person variability of the measurements, which few studies have addressed in the setting of chronic kidney disease.

Cross-sectional study with multiple collections over less than 4 weeks.

Clinically stable outpatients with chronic kidney disease (N=50; mean age, 56.8 years; median eGFR, 40mL/min/1.73m²; median urinary albumin-creatinine ratio (UACR), 173mg/g).

Repeat measurements from serially collected samples across 3 study visits.

Measurements of urine albumin concentration (UAC), UACR, and plasma creatinine, cystatin C, β₂-microglobulin (B2M), and beta trace protein (BTP).

We calculated within-person coefficients of variation (CV_w) values and corresponding reference change positive and negative (RCV_pos and RCV_neg) values using log-transformed measurements.

Median CV_w (RCV_pos; RCV_neg) values of filtration markers were 5.4% (+16%; -14%) for serum creatinine, 4.1% (+12%; -11%) for cystatin C, 7.4% (+23%; -18%) for BTP, and 5.6% (+17%; -14%) for B2M. Results for albuminuria were 33.2% (+145%; -59%) for first-morning UAC, 50.6% (+276%; -73%) for random spot UAC, 32.5% (+141%; -58%) for first-morning UACR, and 29.7% (124%; -55%) for random spot UACR. CV_w values for filtration markers were comparable across the range of baseline eGFRs. CV_w values for UAC and UACR were comparable across the range of baseline albuminuria values.

Small sample size limits the ability to detect differences in variability across markers. Participants were recruited and followed up in a clinical and not research setting, so some preanalytical factors could not be controlled.

eGFR markers appear to have relatively low short-term within-person variability, whereas variability in albuminuria appears to be high, making it difficult to distinguish random variability from meaningful biologic changes.