Biological Variability of Estimated GFR and Albuminuria in CKD

Abstract

Rationale & objective: 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.

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

Setting & participants: 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).

Exposure: Repeat measurements from serially collected samples across 3 study visits.

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

Analytical approach: 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.

Results: 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.

Limitations: 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.

Conclusions: 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.

Keywords: Albuminuria; beta trace protein (BTP); biological variability; biomarker; clinically meaningful differences; coefficient of variation (CV); cystatin C; estimated glomerular filtration rate (eGFR); filtration marker; intraindividual variation; kidney function; laboratory measurement; reproducibility; serum creatinine; urinary albumin-creatinine ratio (UACR); β(2)-microglobulin (B2M).

Figure 1.

Scatterplots of within-person coefficients of variation (CVs) for filtration markers (creatinine, cystatin C, beta trace protein [BTP], and β₂-microglobulin [B2M]) against mean values for each marker. Two individuals (highlighted in red and blue circles) had high levels of variability across all four makers.

Figure 2.

Scatterplots of within-person coefficients of variation (CVs) for random and first-void albuminuria (urine albumin concentration [UAC] and urinary albumin-creatinine ratio [UACR]) against mean values of UAC and UACR.