Biological Variability of Estimated GFR and Albuminuria in CKD

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, 40 mL/min/1.73 m²; median urinary albumin-creatinine ratio (UACR), 173 mg/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.