Biological Variability of Estimated GFR and Albuminuria in CKD

Am J Kidney Dis. 2018 Oct;72(4):538-546. doi: 10.1053/j.ajkd.2018.04.023. Epub 2018 Jul 18.


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 (CVw) values and corresponding reference change positive and negative (RCVpos and RCVneg) values using log-transformed measurements.

Results: Median CVw (RCVpos; RCVneg) 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. CVw values for filtration markers were comparable across the range of baseline eGFRs. CVw 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).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Albuminuria / diagnosis*
  • Albuminuria / epidemiology
  • Biomarkers / blood
  • Blood Chemical Analysis
  • Creatinine / blood
  • Cross-Sectional Studies
  • Cystatin C / blood*
  • Female
  • Glomerular Filtration Rate / physiology*
  • Humans
  • Intramolecular Oxidoreductases / blood*
  • Lipocalins / blood*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / physiopathology*
  • Renal Insufficiency, Chronic / urine
  • Severity of Illness Index
  • Urinalysis
  • beta 2-Microglobulin / blood*


  • Biomarkers
  • Cystatin C
  • Lipocalins
  • beta 2-Microglobulin
  • Creatinine
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase