Biological Variability of Estimated GFR and Albuminuria in CKD

Sushrut S. Waikar, Casey M. Rebholz, Zihe Zheng, Shelley Hurwitz, Chi yuan Hsu, Harold I. Feldman, Dawei Xie, Kathleen D. Liu, Theodore E. Mifflin, John H. Eckfeldt, Paul L. Kimmel, Ramachandran S. Vasan, Joseph V. Bonventre, Lesley A. Inker, Josef Coresh, Vasan S. Ramachandran, Joseph Bonventre, Sushrut Waikar, Venkata Sabbisetti, Jennifer Van EykDawn Chen, Qin Fu, Hermine Brunner, Vivette D'Agati, Jonathan Barasch, Josef Coresh, Casey Rebholz, Alan S. Go, Erwin Bottinger, Avelino Teixeira, Ilse Daehn, Mark Molitch, Daniel Batlle, Brad Rovin, Haifeng Wu, Andrew S. Levey, Lesley A. Inker, Meredith Foster, Chi yuan Hsu, Kathleen Liu, Jon Klein, Paola Fioretto, Michael Mauer, John H. Eckfeldt, Harold I. Feldman, Amy Karger, Krista Whitehead, Dawei Xie

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


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 (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.

Original languageEnglish (US)
Pages (from-to)538-546
Number of pages9
JournalAmerican Journal of Kidney Diseases
Issue number4
StatePublished - Oct 1 2018

Bibliographical note

Funding Information:
Support: This work was supported by the CKD Biomarker Consortium (funded by National Institute of Diabetes and Digestive and Kidney Diseases U01DK85649, U01DK085673, U01DK085660, U01DK085688, U01DK085651, and U01DK085689) by DK107782 (to CMR) and by R37 DK039773 (to JVB). The funders of this study had no role in study design; data collection, analysis, or reporting; or the decision to submit for publication.

Publisher Copyright:
© 2018 National Kidney Foundation, Inc.


  • 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-microglobulin (B2M)


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