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, Chronic Kidney Disease Biomarkers Consortium Investigators, Vasan S Ramachandran, Joseph Bonventre, Sushrut Waikar, Venkata Sabbisetti, Jennifer Van Eyk, Dawn 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, Michael Mauer, Paola Fioretto, Gary Nelsestuen, John H Eckfeldt, Amy Karger, Paola Fioretto, Harold I Feldman, Shawn Ballard, Krista Whitehead, Dawei Xie, Phyllis Gimotty, Haochang Shou, Xiaoming Zhang, Kellie Ryan, Theodore E Mifflin, Tom Greene, Robert G Nelson, Paul L Kimmel, John W Kusek, 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, Chronic Kidney Disease Biomarkers Consortium Investigators, Vasan S Ramachandran, Joseph Bonventre, Sushrut Waikar, Venkata Sabbisetti, Jennifer Van Eyk, Dawn 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, Michael Mauer, Paola Fioretto, Gary Nelsestuen, John H Eckfeldt, Amy Karger, Paola Fioretto, Harold I Feldman, Shawn Ballard, Krista Whitehead, Dawei Xie, Phyllis Gimotty, Haochang Shou, Xiaoming Zhang, Kellie Ryan, Theodore E Mifflin, Tom Greene, Robert G Nelson, Paul L Kimmel, John W Kusek
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 (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).
Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Figures
Source: PubMed