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 Eyk & 30 others 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, Michael Mauer, John H. Eckfeldt, Amy Karger, Harold I. Feldman, Amy Karger, Krista Whitehead, Dawei Xie

Research output: Contribution to journalArticle

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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, 40 mL/min/1.73 m 2 ; 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, β 2 -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.

Original languageEnglish (US)
Pages (from-to)538-546
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume72
Issue number4
DOIs
StatePublished - Oct 1 2018

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Albuminuria
Albumins
Creatinine
prostaglandin R2 D-isomerase
Glomerular Filtration Rate
Urine
Cystatin C
Chronic Renal Insufficiency
Salivary Cystatins
Sample Size
Reference Values
Outpatients
Cross-Sectional Studies

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 -microglobulin (B2M)

PubMed: MeSH publication types

  • Journal Article

Cite this

Waikar, S. S., Rebholz, C. M., Zheng, Z., Hurwitz, S., Hsu, C. Y., Feldman, H. I., ... Xie, D. (2018). Biological Variability of Estimated GFR and Albuminuria in CKD. American Journal of Kidney Diseases, 72(4), 538-546. https://doi.org/10.1053/j.ajkd.2018.04.023

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

In: American Journal of Kidney Diseases, Vol. 72, No. 4, 01.10.2018, p. 538-546.

Research output: Contribution to journalArticle

Waikar, SS, Rebholz, CM, Zheng, Z, Hurwitz, S, Hsu, CY, Feldman, HI, Xie, D, Liu, KD, Mifflin, TE, Eckfeldt, JH, Kimmel, PL, Vasan, RS, Bonventre, JV, Inker, LA, Coresh, J, Ramachandran, VS, Bonventre, J, Waikar, S, Sabbisetti, V, Van Eyk, J, Chen, D, Fu, Q, Brunner, H, D'Agati, V, Barasch, J, Coresh, J, Rebholz, C, Go, AS, Bottinger, E, Teixeira, A, Daehn, I, Molitch, M, Batlle, D, Rovin, B, Wu, H, Levey, AS, Inker, LA, Foster, M, Hsu, CY, Liu, K, Klein, J, Mauer, M, Fioretto, P, Mauer, M, Eckfeldt, JH, Karger, A, Feldman, HI, Karger, A, Whitehead, K & Xie, D 2018, 'Biological Variability of Estimated GFR and Albuminuria in CKD', American Journal of Kidney Diseases, vol. 72, no. 4, pp. 538-546. https://doi.org/10.1053/j.ajkd.2018.04.023
Waikar SS, Rebholz CM, Zheng Z, Hurwitz S, Hsu CY, Feldman HI et al. Biological Variability of Estimated GFR and Albuminuria in CKD. American Journal of Kidney Diseases. 2018 Oct 1;72(4):538-546. https://doi.org/10.1053/j.ajkd.2018.04.023
Waikar, Sushrut S. ; Rebholz, Casey M. ; Zheng, Zihe ; Hurwitz, Shelley ; Hsu, Chi yuan ; Feldman, Harold I. ; Xie, Dawei ; Liu, Kathleen D. ; Mifflin, Theodore E. ; Eckfeldt, John H. ; Kimmel, Paul L. ; Vasan, Ramachandran S. ; Bonventre, Joseph V. ; Inker, Lesley A. ; Coresh, Josef ; Ramachandran, Vasan S. ; Bonventre, Joseph ; Waikar, Sushrut ; Sabbisetti, Venkata ; Van Eyk, Jennifer ; Chen, Dawn ; Fu, Qin ; Brunner, Hermine ; D'Agati, Vivette ; Barasch, Jonathan ; Coresh, Josef ; Rebholz, Casey ; Go, Alan S. ; Bottinger, Erwin ; Teixeira, Avelino ; Daehn, Ilse ; Molitch, Mark ; Batlle, Daniel ; Rovin, Brad ; Wu, Haifeng ; Levey, Andrew S. ; Inker, Lesley A. ; Foster, Meredith ; Hsu, Chi yuan ; Liu, Kathleen ; Klein, Jon ; Mauer, Michael ; Fioretto, Paola ; Mauer, Michael ; Eckfeldt, John H. ; Karger, Amy ; Feldman, Harold I. ; Karger, Amy ; Whitehead, Krista ; Xie, Dawei. / Biological Variability of Estimated GFR and Albuminuria in CKD. In: American Journal of Kidney Diseases. 2018 ; Vol. 72, No. 4. pp. 538-546.
@article{e65841de08794f0985450a879d73e149,
title = "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, 40 mL/min/1.73 m 2 ; 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, β 2 -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 -microglobulin (B2M)",
author = "Waikar, {Sushrut S.} and Rebholz, {Casey M.} and Zihe Zheng and Shelley Hurwitz and Hsu, {Chi yuan} and Feldman, {Harold I.} and Dawei Xie and Liu, {Kathleen D.} and Mifflin, {Theodore E.} and Eckfeldt, {John H.} and Kimmel, {Paul L.} and Vasan, {Ramachandran S.} and Bonventre, {Joseph V.} and Inker, {Lesley A.} and Josef Coresh and Ramachandran, {Vasan S.} and Joseph Bonventre and Sushrut Waikar and Venkata Sabbisetti and {Van Eyk}, Jennifer and Dawn Chen and Qin Fu and Hermine Brunner and Vivette D'Agati and Jonathan Barasch and Josef Coresh and Casey Rebholz and Go, {Alan S.} and Erwin Bottinger and Avelino Teixeira and Ilse Daehn and Mark Molitch and Daniel Batlle and Brad Rovin and Haifeng Wu and Levey, {Andrew S.} and Inker, {Lesley A.} and Meredith Foster and Hsu, {Chi yuan} and Kathleen Liu and Jon Klein and Michael Mauer and Paola Fioretto and Michael Mauer and Eckfeldt, {John H.} and Amy Karger and Feldman, {Harold I.} and Amy Karger and Krista Whitehead and Dawei Xie",
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TY - JOUR

T1 - Biological Variability of Estimated GFR and Albuminuria in CKD

AU - Waikar, Sushrut S.

AU - Rebholz, Casey M.

AU - Zheng, Zihe

AU - Hurwitz, Shelley

AU - Hsu, Chi yuan

AU - Feldman, Harold I.

AU - Xie, Dawei

AU - Liu, Kathleen D.

AU - Mifflin, Theodore E.

AU - Eckfeldt, John H.

AU - Kimmel, Paul L.

AU - Vasan, Ramachandran S.

AU - Bonventre, Joseph V.

AU - Inker, Lesley A.

AU - Coresh, Josef

AU - Ramachandran, Vasan S.

AU - Bonventre, Joseph

AU - Waikar, Sushrut

AU - Sabbisetti, Venkata

AU - Van Eyk, Jennifer

AU - Chen, Dawn

AU - Fu, Qin

AU - Brunner, Hermine

AU - D'Agati, Vivette

AU - Barasch, Jonathan

AU - Coresh, Josef

AU - Rebholz, Casey

AU - Go, Alan S.

AU - Bottinger, Erwin

AU - Teixeira, Avelino

AU - Daehn, Ilse

AU - Molitch, Mark

AU - Batlle, Daniel

AU - Rovin, Brad

AU - Wu, Haifeng

AU - Levey, Andrew S.

AU - Inker, Lesley A.

AU - Foster, Meredith

AU - Hsu, Chi yuan

AU - Liu, Kathleen

AU - Klein, Jon

AU - Mauer, Michael

AU - Fioretto, Paola

AU - Mauer, Michael

AU - Eckfeldt, John H.

AU - Karger, Amy

AU - Feldman, Harold I.

AU - Karger, Amy

AU - Whitehead, Krista

AU - Xie, Dawei

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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 m 2 ; 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, β 2 -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.

AB - 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 m 2 ; 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, β 2 -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.

KW - Albuminuria

KW - beta trace protein (BTP)

KW - biological variability

KW - biomarker

KW - clinically meaningful differences

KW - coefficient of variation (CV)

KW - cystatin C

KW - estimated glomerular filtration rate (eGFR)

KW - filtration marker

KW - intraindividual variation

KW - kidney function

KW - laboratory measurement

KW - reproducibility

KW - serum creatinine

KW - urinary albumin-creatinine ratio (UACR)

KW - β -microglobulin (B2M)

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