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Title: Biological variation of measured and estimated glomerular filtration rate in patients with chronic kidney disease.
Authors: Rowe, C
Sitch, AJ
Barratt, J
Brettell, EA
Cockwell, P
Dalton, RN
Deeks, JJ
Eaglestone, G
Pellatt-Higgins, T
Kalra, PA
Khunti, K
Loud, FC
Morris, FS
Ottridge, RS
Stevens, PE
Sharpe, CC
Sutton, AJ
Taal, MW
Lamb, EJ
eGFR-C study group
First Published: 7-Mar-2019
Publisher: Elsevier for International Society of Nephrology
Citation: Kidney International, 2019
Abstract: When assessing changes in glomerular filtration rate (GFR) it is important to differentiate pathological change from intrinsic biological and analytical variation. GFR is measured using complex reference methods (e.g., iohexol clearance). In clinical practice measurement of creatinine and cystatin C are used in the Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equations to provide estimated GFR. Here we studied the biological variability of measured and estimated GFR in twenty nephrology outpatients (10 male, 10 female; median age 71, range 50-80 years) with moderate CKD (GFR 30-59 ml/min per 1.73 m2). Patients underwent weekly GFR measurement by iohexol clearance over four consecutive weeks. Simultaneously, GFR was estimated using the MDRD, CKD-EPIcreatinine, CKD-EPIcystatinC and CKD-EPIcreatinine+cystatinC equations. Within-subject biological variation expressed as a percentage [95% confidence interval] for the MDRD (5.0% [4.3-6.1]), CKD-EPIcreatinine (5.3% [4.5-6.4]), CKD-EPIcystatinC (5.3% [4.5-6.5]), and CKD-EPIcreatinine+cystatinC (5.0% [4.3-6.2]) equations were broadly equivalent. The within-subject biological variation for MDRD and CKD- EPIcreatinine+cystatinC estimated GFR were each significantly lower than that of the measured GFR (6.7% [5.6-8.2]). Reference change values, the point at which a true change in a biomarker in an individual can be inferred to have occurred with 95% probability were calculated. By the MDRD equation, positive and negative reference change values were 15.1% and 13.1% respectively. If an individual's baseline MDRD estimated GFR (ml/min per 1.73 m2) was 59, significant increases or decreases would be to values over 68 or under 51 respectively. Within-subject variability of estimated GFR was lower than measured GFR. Reference change values can be used to understand GFR changes in clinical practice. Thus, estimates of GFR are at least as reliable as measured GFR for monitoring patients over time.
DOI Link: 10.1016/j.kint.2019.02.021
eISSN: 1523-1755
Embargo on file until: 1-Jan-10000
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Crown Copyright © 2019 Published by Elsevier, Inc., on behalf of the International Society of Nephrology. All rights reserved.
Description: The file associated with this record is under a permanent embargo in accordance with the publisher's policy. The full text may be available through the publisher links provided above.
SUPPLEMENTARY MATERIAL Supplementary Methods.Figure S1. Effect of log transformations on distributions.Table S1. Identification of outliers by Cochran’s and Reed’s criterion.Table S2. Differences between measures using each glomerular filtration rate (GFR) estimate compared with measured GFR (calculated as estimated GFR–measured GFR).Table S3. Summary of components of variation for creatinine and cystatin C and measured and estimated glomerular filtration rate(GFR) without outlier detection and removal.Table S4. Critical appraisal checklist for studies of biological variation.Table S5. Shapiro-Wilk normality test Pvalues before and after log transformation. Supplementary material is linked to the online version of the paper a
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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