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Biological variation of measured and estimated glomerular filtration rate in patients with chronic kidney disease.
journal contribution
posted on 2019-07-09, 14:45 authored by C Rowe, AJ Sitch, J Barratt, EA Brettell, P Cockwell, RN Dalton, JJ Deeks, G Eaglestone, T Pellatt-Higgins, PA Kalra, K Khunti, FC Loud, FS Morris, RS Ottridge, PE Stevens, CC Sharpe, AJ Sutton, MW Taal, EJ Lamb, eGFR-C study groupWhen 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.
Funding
This study was funded by the NIHR Health Technology Assessment Programme (HTA 11/103/01). The NIHR Research Design Service South-East contributed to the development of this study including comments from the patient and public involvement unit. AS and JJD are supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. The NIHR CRN portfolio study number is 15268. The study is registered as ISRCTN42955626 and on clinical trials.gov as NCT02433002. Further information may be found on the study website http://www.birmingham.ac.uk/research/activity/mds/trials/bctu/trials/renal/egfr-c/index.aspx (accessed 23rd July 2018). All authors contributed to the intellectual content and have met the following requirements: (a) significant contributions to the concept, (b) drafting or revising the article for intellectual content, and (c) reading and approval of the final manuscript. Specific contribution: CR and ASi performed the statistical analyses and reported the results. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
History
Citation
Kidney International, 2019Author affiliation
/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and InflammationVersion
- VoR (Version of Record)
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Kidney InternationalPublisher
Elsevier for International Society of Nephrologyeissn
1523-1755Acceptance date
2019-02-21Copyright date
2019Publisher DOI
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https://www.sciencedirect.com/science/article/pii/S0085253819302741?via=ihubNotes
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 www.kidney-international.orgLanguage
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