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The eGFR-C study: accuracy of glomerular filtration rate (GFR) estimation using creatinine and cystatin C and albuminuria for monitoring disease progression in patients with stage 3 chronic kidney disease - prospective longitudinal study in a multiethnic population

Edmund J Lamb1*, Elizabeth A Brettell2, Paul Cockwell3, Neil Dalton4, Jon J Deeks25, Kevin Harris6, Tracy Higgins7, Philip A Kalra8, Kamlesh Khunti9, Fiona Loud10, Ryan S Ottridge2, Claire C Sharpe12, Alice J Sitch5, Paul E Stevens11, Andrew J Sutton13, Maarten W Taal14 and on behalf of the eGFR-C study group

Author Affiliations

1 Clinical Biochemistry, East Kent Hospitals University NHS Foundation Trust, Canterbury, Kent CT1 3NG, UK

2 Birmingham Clinical Trials Unit, School of Cancer Sciences, Robert Aitken Institute, University of Birmingham, Birmingham B15 2TT, UK

3 University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TT, UK

4 Kings College London, London, UK

5 Test Evaluation Research Group, School of Health and Population Sciences, Public Health Building, University of Birmingham, Birmingham, B15 2TT, UK

6 University Hospitals of Leicester, Leicester, UK

7 Centre for Health Services Studies, University of Kent, Canterbury CT2 7NF, UK

8 Salford Royal NHS Foundation Trust, Salford M6 8HD, UK

9 University of Leicester, Leicester, UK

10 British Kidney Patient Association, Hampshire, UK

11 Kent Kidney Care Centre, East Kent Hospitals University NHS Foundation Trust, Canterbury, Kent CT1 3NG, UK

12 King’s College London & King’s College Hospital NHS Foundation Trust SE5 9RJ, London, UK

13 Health Economics Unit, School of Health and Population Sciences, Occupational Health Building, University of Birmingham, Birmingham B15 2TT, UK

14 Royal Derby Hospital, Uttoxeter Road, Derby DE22 3NE, UK

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BMC Nephrology 2014, 15:13  doi:10.1186/1471-2369-15-13

Published: 14 January 2014



Uncertainty exists regarding the optimal method to estimate glomerular filtration rate (GFR) for disease detection and monitoring. Widely used GFR estimates have not been validated in British ethnic minority populations.


Iohexol measured GFR will be the reference against which each estimating equation will be compared. The estimating equations will be based upon serum creatinine and/or cystatin C. The eGFR-C study has 5 components:

1) A prospective longitudinal cohort study of 1300 adults with stage 3 chronic kidney disease followed for 3 years with reference (measured) GFR and test (estimated GFR [eGFR] and urinary albumin-to-creatinine ratio) measurements at baseline and 3 years. Test measurements will also be undertaken every 6 months. The study population will include a representative sample of South-Asians and African-Caribbeans. People with diabetes and proteinuria (ACR ≥30 mg/mmol) will comprise 20-30% of the study cohort.

2) A sub-study of patterns of disease progression of 375 people (125 each of Caucasian, Asian and African-Caribbean origin; in each case containing subjects at high and low risk of renal progression). Additional reference GFR measurements will be undertaken after 1 and 2 years to enable a model of disease progression and error to be built.

3) A biological variability study to establish reference change values for reference and test measures.

4) A modelling study of the performance of monitoring strategies on detecting progression, utilising estimates of accuracy, patterns of disease progression and estimates of measurement error from studies 1), 2) and 3).

5) A comprehensive cost database for each diagnostic approach will be developed to enable cost-effectiveness modelling of the optimal strategy.

The performance of the estimating equations will be evaluated by assessing bias, precision and accuracy. Data will be modelled as a linear function of time utilising all available (maximum 7) time points compared with the difference between baseline and final reference values. The percentage of participants demonstrating large error with the respective estimating equations will be compared. Predictive value of GFR estimates and albumin-to-creatinine ratio will be compared amongst subjects that do or do not show progressive kidney function decline.


The eGFR-C study will provide evidence to inform the optimal GFR estimate to be used in clinical practice.

Trial registration


Albuminuria; Biological variation; Creatinine; Cystatin C; Glomerular filtration rate; Iohexol; Kidney disease