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: the eGFR-C study

ISRCTN	ISRCTN42955626
DOI	https://doi.org/10.1186/ISRCTN42955626
ClinicalTrials.gov (NCT)	NCT02433002
Protocol serial number	HTA 11/103/01, UKCRN ID 15268
Sponsor	University of Birmingham (UK)
Funder	NIHR Health Technology Assessment Programme - HTA (UK)

Submission date: 26/09/2013
Registration date: 08/10/2013
Last edited: 29/07/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Urological and Genital Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.birmingham.ac.uk/research/activity/mds/trials/bctu/trials/renal/egfr-c/participants/index.aspx

Contact information

Mr Ryan Ottridge
Scientific

Birmingham Clinical Trials Unit
Public Health Building
University of Birmingham
Birmingham
B15 2TT
United Kingdom

Study information

Primary study design	Observational
Study design	Observational prospective longitudinal cohort study
Secondary study design	Cohort study
Study type	Participant information sheet
Scientific title	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 multi-ethnic population: the eGFR-C study
Study acronym	eGFR-C
Study objectives	The eGFR-C study will assess the accuracy of current and alternative tests of kidney function against a reference test in people with moderate (stage 3) chronic kidney disease (CKD). More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=15268 More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/1110301 Protocol can be found at: https://www.birmingham.ac.uk/egfrc/documents (version 4.0 02.02.17)
Ethics approval(s)	South East Coast Surrey REC, 09/10/2013, ref 13/LO/1349
Health condition(s) or problem(s) studied	Topic: Renal and Urogenital; Subtopic: Renal and Urogenital (all Subtopics); Disease: Renal
Intervention	Main study: 1300 patients. Biological variability study: In a sub-study 20 participants will undergo the reference test four times over four weeks and then exit the study. Iohexol GFR tests, 1300 participants will undergo baseline (month 0) and final (month 36) reference GFR, estimated GFR (eGFR) and urinary albumin-to-creatinine ratio (ACR) tests. Additionally they will provide ACR and eGFR tests at 6-monthly intervals. A subset of the cohort (n=375) will receive annual reference GFR tests. Participants will be recruited from hospital clinics and GP practices at six major UK centres. Participants will undergo reference GFR testing at study entry with a second follow-up reference test three years later. The reference test involves injecting a small amount of iohexol into a vein and taking blood samples over the next 4 hours to see how quickly the iohexol disappears from the blood stream as a result of glomerular filtration. The rate at which iohexol disappears is equivalent to the level of kidney function. Blood tests for monitoring kidney function, including testing for creatinine and cystatin C, and measurement of urinary albumin will be done every six months during the study period. Iohexol measured GFR will be accepted as the reference (gold standard) measure of kidney function against which each GFR-estimating equations will be compared. The alternative estimated measures of GFR, derived from measuring substances (creatinine and cystatin C) in the blood, will be compared against the reference test. An important outcome is how much the reference test changes over the three years of the study, and how well the surrogate measures reflect this change. We will also collect accurate test cost data for subsequent cost-effectiveness analysis (e.g. do the relative costs of the tests justify any change in practice due to improved performance of one test compared to another?). Follow-up length: 36 months
Intervention type	Other
Primary outcome measure(s)	1. To estimate and compare the accuracy and precision of GFR-estimating equations based on the Modification of Diet in Renal Disease (MDRD) equation and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations using either creatinine or cystatin C or a combination of both in people with stage 3 CKD. 2. To estimate the accuracy and precision of the GFR-estimating equations according to ethnic group (particularly Caucasians, African-Caribbean and South-Asian), and baseline diabetes and proteinuria. Percentage error in eGFR compared to reference GFR. Values will be computed (primary outcome measures 1 and 2) using baseline data for each of the four eGFR equations, and the proportions within 30% (P30) of the reference standard quoted and compared as a measure of accuracy and precision. 3. To evaluate and compare how accurately these GFR-estimating equations reflect change in GFR over three years. Difference in rate of change in eGFR compared to rate of change in reference GFR. Rates of change will be estimated using linear regression and the change per annum and percentage change per annum compared to baseline values will be computed. Large error will be defined as differing by more than 3 mL/min/1.73 m^2/year or by 5 percent points per annum.
Key secondary outcome measure(s)	1. To establish which GFR-estimating equation, together with ACR, or ACR alone, most accurately predicts those people that have progressive loss of kidney function (CKD progression). Progressive loss of kidney function defined as decline in GFR of more than 10 mL/min/1.73 m^2/3 years or increase in albuminuria category as defined by Kidney Disease: Improving Global Outcomes (KDIGO). 2. To compare the effectiveness and costs of monitoring strategies for identifying people that have progressive loss of kidney function (CKD progression) utilising different GFR-estimating equations and test schedules, accounting for differences in risk of progression. Measured using Cost per quality-adjusted life-year (QALY). Sub-study of patterns of disease progression To estimate and model disease progression (decline in GFR or increase in ACR) according to ethnic group (particularly Caucasians, African-Caribbean and South-Asian), and baseline diabetes and proteinuria. Difference in rate of change in eGFR compared to rate of change in reference GFR based on measurements made every 12 months. Additional study of intra-individual biological variation Within-individual (CVI) variation and the critical difference (reference change value, RCV) for reference GFR and the estimated GFR equations.
Completion date	30/06/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	1320
Key inclusion criteria	1. Male and female, aged 18 years or over 2. Patients with stage 3 CKD (GFR 30-59 mL/min/1.73 m2) as defined internationally, diagnosed using Modification of Diet in Renal Disease/Chronic Kidney Disease Epidemiology Collaboration (MDRD/CKD EPI) eGFR (at least two consecutive test results in this range at least 90 days apart, with the most recent test in the last 12 months) 3. Written informed consent
Key exclusion criteria	1. History of untoward reactions to iodinated contrast media or allergy to topical iodine 2. Episode of acute kidney injury in previous 6 months (as defined by the Acute Kidney Injury Network criteria) 3. Amputation of whole or part limb 4. Pregnant or breastfeeding 5. Known alcohol or drug abuse 6. Any clinical condition with an expected survival of less than study duration 7. Inability to comply with study schedule and follow-up 8. Inability to provide informed consent e.g. due to cognitive impairment
Date of first enrolment	01/02/2014
Date of final enrolment	31/07/2015

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Birmingham Clinical Trials Unit

Public Health Building
University of Birmingham
Birmingham
B15 2TT
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		01/08/2019	10/08/2020	Yes	No
Results article		01/07/2024	29/07/2024	Yes	No
Protocol article		14/01/2014		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

29/07/2024: Publication reference added.
10/08/2020: Publication reference added.
14/02/2020: ClinicalTrials.gov number added.
21/02/2019: The following changes were made to the trial record:
1. The overall trial end date was changed from 31/07/2015 to 30/06/2020.
2. The intention to publish date was changed from 31/12/2018 to 30/06/2021.
3. Contact details, protocol link, and publication and dissemination plan updated.
22/10/2018: The following changes were made:
1. The publication and dissemination plan was added.
2. The intention to publish date was added.
18/10/2018: No publications found, verifying study status with principal investigator