Accuracy of Glomerular Filtration Rate (GFR) Estimation Using Creatinine and Cystatin C and Albuminuria

Study Overview
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Brief Summary
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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).

Detailed Description
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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) CKD. Participants will be recruited from hospital clinics and General Practitioner (GP) practices at six major United Kingdom (UK) centres. The best measure of kidney function is accepted to be the glomerular filtration rate (GFR), which measures the ability of the kidney to filter blood and is widely used in clinical practice. A low GFR suggests poor kidney function. An estimate of GFR can be obtained from a simple blood test. 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. The investigators 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?).

Official Title
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Accuracy of Glomerular Filtration Rate Estimation Using Creatinine & Cystatin C & Albuminuria for Monitoring Disease Progression in Patients With Stage 3 Chronic Kidney Disease: Prospective Longitudinal Study in a Multi-ethnic Population

Conditions
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Chronic Kidney Diseases

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with stage 3 CKD (GFR 30-59 mL/min/1.73 m2) as defined internationally, diagnosed using MDRD/CKDEPI 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) Aged 18 years or over Written informed consent Exclusion Criteria: History of untoward reactions to iodinated contrast media or allergy to topical iodine Episode of acute kidney injury in previous 6 months (as defined by the Acute Kidney Injury Network criteria) Amputation of whole or part-limb Pregnant or breastfeeding Known current alcohol or drug abuse Kidney transplant recipient Any condition with an expected survival of less than study duration Inability to comply with study schedule and follow-up Inability to provide informed consent e.g. due to cognitive impairment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Main study<br>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. | |
| Sub-study of patterns of progression<br>A subset of the cohort (n=375) will receive annual reference GFR tests. | |
| Biological variability study<br>In a further sub-study 20 participants will undergo the reference test four times over four weeks. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of estimated Glomerular Filtration Rate values within 30% of 'true' Glomerular Filtration Rate | The accuracy of Glomerular Filtration Rate (GFR) estimating equations is commonly expressed as the P30 value, the percentage of estimated GFR values within 30% of 'true' GFR. The eGFR-C study will 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 Chronic Kidney Disease (CKD), expressed as the P30 value. | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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eGFR, CKD, Cystatin, Creatinine, Albuminuria