Abstract
BackgroundUncertainty 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.Methods/designIohexol 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.DiscussionThe eGFR-C study will provide evidence to inform the optimal GFR estimate to be used in clinical practice.Trial registrationISRCTN42955626.
Highlights
Uncertainty exists regarding the optimal method to estimate glomerular filtration rate (GFR) for disease detection and monitoring
The Estimated glomerular filtration rate (eGFR)-C study will provide evidence to inform the optimal GFR estimate to be used in clinical practice
The data will be analysed to assess the impact of ethnicity, proteinuria and diabetes on equation performance. eGFRC will assess whether eGFR using either creatinine or cystatin C or a combination of both is superior at detecting changes in GFR as measured by a reference GFR method
Summary
Uncertainty exists regarding the optimal method to estimate glomerular filtration rate (GFR) for disease detection and monitoring. Chronic kidney disease (CKD) is prevalent in the general population [1,2,3,4] and is commonly identified using estimation of glomerular filtration rate (GFR) or detection of protein in urine (albuminuria/proteinuria). GFR would be measured using reference procedures which follow the clearance of an infused exogenous substance (e.g. inulin, 125I-iothalamate or iohexol [5]) These methods are cumbersome and impractical for general kidney disease detection and management. Many people with stage 3 CKD are not at increased risk of progressive disease and there are concerns that CKD detection using creatinine-based approaches may be identifying individuals who are at low risk and unlikely to benefit from active management and inappropriate surveillance [8]. Given the high costs of cystatin C testing compared with creatinine, it is critical that its diagnostic accuracy and prognostic ability are carefully validated ahead of widespread introduction into the National Health Service
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