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

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.

What is the best glomerular filtration marker to identify people with chronic kidney disease most likely to have poor outcomes?

“…22 From studies of biological variation, one can calculate that estimated GFR must change by more than 14% between two results for that change to be considered "true" with 95% certainty. 23 This is greater than annual changes in GFR observed in longitudinal studies in people known to have progressive disease. 22 24 Contributors to the insensitivity of estimated GFR to detect progression are the biological variability of both blood creatinine concentration and underlying true GFR itself, 23 25 coupled with the fact that not all progression of chronic kidney disease is linear.…”

“…26 27 Whether cystatin C concentration has lower or higher biological variability than creatinine is uncertain. 23 If it is lower, GFR estimating equations based on serum cystatin C concentration may have higher sensitivity for detecting change in GFR at an individual level. No evidence exists to guide monitoring frequencies in management of chronic kidney disease; current recommendations are based on consensus opinion.…”

“…The eGFR-C study (ISRCTN42955626) is a multicentre prospective cohort study that will assess the ability of creatinine and cystatin C based estimates of GFR to detect changes in measured GFR over a period of three years in 1300 people with moderate chronic kidney disease. 23 The study has power to detect differences in the abilities of the GFR estimating equations to detect change in measured GFR in the cohort overall but insufficient power to assess such differences in racial and disease subgroups. It will collect long term outcome data but has not been powered to assess relative predictive equation performance in this context (see box).…”

Exercise and lifestyle intervention and high intensity interval training in patients with chronic kidney disease

“…However, the effects of exercise training on kidney function, the progression and development of cardiovascular disease, morbidity and mortality are still unknown. The majority of findings suggest that kidney function is not affected by exercise training, although the sample size needed (n>1000) (136) to adequately assess this change has not been studied. Although the benefits of exercise training in CKD reported in the literature are promising, significantly more research is needed to delineate the effects of exercise on the above outcomes.…”

“…Rather, it seems the Section 1; Chapter 6 Effects of a 36 month lifestyle intervention on exercise capacity and cardiovascular disease risk factors As such, it seems reasonable to suggest that the current findings indicate that physical activity does provide a protective benefit to kidney function. However, the large sample size needed to adequately assess changes in eGFR (~n=1000) (136) indicates any changes in kidney function in smaller sample sizes should be interpreted with caution.…”