| Summary: | <h4>Background</h4>Chronic kidney disease (CKD) diagnosis relies on glomerular filtration rate (eGFR) estimation, traditionally using the creatinine-based Modification of Diet in Renal Disease (MDRD) equation. The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) equation performs better in estimating eGFR and predicting mortality and CKD progression risk. Cystatin C is an alternative glomerular filtration marker less influenced by muscle mass. CKD risk stratification is improved by combining creatinine eGFR with cystatin C and urinary albumin to creatinine ratio (uACR). We aimed to identify the impact of introducing CKDEPI and cystatin C on the estimated prevalence and risk stratification of CKD in England and to describe prevalence and associations of cystatin C.<h4>Methods and findings</h4>Cross sectional study of 5799 people in the nationally representative 2009 and 2010 Health Surveys for England.<h4>Primary outcome measures</h4>prevalence of MDRD, CKDEPI and cystatin C-defined eGFR<60 ml/min/1.73 m(2); prevalence of CKD biomarker combinations (creatinine, cystatin C, uACR). Using CKDEPI instead of MDRD reduced the prevalence of eGFR<60 ml/min/1.73 m(2) from 6.0% (95% CI 5.4-6.6%) to 5.2% (4.7-5.8%) equivalent to around 340,000 fewer individuals in England. Those reclassified as not having CKD evidenced a lower risk profile. Prevalence of cystatin C eGFR<60 ml/min/1.73 m(2) was 7.7% and independently associated with age, lack of qualifications, being an ex-smoker, BMI, hypertension, and albuminuria. Measuring cystatin C in the 3.9% people with CKDEPI-defined eGFR<60 ml/min/1.73 m(2) without albuminuria (CKD Category G3a A1) reclassified about a third into a lower risk group with one of three biomarkers and two thirds into a group with two of three. Measuring cystatin C in the 6.7% people with CKDEPI eGFR >60 ml/min/1.73 m(2) with albuminuria (CKD Category G1-2) reclassified almost a tenth into a higher risk group.<h4>Limitations</h4>Cross sectional study, single eGFR measure, no measured ('true') GFR.<h4>Conclusions</h4>Introducing the CKDEPI equation and targeted cystatin C measurement reduces estimated CKD prevalence and improves risk stratification.
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