To reduce over-diagnosis of chronic kidney disease (CKD) resulting from the inaccuracy of creatinine-based estimates of glomerular filtration rate (GFR), UK and international guidelines recommend that cystatin-C-based estimates of GFR be used to confirm or exclude the diagnosis in people with GFR 45–59 ml/min/1.73 m 2 and no albuminuria (CKD G3aA1). Whilst there is good evidence for cystatin C being a marker of GFR and risk in people with CKD, its use to define CKD in this manner has not been evaluated in primary care, the setting in which most people with GFR in this range are managed.
A total of 1,741 people with CKD G3a or G3b defined by 2 estimated GFR (eGFR) values more than 90 days apart were recruited to the Renal Risk in Derby study between June 2008 and March 2010. Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, we compared GFR estimated from creatinine (eGFR creat), cystatin C (eGFR cys), and both (eGFR creat-cys) at baseline and over 5 years of follow-up. We analysed the proportion of participants with CKD G3aA1 reclassified to ‘no CKD’ or more advanced CKD with the latter two equations. We further assessed the impact of using cystatin-C-based eGFR in risk prediction equations for CKD progression and all-cause mortality and investigated non-GFR determinants of eGFR cys. Finally, we estimated the cost implications of implementing National Institute for Health and Care Excellence (NICE) guidance to use eGFR cys to confirm the diagnosis in people classified as CKD G3aA1 by eGFR creat. Mean eGFR cys was significantly lower than mean eGFR creat (45.1 ml/min/1.73 m 2, 95% CI 44.4 to 45.9, versus 53.6 ml/min/1.73 m 2, 95% CI 53.0 to 54.1, P < 0.001). eGFR cys reclassified 7.7% (50 of 653) of those with CKD G3aA1 by eGFR creat to eGFR ≥ 60 ml/min/1.73 m 2. However, a much greater proportion (59.0%, 385 of 653) were classified to an eGFR category indicating more severe CKD. A similar pattern was seen using eGFR creat-cys, but lower proportions were reclassified. Change in eGFR creat and eGFR cys over 5 years were weakly correlated ( r = 0.33, P < 0.001), but eGFR cys identified more people as having CKD progression (18.2% versus 10.5%). Multivariable analysis using eGFR creat as an independent variable identified age, smoking status, body mass index, haemoglobin, serum uric acid, serum albumin, albuminuria, and C reactive protein as non-GFR determinants of eGFR cys. Use of eGFR cys or eGFR creat-cys did not improve discrimination in risk prediction models for CKD progression and all-cause mortality compared to similar models with eGFR creat. Application of the NICE guidance, which assumed cost savings, to participants with CKD G3aA1 increased the cost of monitoring by £23 per patient, which if extrapolated to be applied throughout England would increase the cost of testing and monitoring CKD by approximately £31 million per year. Limitations of this study include the lack of a measured GFR and the potential lack of ethnic diversity in the study cohort.
Implementation of current guidelines on eGFR cys testing in our study population of older people in primary care resulted in only a small reduction in diagnosed CKD but classified a greater proportion as having more advanced CKD than eGFR creat. Use of eGFR cys did not improve risk prediction in this population and was associated with increased cost. Our data therefore do not support implementation of these recommendations in primary care. Further studies are warranted to define the most appropriate clinical application of eGFR cys and eGFR creat-cys.
Adam Shardlow and colleagues investigate whether using cystatin C in addition to serum creatinine can improve diagnosis and risk prediction for progression of CKD among patients in primary care, and estimate the costs of additional testing and monitoring.
Estimation of kidney function (glomerular filtration rate) from serum creatinine concentration may be inaccurate in some people due to the impact of muscle mass, diet, and drugs on creatinine concentration.
To reduce over-diagnosis of chronic kidney disease, international and UK guidelines recommend that the diagnosis of chronic kidney disease should be confirmed with an estimate of kidney function based on a different marker of glomerular filtration, cystatin C, in those people with only a mild reduction in glomerular filtration rate and no albuminuria.
The clinical utility of this guidance has not been adequately evaluated in primary care, the setting in which most people with chronic kidney disease are cared for.
We estimated glomerular filtration rate from serum creatinine and cystatin C in a cohort of 1,741 mainly older people diagnosed with chronic kidney disease in primary care.
The use of cystatin C to confirm a diagnosis of chronic kidney disease resulted in reclassification of a small proportion (7.7%) of people as not having chronic kidney disease, but a much greater proportion were reclassified as having more advanced disease (59%).
In this cohort, the use of cystatin C did not result in improved risk prediction for all-cause mortality or progression of chronic kidney disease.
We estimate that the use of cystatin C as recommended in current guidelines would result in increased healthcare costs of £23 per person in the first year of implementation.