Pro: Estimating GFR using the chronic kidney disease epidemiology collaboration (CKD-EPI) 2009 creatinine equation: the time for change is now

Nephrol Dial Transplant (2013) 28: 1390–1396 doi: 10.1093/ndt/gft003 Polar Views in Nephrology Pro: Estimating GFR using the chronic kidney disease epidemiology collaboration (CKD-EPI) 2009 creatinine equation: the time for change is now Tufts Medical Center, 800 Washington St, PO Box 391, Boston, MA, Lesley A. Inker USA and Andrew S. Levey Correspondence and offprint requests to: Lesley A. Inker; Email: Clinical assessment of kidney function is central to the practice of medicine. Glomerular filtration rate (GFR) is widely accepted as the best index of kidney function in health and disease and accurate values are required for optimal decisionmaking in many clinical settings. GFR is generally not measured in clinical practice, but is estimated from the serum level of an endogenous filtration marker. GFR-estimating equations are useful because they provide a more accurate estimate of measured GFR than the serum level of the filtration marker alone, and they are expressed in the same units as measured GFR, which facilitates clinical decisions based on the level of kidney function. Serum creatinine is ordered to estimate the GFR more than 281 million times annually in the USA [1], and recent reports show that more than 80% of US clinical laboratories now report estimated GFR (eGFR) whenever serum creatinine is ordered [2]. Worldwide estimates are not known, but eGFR is routinely reported in the UK, France and Australia. The majority of laboratories report eGFR using the Modification of Diet in Renal Disease (MDRD) study equation. However, an increasing number of laboratories are now beginning to use the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 creatinine equation [3, 4] (Olivier Allaire, personal communication), which uses the same variables as the MDRD study but is more accurate across the range of GFR [1, 5, 6]. Widespread implementation of GFR estimation would be facilitated by the use of a single equation expressed for the use with standardized creatinine that is accurate over the full range of GFR and applicable throughout the world. Three years have passed since we first reported the development and validation of the CKD-EPI creatinine equation and © The Author 2013. Published by Oxford University Press on Downloaded frombehalf https://academic.oup.com/ndt/article-abstract/28/6/1390/1838508 of ERA-EDTA. All rights reserved. by guest on 07 July 2018 proposed that it replace the MDRD study equation for routine eGFR reporting [5]. At that time, there were some who resisted this change, arguing that further validation was needed, that the improvement in accuracy was small, and that there would likely be a newer equation later, so why change now? It is now apparent from an extensive body of literature that the CKDEPI equation provides a more accurate estimate of measured GFR, it provides a better tool for clinical practice, research and public health, no other widely applicable creatinine-based estimating equation is more accurate, and we are not aware of ongoing efforts to develop an alternative creatinine-based equation for widespread application. In this editorial, we briefly review the physiologic and statistical basis for development and validation of GFR-estimating equations and the literature comparing the MDRD study and CKD-EPI equations for estimating measured GFR, detecting chronic kidney disease (CKD), estimating CKD prevalence and prognosis and guiding therapy. We conclude with considerations for implementing the change from the MDRD study equation to the CKD-EPI equation for reporting eGFR by clinical laboratories. In our opinion, it is clear that the time for change is now. D E V E LO P M E N T A N D VA L I D AT I O N O F G F R E S T I M AT I N G E Q U AT I O N S The goal in developing an estimating equation is to ensure that it performs well not only in the population in which it is developed, but also in populations in which it is intended for use. GFR-estimating equations are derived from regression analysis relating the level of measured GFR to the serum concentration 1390 of an endogenous filtration marker and observed clinical and demographic variables that serve as surrogates for the nonGFR determinants of its serum concentration [7]. For example, age, sex, race and body weight are surrogates for creatinine generation from muscle, which affects serum creatinine concentration independently from GFR. The coefficients reflect relationships observed in the development population, and thus the measurement methods and the population used to develop the equation are critical to the performance of the equation in other populations. Inaccuracy in the estimation of GFR may be due to bias, defined as systematic deviation of estimated GFR compared with measured GFR using the reference (‘gold’) standard, or due to imprecision, defined as random variation (or ‘spread’) of estimated GFR values centered around the measured values. Full review of the causes of bias and imprecision is beyond the scope of this article [8]. Critically, bias reflects systematic differences in measurement methods and non-GFR determinants of the filtration marker between the development dataset and the populations in which the equation are to be used. Imprecision reflects inherent limitations in GFR measurement and in using clinical and demographic variables to model nonGFR determinants of the filtration markers. study equation at higher serum creatinine values but less steep at low values, as has been observed in studies of subjects without CKD, such as kidney donors and young people with Type 1 diabetes without albuminuria [11]. Other differences between the CKD-EPI and MDRD study equations include the following: a linear rather than a logarithmic relationship with age, resulting in a steeper slope of eGFR with age and similar GFR estimates at older age; a smaller coefficient for blacks, resulting in lesser differences in GFR estimates between blacks versus white and others; and at low serum creatinine concentrations, a smaller coefficient for women than men, resulting in smaller differences between men and women at higher GFR ranges. C O M P A R I S O N O F T H E M D R D S T U DY A N D C K D - E P I C R E AT I N I N E E Q U AT I O N S Development process and formulation The MDRD study equation was developed in 1999 using data from a study of 1628 people using non-standardized serum creatinine assays and re-expressed for use with standardized creatinine in 2006 (Table 1) [9]. GFR is estimated from only four variables, serum creatinine, age, sex and race (black versus white and other). Because it was developed in a population with CKD, a linear relationship appeared sufficient to express the relationship of log-GFR to log-serum creatinine across the range of GFR. It now appears that this relationship is more complicated, as multiple studies show that the MDRD study equation systematically underestimates measured GFR in the range of ∼60–120 mL/min/1.73 m2 and overestima (...truncated)