Chronic Kidney Disease
Estimating Glomerular Filtration Rate in 2012 – Does the New Chronic Kidney Disease Epidemiology Equation Fare Better than Older Equations?
Pierre Delanaye1 and Jean-Marie Krzesinski2 1. Co-leader of the Dialysis Unit; 2. Professor and Head, Department of Nephrology-Dialysis-Transplantation, University of Liège
Abstract
Measuring or estimating glomerular filtration rate (GFR) is still considered the best way to apprehend global renal function. In 2009, the Chronic Kidney Disease Epidemiology (CKD-EPI) equation was proposed as a better estimator of GFR than the Modification of Diet in Renal Disease (MDRD) study equation. It is supposed to underestimate GFR to a lesser degree in higher GFR levels. In this article, we present and discuss the performances of this new equation. Based on articles published between 2009 and 2012, we underline its advantages, notably better knowledge of chronic kidney disease prevalence, but also its limitations, especially in some specific populations. Our conclusion is that all equations are estimations and that nephrologists should always remain cautious in their interpretation.
Keywords
Glomerular filtration rate, creatinine, Modification of Diet in Renal Disease (MDRD) study equation, Chronic Kidney Disease Epidemiology (CKD-EPI) equation
Disclosure: The authors have no conflicts of interest to declare. Received: 17 January 2012 Accepted: 27 February 2012 Citation: European Nephrology, 2012;6(1):15–20 Correspondence: Pierre Delanaye, Service de Dialyse, Université de Liège, CHU Sart Tilman, 4000 Liège, Belgium. E:
pierre_delanaye@yahoo.fr
Measuring glomerular filtration rate (GFR) is still considered as the best way, with proteinuria (or albuminuria) measurement, to assess the global function of the kidneys.1
However, measuring GFR by a
reference method implies some experience and infrastructure, which thus limits its use, most often, to the tertiary hospitals.2
Therefore, in
clinical practice, nephrologists and other physicians evaluate renal function through an estimated GFR (eGFR). For this purpose, serum creatinine is the most used biomarker; however, it is not a perfect renal biomarker from a physiological point of view, notably because its concentration will be influenced by GFR but also by muscular mass (creatinine is the catabolite of creatine, a muscular protein).3
Because
of this ‘muscular’ effect, serum creatinine concentration is logically influenced by age, weight and ethnicity.3–5
To take these potential influences into account, several authors have proposed equations based on serum creatinine that integrated some or all of these variables. Among these equations, the Cockcroft–Gault and the Modification of Diet in Renal Disease (MDRD) study equations are by far the most popular in the adult population.6–8
The MDRD study equation
(see Table 1), published in 1999, has been shown to outperform the Cockcroft–Gault equation, especially in terms of precision, and it has thus been preferred by most experts in the field.7–12
Unfortunately, the
MDRD study equation also has severe limitations. It was developed from the MDRD study patients (n=1,628), who all suffered from chronic kidney disease (CKD). Their mean GFR measured by iothalamate clearance was 40 ml/min/1.73 m2.7
However, there is evidence that the relationship
between serum creatinine and GFR is not identical in CKD patients and in healthy subjects.13–16
Therefore, it is not surprising that most studies
have demonstrated a bias (bias is the systematic error, i.e., the mean or median difference between eGFR and measured GFR [mGFR]) in healthy
© TOUCH BRIEFINGS 2012
subjects, in whom the MDRD study equation tends to systematically underestimate mGFR.9,10,16–20
We have also pointed out the lack of
precision (precision is the random error, i.e., the standard deviation [SD] or interquartile range [IQR] around the bias) of the MDRD study equation in the higher GFR levels, notably for analytical reasons.13,16
The main
reason why the Chronic Kidney Disease Epidemiology (CKD-EPI) equation (see Table 1) has been developed is thus to improve the performance of the GFR estimation in the higher levels – i.e., for GFR above 60 ml/min/1.73 m2.21
What’s New in the New Equation? The CKD-EPI equation has been built from a very impressive sample of patients. It was devised by a collaborative research group (the Chronic Kidney Disease Epidemiology Collaboration) under the leadership of Andrew Levey (already the first author of the MDRD study equation), Lesley Stevens and Jo Coresh.21
This collaborative group brought the
data available from 26 studies with mGFR and calibrated serum creatinine. The new equation was built from a development data set including 5,504 subjects and validated in an internal validation data set including 2,750 subjects. GFR was measured by iothalamate clearance, both in the development and internal validation data set. Moreover, the CKD-EPI equation was also validated in an ‘external’ validation data set (n=3,896) in which GFR could be measured by other reference methods. The samples, both of the development and validation data sets, were therefore much larger than for the MDRD study equation. Importantly, considering the limitations of the MDRD study equation, a substantial proportion of subjects included in these data sets had a mGFR above 60 ml/min/1.73 m2. Most of these patients were potential kidney donors. Logically, the mean GFR was 68 ± 40 ml/min/1.73 m2 and was thus higher than in the MDRD study.
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