Background-Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher levels.

The 4-variable MDRD Study equation provides reasonably accurate GFR estimates in patients with chronic kidney disease and a measured GFR of less than 90 mL/min per 1.73 m2. By using the reexpressed MDRD Study equation with the standardized serum creatinine assay, clinical laboratories can report more accurate GFR estimates.

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T h e ne w e ngl a nd jou r na l o f m e dic i ne n engl j med 354;23 www.nejm.

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Serum cystatin C level alone provides GFR estimates that are nearly as accurate as serum creatinine level adjusted for age, sex, and race, thus providing an alternative GFR estimate that is not linked to muscle mass. An equation including serum cystatin C level in combination with serum creatinine level, age, sex, and race provides the most accurate estimates.

Serum creatinine is ordered more than 281 million times annually in the United States (based on the 191,354,358 creatinine tests reported in 1996 and assuming annual growth rate in testing of 3%),1 and recent reports show that more than 70% of laboratories now report estimated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) Study equation.2 Recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) developed and validated a new equation, the CKD-EPI creatinine equation, which uses the same variables as the MDRD Study, but is more accurate.3 , 4 Accuracy of GFR estimating equations is evaluated in comparison to measured GFR. However, as for other diagnostic tests, other criteria are also important in clinical practice and public health, including detecting disease, predicting prognosis, and guiding therapy. In this issue of the American Journal of Kidney Diseases, 2 articles compare the CKD-EPI equation with the MDRD Study equation for estimating the prevalence of CKD and predicting the risk of subsequent events in the general population. 5,6 In this editorial, we comment briefly on these articles and review the accuracy and applications of current GFR estimating equations (Table 1). ACCURACYGFR estimating equations are derived from regression analysis in which the level of measured GFR is related to the serum concentration of an endogenous filtration marker and to observed clinical and demographic variables that serve as surrogates for the non-GFR determinants of the serum concentration. Age, sex, race, and body weight are surrogates for creatinine generation from muscle, which affects serum creatinine concentration independently from GFR. In principle, GFR estimating equations provide a more accurate estimate of measured GFR than the serum level of the filtration marker alone. In addition, GFR estimates are provided in the same units as measured GFR, thereby simplifying clinical decisions based on the level of kidney function. Inaccuracy of GFR estimates may be due to bias, defined as systematic deviation of estimated GFR compared with measured GFR using the reference (or "gold") standard, or may be due to imprecision, defined as random variation (or "spread") of estimated GFR values centered around the measured values. 7 © 2010 The National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. N Section: Address correspondence to Andrew S. Levey, MD, Division of Nephrology, Tufts Medical Center Box 391, 800 Washington St, Boston, MA 02111. alevey@tuftsmedicalcenter.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to t...

Cystatin C is gaining acceptance as an endogenous filtration marker. Factors other than glomerular filtration rate (GFR) that affect the serum level have not been carefully studied. In a cross-sectional analysis of a pooled dataset of participants from clinical trials and a clinical population with chronic kidney disease (N=3418), we related serum levels of cystatin C and creatinine to clinical and biochemical variables after adjustment for GFR using errors-in-variables models to account for GFR measurement error. GFR was measured as urinary clearance of 125I-iothalamate and 15Cr-EDTA. Cystatin C was assayed at a single laboratory and creatinine was standardized to reference methods. Mean (SD) creatinine and cystatin C were 2.1 (1.1) mg/dL and 1.8 (0.8) mg/L, respectively. After adjustment for GFR, cystatin C was 4.3% lower for every 20 years of age, 9.2% lower for female sex but only 1.9% lower in blacks. Diabetes was associated with 8.5% higher levels of cystatin C and 3.9% lower levels of creatinine. Higher C-reactive protein and white blood cell count and lower serum albumin were associated with higher levels of cystatin C and lower levels of creatinine. Adjustment for age, sex and race had a greater effect on association of factors with creatinine than cystatin C. In conclusion, cystatin C is affected by factors other than GFR. Clinicians should consider these factors when interpreting the serum levels or GFR estimates from cystatin C.