0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Articles |

Using Standardized Serum Creatinine Values in the Modification of Diet in Renal Disease Study Equation for Estimating Glomerular Filtration Rate

Andrew S. Levey, MD; Josef Coresh, MD, PhD, MHS; Tom Greene, PhD; Lesley A. Stevens, MD, MS; Yaping (Lucy) Zhang, MS; Stephen Hendriksen, BA; John W. Kusek, PhD; Frederick Van Lente, PhD, Chronic Kidney Disease Epidemiology Collaboration*
[+] Article and Author Information

From Tufts-New England Medical Center, Boston, Massachusetts; Johns Hopkins Medical Institution, Baltimore, Maryland; Cleveland Clinic Foundation, Cleveland, Ohio; and National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.


Acknowledgments: The authors thank John Eckfeldt, PhD, and Amy Deysher for assistance.

Grant Support: By grants UO1 DK 053869, UO1 DK 067651, and UO1 DK 35073.

Potential Financial Conflicts of Interest:Grants received: A.S. Levey (National Institutes of Health, Amgen, National Kidney Foundation).

Requests for Single Reprints: Andrew S. Levey, MD, Division of Nephrology, Tufts-New England Medical Center, 750 Washington Street, Box 391, Boston, MA 02111.

Current Author Addresses: Drs. Levey and Stevens, Ms. Zhang, and Mr. Hendriksen: Division of Nephrology, Tufts-New England Medical Center, 750 Washington Street, Box 391, Boston, MA 02111.

Dr. Coresh: Johns Hopkins Medical Institution, 2024 East Monument Street, 2-645, Baltimore, MD 21205.

Drs. Greene and Van Lente: Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195.

Dr. Kusek: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 6707 Democracy Boulevard, Room 617, Bethesda, MD 20817.

Author Contributions: Conception and design: A.S. Levey, J. Coresh, T. Greene, L.A. Stevens, Y. Zhang, S. Hendriksen, J.W. Kusek, F. Van Lente.

Analysis and interpretation of the data: A.S. Levey, J. Coresh, T. Greene, L.A. Stevens, J.W. Kusek, F. Van Lente.

Drafting of the article: A.S. Levey, L.A. Stevens.

Critical revision of the article for important intellectual content: A.S. Levey, J. Coresh, T. Greene, L.A. Stevens, Y. Zhang, S. Hendriksen, J.W. Kusek, F. Van Lente.

Final approval of the article: A.S. Levey, J. Coresh, T. Greene, L.A. Stevens, Y. Zhang, S. Hendriksen, J.W. Kusek, F. Van Lente.

Provision of study materials or patients: A.S. Levey, T. Greene, J.W. Kusek, F. Van Lente.

Statistical expertise: J. Coresh, T. Greene, Y. Zhang.

Obtaining of funding: A.S. Levey, J. Coresh, T. Greene, F. Van Lente.

Administrative, technical, or logistic support: A.S. Levey, J. Coresh, T. Greene, L.A. Stevens, Y. Zhang, S. Hendriksen, J.W. Kusek, F. Van Lente.

Collection and assembly of data: A.S. Levey, J. Coresh, T. Greene, Y. Zhang, S. Hendriksen, F. Van Lente.


Ann Intern Med. 2006;145(4):247-254. doi:10.7326/0003-4819-145-4-200608150-00004
Text Size: A A A

Clinical characteristics of the 1628 MDRD Study participants from whom the MDRD Study equation was derived are shown in Table 1(11). Mean measured GFR was 39.8 mL/min per 1.73 m2 (SD, 21.2). Figure 1 shows the difference in measured GFR minus estimated GFR versus the level of estimated GFR using the 4-variable MDRD Study equation and other equations. Table 2 compares the performance of these equations in the MDRD Study participants according to the level of estimated GFR. For the overall study sample, precision and accuracy for the 4-variable equation are almost as good as for the 6-variable equation. As expected, within the MDRD Study sample, the 4-variable MDRD Study equation has less bias than the Cockcroft–Gault equation, even when the latter is adjusted for body surface area. This equation also has greater precision and accuracy than the Cockcroft–Gault equation, even when the latter is corrected for systematic bias. Percentages of estimates within 30% of measured GFR were 90% and 91% for the 4-variable and 6-variable MDRD Study equations, respectively, and 60% and 83% for the Cockcroft–Gault equation without and with correction for bias, respectively.

First Page Preview

View Large
First page PDF preview

Figures

Grahic Jump Location
Figure 1.
Differences between measured and estimated glomerular filtration rate (GFR) for 4 estimating equations, according to the level of estimated GFR.

A. Four-variable Modification of Diet in Renal Disease (MDRD) Study equation. B. 6-variable MDRD Study equation. C. Cockcroft–Gault equation adjusted for body surface area. D. Cockcroft–Gault equation adjusted for body surface area and corrected for bias. Points indicate individual patients. Patients with differences between measured and estimated GFR greater than 60 mL/min per 1.73 m2 are not shown. The dashed horizontal line is the reference line. The solid black line is the smooth estimate of the mean difference, and the 2 dotted lines represent the 95% of the population of differences across the range of estimated GFR. Curves are drawn through the 2.5% to 97.5% of the range of GFR estimates. Values for R2 (95% CIs) are for the regression of measured GFR versus estimated GFR.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Receiver-operating characteristic curves for 4 estimating equations.

For each curve, the sensitivity and specificity were computed for varying cutoff values for estimated glomerular filtration rate (GFR) to detect a measured GFR of less than 60 mL/min per 1.73 m2. AUC = area under the curve; MDRD = Modification of Diet in Renal Disease; NPV = negative predictive value; PPV = positive predictive value.* P < 0.001 for the comparison of the AUCs with the 4-variable MDRD Study equation. The AUCs for the Cockcroft–Gault equation with and without adjustment for bias are identical because these equations are equivalent except for a constant multiplier.

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Estimated glomerular filtration rate: impact of the precision of the creatinine assay
Posted on August 17, 2006
Pierre Delanaye
University of Liège, Department of Nephrology, CHU Sart Tilman
Conflict of Interest: None Declared

The recent article about estimated glomerular filtration rate (GFR) published by Levey et al is remarkable (1). The authors suggest that the new equation may still have some bias and, especially, less precision in patients with GFR over 60 ml/min/1.73 m². This is even more important if GFR is over 90 ml/min/1.73 m². In the method section, the authors don't give the analytical coefficient of variation (CVa) of their assays (Beckman and enzymatic). This data is of importance especially for low or normal creatinine values. Indeed, the concept of critical difference (CD) is familiar to clinical biologists but should perhaps be reminded to internists. The CD of a biological variable includes the CVa and the intra -individual coefficient of variation (CVi). It is defined as the smallest change in a biological result which is not due to chance (2). The CD is calculated as followed: 1.414 x 1.96 x (CVa² + CVi²)0.5. The CVi of serum creatinine is 4% (3). The CVa of serum creatinine varies belong assays used and laboratories. A creatinine CVa as low as 2 % is rare but conceivable (4). With these CV values, the lowest CD for creatinine is 12%. A value of 0.8 mg/dl is thus not different from 0.704 and 0.896 mg/dl. However, as we have illustrated (5), these differences are not negligible for GFR estimation if creatinine and GFR are normal because small creatinine changes induce large GFR variations in this range. If we take the example of a white, 60 years old man, a creatinine of 0.8 mg/dl gives a result of 98.6 ml/min/1.73 m² with the MDRD equation. If creatinine values of 0.704 and 0.896 mg/dl are introduced, the results of the MDRD equations will be 114.3 and 86.5 ml/min/1.73m², respectively. The low precision of the MDRD equation, when GFR is normal, is thus also linked to the precision of the creatinine assay and to the biological variation of creatinine. This assertion is true for all creatinine-based equations. We think that an improvement of the precision of creatinine- based equation may be illusive in a non renal population. It is important for clinicians to keep this fact in mind when they analyze an estimated GFR and even more when they longitudinally follow a serial of estimated GFR in a patient with GFR over 60 ml/min/1.73m². It is perhaps more cautious to still give MDRD results as "over 60 and 90 ml/min/1.73m²" without giving precise, absolute values of GFR.

References

(1) Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006;145:247-54.

(2) Costongs GM, Janson PC, Bas BM, Hermans J, van Wersch JW, Brombacher PJ. Short-term and long-term intra-individual variations and critical differences of clinical chemical laboratory parameters. J Clin Chem Clin Biochem 1985;23:7-16.

(3) Ricos C, Alvarez V, Cava F, Garcia-Lario JV, Hernandez A, Jimenez CV et al. Current databases on biological variation: pros, cons and progress. Scand J Clin Lab Invest 1999;59:491-500.

(4) Froissart M, Rossert J, Jacquot C, Paillard M, Houillier P. Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function. J Am Soc Nephrol 2005;16:763-73.

(5) Delanaye P, Cavalier E, Krzesinski JM, Chapelle JP. Why the MDRD equation should not be used in patients with normal renal function (and normal creatinine values)? Clin Nephrol 2006;66:147-8.

Conflict of Interest:

None declared

Estimated glomerular filtration rate: impact of the precision of the creatinine assay
Posted on November 4, 2006
Andrew S. Levey
Tufts-New England Medical Center
Conflict of Interest: None Declared

To the Editor,

Dr. Delanaye and colleagues question whether the precision of the creatinine assay within the reference range is sufficient for accurate GFR estimation. The Beckman Synchron CX3 assay used during the Modification of Diet in Renal Disease (MDRD) Study had an analytical coefficient of variation (CV) of 4.3% and 1.5% at creatinine values of 1.0 and 5.4 mg/dL, respectively (1). The Roche enzymatic assay used to calibrate the MDRD Study laboratory to standardized creatinine had an analytical CV of 2.0% and 1.8% at creatinine values of 0.89 and 5.86 mg/dL, respectively, in 2004 (n = 194) and 1.6% and 1.1% at creatinine values of 1.00 and 3.84 and gm/dL, respectively, in 2005 (n = 409). Thus, the analytical CV for the Roche enzymatic is as low or lower than that stated by Dr. Delanaye.

We agree with Dr. Delanaye that the effect of imprecision in the serum creatinine assay and biological variation in GFR estimates is greater at lower values for serum creatinine (equivalent to higher values for estimated GFR), and that is one of several important reasons for lesser accuracy of higher GFR estimates (2). For these reasons, current recommendations are to report estimated GFR as a numeric value only when it is less than 60 ml/min/1.73 m2 and to report ">60 ml/min/1.73 m2" for higher values. We believe this is sufficient for most clinical circumstances requiring the clinical assessment of kidney function. New filtration markers, such as cystatin C, and improvement in estimation equations may be required for more accurate GFR estimation at higher values. Until then, if more accurate assessment of kidney function is required in patients with estimated GFR >60 ml/min/1.73 m2, it is necessary to measure the clearance of an exogenous filtration marker or creatinine.

References:

1. Coresh J, Astor BC, McQuillen G, et al. Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate. Am J Kidney Dis 2002;39:920-9.

2. Stevens LA, Coresh J, Levey AS. Assessing kidney function "“ measured and estimated glomerular filtration rate. N Engl J Med 2006; 354:2473-83.

Conflict of Interest:

None declared

Submit a Comment

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)