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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, for the Chronic Kidney Disease Epidemiology Collaboration*

15 August 2006 | Volume 145 Issue 4 | Pages 247-254

Background: Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease but require calibration of the serum creatinine assay to the laboratory that developed the equation. The 4-variable equation from the Modification of Diet in Renal Disease (MDRD) Study has been reexpressed for use with a standardized assay.

Objective: To describe the performance of the revised 4-variable MDRD Study equation and compare it with the performance of the 6-variable MDRD Study and Cockcroft–Gault equations.

Design: Comparison of estimated and measured GFR.

Setting: 15 clinical centers participating in a randomized, controlled trial.

Patients: 1628 patients with chronic kidney disease participating in the MDRD Study.

Measurements: Serum creatinine levels were calibrated to an assay traceable to isotope-dilution mass spectrometry. Glomerular filtration rate was measured as urinary clearance of ¹²⁵I-iothalamate.

Results: Mean measured GFR was 39.8 mL/min per 1.73 m² (SD, 21.2). Accuracy and precision of the revised 4-variable equation were similar to those of the original 6-variable equation and better than in the Cockcroft–Gault equation, even when the latter was corrected for bias, with 90%, 91%, 60%, and 83% of estimates within 30% of measured GFR, respectively. Differences between measured and estimated GFR were greater for all equations when the estimated GFR was 60 mL/min per 1.73 m² or greater.

Limitations: The MDRD Study included few patients with a GFR greater than 90 mL/min per 1.73 m². Equations were not compared in a separate study sample.

Conclusions: 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.

*For a list of investigators of the Chronic Kidney Disease Epidemiology Collaboration, see the Appendix.

Editors' Notes Context Guidelines recommend that laboratories estimate glomerular filtration rate (GFR) with equations that use serum creatinine level, age, sex, and ethnicity. Standardizing creatinine measurements across clinical laboratories should reduce variability in estimated GFR. Contribution Using standardized creatinine assays, the authors calibrated serum creatinine levels in 1628 patients whose GFR had been measured by urinary clearance of 125I-iothalamate. They used these data to derive new equations for estimating GFR and to measure their accuracy. The equations were inaccurate only when kidney function was near-normal. Cautions There was no independent sample of patients for measuring accuracy. Implications By using this equation and a standardized creatinine assay, different laboratories can report estimated GFR more uniformly and accurately. —The Editors

 

Author and Article 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.

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				P. Massoudy, S. Wagner, M. Thielmann, U. Herold, E. Kottenberg-Assenmacher, G. Marggraf, A. Kribben, T. Philipp, H. Jakob, and S. Herget-Rosenthal Coronary artery bypass surgery and acute kidney injury--impact of the off-pump technique Nephrol. Dial. Transplant., September 1, 2008; 23(9): 2853 - 2860. [Abstract] [Full Text] [PDF]

				J. Lin and G. C. Curhan Kidney function decline and physical function in women Nephrol. Dial. Transplant., September 1, 2008; 23(9): 2827 - 2833. [Abstract] [Full Text] [PDF]

				J. Kronborg, M. Solbu, I. Njolstad, I. Toft, B. O. Eriksen, and T. Jenssen Predictors of change in estimated GFR: a population-based 7-year follow-up from the Tromso study Nephrol. Dial. Transplant., September 1, 2008; 23(9): 2818 - 2826. [Abstract] [Full Text] [PDF]

				U. Poge, T. Gerhardt, and R. P. Woitas Estimation of Glomerular Filtration Rate by Use of Beta-Trace Protein Clin. Chem., August 1, 2008; 54(8): 1403 - 1405. [Full Text] [PDF]

				J. P Reis, D. von Muhlen, and E. R Miller III Relation of 25-hydroxyvitamin D and parathyroid hormone levels with metabolic syndrome among US adults. Eur. J. Endocrinol., July 1, 2008; 159(1): 41 - 48. [Abstract] [Full Text] [PDF]

				R. L. Pande, T. S. Perlstein, J. A. Beckman, and M. A. Creager Association of Insulin Resistance and Inflammation With Peripheral Arterial Disease: The National Health and Nutrition Examination Survey, 1999 to 2004 Circulation, July 1, 2008; 118(1): 33 - 41. [Abstract] [Full Text] [PDF]

				D. Rusinaru, L. Leborgne, M. Peltier, and C. Tribouilloy Effect of atrial fibrillation on long-term survival in patients hospitalised for heart failure with preserved ejection fraction Eur J Heart Fail, June 1, 2008; 10(6): 566 - 572. [Abstract] [Full Text] [PDF]

				A. D. Dangour, E. Breeze, R. Clarke, P. S. Shetty, R. Uauy, and A. E. Fletcher Plasma Homocysteine, but Not Folate or Vitamin B-12, Predicts Mortality in Older People in the United Kingdom J. Nutr., June 1, 2008; 138(6): 1121 - 1128. [Abstract] [Full Text] [PDF]

				K. Potter, G. J. Hankey, D. J. Green, J. W. Eikelboom, and L. F. Arnolda Homocysteine or Renal Impairment: Which Is the Real Cardiovascular Risk Factor? Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1158 - 1164. [Abstract] [Full Text] [PDF]

				R. Deo, F. Lin, E. Vittinghoff, Z. H. Tseng, S. B. Hulley, and M. G. Shlipak Kidney Dysfunction and Sudden Cardiac Death Among Women With Coronary Heart Disease Hypertension, June 1, 2008; 51(6): 1578 - 1582. [Abstract] [Full Text] [PDF]

				B. C. Astor, S. I. Hallan, E. R. Miller III, E. Yeung, and J. Coresh Glomerular Filtration Rate, Albuminuria, and Risk of Cardiovascular and All-Cause Mortality in the US Population Am. J. Epidemiol., May 15, 2008; 167(10): 1226 - 1234. [Abstract] [Full Text] [PDF]

				R. W. Schrier Blood Urea Nitrogen and Serum Creatinine: Not Married in Heart Failure Circ Heart Fail, May 1, 2008; 1(1): 2 - 5. [Full Text] [PDF]

				L. Klein, B. M. Massie, J. D. Leimberger, C. M. O'Connor, I. L. Pina, K. F. Adams Jr, R. M. Califf, M. Gheorghiade, and for the OPTIME-CHF Investigators Admission or Changes in Renal Function During Hospitalization for Worsening Heart Failure Predict Postdischarge Survival: Results From the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) Circ Heart Fail, May 1, 2008; 1(1): 25 - 33. [Abstract] [Full Text] [PDF]

				K. Gupta, S. S. Iskandar, P. Daeihagh, H. L. Ratliff, and A. J. Bleyer Distribution of pathologic findings in individuals with nephrotic proteinuria according to serum albumin Nephrol. Dial. Transplant., May 1, 2008; 23(5): 1595 - 1599. [Abstract] [Full Text] [PDF]

				C. M. Pfeiffer, J. D. Osterloh, J. Kennedy-Stephenson, M. F. Picciano, E. A. Yetley, J. I. Rader, and C. L. Johnson Trends in Circulating Concentrations of Total Homocysteine among US Adolescents and Adults: Findings from the 1991-1994 and 1999-2004 National Health and Nutrition Examination Surveys Clin. Chem., May 1, 2008; 54(5): 801 - 813. [Abstract] [Full Text] [PDF]

				L. S. Lim, H. A. Fink, M. A. Kuskowski, B. C. Taylor, J. T. Schousboe, K. E. Ensrud, and for the Osteoporotic Fractures in Men (MrOS) Study Loop Diuretic Use and Increased Rates of Hip Bone Loss in Older Men: The Osteoporotic Fractures in Men Study Arch Intern Med, April 14, 2008; 168(7): 735 - 740. [Abstract] [Full Text] [PDF]

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