Abstract
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.
References
- 1.
Levey AS ,Coresh J ,Balk E ,Kausz AT ,Levin A ,Steffes MW ,et al . National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;139:137-47. [PMID: 12859163] LinkGoogle Scholar - 2.
Levey AS ,Eckardt KU ,Tsukamoto Y ,Levin A ,Coresh J ,Rossert J ,et al . Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005;67:2089-100. [PMID: 15882252] CrossrefMedlineGoogle Scholar - 3.
National Kidney Foundation . K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis. 2002;2 Suppl 1 S1-266. [PMID: 11904577] MedlineGoogle Scholar - 4.
Wesson L . Physiology of the Human Kidney. New York: Grune & Stratton; 1969. Google Scholar - 5. Siegel N. Renal Express. Accessed at www.asn-online.org/newsletter/renal_express/2003/03-10_Rxpress.aspx on 23 June 2006. Google Scholar
- 6. National Kidney Disease Education Program. Information of Health Professionals. Creatinine Standardization Program. Accessed at www.nkdep.nih.gov/labprofessionals/index.htm on 9 February 2006. Google Scholar
- 7. New Jersey State Senate, 211th Legislature. S2232 Madden: Bryant; 2005:1-2. Google Scholar
- 8.
Mathew TH ;Australasian Creatinine Consensus Working Group . Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: a position statement. Med J Aust. 2005;183:138-41. [PMID: 16053416] CrossrefMedlineGoogle Scholar - 9. La Caisse Nationale d'Assurance Maladie des Professions Indépendantes. Avenant à la convention nationale des directeurs de laboratoire privé d'analyses médicales. Accessed at www.admi.net/jo/20030227/SANS0320604X.html on 8 November 2004. Google Scholar
- 10. British Columbia Ministry of Health. Guidelines and Protocols, Advisory Committee. Accessed at www.healthservices.gov.bc.ca/msp/protoguides/gps/ckd.pdf on 21 October 2005. Google Scholar
- 11.
Levey AS ,Bosch JP ,Lewis JB ,Greene T ,Rogers N ,Roth D . A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461-70. [PMID: 10075613] LinkGoogle Scholar - 12.
Levey AS ,Greene T ,Kusek J ,Beck G . A simplified equation to predict glomerular filtration rate from serum creatinine [Abstract]. J Am Soc Nephrol. 2000;11:155A. Google Scholar - 13.
Stevens LA ,Levey AS . Clinical implications of estimating equations for glomerular filtration rate [Editorial]. Ann Intern Med. 2004;141:959-61. [PMID: 15611494] LinkGoogle Scholar - 14.
Poggio ED ,Wang X ,Greene T ,Van Lente F ,Hall PM . Performance of the Modification of Diet in Renal Disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol. 2005;16:459-66. [PMID: 15615823] CrossrefMedlineGoogle Scholar - 15.
Lewis J ,Agodoa L ,Cheek D ,Greene T ,Middleton J ,O'Connor D ,et al . Comparison of cross-sectional renal function measurements in African Americans with hypertensive nephrosclerosis and of primary formulas to estimate glomerular filtration rate. Am J Kidney Dis. 2001;38:744-53. [PMID: 11576877] CrossrefMedlineGoogle Scholar - 16.
Rule AD ,Larson TS ,Bergstralh EJ ,Slezak JM ,Jacobsen SJ ,Cosio FG . Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med. 2004;141:929-37. [PMID: 15611490] LinkGoogle Scholar - 17.
Gonwa TA ,Jennings L ,Mai ML ,Stark PC ,Levey AS ,Klintmalm GB . Estimation of glomerular filtration rates before and after orthotopic liver transplantation: evaluation of current equations. Liver Transpl. 2004;10:301-9. [PMID: 14762871] CrossrefMedlineGoogle Scholar - 18.
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. [PMID: 15659562] CrossrefMedlineGoogle Scholar - 19.
Hallan S ,Asberg A ,Lindberg M ,Johnsen H . Validation of the Modification of Diet in Renal Disease formula for estimating GFR with special emphasis on calibration of the serum creatinine assay. Am J Kidney Dis. 2004;44:84-93. [PMID: 15211442] CrossrefMedlineGoogle Scholar - 20.
Lin J ,Knight EL ,Hogan ML ,Singh AK . A comparison of prediction equations for estimating glomerular filtration rate in adults without kidney disease. J Am Soc Nephrol. 2003;14:2573-80. [PMID: 14514734] CrossrefMedlineGoogle Scholar - 21.
Bostom AG ,Kronenberg F ,Ritz E . Predictive performance of renal function equations for patients with chronic kidney disease and normal serum creatinine levels. J Am Soc Nephrol. 2002;13:2140-4. [PMID: 12138147] CrossrefMedlineGoogle Scholar - 22.
Zuo L ,Ma YC ,Zhou YH ,Wang M ,Xu GB ,Wang HY . Application of GFR-estimating equations in Chinese patients with chronic kidney disease. Am J Kidney Dis. 2005;45:463-72. [PMID: 15754268] CrossrefMedlineGoogle Scholar - 23.
Gaspari F ,Ferrari S ,Stucchi N ,Centemeri E ,Carrara F ,Pellegrino M ,et al . Performance of different prediction equations for estimating renal function in kidney transplantation. Am J Transplant. 2004;4:1826-35. [PMID: 15476483] CrossrefMedlineGoogle Scholar - 24.
Lamb EJ ,Webb MC ,Simpson DE ,Coakley AJ ,Newman DJ ,O'Riordan SE . Estimation of glomerular filtration rate in older patients with chronic renal insufficiency: is the Modification of Diet in Renal Disease formula an improvement? J Am Geriatr Soc. 2003;51:1012-7. [PMID: 12834524] CrossrefMedlineGoogle Scholar - 25.
Vervoort G ,Willems HL ,Wetzels JF . Assessment of glomerular filtration rate in healthy subjects and normoalbuminuric diabetic patients: validity of a new (MDRD) prediction equation. Nephrol Dial Transplant. 2002;17:1909-13. [PMID: 12401845] CrossrefMedlineGoogle Scholar - 26.
Skluzacek PA ,Szewc RG ,Nolan CR ,Riley DJ ,Lee S ,Pergola PE . Prediction of GFR in liver transplant candidates. Am J Kidney Dis. 2003;42:1169-76. [PMID: 14655188] CrossrefMedlineGoogle Scholar - 27.
Ibrahim H ,Mondress M ,Tello A ,Fan Y ,Koopmeiners J ,Thomas W . An alternative formula to the Cockcroft-Gault and the Modification of Diet in Renal Diseases formulas in predicting GFR in individuals with type 1 diabetes. J Am Soc Nephrol. 2005;16:1051-60. [PMID: 15716336] CrossrefMedlineGoogle Scholar - 28.
Rigalleau V ,Lasseur C ,Perlemoine C ,Barthe N ,Raffaitin C ,Liu C ,et al . Estimation of glomerular filtration rate in diabetic subjects: Cockcroft formula or Modification of Diet in Renal Disease study equation? Diabetes Care. 2005;28:838-43. [PMID: 15793182] CrossrefMedlineGoogle Scholar - 29.
Pöge U ,Gerhardt T ,Palmedo H ,Klehr HU ,Sauerbruch T ,Woitas RP . MDRD equations for estimation of GFR in renal transplant recipients. Am J Transplant. 2005;5:1306-11. [PMID: 15888034] CrossrefMedlineGoogle Scholar - 30.
Grubb A ,Björk J ,Lindström V ,Sterner G ,Bondesson P ,Nyman U . A cystatin C-based formula without anthropometric variables estimates glomerular filtration rate better than creatinine clearance using the Cockcroft-Gault formula. Scand J Clin Lab Invest. 2005;65:153-62. [PMID: 16025838] CrossrefMedlineGoogle Scholar - 31.
Fehrman-Ekholm I ,Skeppholm L . Renal function in the elderly (>70 years old) measured by means of iohexol clearance, serum creatinine, serum urea and estimated clearance. Scand J Urol Nephrol. 2004;38:73-7. [PMID: 15204431] CrossrefMedlineGoogle Scholar - 32.
Coresh J ,Stevens LA . Kidney function estimating equations: where do we stand? Curr Opin Nephrol Hypertens. 2006;15:276-84. [PMID: 16609295] CrossrefMedlineGoogle Scholar - 33.
Coresh J ,Astor BC ,McQuillan G ,Kusek J ,Greene T ,Van Lente F ,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. [PMID: 11979335] CrossrefMedlineGoogle Scholar - 34.
Miller WG ,Myers GL ,Ashwood ER ,Killeen AA ,Wang E ,Thienpont LM ,et al . Creatinine measurement: state of the art in accuracy and interlaboratory harmonization. Arch Pathol Lab Med. 2005;129:297-304. [PMID: 15737021] CrossrefMedlineGoogle Scholar - 35.
Murthy K ,Stevens LA ,Stark PC ,Levey AS . Variation in the serum creatinine assay calibration: a practical application to glomerular filtration rate estimation. Kidney Int. 2005;68:1884-7. [PMID: 16164667] CrossrefMedlineGoogle Scholar - 36.
Myers GL ,Miller WG ,Coresh J ,Fleming J ,Greenberg N ,Greene T ,et al . Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clin Chem. 2006;52:5-18. [PMID: 16332993] CrossrefMedlineGoogle Scholar - 37.
Levey AS ,Coresh J ,Greene T ,Marsh J ,Stevens LA ,Kusek J ,et al . Expressing the MDRD Study equation for estimating GFR with IDMS traceable (gold standard) serum creatinine values [Abstract]. J Am Soc Nephrol. 2005;16:69A. Google Scholar - 38.
Cockcroft DW ,Gault MH . Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31-41. [PMID: 1244564] CrossrefMedlineGoogle Scholar - 39.
Junge W ,Wilke B ,Halabi A ,Klein G . Determination of reference intervals for serum creatinine, creatinine excretion and creatinine clearance with an enzymatic and a modified Jaffé method. Clin Chim Acta. 2004;344:137-48. [PMID: 15149882] CrossrefMedlineGoogle Scholar - 40.
Klahr S ,Levey AS ,Beck GJ ,Caggiula AW ,Hunsicker L ,Kusek JW ,et al . The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med. 1994;330:877-84. [PMID: 8114857] CrossrefMedlineGoogle Scholar - 41.
DeLong ER ,DeLong DM ,Clarke-Pearson DL . Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837-45. [PMID: 3203132] CrossrefMedlineGoogle Scholar - 42.
Cirillo M ,Anastasio P ,De Santo NG . Relationship of gender, age, and body mass index to errors in predicted kidney function. Nephrol Dial Transplant. 2005;20:1791-8. [PMID: 15998649] CrossrefMedlineGoogle Scholar - 43.
Verhave JC ,Fesler P ,Ribstein J ,du Cailar G ,Mimran A . Estimation of renal function in subjects with normal serum creatinine levels: influence of age and body mass index. Am J Kidney Dis. 2005;46:233-41. [PMID: 16112041] CrossrefMedlineGoogle Scholar - 44.
Rule AD ,Gussak HM ,Pond GR ,Bergstralh EJ ,Stegall MD ,Cosio FG ,et al . Measured and estimated GFR in healthy potential kidney donors. Am J Kidney Dis. 2004;43:112-9. [PMID: 14712434] CrossrefMedlineGoogle Scholar - 45.
Greene T ,Li L ,Coresh J ,Poggio P ,Schimd C ,Stark P ,et al . A statistical explanation for different relationships of serum creatinine (Scr) vs. GFR across populations: preliminary results [Abstract]. J Am Soc Nephrol. 2005;16:319A. Google Scholar - 46.
Stevens LA ,Levey AS . Chronic kidney disease in the elderly—how to assess risk [Editorial]. N Engl J Med. 2005;352:2122-4. [PMID: 15901867] CrossrefMedlineGoogle Scholar - 47.
Coresh J ,Stevens LA ,Greene T ,Eggers O ,Kusek J ,Van Lente F ,et al . Comparison of GFR estimating equations using serum cystatin and creatinine: a pooled analysis of 1706 individuals [Abstract]. J Am Soc Nephrol. 2005;16:69A. Google Scholar
Author, Article, and Disclosure Information
Andrew S. Levey,
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.
Disclosures:Grants received: A.S. Levey (National Institutes of Health, Amgen, National Kidney Foundation).
Corresponding Author: Andrew S. Levey, MD, Division of Nephrology, Tufts-New England Medical Center, 750 Washington Street, Box 391, Boston, MA 02111.
Correction: This article was corrected on 16 March 2021 to correct a statement about ascertainment of the participants' ethnicity.
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.