Background:
Serum creatinine concentration is widely used as an index of renal function, but this concentration is affected by factors other than glomerular filtration rate (GFR).
Objective:
To develop an equation to predict GFR from serum creatinine concentration and other factors.
Design:
Cross-sectional study of GFR, creatinine clearance, serum creatinine concentration, and demographic and clinical characteristics in patients with chronic renal disease.
Patients:
1628 patients enrolled in the baseline period of the Modification of Diet in Renal Disease (MDRD) Study, of whom 1070 were randomly selected as the training sample; the remaining 558 patients constituted the validation sample.
Methods:
The prediction equation was developed by stepwise regression applied to the training sample. The equation was then tested and compared with other prediction equations in the validation sample.
Results:
To simplify prediction of GFR, the equation included only demographic and serum variables. Independent factors associated with a lower GFR included a higher serum creatinine concentration, older age, female sex, nonblack ethnicity, higher serum urea nitrogen levels, and lower serum albumin levels (P < 0.001 for all factors). The multiple regression model explained 90.3% of the variance in the logarithm of GFR in the validation sample. Measured creatinine clearance overestimated GFR by 19%, and creatinine clearance predicted by the Cockcroft-Gault formula overestimated GFR by 16%. After adjustment for this overestimation, the percentage of variance of the logarithm of GFR predicted by measured creatinine clearance or the Cockcroft-Gault formula was 86.6% and 84.2%, respectively.
Conclusion:
The equation developed from the MDRD Study provided a more accurate estimate of GFR in our study group than measured creatinine clearance or other commonly used equations.
*For members of the Modification of Diet in Renal Disease Study Group, see N Engl J Med. 1994; 330:877-84.
References
- 1.
Smith HW . The Kidney: Structure and Function in Health and Disease. New York: Oxford Univ Pr; 1951:836-87. Google Scholar - 2.
Levey AS . Measurement of renal function in chronic renal disease. Kidney Int. 1990;38:167-84. CrossrefMedlineGoogle Scholar - 3.
Perrone RD ,Madias NE ,Levey AS . Serum creatinine as an index of renal function: new insights into old concepts. Clinical Chem. 1992;38:1933-53. CrossrefMedlineGoogle Scholar - 4.
Cockcroft DW ,Gault MH . Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31-41. CrossrefMedlineGoogle Scholar - 5.
Parker RA ,Bennett WM ,Porter GA . Clinical estimation of creatinine clearance without urine collection. Dialysis and Transplantation. 1980;9:251-2. Google Scholar - 6.
Sawyer WT ,Canaday BR ,Poe TE ,Webb CE ,Gal P ,Joyner PU ,et al . Variables affecting creatinine clearance prediction. Am J Hosp Pharm. 1983;40:2175-80. MedlineGoogle Scholar - 7.
Bjornsson TD ,Cocchetto DM ,McGowan FX ,Verghese CP ,Sedor F . Nomogram for estimating creatinine clearance. Clin Pharmacokinet. 1983;8:365-9. CrossrefMedlineGoogle Scholar - 8.
Taylor GO ,Bamgboye EA ,Oyediran AB ,Longe O . Serum creatinine and prediction formulae for creatinine clearance. Afr J Med Med Sci. 1982;11:175-81. MedlineGoogle Scholar - 9.
Gates GF . Creatinine clearance estimation from serum creatinine values: an analysis of three mathematical models of glomerular function. Am J Kidney Dis. 1985;5:199-205. CrossrefMedlineGoogle Scholar - 10.
Jelliffe RW . Creatinine clearance: bedside estimate [Letter]. Ann Intern Med. 1973;79:604-5. LinkGoogle Scholar - 11.
Hallynck T ,Soep HH ,Thomis J ,Boelaert J ,Daneels R ,Fillastre JP ,et al . Prediction of creatinine clearance from serum creatinine concentration based on lean body mass. Clin Pharm Ther. 1981;30:414-21. CrossrefMedlineGoogle Scholar - 12.
Kampmann J ,Siersbaek-Nielsen K ,Kristensen M ,Hansen JM . Rapid evaluation of creatinine clearance. Acta Med Scand. 1974;196:517-20. CrossrefMedlineGoogle Scholar - 13.
Bröchner-Mortensen J ,Rödbro P . Selection of routine method for determination of glomerular filtration rate in adult patients. Scand J Clin Lab Invest. 1976;36:35-43. CrossrefMedlineGoogle Scholar - 14.
Tessitore N ,Lo Schiavo C ,Corgnati A ,Previato G ,Valvo E ,Lupo A ,et al . 125I-iothalamate and creatinine clearances in patients with chronic renal diseases. Nephron. 1979;24:41-5. CrossrefMedlineGoogle Scholar - 15.
Bauer JH ,Brooks CS ,Burch RN . Renal function studies in man with advanced renal insufficiency. Am J Kidney Dis. 1982;2:30-5. CrossrefMedlineGoogle Scholar - 16.
Van Lente F ,Suit P . Assessment of renal function by serum creatinine and creatinine clearance: glomerular filtration rate estimated by four procedures. Clin Chem. 1989;35:2326-30. CrossrefMedlineGoogle Scholar - 17.
Trollfors B ,Alestig K ,Jagenburg R . Prediction of glomerular filtration rate from serum creatinine, age, sex and body weight. Acta Med Scand. 1987;221:495-8. CrossrefMedlineGoogle Scholar - 18.
Groth S ,Aasted M ,Vestergaard B . Screening of kidney function by plasma creatinine and single-sample 51Cr-EDTA clearance determination—a comparison. Scand J Clin Lab Invest. 1989;49:707-10. CrossrefMedlineGoogle Scholar - 19.
Lemann J ,Bidani AK ,Bain RP ,Lewis EJ ,Ronde RD . Use of the serum creatinine to estimate glomerular filtration rate in health and early diabetic nephropathy. Collaborative Study Group of Angiotensin Converting Enzyme Inhibition in Diabetic Nephropathy. Am J Kidney Dis. 1990;16:236-43. CrossrefMedlineGoogle Scholar - 20.
DeSanto NG ,Coppola S ,Anastasio P ,Coscarella G ,Capasso G ,Bellini L ,et al . Predicted creatinine clearance to assess glomerular filtration rate in chronic renal disease in humans. Am J Nephrol. 1991;11:181-5. CrossrefMedlineGoogle Scholar - 21.
Sampson MJ ,Drury PL . Accurate estimation of glomerular filtration rate in diabetic nephropathy from age, body weight, and serum creatinine. Diabetes Care. 1992;15:609-12. CrossrefMedlineGoogle Scholar - 22.
Walser M ,Drew HH ,Guldan JL . Prediction of glomerular filtration rate from serum creatinine concentration in advanced chronic renal failure. Kidney Int. 1993;44:1145-8. CrossrefMedlineGoogle Scholar - 23.
Cochran M ,St John A . A comparison between estimates of GFR using [99mTc]DTPA clearance and the approximation of Cockroft and Gault. Aust N Z J Med. 1993;23:494-7. CrossrefMedlineGoogle Scholar - 24.
Pollock C ,Gyory AZ ,Hawkins T ,Ross M ,Ibels L . Comparison of simultaneous renal clearances of true endogenous creatinine and subcutaneously administered iothalamate in man. Am J Nephrol. 1995;15:277-82. CrossrefMedlineGoogle Scholar - 25. U.S. Department of Health and Human Services. HCFA-2728-U4 (4-95). Form Approved: OMB No. 0938-0046, Health Care Financing Administration. Google Scholar
- 26. American Society of Transplant Physicians. Scientific Symposium on Listing Criteria: Kidney. Bethesda, MD; 30 January 1997. Google Scholar
- 27.
Klahr S ,Levey AS ,Beck GJ ,Caggiula AW ,Hunsicker L ,Kusek JW ,Striker G . The effects of dietary protein restriction and blood-pressure control on the progression of renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med. 1994;330:877-84. CrossrefMedlineGoogle Scholar - 28.
Peterson JC ,Adler S ,Burkhart JM ,Greene T ,Hebert LA ,King AJ ,et al . Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study. Ann Intern Med. 1995;123:754-62. LinkGoogle Scholar - 29.
Levey AS ,Adler S ,Caggiula AW ,England BK ,Greene T ,Hunsicker LG ,et al . Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study. Am J Kidney Dis. 1996;27:652-63. CrossrefMedlineGoogle Scholar - 30. Effects of dietary protein restriction on the progression of moderate renal disease in the Modification of Diet in Renal Disease Study. J Am Soc Nephrol. 1996; 7:2616-25. Google Scholar
- 31.
Beck GJ ,Berg RL ,Coggins CH ,Gassman JJ ,Hunsicker LG ,Williams GW . Design and statistical issues of the Modification of Diet in Renal Disease Trial. The Modification of Diet in Renal Disease Study Group. Control Clin Trials. 1991;12:566-86. CrossrefMedlineGoogle Scholar - 32.
Kusek JW ,Coyne T ,de Velasco A ,Drabik MJ ,Finlay RA ,Gassman JJ ,et al . Recruitment experience in the full-scale phase of the Modification of Diet in Renal Disease Study. Control Clin Trials. 1993;14:538-57. CrossrefMedlineGoogle Scholar - 33.
Perrone R ,Steinman TI ,Beck GJ ,Skibinski CI ,Royal H ,Lawlor M ,et al . Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study Group. Am J Kidney Dis. 1990;16:224-35. CrossrefMedlineGoogle Scholar - 34.
Levey AS ,Greene T ,Schluchter MD ,Cleary PA ,Teschan PE ,Lorenz RA ,et al . Glomerular filtration rate measurements in clinical trials. Modification of Diet in Renal Disease Study Group and the Diabetes Control and Complications Trial Research Group. J Am Soc Nephrol. 1993;4:1159-71. CrossrefMedlineGoogle Scholar - 35. Astra-8 Operations Manual. Fullerton, CA: Beckman. Google Scholar
- 36.
DuBois D ,DuBois EF . A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med. 1916;17:863-71. CrossrefGoogle Scholar - 37.
Frisancho AR . Anthropometric Standards for the Assessment of Growth and Nutritional Status. Ann Arbor, MI: Univ of Michigan Pr; 1990. Google Scholar - 38.
Maroni BJ ,Steinman TI ,Mitch WE . A method for estimating nitrogen intake of patients with chronic renal failure. Kidney Int. 1985;27:58-65. CrossrefMedlineGoogle Scholar - 39.
Buckalew VM Jr ,Berg RL ,Wang SR ,Porush JG ,Rauch S ,Schulman G . Prevalence of hypertension in 1,795 subjects with chronic renal disease: the modification of diet in renal disease study baseline cohort. Modification of Diet in Renal Disease Study Group. Am J Kidney Dis. 1996;28:811-21. CrossrefMedlineGoogle Scholar - 40.
Heymsfield SB ,Arteaga C ,McManus C ,Smith J ,Moffitt S . Measurement of muscle mass in humans: validity of the 24-hour urinary creatinine method. Am J Clin Nutr. 1983;37:478-94. CrossrefMedlineGoogle Scholar - 41.
Cohn SH ,Abesemis C ,Zanzi I ,Aloia JF ,Yasumura S ,Ellis KJ . Body elemental composition: comparison between black and white adults. Am J Physiol. 1977;232:E419-22. MedlineGoogle Scholar - 42.
Harsha DW ,Frerichs RR ,Berenson GS . Densitometry and anthropometry of black and white children. Hum Biol. 1978;50:261-80. MedlineGoogle Scholar - 43.
Worrall JG ,Phongsathorn V ,Hooper RJ . Racial variation in serum creatine kinase unrelated to lean body mass. Br J Rheumatol. 1990;29:371-3. CrossrefMedlineGoogle Scholar - 44. Effects of diet and antihypertensive therapy on creatinine clearance and serum creatinine concentration in the Modification of Diet in Renal Disease Study. J Am Soc Nephrol. 1996; 7:556-65. Google Scholar
- 45. Short-term effects of protein intake, blood pressure, and antihypertensive therapy on glomerular filtration rate in the Modification of Diet in Renal Disease Study. J Am Soc Nephrol. 1996; 7:2097-109. Google Scholar
- 46.
Hartmann AE . Accuracy of creatinine results reported by participants in the CAP Chemistry Survey Program. Arch Pathol Lab Med. 1985;109:1068-71. MedlineGoogle Scholar - 47.
Levey AS ,Greene P ,Burkart J . Comprehensive assessment of the level of renal function at the initiation of dialysis in the MDRD study [Abstract]. MDRD Study Group. J Am Soc Nephrol. 1998;9:153A. Google Scholar - 48.
Breyer-Lewis J ,Agodoa L ,Cheek D ,Greene P ,Middleton J ,O'Connor D ,et al . Estimation of GFR from serum creatinine in the African-American Study of Kidney Disease [Abstract]. AASK Study Group. J Am Soc Nephrol. 1998;9:153A. Google Scholar - 49.
Bedros FV ,Kasiske BL . Estimating glomerular filtration rate from serum creatinine in renal transplant recipients [Abstract]. J Am Soc Nephrol. 1998;9:666A. Google Scholar
Author, Article and Disclosure Information
Presented in part at the Seventh International Congress on Nutrition and Metabolism in Renal Disease, Stockholm, Sweden, 29 May-1 June 1994, and the 30th Annual Meeting of the American Society of Nephrology, San Antonio, Texas, 2-6 November 1997.
Grant Support: By the National Institute of Diabetes and Digestive and Kidney Diseases and the Health Care Financing Administration.
Corresponding Author: Andrew S. Levey, MD, New England Medical Center, 750 Washington Street, Box 391, Boston, MA 02111.
Current Author Addresses: Dr. Levey: New England Medical Center, 750 Washington Street, Box 391, Boston, MA 02111; e-mail, Andrew.
Dr. Bosch: George Washington University, 901 23rd Street SW, Washington, DC 20037.
Dr. Lewis and Ms. Rogers: Vanderbilt University Medical Center, 1211 22nd Avenue S, Nashville, TN 37232.
Dr. Greene: Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195.
Dr. Roth: University of Miami Medical Center, 1475 NW 12th Avenue, Miami, FL 33136.
Submit a Comment
Contributors must reveal any conflict of interest. Comments are moderated. Please see our information for authorsregarding comments on an Annals publication.
*All comments submitted after October 1, 2021 and selected for publication will be published online only.