QJM Advance Access originally published online on October 14, 2006
QJM 2006 99(11):804-805; doi:10.1093/qjmed/hcl108
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Correspondence |
The MDRD formula and validation
Sir,MacGregor et al. are quite correct to point out that the MDRD equation will improve identification and management of chronic kidney disease.1 However, the MDRD four-variable formula is not as well-validated as one might hope.
Firstly, despite the initial MDRD equation being based on 1628 samples,2 there were insufficient patients with K/DOQI stages 1 and 2, as pointed out by MacGregor et al. However, this may be responsible for the significant negative bias of 29% reported in healthy persons.3
Secondly, the four-variable equation was published as an abstract,4 although the seven-variable paper2 was subject to full peer review.
Thirdly, the authors unnecessarily log-transformed the data, to reduce the increasing absolute difference between the reference method and the estimated values with increasing glomerular filtration rate (GFR). As a result, the model used may not be optimal or mathematically justifiable. Indeed, the formula was developed4 by empirical means, with no attempt to use an appropriate mathematical model. Such models may be acceptable as rough sketches of relationships, but one should not depend on them for making precise clinical decisions. Empirical models, and in particular those built using log-transformed data, are weak, because they can result in the propagation of errors.
Fourthly, the reference method used, iothalamate, is positively biased when compared to the gold standard GFR method (inulin 3–5 ml/min at low levels of GFR and 15–25 ml/min in healthy subjects5–8).
Finally, there is the issue of creatinine standardization, which MacGregor et al. mentioned: the constant factor in the four-variable MDRD equation has been changed from 185 to 1769 for creatinine methods that have been calibrated to be traceable to isotope dilution mass spectroscopy. It was subsequently suggested by the UK National External Quality Assessment Service (UKNEQAS) that slope and intercept adjusters for the creatinine methods could be used to approximate non-IDMS traceable creatinine results to an IDMS standardized method.10 We have shown that depending on which equation is used, there is the potential for a significant effect on the classification of chronic kidney disease primary care.11
Estimated GFR is potentially an excellent method of detecting and monitoring chronic kidney disease, as it is quick, cheap and simple. Answers to some of our questions will not negatively affect eGFR. However, as long as they remain unanswered, eGFR may remain open to criticism.
Department of Clinical Biochemistry
The Ipswich Hospital
Ipswich
Department of Chemical Pathology
Queen's Hospital
Burton-on-Trent
email: patrick.twomey{at}ipswichhospital.nhs.uk
References
1. MacGregor MS, Boag DE, Innes A. Chronic kidney disease: evolving strategies for detection and management of impaired renal function. Q J Med 2006; 99:365–75.
2. Level AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. for the MDRD Study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Int Med 1999; 130:461–70.
3. Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Coslo 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.
4. 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.
5. Perrone RD, Steinman TI, Beck GJ, et al. Utility of radioisotopic filtratration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalmate, 169Yb-DTPA, 99mTc-DTPA and inulin. The Modification of Diet in Renal Disease Study. Am J Kidney Dis 1990; 16:224–35.[Web of Science][Medline]
6. Odlind B, Hallgren R, Sohtell M, Lindstrom B. Is 125I-iothalmate an ideal marker for glomerular filtration? Kidney Int 1985; 27:9–16.[Web of Science][Medline]
7. Back SE, Krutzen E, Nilsson-Ehle P. Contrast media and glomerular filtration: dose dependence of clearance for three agents. J Pharma Sci 1988; 48:765–7.
8. Petri M, Bockenstedt L, Colman J, et al. Serial assessment of glomerular filtration rate in lupus nephropathy. Kidney Int 1988; 34:832–9.[Web of Science][Medline]
9. National Kidney Disease Education Program (NKDEP). Suggestions for laboratories (December 2005) [http://www.nkdep.nih.gov/resources/laboratory_reporting.htm]. Accessed 1 June 2006.
10. Mackenzie F. UKNEQAS of GFR Estimations (Pilot) [http://www.ukneqas.org.uk/GFR%20Estimations.pdf]. Accessed 1 June 2006.
11. Reynolds TM and Twomey PJ. Implications of method specific creatinine adjustments on GMS chronic kidney disease classification. J Clin Path 2006; (in press).
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Q.-P. Wang, J.-W. Gu, X.-H. Zhan, H. Li, and X.-H. Luo Assessment of glomerular filtration rate by serum cystatin C in patients undergoing coronary artery bypass grafting Ann Clin Biochem, November 1, 2009; 46(6): 495 - 500. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||