Variability of creatinine measurements in clinical laboratories: results from the CRIC study.
OBJECTIVE
Estimating equations using serum creatinine (SCr) are often used to assess glomerular filtration rate (GFR). Such creatinine (Cr)-based formulae may produce biased estimates of GFR when using Cr measurements that have not been calibrated to reference laboratories. In this paper, we sought to examine the degree of this variation in Cr assays in several laboratories associated with academic medical centers affiliated with the Chronic Renal Insufficiency Cohort (CRIC) Study; to consider how best to correct for this variation, and to quantify the impact of such corrections on eligibility for participation in CRIC. Variability of Cr is of particular concern in the conduct of CRIC, a large multicenter study of subjects with chronic renal disease, because eligibility for the study depends on Cr-based assessment of GFR.


METHODS
A library of 5 large volume plasma specimens from apheresis patients was assembled, representing levels of plasma Cr from 0.8 to 2.4 mg/dl. Samples from this library were used for measurement of Cr at each of the 14 CRIC laboratories repetitively over time. We used graphical displays and linear regression methods to examine the variability in Cr, and used linear regression to develop calibration equations. We also examined the impact of the various calibration equations on the proportion of subjects screened as potential participants who were actually eligible for the study.


RESULTS
There was substantial variability in Cr assays across laboratories and over time. We developed calibration equations for each laboratory; these equations varied substantially among laboratories and somewhat over time in some laboratories. The laboratory site contributed the most to variability (51% of the variance unexplained by the specimen) and variation with time accounted for another 15%. In some laboratories, calibration equations resulted in differences in eligibility for CRIC of as much as 20%.


CONCLUSIONS
The substantial variability in SCr assays across laboratories necessitates calibration of SCr measures to a common standard. Failing to do so may substantially affect study eligibility and clinical interpretations when they are determined by Cr-based estimates of GFR.
Joffe
Marshall
M
Department of Medicine and Hypertension and Renal Center, Tulane University, New Orleans, LA 70112, USA.
Hsu
Chi-yuan
CY
Feldman
Harold I
HI
Weir
Matthew
M
Landis
J R
JR
Hamm
L Lee
LL
D000328:Adult; D001781:Blood Component Removal; D002138:Calibration; D002624:Chemistry, Clinical / Q000379:methods*; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007753:Laboratories; D008297:Male; D015233:Models, Statistical; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D015203:Reproducibility of Results; D013997:Time Factors
D003404:Creatinine
JAMA. 2007 Nov 7;298(17):2038-47
17986697
Arch Pathol Lab Med. 1998 Jul;122(7):587-608
9674541
J Am Soc Nephrol. 2002 May;13(5):1338-49
11961022
Ann Intern Med. 1999 Mar 16;130(6):461-70
10075613
Ann Intern Med. 2006 Aug 15;145(4):247-54
16908915
N Engl J Med. 2006 Jun 8;354(23):2473-83
16760447
Arch Pathol Lab Med. 2005 Mar;129(3):297-304
15737021
Am J Kidney Dis. 2007 Jul;50(1):21-35
17591522
Am J Kidney Dis. 1998 Jul;32(1):32-42
9669421
J Am Soc Nephrol. 2002 Nov;13(11):2811-2; author reply 2812-6
12397055
Kidney Int. 2002 May;61(5):1567-76
11967006
Am J Kidney Dis. 2005 Aug;46(2):233-41
16112041
Kidney Int. 2005 Oct;68(4):1884-7
16164667
Am J Kidney Dis. 2003 Jan;41(1):1-12
12500213
Clin Chem. 2007 Apr;53(4):766-72
17332152
J Am Soc Nephrol. 2003 Jul;14(7 Suppl 2):S148-53
12819321
N Engl J Med. 2004 Sep 23;351(13):1296-305
15385656
Am J Kidney Dis. 2002 May;39(5):920-9
11979335
Clin Chem. 2006 Jan;52(1):5-18
16332993