Correspondence

“Bouncing” Creatinine Levels

N Engl J Med 1996; 334:1749-1750June 27, 1996

Article

To the Editor:

We studied a series of unusual creatinine values in a 38-year-old man with end-stage cardiac disease and acute renal failure. The initial plasma creatinine levels ranged from 4.0 to 4.8 mg per deciliter and gradually decreased to 2.0 to 2.5 mg per deciliter over a period of several weeks. On multiple occasions, the level abruptly dropped to less than half of the preceding measurement, only to return to the previous value with the next sample. No clinical changes were associated with these events.

Routine creatinine analyses are done with a colorimetric method on a Hitachi 747 machine (Boehringer Mannheim), and immediate analyses with an enzymatic method on an Ektachem 750 machine (Johnson & Johnson). Although most of this patient's samples yielded equivalent creatinine values by both methods, all the values that represented abrupt decreases were obtained by the enzymatic method. When the samples with aberrant values were analyzed by the colorimetric method, the creatinine values obtained were consistent with the patient's clinical state. This was surprising, because the enzymatic method is associated with few reported types of interference and is thought to be more specific1,2 than the colorimetric technique.3

Initially, no correlation was found between the patient's medications and the unusual readings. However, an activated partial-thromboplastin time of more than 106 seconds was frequently measured in blood samples obtained at the same time as the samples that produced the falsely decreased creatinine values. After discussion with the nursing staff, we determined that the elevated partial-thromboplastin times were due to an error in sample collection. The samples were drawn from an indwelling triple-lumen catheter through which a solution containing 100 U of heparin, 3.2 mg of dopamine, and 8.3 mg of dobutamine per milliliter was being administered. Although the samples were collected after the intravenous medications were stopped and 10 ml of blood was discarded, the connection to the medication solution was not always clamped. Thus, the blood samples were contaminated with residual fluid.

We ruled out heparin as a source of the interference. However, dobutamine produced a profound negative interference with the enzymatic method of creatinine determination, as did dopamine to a lesser extent. As little as 1 percent (vol/vol) contamination of the blood sample with the intravenous fluid caused a reduction of more than 60 percent in the enzymatic creatinine measurements (Table 1Table 1Interference with Creatinine Measurements by Dobutamine and Dopamine.).

The colorimetric method relies on the direct reaction between creatinine and picric acid to form a yellow-orange product, whereas the enzymatic technique involves the liberation of hydrogen peroxide, which produces color by oxidizing a chromogenic dye. Dobutamine is easily oxidized and may interfere with the dye by competing directly for oxidation by hydrogen peroxide. Several other assays that use hydrogen peroxide as an end product (such as the cholesterol test using the Hitachi analyzer and uric acid tests with both machines) have similar patterns of negative interference.

Thomas M. Daly, M.D.
Kirsten C. Kempe, Ph.D.
Mitchell G. Scott, Ph.D.
Washington University School of Medicine, St. Louis, MO 63110

3 References

1. 1

   Gosney K, Adachi-Kirkland J, Schiller HS. Evaluation of lidocaine interference in the Kodak Ektachem 700 analyzer single-slide method for creatinine. Clin Chem 1987;33:2311-2311
   Web of Science | Medline

2. 2

   Bissell MG, Ward E, Sanghavi P, et al. Multilaboratory evaluation of the new, single-slide enzymatic creatinine method on the Kodak Ektachem analyzer. Clin Chem 1987;33:951-951 abstract.
   Web of Science

3. 3

   Spencer K. Analytical reviews in clinical biochemistry: the estimation of creatinine. Ann Clin Biochem 1986;23:1-25
   Web of Science | Medline

Author/Editor Response

The above letter was referred to the Boehringer Mannheim Corporation, which declined to comment, and to Johnson & Johnson Clinical Diagnostics, which offers the following reply:

To the Editor: We find the report objective and well written. Daly et al. point out that regardless of the method used, contaminated specimens can produce false readings, and therefore proper sampling procedures should always be followed. We will make sure the appropriate information is in our technical data base.

Richard J. Lees
Johnson & Johnson Clinical Diagnostics, Rochester, NY 14650

Citing Articles (5)

Citing Articles

1. 1

   Michael T. White, Lawrence N. Diebel, Anna M. Ledgerwood, Charles E. Lucas. (2011) The Significance of a Serum Creatinine in Defining Renal Function in Seriously Injured and Septic Patients. The Journal of Trauma: Injury, Infection, and Critical Care 70:2, 421-427
   CrossRef

2. 2

   Ivana Kralova, Ola Winsö, Magnus Olivecrona, Silvana Naredi. (2010) Non-traumatic subarachnoid hemorrhage is associated with subnormal blood creatinine levels. Scandinavian Journal of Clinical & Laboratory Investigation 70:6, 438-446
   CrossRef

3. 3

   Adeline Su-Yin Ngo, Freda Rowley, Kent R. Olson. (2010) Case Files of the California Poison Control System, San Francisco Division: Blue Thunder Ingestion: Methanol, Nitromethane, and Elevated Creatinine. Journal of Medical Toxicology 6:1, 67-71
   CrossRef

4. 4

   Michael Lognard, Etienne Cavalier, Jean-Paul Chapelle, Bernard Lambermont, Jean-Marie Krzesinski, Pierre Delanaye. (2008) Acetylcysteine and enzymatic creatinine: beware of laboratory artefact!. Intensive Care Medicine 34:5, 973-974
   CrossRef

5. 5

   Matthew D. Cook, Richard F. Clark. (2007) Creatinine Elevation Associated with Nitromethane Exposure: A Marker of Potential Methanol Toxicity. The Journal of Emergency Medicine 33:3, 249-253
   CrossRef