Q & A

March 2006

Richard A. Savage, MD

Q. For years, the benchmark quality assurance marker in the blood bank has monitored the crossmatch-to-transfusion ratio. Since the introduction of the electronic crossmatch, this ratio has become meaningless. What marker should we review in its absence?

A. I’m not sure there needs to be a successor. The purpose of tracking the crossmatch-to-transfusion ratio, or C:T ratio, was to document the efficient use of laboratory personnel and to limit the growing number of outdated units resulting from reserving blood that had a low probability of use. You are correct that with electronic crossmatching, the C:T ratio is meaningless because the problems it was meant to reflect are no longer controlled by crossmatching orders when using electronic, or on-demand, crossmatching.

While the issues of staffing and outdated blood remain important in this era of electronic crossmatching, other metrics may be more useful. For example, do you have many units returned after being sent to the floor that, by virtue of their time outside refrigeration, cannot be returned to inventory? If so, then perhaps this rate might be tracked and the sources of the problem investigated. Are type and screen samples being sent when there is little likelihood of transfusion? Beyond implementing a surgical blood order schedule, perhaps labs could tally and ivestigate the frequency of unused type and screen results and the situations in which they occur with an eye toward altering clinical practice.

James P. AuBuchon, MD
E. Elizabeth French Professor and Chair of Pathology
Dartmouth-Hitchcock Medical Center
Lebanon, NH

Chair, CAP Transfusion
Medicine Resource Committe

Q: We perform 24-hour urine creatinines in-house. A resident physician, who is our chief of nephrology, director of dialysis, and a board-certified nephrologist, requested we set up a six-hour urine creatinine panel because the test helps him manage his acute renal failure patients. I do not dispute the test panel’s usefulness for his purpose, but I think a reference statement should be made available for other physicians who may not be aware of this test panel’s limitations and appropriate use.

Should this test be available for general provider use, with or without a reference statement? Also, can you obtain the six-hour panel range simply by dividing the 24-hour range by four? Would the calculation for the six hour be similar to that for the 24 hour? A. Although creatinine clearance calculations are typically done on 24-hour urine collections, they can, theoretically at least, be performed on any timed urine collection. Consider the following version of the clearance formula:

Ccreatinine = (Ucreatinine x V) / (Pcreatinine x T)

C is clearance (mL/min), U is urine concentration (mg/dL), V is volume collected (mL), T is the time period of the collection (minutes), and P is plasma (or serum) concentration (mg/dL).

For a 24-hour urine, the time is 1,440 minutes (24 hours x 60 minutes); for a six-hour collection, the time is 240 minutes. U x V represents the creatinine excretion for the time period in question (mg); V/T is the urine flow rate (mL/min).

The underlying physiology is that creatinine is produced at a relatively constant rate, freely filtered through the glomerulus, and not appreciably reabsorbed or secreted by the tubules. Thus, its clearance reflects the glomerular filtration rate, or GFR.¹

One major problem with creatinine clearance as an estimate of GFR is that any inaccuracies in collection will translate to inaccuracies in the calculated clearance. Inaccuracies are common,² even with 24-hour collections, where the beginning and end of the collection have well-defined endpoints, that is the first morning urine is collected as the beginning or as the end of the collection. With a six-hour collection, any errors in collection have a proportionately greater effect, such as when the patient has difficulty voiding completely at the beginning or end of the time period. However, if the bladder were already catheterized, errors in collection might be eliminated.

Some references support the practice of shorter time intervals while others argue against the practice.^3-6 I would not encourage using six-hour creatinine clearance calculations, though there’s no reason why they can’t be done. I would add a disclaimer to the results, something to the effect that "because of the inherent difficulties in accurately collecting a six-hour urine, a six-hour creatinine clearance should be interpreted cautiously." Because the calculation results are a value expressed in mL/min, the reference range would be unchanged.

For the record, an alternative for estimating GFR, which has many advantages over the traditional creatinine clearance, simply uses the serum creatinine along with the patient’s age, gender, and race. Laboratories can then calculate, from the MDRD—modification of diet in renal disease—equation, a reasonably accurate GFR.^7,8 However, in any setting where the serum creatinine is not stable—for example, the onset of, or recovery from, acute renal failure—all calculations of GFR based on serum creatinine will be inaccurate.⁹ This would include 24- and six-hour creatinine clearances as well as the MDRD-derived estimated GFR.

References

1. Burtis CA, Ashwood ER. Tietz Textbook of Clinical Chemistry. 3rd ed. Philadelphia, Pa.: W.B. Saunders Company; 1998:821–822.
2. Burtis CA, Ashwood ER. Tietz Textbook of Clinical Chemistry. 3rd ed. Philadelphia, Pa.: W.B. Saunders Company; 1998:50,1242.
3. Herget-Rosenthal S, Kribben A, Pietruck F, et al. Two by two hour creatinine clearance—repeatable and valid. Clin Nephrol. 1999;51:348–354.
4. Wilson RF, Soullier G. The validity of two-hour creatinine clearance studies in critically ill patients. Crit Care Med. 1980;8:281–284.
5. Cherry RA, Eachempati SR, Hydo L, et al. Accuracy of short-duration creatinine clearance in critically ill and injured patients. J Trauma. 2002;53: 267– 271.
6. Pong S, Seto W, Abdolell M, et al. Twelve-hour versus 24-hour creatinine clearance in critically ill pediatric patients. Pediatr Res. 2005;58: 83–88.
7. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtratrion rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130:461–470.
8. Levey AS, Greene T, Kusek JW, et al. A simplified equation to predict glomerular filtration rate from serum creatinine [Abstract]. J Am Soc Nephrol. 2000;11: A0828.
9. Jelliffe R. Estimation of creatinine clearance in patients with unstable renal function, without a urine specimen. Am J Nephrol. 2002;22:320–324.

Gary Horowitz, MD
Department of Pathology
Beth Israel Deaconess Medical Center
Boston

Vice Chair, CAP
Chemistry Resource Committee