NACB - Scientific Shorts
NACB - Scientific Shorts (formerly NACB Blog)
By James H. Nichols, PhD, DABCC, FACB
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The need for rapid estimates of renal function is leading to greater demand for point-of-care creatinine testing in a variety of patient settings including Radiology, to determine patient ability to clear contrast dyes, and Hematology/Oncology, for dosing chemotherapeutic agents.  This demand has led to the development of a number of POCT devices, and creatinine sensors have even been added by manufacturers to existing blood gas instrumentation to allow for expansion of testing on current analyzers into new settings.  With such demand for faster test results, the question arises whether the technical performance (accuracy/precision) of the POCT creatinine methods is keeping pace with the central laboratory tests.

 

A number of studies have examined the performance of POCT creatinine methods (1-3).  These studies have shown positive and negative biases compared to laboratory methods, some significant in the 1.5 – 3 mg/dL, clinically important range(1) with variable imprecision.  In general, the studies conclude that POCT methods have adequate performance to meet the clinical needs of the specified settings provided that physicians keep the differences between POCT and laboratory creatinine methods in mind when interpreting the results.  However, the National Kidney Disease Education Program (NKDEP) has recently recommended that manufacturers work to ensure that creatinine methods be traceable to isotope dilution mass spectrometry (IDMS) and achieve total error goals of analytical imprecision (including interlaboratory calibration variability) SD <0.08 mg/dL (7.1 µmol/L) and analytical bias (compared to an IDMS reference measurement procedure) <0.05 mg/dL (4.4 µmol/L) at a serum creatinine concentration of 1.00 mg/dL (88.4 µmol/L).(4)  The NKDEP also recommends manufacturers design instruments that report serum creatinine values as mg/dL to two decimal places, or as µmol/L to the nearest whole number. This will reduce the contribution of a rounding error when using the MDRD Study equation.(4)

 

Clearly current POCT devices do not report creatinine to 2 decimal places, and whether all POCT devices can achieve the NKDEP total error goals is questionable.  Do all POCT devices have IDMS treaceable calibrations?  What about drug and other patient interferences with the POCT methods, as the NKDEP recommendations for total error are expected despite the potential for method interference? These issues remind me of the current debate over the technical performance of POCT HgbA1c tests after the ADA recommended that HgbA1c could be used for diagnosis of diabetes.  Similar debate is also surrounding POCT glucose testing and intensive insulin management, particularly with regard to technical performance criteria and which methods, blood gas sensors or glucose meter, are better suited for intensive insulin protocols.  

 

So, what is the optimal performance for POCT creatinine and who should make that determination, the clinician using the method, a consensus panel of clinicians with disease focus, laboratory specialists, or someone else?  I would ultimately argue that it should be the physician who is legally responsible for the care of the patient, but that is contingent on the physician being educated on the limitations of the test result they are receiving.  Many clinicians that I speak with on a day-to-day basis do not understand the differences between POCT and laboratory results.  In addition, different clinicians utilize results in different ways, some for screening organ function while others are looking to progression of disease, prognosis, or even pharmacist dosing medications. Each of these clinical applications may have different performance goals required of the testing methodology, and one standard may not fit all clinical scenarios.  If we are guided by consensus guidelines, then what if the performance of POCT creatinine devices doesn’t meet those guidelines?  Should such methods even be utilized to estimate renal function?  Or, should the devices only be utilized in selective populations, like Radiology or Hematology/Oncology where the performance may be adequate for the clinical application?  Or, can the device be used more widely to estimate renal function in the general patient population?  If POCT devices have greater imprecision and biases compared to IDMS traceable laboratory methods, should GFR be estimated from these methods at all, or should the physicians rely on the creatinine result alone to guide management?  Should we have a separate eGFR equation that considers the variability of current POCT methods, separate from the MDRD equation, possibly for specific clinical applications? Given the differences that are possible between POCT and laboratory methods, there will be a further need to ensure separation of test results in a clear manner in the medical records, so clinicians understand the source of the test result with its inherent biases and interferences when interpreting results.  There are obviously a number of unanswered questions that need exploring in future POCT creatinine research.

 

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Posted by
On 3/27/2011

Excellent and helpful blog. Thank you. Jocelyn

Posted by
On 3/25/2011

The total error goal of <0.08 mg/dL will be difficult but is necessary to realize the full clinical benefit of creatinine measurements, especially for serial monitoring on a patient. One of the great (and often unappreciated) benefits of creatinine is its remarkably low variation, even over several months, in persons with normal renal function, which contrasts markedly with the much greater variation of actual GFR measurements by clearance (Clin Chim Acta 2008; 395: 115). While most creatinine methods on large analyzers are acceptably precise (especially that on a popular dry-slide enzymatic method), I have a sense that many of the whole-blood POC and blood gas analyzer methods (with one exception) have significantly higher imprecision. As Jim Nichols stated, this could limit their clinical value to detecting only gross changes in renal function. John Toffaletti Duke Univ Medical Center

Posted by
On 3/24/2011

Very nice summary of a difficult issue. I find that most radiologists do not appreciate the difficulty in getting a POCT method to be concordant with the lab method around an eGFR cut-offf of 60. My colleague in radiology has presented data on limitations of POCT eGFR screening and reports that his colleagues do not get it, responding simply "We do a fingerstick and get a number, what's the big deal". To answer your question the decision should be a collaboration between lab and/or POCT program and the clinical group requesting the service. That's what we have done here, and made the decision not to report the POCT eGFR/creatinine in the lab section of the medical record at all, because of the high number of discordant results with lab. We also developed protocols for confirmation of POCT eGFR between 45-60 and below 45. Working together we were able to come up with a protocol that makes sense, based on the observed concordance and correlation of POCT with an IDMS lab method.

Posted by
On 3/23/2011

Really nice blog post, Jim. I will say that I get a LOT of push-back from physicians when I suggest separate lines in the medical record for POC results vs main lab results. They claim they cannot track their patients if these values are separated, no matter how often I try to explain that they should be tracking with either the lab values OR the POC values. In the real world, it's sometimes difficult to educate the physicians enough. Or they may know the difference but still want all their values where they can track them. I find they often use tests the way they want to use them, not the way they were intended to be used. I'm open to suggestions. Patti Jones CMC Dallas

About the Author
James H. Nichols, PhD, DABCC, FACB
James H. Nichols, PhD, DABCC, FACB 
 

References

 

1. Nichols JH, Bartholomew C, Bonzagi A, GarbJL, Jin L. Evaluation of the IRMA TRUpoint and i-STAT creatinine assays. Clin Chim Acta 2007;377(1-2):201-5.

 

2. Aumatell A, Sharpe D, Reed W. Validation of the StatSensor meter for testing blood before contrast computed tomography studies.  Point of Care 2010;9(1):25-31.

 

3. Skurup A, Kristensen T, Wennecke F. New creatinine sensor for point-of-care testing of creatinine meets the National Kidney Disease Education Program Guidelines. Clin Chem Lab Med 2008;46(1):3-8.

 

4. National Kidney Disease Education Program (NKDEP). Creatinine Standardization Recommendations.