General Clinical Chemistry
Reference Intervals for Serum Creatinine Concentrations: Assessment of Available Data for Global Application
Ferruccio Ceriotti,1* James C. Boyd,2 Gerhard Klein,3 Joseph Henny,4 Josep Queralto,5 Veli Kairisto,6 and ´ Mauro Panteghini,7 on behalf of the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL)BACKGROUND: Reference intervals for serum creatinine remain relevant despite the current emphasis on the use of the estimated glomerular filtration rate for assessing renal function. Many studies on creatinine reference values have been published in the last 20 years. Using criteria derived from published IFCC documents, we sought to identify universally applicable reference intervals for creatininevia a systematic review of the literature. METHODS:
Studies were selected for inclusion in the systematic review only if the following criteria were met: (a) reference individuals were selected using an “a priori” selection scheme, (b) preanalytical conditions were adequately described; (c) traceability of the produced results to the isotope dilution–mass spectrometry (IDMS) reference methodwas demonstrated experimentally, and (d) the collected data received adequate statistical treatment. Of 37 reports dealing specifically with serum creatinine reference values, only 1 report with pediatric data and 5 reports with adult data met these criteria. The primary reason for exclusion of most papers was an inadequate demonstration of measurement traceability. Based on the data of the selectedstudies, we have collated recommended reference intervals for white adults and children.
CONCLUSION: Laboratories using methods producing traceable results to IDMS can apply the selected reference intervals for serum creatinine in evaluating white individuals.
© 2008 American Association for Clinical Chemistry
The usefulness of plasma or serum creatinine measurements for theidentification of renal insufficiency is
hampered by its covariation with sex, age, race, diet, and muscle mass of each individual in whom it is being measured (1, 2 ). Moreover, the analytical quality of the test is often suboptimal due to the nonspecificity of the Jaffe method used in most routine laboratories (3 ). The recent campaign of the National Kidney Disease Education Program,initiated in 2000 by the US National Institutes of Health (4 ), has led to increased focus on the measurement of creatinine in serum (5 ). Concurrently, there has been an international effort to improve creatinine standardization by assuring traceability to the reference system (6 ). These efforts highlighted limitations of commercially available methods for creatinine measurement as well as thedifferences in results among methods resulting from a lack of assay standardization and the nonspecificity of the alkaline picrate method used in the majority of clinical laboratories (3, 7, 8 ). A further difficulty associated with these efforts is the need for development of scientifically sound reference intervals for creatinine assays once they have been aligned with high-order reference standards. Infact, the Modification of Diet in Renal Disease (MDRD) formula is validated only for adults ( 18 years) and those with renal disease (9 ), and thus there is still the need for reference intervals. The variation of creatinine concentration with age and sex makes the task of defining scientifically sound reference intervals very demanding. To determine whether data obtained using standardizedassays already exist in the peer-reviewed literature, which could thus be endorsed for global application, the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) undertook a systematic review of the literature. The presence of clear demonstration of the traceability of the results to higher-order reference methods (10, 11 ) or reference materials was the main criterion that guided our...