The influence of ketoacids on plasma creatinine assays in diabetic ketoacidosis


F.A.W. Kemperman, Academic Medical Centre, University of Amsterdam, Department of Nephrology, F4–215, PO Box 22700, 1100 DE Amsterdam, The Netherlands (fax: + 31 20 6914904; e-mail:


Abstract. Kemperman FAW, Weber JA, Gorgels J, van Zanten AP, Krediet RT, Arisz L (University of Amsterdam and Slotervaart Hospital, Amsterdam, The Netherlands). The influence of ketoacids on plasma creatinine assays in diabetic ketoacidosis. J Intern Med 2000; 248: 513–519.

Objective. Analysis of the interference of ketoacids on various routine plasma creatinine assays during a clinical episode of diabetic ketoacidosis (DKA).

Design. Observational study. Blood samples were drawn before, during and after standard in-hospital treatment. Plasma creatinine was measured with two dissimilar enzymatic assays (creatininase PAP + and creatinine iminohydrolase Serapak), a kinetic alkaline picrate method (Jaffé) and a high-performance liquid chromatography (HPLC) procedure. Acetoacetate and β-hydroxybutyrate were analysed by enzymatic methods.

Setting. Department of Medicine, University Hospital.

Subjects. Nine patients who experienced 10 episodes of DKA.

Main outcome measures. Agreement of the routine plasma creatinine assays with HPLC and analysis of possible interferents.

Results. At presentation, the Jaffé assay gave falsely high values of plasma creatinine (median 99 µmol L–1), in contrast to the PAP+ (median 60.5 µmol L–1) and HPLC assays (median 67.5 µmol L–1). This positive error decreased during treatment. This was due to a decrease in acetoacetate, as the positive error by the Jaffé method correlated with the acetoacetate concentration (r = 0.79, P < 0.0001). In the multiple regression analysis, β-hydroxybutyrate caused no additional interference by the Jaffé assay, confirmed by in vitro experiments. Analysis of agreement showed that the difference between PAP+ and HPLC creatinine was – 4.6 ± 3.0 µmol L–1 (mean ± SD), and 2.0 ± 5.3 µmol L–1 between Serapak and HPLC. This was statistically significant, but clinically negligible.

Conclusion. Acetoacetate caused severe interference of the alkaline picrate (Jaffé) assay, which might influence therapeutic decisions at the start of diabetic ketoacidosis. Enzymatic assays lack this interference.