Investigating the effect of icterus interference on a creatinine Roche enzymatic methodology

Abstract

Background

It is well established that high bilirubin concentrations can lead to erroneous creatinine results when measured by a Jaffe-based method. However, the effects of bilirubin on enzymatic methods appear less well-defined. The Roche Cobas 8000 enzymatic creatinine (CREP2) has an unconjugated bilirubin icterus limit of 20 mg/dL, equivalent to a bilirubin concentration of 342 µmol/L. Many hepatology patients have bilirubin levels much higher than this limit, and laboratories are unable to release creatinine results on these complex patients. This is particularly challenging for patient management, as creatinine is a key test and is a prerequisite for many procedures, imaging studies and treatments.

Methods

Two spiking studies were carried out, the first to define the interference effect of bilirubin on enzymatic creatinine measurement, and the second to see if this interference could be mitigated via dilution. Serum samples (n = 50) were spiked with a concentrated bilirubin solution. Indices, bilirubin and creatinine were measured using the Roche Cobas 8000 c702 automated analyser according to manufacturer instructions.

Results

The spiking study found a negative linear relationship and as bilirubin concentrations increased, the measured creatinine concentration decreased (R² = 0.7828, y = −0.0597x + 15.603). Samples with a bilirubin concentration over 246 µmol/L demonstrated an average 1.48% drop in creatinine concentration per 25 µmol/L increase in bilirubin.

Conclusions

A service improvement was applied where creatinine results can be released on samples with a bilirubin concentration up to 550 µmol/L, with an appropriate comment, upon request by the clinician.