Comparison of the MesoScale Discovery and Luminex multiplex platforms for measurement of urinary biomarkers in a cisplatin rat kidney injury model.

INTRODUCTION

In the past years several new urinary nephrotoxicity biomarkers have been qualified for use in preclinical studies by the FDA and EMA. Subsequently, kits have been developed to measure these urinary biomarkers on multiplex platforms such as the electro-chemiluminescent based immunoassay from MesoScale Discovery (MSD) and the bead-based immunoassay using Luminex xMAP technology (LMX). The aim of the present study was to compare the two multiplex platforms with respect to the capability of their qualified urinary biomarker panels to measure an increase of these biomarkers relative to histopathological changes in an animal model of nephrotoxicity.

METHODS

For comparison of the two platforms we used urine samples from a study with the well-characterized nephrotoxin cisplatin (Cp) in male Wistar rats. The following five biomarkers were measured on both platforms: glutathione S-transferase α (αGST), clusterin (CLU), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL, a.k.a. lipocalin-2) and osteopontin (OPN). The measurements were compared with respect to both the fold increase observed for each biomarker and the absolute concentrations measured in relation to traditional endpoints for nephrotoxicity in clinical pathology and histopathology.

RESULTS

The platform comparison revealed the expected increases of urinary biomarkers after Cp treatment with similar results at the fold change level enabling consistent detection of kidney injury. The comparison of the absolute concentrations of biomarkers measured in the two platforms showed differences, the extent of which was analyte-dependent.

DISCUSSION

By comparison of two widely used multiplex platforms, MSD and LMX, for the detection of renal toxicity biomarkers in urine, we observed the expected increases of these biomarkers in response to Cp administration. Depending on the marker, significant differences could be found when comparing the absolute concentrations thus suggesting that baseline levels for each platform will have to be set separately.