Plasma oxalate: comparison of methodologies

Abstract

Measurement of oxalate in the blood is essential for monitoring primary hyperoxaluria patients with progressive renal impairment and on dialysis prior to transplantation. As no external quality assurance scheme is available for this analyte, we conducted a sample exchange scheme between six laboratories specifically involved with the investigation of primary hyperoxaluria to compare results. The methodologies compared were gas chromatography/mass spectrometry (GCMS), ion chromatography with mass spectrometry (ICMS), and enzymatic methods using oxalate oxidase and spectrophotometry. Although individual laboratories performed well in terms of reproducibility and linearity, there was poor agreement (absolute values) between centres as illustrated by a longer-term comparison of patient results from two of the participating laboratories. This situation was only partly related to differences in calibration and mainly reflected the lower recoveries seen with the ultrafiltration of samples. These findings lead us to conclude that longitudinal monitoring of primary hyperoxaluria patients with deteriorating kidney function should be performed by a single consistent laboratory and the methodology used should always be defined. In addition, plasma oxalate concentrations reported in registry studies and those associated with the risk of systemic oxalosis in published studies need to be interpreted in light of the methodology used. A reference method and external quality assurance scheme for plasma oxalate analysis would be beneficial.

A report from the European Hyperoxaluria Consortium (OxalEurope) Registry on a large cohort of patients with primary hyperoxaluria type 3

“…Detailed analyses were performed in a subgroup of 49 patients, whose laboratory evaluations were all processed at the GHC in Cologne/Bonn (Germany), to avoid variability of results by different methods used in different laboratories. 16,17 For comparison of Uox between PH subtypes, we used all urine samples, excluding those collected for study purposes, analyzed in the GHC laboratory from all patients with PH1 and PH2 from 2012 to 2020 (B6-responsive PH1, n ¼ 200; B6-unresponsive PH1, n ¼ 51; and PH2, n ¼ 44), and all PH3 urine samples (n ¼ 270). Urines were collected either over a 24-hour period or as random-void urine samples (spot urines).…”

Long-Term Transplantation Outcomes in Patients With Primary Hyperoxaluria Type 1 Included in the European Hyperoxaluria Consortium (OxalEurope) Registry

“…In patients who do actually respond to B6 with decrease of endogenous oxalate production, a decrease in plasma oxalate may be hampered due to release of systemically stored oxalate. Besides, interpretation of plasma oxalate values is complicated by the lack of consensus on reference values both due to differences in laboratory techniques [37] and due to the paucity of data on plasma oxalate levels in non-PH patients with ESKD. Finally, plasma glycolate levels were rarely available in the registry since only three laboratories measure plasma glycolate.…”

Detection and localization of calcium oxalate in kidney using synchrotron deep ultraviolet fluorescence microscopy

“…It is also highly dependent on renal excretion (and therefore GFR) which likely explains why its interest as a prognosis marker is still under debate (Hillebrand & Hoppe, 2020;Shah et al, 2020). Oxalemia measurement can be challenging and is not well standardized (Stokes et al, 2020). We believe that UV measurement of oxalate impregnation of the kidney could be a powerful tool to assess this new treatment efficiency especially after kidney transplantation since these patients often benefit from a close longitudinal follow-up with serial kidney sampling.…”