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Plasma oxalate levels in primary hyperoxaluria type I show significant intra-individual variation and do not correlate with kidney function

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Abstract

Background

Primary hyperoxalurias are rare diseases with endogenous overproduction of oxalate, thus leading to hyperoxaluria, hyperoxalemia, urolithiasis, and/or nephrocalcinosis and eventually early kidney failure. Plasma oxalate (POx) is an important diagnostic parameter in clinical studies on primary hyperoxaluria (PH). This is especially the case in kidney failure, where urinary parameters are no longer suitable. We aimed to evaluate whether POx would be an adequate endpoint for clinical studies in PH patients with stable kidney function. In addition, the correlation of POx to serum creatinine (SCr) and calculated glomerular filtration rate (eGFR) was examined.

Methods

We retrospectively analyzed follow-up of individual POx values over time, as well as POx correlation to SCr, eGFR, and vitamin B6 (VB6), a common therapeutic in PH1. Results from 187 blood samples taken between 2009 and 2017, during routine laboratory evaluations from 41 patients with PH1 who had neither undergone dialysis nor transplantation, were evaluated.

Results

Negligibly low correlation coefficients (CCs) between POx vs. SCr (CC = -0.0950), POx vs. eGFR (CC = −0.1237), and POx vs. VB6 (CC = 0.1879) were found, with the exception of CKD stage 3a patients, who showed a positive correlation (CC of − 0.7329, POx vs eGFR). The intra-individual analysis of POx over time showed a high fluctuation of POx values.

Conclusion

We conclude that POx has a limited validity as a primary endpoint for clinical studies in PH1 patients with stable kidney function. In addition, it does not correlate to SCr and eGFR in this group of patients.

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Authors and Affiliations

  1. Division of Pediatric Nephrology, Department of Pediatrics, University Children’s Hospital Bonn, Bonn, Germany

    Philip Hillebrand & Bernd Hoppe

  2. German Hyperoxaluria Center, Im Mühlenbach 2b, 53127, Bonn, Germany

    Bernd Hoppe

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  1. Philip Hillebrand
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Correspondence to Bernd Hoppe.

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Conflict of interest

BH now also is an employee of Dicerna Pharmaceuticals, Cambridge, USA. PH declares that there is no conflict of interest.

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This retrospective study was performed in accordance with the ethical standards of the ethical committees in Cologne (06-231) and Bonn (113/14), and the 1964 Helsinki Declaration and its later amendments.

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Informed consent was obtained from all individual participants included in this study.

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Hillebrand, P., Hoppe, B. Plasma oxalate levels in primary hyperoxaluria type I show significant intra-individual variation and do not correlate with kidney function. Pediatr Nephrol 35, 1227–1233 (2020). https://doi.org/10.1007/s00467-020-04531-5

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  • DOI: https://doi.org/10.1007/s00467-020-04531-5

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