Abstract
Hyperoxaluria is a well-recognised risk factor for urolithiasis and patients with primary hyperoxaluria (PH) gradually build up calcium oxalate deposits leading to chronic kidney disease. Efforts to improve treatment for PH have focused on reducing urine oxalate excretion and thus decreasing lithogenesis. To determine the efficacy of treatments designed to alter a biochemical parameter it is necessary to know the biological and analytical variation of that parameter. In this study, we estimated the intra-individual biological variation of urine oxalate excretion in patients with PH, and from this determined what would constitute a significant change in the form of a reference change value (RCV). Each patient collected four 24-h urines on consecutive weeks. The intra-individual biological variation of oxalate excretion calculated from these samples ranged from 0 to 36 % with a mean of 14 %. The corresponding RCVs were 4–84 % with a mean of 32 %. This result implies that, on average, a reduction of almost one-third in urine oxalate excretion is required to prove an effect from treatment. The wide range of biological variation between individuals may reflect other, as yet unknown, determinants of oxaluria in PH, as well as inaccuracies in urine collection. The data suggest that it is more appropriate to use individual RCVs established prior to treatment to determine its efficacy: a relatively small fall in urine oxalate excretion may be outside the biological variation of some patients but not of others.
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Acknowledgments
The authors would like to acknowledge the investigating doctors who made the study possible: Bernd Hoppe, UKB Bonn; Pierre Cochat, CHU de Lyon; Rémi Salomon, Hopital Necker, Paris; Jérome Harambat, CHU, Bordeaux; Sally Hulton, Birmingham Children’s Hospital; William Van’t Hoff, Great Ormond Street Hospital, London; Shabbir Moochhala, Royal Free Hospital, London.
Funding
OxThera AB: This research has received funding from the European Union’s Seventh Framework Programme managed by REA-Research Executive Agency http://ec.europa.eu/research/rea (FP7/2007–2013) under Grant Agreement No. FP7-SME-2013.
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OxThera AB is a biopharmaceutical company with products in development for treating hyperoxaluria with bacteria and enzymes.
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Clifford-Mobley, O., Sjögren, A., Lindner, E. et al. Urine oxalate biological variation in patients with primary hyperoxaluria. Urolithiasis 44, 333–337 (2016). https://doi.org/10.1007/s00240-016-0860-2
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DOI: https://doi.org/10.1007/s00240-016-0860-2