Systematic assessment of urinary hydroxy-oxo-glutarate for diagnosis and follow-up of primary hyperoxaluria type III
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There are currently three distinct autosomal recessive inherited types of primary hyperoxaluria (PH: PHI, PHII, and PHIII), all characterized by the endogenous overproduction of oxalate. The PH type is difficult to differentiate by clinical features alone. In addition to universal general characteristics to all hyperoxaluria subtypes, specific urinary metabolites can be detected: glycolate in PHI, L-glyceric acid in PHII, and hydroxy-oxo-glutarate (HOG) in PHIII. PHIII is considered to be the most benign form and is characterized by severe recurrent urolithiasis in early life, followed by clinical remission in many, but not all patients. We examined urinary HOG (UHOG) excretion as a diagnostic marker and its correlation to progression of the clinical course of PHIII.
UHOG was analyzed by combined ion chromatography/mass spectrometry (IC/MS) in urine samples from 30 PHIII and 68 PHI/II patients and 79 non-PH hyperoxaluria patients.
Mean UHOG excretion was significantly higher in patients with PHIII than in those with PHI/II and in non-PH patients(51.6 vs. 6.61 vs. 8.36 μmol/1.73 m2/24 h, respectively; p<0.01).
Significantly elevated UHOG excretion was exclusively seen in PHIII patients and showed a 100 % consensus with the results of hydroxy-oxo-glutarate aldolase (HOGA1) mutational analysis in newly diagnosed patients. However, UHOG excretion did not correlate with clinical course on follow-up and could not be used to discriminate between active stone formers and patients with a clinically uneventful follow-up.
KeywordsPrimary hyperoxaluria Primary hyperoxaluria type III Diagnosis Follow-up Hydroxy-oxo-glutarate
We thank Przemyslaw Sikora (Lublin, Poland), Katarzyna Jobs (Warzaw, Poland), Marcin Zaniew, Lars Pape (Hannover, Germany), Burkhard Tönshoff (Heidelberg, Germany), Martin Bald (Stuttgart, Germany), Martin Pohl (Freiburg, Germany), Bärbel Lange-Sperandio (Munich, Germany), and Markus J. Kemper (Hamburg, Germany) for providing us with patient information and urine samples. We also thank B. Bär and D. Armborst (Germany) and F. Blanco (Spain) for extensive laboratory support. The work was partially supported by a grant from the German-Israeli Foundation (GIF) to (Bodo B. Beck & Bernd Hoppe)
Compliance with ethical standards
This study was approved by the local ethics committee and all material was obtained after written informed consent.
Conflict of interest
The authors declare no conflict of interest.
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