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Kidney Week

Abstract: TH-PO783

Differential Metabolomic Profile Within Primary Hyperoxaluria Patients

Session Information

  • Pediatric CKD
    November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology


  • Martin Higueras, Cristina, Institute of Experimental Immunology, Bonn, Germany
  • Salido, Eduardo C., Hospital Universitario Canarias, La Laguna, Tenerife, Spain
  • Hoppe, Bernd, University Hospital Bonn, Bonn, Germany
  • Kurts, Christian, Institute of Experimental Immunology, Bonn, Germany

The three types of primary hyperoxaluria (PH) are liver specific enzyme defects inducing endogenous oxalate overproduction, thus hyperoxaluria, urolithiasis and/or nephrocalcinosis, as well as intrarenal deposition of calcium oxalate crystals, leading to chronic kidney disease and renal failure (PH1&2). Severe infantile cases (PH1) directly present systemic crystal deposition (oxalosis), but otherwise the clinical progression of PH subtypes profoundly differs, for unknown reasons. PH patients bear pathogenic mutations in either AGXT (PH1), GRHPR (PH2) or HOGA1 (PH3) genes, causing a misbalanced hepatic glyoxylate metabolism that overproduces oxalate. Here, we aimed to unveil other misbalanced metabolites in PH1, PH2 and PH3 both in mouse models and patients to understand the heterogenous pathogenesis of PH, to reveal new biomarkers for differential diagnosis and to find modulators of their immune response.


All patients signed an informed consent. Serum from 19 PH1, 5 PH2, 7 PH3 and 9 control patients as well as plasma from 4 PH1, 4 PH3, 4 PH1/PH3 and 4 wildtype mice were obtained. Samples were analyzed by the global metabolomics technology of Metabolon®, and stool samples (18 PH1, 6 PH3 patients; 4 PH1 and 4 wt mice) by the Institute of Microecology (Germany). Data followed log transformation and Welch’s two-sample t-test for statistical analysis.


PH3 mice metabolome showed stronger differences to wt than PH1, mostly in aminoacid, carbohydrate and xenobiotic related metabolism. Both PH1 and PH3 mice shared a strong misbalanced lipid metabolism. Xenobiotic metabolism correlated with differential microbiota in PH1 compared to wt mice. Ongoing human metabolome and microbiota analysis is aimed at translating our findings into the human situation.


Our preliminary findings suggest: i) increased levels of diverse metabolites may reflect impaired kidney function accumulating these compounds in the blood; ii) general reduction on lipid levels may reflect a weakened oxidative metabolism for energy production and impaired intracellular cascades, some of them related to inflammatory signaling; iii) microbiota may influence PH pathogenesis. Further exploration of candidate metabolites in vitro and in vivo may help elucidating their role in mechanisms of disease and their use as biomarkers for diagnosis and treatment.


  • Government Support - Non-U.S.