ArticleBiochimica et biophysica acta. Molecular basis of disease2020
The effects of the inactivation of Hydroxyproline dehydrogenase on urinary oxalate and glycolate excretion in mouse models of primary hyperoxaluria.
Article in Biochimica et biophysica acta. Molecular basis of disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Animal Models of Hyperoxaluria and Their Relevance for Fundamental Research and Clinical Practice.International journal of molecular sciences · 2026Review
- Animal models for calcium oxalate kidney stone research.Zoological research · 2026Review
- Structural Principles of Covalent Flavin Modification in Oxidoreductases.Biochemistry · 2026Review
- Host immunosenescence compromisesAging · 2026Article
- PRODH2-Mediated Metabolism in the Bone Microenvironment Promotes Breast Cancer Metastasis.Cancer research · 2025Article
- Biochemical, structural, and cellular characterization of S-but-3-yn-2-ylglycine as a mechanism-based covalent inactivator of the flavoenzyme proline dehydrogenase.Archives of biochemistry and biophysics · 2025Article
- Human glyoxylate metabolism revisited: New insights pointing to multi-organ involvement with implications for siRNA-based therapies in primary hyperoxaluria.Journal of inherited metabolic disease · 2025Review
- Metabolic reprogramming in bone metastasis of human cancers.Frontiers in cell and developmental biology · 2025Review
- Noncovalent Inhibition and Covalent Inactivation of Proline Dehydrogenase by Analogs ofBiochemistry · 2024Article
- Opportunities in Primary and Enteric Hyperoxaluria at the Cross-Roads Between the Clinic and Laboratory.Kidney international reports · 2024Article
- Therapeutic targeting of HYPDH/PRODH2 with N-propargylglycine offers a Hyperoxaluria treatment opportunity.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Application of metabolomics in urolithiasis: the discovery and usage of succinate.Signal transduction and targeted therapy · 2023Article
- Review
- Catabolism of Hydroxyproline in Vertebrates: Physiology, Evolution, Genetic Diseases and New siRNA Approach for Treatment.International journal of molecular sciences · 2022Review
- Current research and future directions in non-malignant urologic research - proceedings of the annual CAIRIBU meeting.American journal of clinical and experimental urology · 2022Article
- Generation of a GLO-2 deficient mouse reveals its effects on liver carbonyl and glutathione levels.Biochemistry and biophysics reports · 2021Article
- Novel therapeutic approaches for the primary hyperoxalurias.Pediatric nephrology (Berlin, Germany) · 2021Review
- Structural basis for the stereospecific inhibition of the dual proline/hydroxyproline catabolic enzyme ALDH4A1 by trans-4-hydroxy-L-proline.Protein science : a publication of the Protein Society · 2021Article
- Small Molecule-Based Enzyme Inhibitors in the Treatment of Primary Hyperoxalurias.Journal of personalized medicine · 2021Review
Corrections and comments
- Commented on by
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The major clinical manifestation of the Primary Hyperoxalurias (PH) is increased production of oxalate, as a consequence of genetic mutations that lead to aberrant glyoxylate and hydroxyproline metabolism. Hyperoxaluria can lead to the formation of calcium-oxalate kidney stones, nephrocalcinosis and renal failure. Current therapeutic approaches rely on organ transplants and more recently modifying the pathway of oxalate synthesis using siRNA therapy. We have recently reported that the metabolism of trans-4-hydroxy-L-proline (Hyp), an amino acid derived predominantly from collagen metabolism, is a significant source of oxalate production in individuals with PH2 and PH3. Thus, the first enzyme in the Hyp degradation pathway, hydroxyproline dehydrogenase (HYPDH), represents a promising therapeutic target for reducing endogenous oxalate production in these individuals. This is supported by the observation that individuals with inherited mutations in HYPDH (PRODH2 gene) have no pathological consequences. The creation of mouse models that do not express HYPDH will facilitate research evaluating HYPDH as a target. We describe the phenotype of the Prodh2 knock out mouse model and show that the lack of HYPDH in PH mouse models results in lower levels of urinary oxalate excretion, consistent with our previous metabolic tracer and siRNA-based knockdown studies. The double knockout mouse, Grhpr KO (PH2 model) and Prodh2 KO, prevented calcium-oxalate crystal deposition in the kidney, when placed on a 1% Hyp diet. These observations support the use of the Grhpr KO mice to screen HYPDH inhibitors in vivo. Altogether these data support HYPDH as an attractive therapeutic target for PH2 and PH3 patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.