Rapid liquid chromatography tandem mass-spectrometry screening method for urinary metabolites of primary hyperoxaluria

Woodward, Gary; Pryke, Robin; Höppe, Bernd; Rumsby, Gill

doi:10.1177/0004563218811365

Cited by 6 publications

(4 citation statements)

References 15 publications

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“…Unfortunately, the methodology used to ascertain this result was not recorded, but it has been shown by distribution of external quality assurance material that methods for urine organic acids may give false-negative results for glycerate as a consequence of the poor extraction of this analyte. The development of more specific methodologies 25,32 should make this less likely to occur but is currently affected by the lack of certified reference materials and internal standards. Demonstration of glyceric aciduria will allow focusing of genetic testing; however, the combination of CKD5 and elevated urine oxalate excretion should not exclude consideration of PH2.…”

Section: Discussionmentioning

confidence: 99%

Patients with primary hyperoxaluria type 2 have significant morbidity and require careful follow-up

Garrelfs

Rumsby

Peters‐Sengers

et al. 2019

Kidney International

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Primary hyperoxaluria type 2 is a rare inherited disorder of glyoxylate metabolism causing nephrocalcinosis, renal stone formation and ultimately kidney failure. Previously, primary hyperoxaluria type 2 was considered to have a more favorable prognosis than primary hyperoxaluria type 1, but earlier reports are limited by low patient numbers and short follow up periods. Here we report on the clinical, genetic, and biochemical findings from the largest cohort of patients with primary hyperoxaluria type 2, obtained by a retrospective record review of genetically confirmed cases in the OxalEurope registry, a dataset containing 101 patients from eleven countries. Median follow up was 12.4 years. Median ages at first symptom and diagnosis for index cases were 3.2 years and 8.0 years, respectively. Urolithiasis was the most common presenting feature (82.8% of patients). Genetic analysis revealed 18 novel mutations in the GRHPR gene. Of 238 spot-urine analyses, 23 (9.7%) were within the normal range for oxalate as compared to less than 4% of 24-hour urine collections. Median intra-individual variation of 24-hour oxalate excretion was substantial (34.1%). At time of review, 12 patients were lost to follow-up; 45 of the remaining 89 patients experienced chronic kidney disease stage 2 or greater and 22 patients had reached stage 5. Median renal survival was 43.3 years, including 15 kidney transplantations in 11 patients (1 combined with liver transplantation). Renal outcome did not correlate with genotype, biochemical parameters or initially present nephrocalcinosis. Thus, primary hyperoxaluria type 2 is a disease with significant morbidity. Accurate diagnosis by 24-hour urine analysis and genetic testing are required with careful follow-up.

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Section: Discussionmentioning

confidence: 99%

Patients with primary hyperoxaluria type 2 have significant morbidity and require careful follow-up

Garrelfs

Rumsby

Peters‐Sengers

et al. 2019

Kidney International

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“…Concentrations of plasma oxalate in PH patients can overlap with those of patients seen in renal failure from any cause [3,4] and therefore are not always diagnostic for PH. However, in CKD stage 4 or greater, values > 50 µmol/L are often observed in PH and is thus highly suggestive of the diagnosis and warrants further diagnostic testing: urinary PH metabolites (glycolate, glycerate and dihydroxyglutarate [5]) and genetic testing for the 3 known causative genes (AGXT, GRHPR, HOGA1) [6].…”

Section: Introductionmentioning

confidence: 99%

Plasma oxalate: comparison of methodologies

Stokes¹,

Acquaviva‐Bourdain

Höppe

et al. 2020

Urolithiasis

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Measurement of oxalate in the blood is essential for monitoring primary hyperoxaluria patients with progressive renal impairment and on dialysis prior to transplantation. As no external quality assurance scheme is available for this analyte, we conducted a sample exchange scheme between six laboratories specifically involved with the investigation of primary hyperoxaluria to compare results. The methodologies compared were gas chromatography/mass spectrometry (GCMS), ion chromatography with mass spectrometry (ICMS), and enzymatic methods using oxalate oxidase and spectrophotometry. Although individual laboratories performed well in terms of reproducibility and linearity, there was poor agreement (absolute values) between centres as illustrated by a longer-term comparison of patient results from two of the participating laboratories. This situation was only partly related to differences in calibration and mainly reflected the lower recoveries seen with the ultrafiltration of samples. These findings lead us to conclude that longitudinal monitoring of primary hyperoxaluria patients with deteriorating kidney function should be performed by a single consistent laboratory and the methodology used should always be defined. In addition, plasma oxalate concentrations reported in registry studies and those associated with the risk of systemic oxalosis in published studies need to be interpreted in light of the methodology used. A reference method and external quality assurance scheme for plasma oxalate analysis would be beneficial.

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“…• Check thyroid stimulating hormone and thyroxine levels at least yearly; more frequently if after treatment • Check 25-hydroxy vitamin D levels at least yearly • In teenagers and adults, be aware of the risk of hypogonadism markers of PH3; however, HOG is unstable 34 and can lead to false negative results 35 whereas DHG has 100% sensitivity 36 . Comparison of results between laboratories is currently impossible for these analytes as no international calibrators exist and one must therefore rely on local reference ranges.…”

Section: Endocrine Functionsmentioning

confidence: 99%

“…Data on the impact of liver transplantation among patients with PH2 are scarce owing to the rarity of the disease and the assumed better outcome of these patients compared with patients with PH1. However, a 2019 study of 101 patients with PH2 found that 22 patients reached stage 5 CKD at a median age of 40 (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48) years of age. Ten of these 22 patients underwent isolated kidney transplantation, for which 1-year and 5-year cumulative kidney allograft survival (censored for death) were only 43% and 29%, respectively 2 .…”

Section: Rationale For Transplantationmentioning

confidence: 99%

Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope

et al. 2023

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Primary hyperoxaluria (PH) is an inherited disorder that results from the overproduction of endogenous oxalate, leading to recurrent kidney stones, nephrocalcinosis and eventually kidney failure; the subsequent storage of oxalate can cause life-threatening systemic disease. Diagnosis of PH is often delayed or missed owing to its rarity, variable clinical expression and other diagnostic challenges. Management of patients with PH and kidney failure is also extremely challenging. However, in the past few years, several new developments, including new outcome data from patients with infantile oxalosis, from transplanted patients with type 1 PH (PH1) and from patients with the rarer PH types 2 and 3, have emerged. In addition, two promising therapies based on RNA interference have been introduced. These developments warrant an update of existing guidelines on PH, based on new evidence and on a broad consensus. In response to this need, a consensus development core group, comprising (paediatric) nephrologists, (paediatric) urologists, biochemists and geneticists from OxalEurope and the European Rare Kidney Disease Reference Network (ERKNet), formulated and graded statements relating to the management of PH on the basis of existing evidence. Consensus was reached following review of the recommendations by representatives of OxalEurope, ESPN, ERKNet and ERA, resulting in 48 practical statements relating to the diagnosis and management of PH, including consideration of conventional therapy (conservative therapy, dialysis and transplantation), new therapies and recommendations for patient follow-up. SectionsUnanswered questions and research agenda Conclusions

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Rapid liquid chromatography tandem mass-spectrometry screening method for urinary metabolites of primary hyperoxaluria

Cited by 6 publications

References 15 publications

Patients with primary hyperoxaluria type 2 have significant morbidity and require careful follow-up

Patients with primary hyperoxaluria type 2 have significant morbidity and require careful follow-up

Plasma oxalate: comparison of methodologies

Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope

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