Novel therapeutic approaches for the primary hyperoxalurias

Belostotsky, Ruth; Frishberg, Yaacov

doi:10.1007/s00467-020-04817-8

Cited by 18 publications

(30 citation statements)

References 104 publications

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“…The primary hyperoxalurias(PH) are autosomal recessive disorders that result in calciumoxalate-related kidney disease due to defects in the enzymes of glyoxylate metabolism (86)(87)(88). Excessive production of glyoxylate by the liver leads to increased oxalate synthesis, elevated plasma oxalate levels and hyperoxaluria.…”

Section: Crystalline Nephropathy From Primary Hyperoxaluriamentioning

confidence: 99%

“…While symptomatic nephrolithiasis is common, calcium-oxalate crystalline nephropathy occurs in up to 50% of patients. Primary hyperoxaluria-1 is most common and kidney involvement often leads to CKD and ESKD (86)(87)(88). Urine sediment examination may demonstrate monohydrated(Figure 4C) and/or dihydrated calcium-oxalate crystals that can be free and/or found within casts.…”

Section: Crystalline Nephropathy From Primary Hyperoxaluriamentioning

confidence: 99%

“…Standard management includes oral potassium citrate, volume repletion, and pyridoxine supplementation along with genetic counseling. When ESKD develops, dialysis and kidney alone or along with liver transplantation(primarily for PH-1) are also undertaken (86)(87)(88). New therapies for the primary hyperoxalurias have recently become available.…”

Section: Crystalline Nephropathy From Primary Hyperoxaluriamentioning

confidence: 99%

“…Subcutaneous lumasiran is a small interfering RNA medication that targets hydroxyacid oxidase-1 gene and silences mRNA encoding glycolate oxidase. Through this effect, lumasiran depletes glycolate oxidase and inhibits oxalate synthesis thereby significantly reducing hyperoxaluria (88,89). One dose of this drug reduced urinary oxalate concentration up to 50% in a PH-1 genetic mouse model, and up to 98% with multiple doses in a rat model of hyperoxaluria (88,90).…”

Section: Crystalline Nephropathy From Primary Hyperoxaluriamentioning

confidence: 99%

“…Through this effect, lumasiran depletes glycolate oxidase and inhibits oxalate synthesis thereby significantly reducing hyperoxaluria (88,89). One dose of this drug reduced urinary oxalate concentration up to 50% in a PH-1 genetic mouse model, and up to 98% with multiple doses in a rat model of hyperoxaluria (88,90). Illuminate-A, the phase 3 clinical trial in PH patients with age6 years of age and eGFR30ml/minute/1.73m 2 showed a 65% reduction in 24-hour urinary oxalate at 6 months with no adverse effects (91).…”

Section: Crystalline Nephropathy From Primary Hyperoxaluriamentioning

confidence: 99%

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The Crystalline Nephropathies

Perazella

Herlitz

2021

Kidney International Reports

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Section: Crystalline Nephropathy From Primary Hyperoxaluriamentioning

confidence: 99%

Section: Crystalline Nephropathy From Primary Hyperoxaluriamentioning

confidence: 99%

Section: Crystalline Nephropathy From Primary Hyperoxaluriamentioning

confidence: 99%

Section: Crystalline Nephropathy From Primary Hyperoxaluriamentioning

confidence: 99%

Section: Crystalline Nephropathy From Primary Hyperoxaluriamentioning

confidence: 99%

See 3 more Smart Citations

The Crystalline Nephropathies

Perazella

Herlitz

2021

Kidney International Reports

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Clinical Approach to Inborn Errors of Metabolism in Paediatrics

Saudubray¹,

García‐Cazorla

2022

Inborn Metabolic Diseases

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Primary hyperoxaluria in Italy: the past 30 years and the near future of a (not so) rare disease

et al. 2022

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Background Primary hyperoxalurias (PHs) are rare autosomal recessive diseases of the glyoxylate metabolism; PH1 is caused by mutations in the AGXT gene, PH2 in GRHPR and PH3 in HOGA1. Methods Here we report the first large multi-center cohort of Italian PH patients collected over 30 years (1992–2020 median follow-up time 8.5 years). Complete genotype was available for 94/95 PH1 patients and for all PH2 (n = 3) and PH3 (n = 5) patients. Symptoms at onset were mainly nephrolithiasis (46.3%) and nephrocalcinosis (33.7%). Median age at onset of symptoms and diagnosis were 4.0 years and 9.9 years, respectively. Results Fifty-four patients (56.8%) were diagnosed after chronic kidney disease. Sixty-three patients (66.3%) developed end stage kidney disease (median age 14.0 years). Twenty-one patients had a kidney-only transplant and, among them, seven had a second kidney transplant combined with liver transplant. A combined kidney–liver transplant was carried out in 29 patients and a sequential kidney–liver transplant was performed in two. In five cases a preemptive liver transplant was performed. Those receiving a liver-only transplant tended to have lower kidney function at last follow-up. Conclusion Our study of PHs in Italy underlines a considerable diagnostic delay, which has only slightly decreased in recent years. Therefore, we suggest a more extensive use of both metabolic screening among patients with recurrent kidney stones and genotyping, including unambiguous assignment of minor/major allele status in order to promptly begin appropriate treatment. This will be fundamental in order to have access to the new therapies, which are mainly focused on substrate reduction for the oxalate-producing enzymes using RNA-interference. Graphical abstract

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Novel therapeutic approaches for the primary hyperoxalurias

Cited by 18 publications

References 104 publications

The Crystalline Nephropathies

The Crystalline Nephropathies

Clinical Approach to Inborn Errors of Metabolism in Paediatrics

Primary hyperoxaluria in Italy: the past 30 years and the near future of a (not so) rare disease

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