Primary hyperoxaluria in infants: Medical, ethical, and economic issues

Cochat, Pierre; Nogueira, Paulo Roberto; Mahmoud, Mahtab; Jamieson, Neville V.; Scheinman, Jon I.; Rolland, Marie-Odile

doi:10.1016/s0022-3476(99)70095-8

Cited by 77 publications

(60 citation statements)

References 24 publications

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“…They are listed on Table 1. Some of them are rare, involved in type 1 hyperoxaluria (15,16). They are located on exons 1, 4, 7, and 10.…”

Section: Methodsmentioning

confidence: 99%

“…A deficiency in one of these two enzymes, AGT and GRHPR, known as genetic disease, can lead to an abnormal accumulation of oxalate called hyperoxaluria (16). AGXT gene variants are very rare, but besides the genetic disease, two variants are frequent, the wild-type known as a major allele and less frequent minor allele, found in 20% of Caucasian patients, a haplotype characterized by three mutations: two substitutions Pro11Leu and Ile1142Met and a duplication of 74 bp (17).…”

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confidence: 99%

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Predictive Factors of Oxaliplatin Neurotoxicity: The Involvement of the Oxalate Outcome Pathway

Gamelin¹,

Capitain

Morel³

et al. 2007

Clinical Cancer Research

111

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Purpose: Oxaliplatin displays a frequent dose-limiting neurotoxicity due to its interference with neuron voltage-gated sodium channels through one of its metabolites, oxalate, a calcium chelator. Different clinical approaches failed in neurotoxicity prevention, except calcium-magnesium infusions. We characterized oxalate outcome following oxaliplatin administration and its interference with cations and amino acids. We then looked for genetic predictive factors of oxaliplatininduced neurotoxicity.Experimental Design: We first tested patients for cations and oxalate levels and did amino acid chromatograms in urine following oxaliplatin infusion. In the second stage, before treatment with FOLFOX regimen, we prospectively looked for variants in genes coding for the enzymes involved (a) in the oxalate metabolism, especially glyoxylate aminotransferase (AGXT), and (b) in the detoxification glutathione cycle, glutathione S-transferase k, and for genes coding for membrane efflux proteins (ABCC2). Results: In the first 10 patients, urinary excretions of oxalate and cations increased significantly within hours following oxaliplatin infusion, accompanied by increased excretions of four amino acids (glycine, alanine, serine, and taurine) linked to oxalate metabolism. In a further 135 patients, a minor haplotype of AGXT was found significantly predictive of both acute and chronic neurotoxicity. Neither glutathione S-transferase k nor ABCC2 single nucleotide polymorphisms we looked for were linked to neurotoxicity. Conclusion: These data confirm the involvement of oxalate in oxaliplatin neurotoxicity and support the future use of AGXTgenotyping as a pretherapeutic screening test to predict individual susceptibility to neurotoxicity.Oxaliplatin, a platinum-based chemotherapeutic agent with a 1,2-diaminocyclohexane (DACH) carrier ligand, displays a characteristic pattern of neurotoxicity, which is the most frequent dose-limiting toxicity, with an acute onset of distal dysesthesia and/or paresthesia, induced or exacerbated by cold and prolonged muscular contraction after a voluntary contraction. Although these symptoms that occur during or short after infusion are transient and generally mild, when treatment is continued, a persistent sensory peripheral neuropathy can develop, eventually causing superficial and deep sensory loss, sensory ataxia, and functional impairment (1). The mechanism of chronic neurotoxicity evoked by some authors is close to that of cisplatin-being the progressive accumulation of a heavy metal, the DACH platin, in neurons and the implication of the detoxication system of glutathione (2).However, clinical neurophysiologic examinations and nerve biopsy studies have shown that patients displaying sensory symptoms have no signs or very mild signs of axonal degeneration (1). Oxaliplatin has a direct ''pharmacologic'' effect on the excitability of sensory neurons and muscle cells that has not previously been described with other platinum agents (3). Furthermore, the acute symptoms induced by oxaliplati...

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“…They are listed on Table 1. Some of them are rare, involved in type 1 hyperoxaluria (15,16). They are located on exons 1, 4, 7, and 10.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Predictive Factors of Oxaliplatin Neurotoxicity: The Involvement of the Oxalate Outcome Pathway

Gamelin¹,

Capitain

Morel³

et al. 2007

Clinical Cancer Research

111

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“…Children who are symptomatic during infancy have a more severe course and most of them reach ESRD before the age of 3 years (9).…”

Section: Introductionmentioning

confidence: 99%

Characteristics and Outcomes of Children with Primary Oxalosis Requiring Renal Replacement Therapy

Harambat

Stralen

Espinosa

et al. 2012

Clinical Journal of the American Society of Nephrology

Self Cite

129

105

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SummaryBackground and objectives Primary hyperoxaluria (PH) as a cause of ESRD in children is believed to have poor outcomes. Data on management and outcomes of these children remain scarce.Design, setting, participants, & measurements This study included patients aged ,19 years who started renal replacement therapy (RRT) between 1979 and 2009 from 31 countries providing data to a large European registry.Results Of 9247 incident patients receiving RRT, 100 patients had PH. PH children were significantly younger than non-PH children at the start of RRT. The median age at RRT of PH children decreased from 9.8 years in 1979-1989 to 1.5 years in 2000-2009. Survival was 86%, 79%, and 76% among PH patients at 1, 3, and 5 years after the start of RRT, compared with 97%, 94%, and 92% in non-PH patients, resulting in a three-fold increased risk of death over non-PH patients. PH and non-PH patient survival improved over time. Sixty-eight PH children received a first kidney (n=13) or liver-kidney transplantation (n=55). Although the comparison was hampered by the lower number of kidney transplantations primarily derived from the earlier era of RRT, kidney graft survival in PH patients was 82%, 79%, and 76% at 1, 3, and 5 years for liver-kidney transplantation and 46%, 28%, and 14% at 1, 3, and 5 years for kidney transplantation alone, compared with 95%, 90%, and 85% in non-PH patients. ConclusionsThe outcomes of PH children with ESRD are still poorer than in non-PH children but have substantially improved over time.

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“…The elevated urinary oxalate concentration results in formation of calcium-oxalate crystals and subsequently renal stones, nephrocalcinosis, and in severe cases end-stage renal disease (ESRD) and systemic oxalosis. The clinical manifestations of PH1 are heterogeneous with respect to the timing and rate of progression: the disease may present as ESRD in infancy or remain asymptomatic throughout life [2]. The incidence varies in different geographical regions with increased frequency in highly consanguineous communities [3].…”

Section: Introductionmentioning

confidence: 99%

Intra-Familial Clinical Heterogeneity: Absence of Genotype-Phenotype Correlation in Primary Hyperoxaluria Type 1 in Israel

et al. 2005

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Background/Aims: Primary hyperoxaluria type 1 (PH1) is caused by the deficiency of the liver enzyme alanine:glyoxylate aminotransferase which results in increased synthesis and excretion of oxalate. The clinical manifestations of PH1 are heterogeneous with respect to the age of onset and rate of progression. The aim of this study was to investigate possible relationships between a given genotype, the biochemical profile and the clinical phenotype. Methods: We conducted a study of 56 patients from 22 families with PH1 from Israel. The clinical and biochemical data were compiled and the genotype was determined for each family. Results: The prevalent phenotype was of early onset with progression to end-stage renal disease during the first decade of life. Fifteen PH1-causing mutations were detected in 21 families: 10 were first described in this patient population. Marked intra-familial clinical heterogeneity was noted, meaning that there was no correlation between a given genotype and the phenotype. Conclusions: The clinical course of patients with PH1 is not dictated primarily by its genotype. Other genetic and/or environmental factors play a role in determining the ultimate phenotype.

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Primary hyperoxaluria in infants: Medical, ethical, and economic issues

Cited by 77 publications

References 24 publications

Predictive Factors of Oxaliplatin Neurotoxicity: The Involvement of the Oxalate Outcome Pathway

Predictive Factors of Oxaliplatin Neurotoxicity: The Involvement of the Oxalate Outcome Pathway

Characteristics and Outcomes of Children with Primary Oxalosis Requiring Renal Replacement Therapy

Intra-Familial Clinical Heterogeneity: Absence of Genotype-Phenotype Correlation in Primary Hyperoxaluria Type 1 in Israel

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