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Query: UMLS:C0020500 (hyperoxaluria)
 912 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 1 primary hyperoxaluria is a genetic disorder caused by deficiency of the liver-specific peroxisomal enzyme alanine-glyoxylate aminotransferase. This enzyme deficiency leads to excess oxalate production and deposition of calcium oxalate salts, resulting in kidney failure and systemic oxalosis. Aside from combined liver/kidney transplantation, no curative treatment exists. Various strategies for optimizing dialysis treatment have been evaluated, but neither conventional hemodialysis nor peritoneal dialysis can keep pace with oxalate production in this patient population. In this report, we describe a patient with end-stage renal disease from type 1 primary hyperoxaluria managed with nocturnal home hemodialysis. Performing hemodialysis 8-10 hours each night with blood flow of 350 mL/min and total dialysate volume of 60 L, she has maintained pre- and postdialysis serum oxalate levels at or below the level of supersaturation. We also review published literature regarding oxalate removal in various modalities of dialysis in patients with type 1 primary hyperoxaluria. In our patient, nocturnal hemodialysis has controlled serum oxalate levels better than conventional hemodialysis therapies. Home nocturnal hemodialysis should be considered an option for management of patients with end-stage renal disease from type 1 hyperoxaluria who are awaiting transplantation.
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PMID:Nocturnal home hemodialysis for a patient with type 1 hyperoxaluria. 2383 Aug

Primary hyperoxaluria (PH) occurs due to an autosomal recessive hereditary disorder of the metabolism of glyoxylate, which causes excessive oxalate production. The most frequent and serious disorder is due to enzyme deficit of alanine-glyoxylate aminotransferase (PH type I) specific to hepatic peroxisome. As oxalate is not metabolised in humans and is excreted through the kidneys, the kidney is the first organ affected, causing recurrent lithiasis, nephrocalcinosis and early renal failure. With advance of renal failure, particularly in patients on haemodialysis (HD), calcium oxalate is massively deposited in tissues, which is known as oxalosis. Diagnosis is based on family history, the presence of urolithiasis and/or nephrocalcinosis, hyperoxaluria, oxalate deposits in tissue forming granulomas, molecular analysis of DNA and enzyme analysis if applicable. High diagnostic suspicion is required; therefore, unfortunately, in many cases it is diagnosed after its recurrence following kidney transplantation. Conservative management of this disease (high liquid intake, pyridoxine and crystallisation inhibitors) needs to be adopted early in order to delay kidney damage. Treatment by dialysis is ineffective in treating excess oxalate. After the kidney transplant, we normally observe a rapid appearance of oxalate deposits in the graft and the results of this technique are discouraging, with very few exceptions. Pre-emptive liver transplantation, or simultaneous liver and kidney transplants when there is already irreversible damage to the kidney, is the treatment of choice to treat the underlying disease and suppress oxalate overproduction. Given its condition as a rare disease and its genetic and clinical heterogeneity, it is not possible to gain evidence through randomised clinical trials. As a result, the recommendations are established by groups of experts based on publications of renowned scientific rigour. In this regard, a group of European experts (OxalEurope) has drawn up recommendations for diagnosis and treatment, which were published in 2012.
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PMID:Primary hyperoxaluria. 2479 59

Hyperoxaluria significantly increases the risk of calcium oxalate kidney stone formation. Since several bacteria have been shown to metabolize oxalate in vitro, including probiotic bifidobacteria, we focused on the efficiency and possible mechanisms by which bifidobacteria can influence oxalate handling in vivo, especially in the intestines, and compared these results with the reported effects of Oxalobacter formigenes. Bifidobacterium animalis subsp. lactis DSM 10140 and B. adolescentis ATCC 15703 were administered to wild-type (WT) mice and to mice deficient in the hepatic enzyme alanine-glyoxylate aminotransferase (Agxt(-/-), a mouse model of Primary Hyperoxaluria) that were fed an oxalate-supplemented diet. The administration of B. animalis subsp. lactis led to a significant decrease in urinary oxalate excretion in WT and Agxt(-/-) mice when compared to treatment with B. adolescentis. Detection of B. animalis subsp. lactis in feces revealed that 3 weeks after oral gavage with the bacteria 64% of WT mice, but only 37% of Agxt(-/-) mice were colonized. Examining intestinal oxalate fluxes showed there were no significant changes to net oxalate secretion in colonized animals and were therefore not associated with the changes in urinary oxalate excretion. These results indicate that colonization with B. animalis subsp. lactis decreased urinary oxalate excretion by degrading dietary oxalate thus limiting its absorption across the intestine but it did not promote enteric oxalate excretion as reported for O. formigenes. Preventive or therapeutic administration of B. animalis subsp. lactis appears to have some potential to beneficially influence dietary hyperoxaluria in mice.
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PMID:Bifidobacterium animalis subsp. lactis decreases urinary oxalate excretion in a mouse model of primary hyperoxaluria. 2526 40

Primary hyperoxaluria type 1 is a rare autosomal-recessive disease caused by the deficient activity of the liver specific enzyme alanine-glyoxylate aminotransferase. Increased endogenous oxalate production induces severe hyperoxaluria, recurrent urolithiasis, progressive nephrocalcinosis and renal failure. Here we report a 6 month old boy who presented with vomiting and decreased urine volume. He was diagnosed with chronic kidney failure at 4 months of age and peritoneal dialysis was introduced at a local hospital. His parents were third degree cousins and family history revealed 2 maternal cousins who developed end stage renal disease during childhood. When he was admitted to our hospital, laboratory studies were consistent with end stage renal disease, ultrasound showed bilateral massive nephrocalcinosis. As clinical presentation was suggestive for primary hyperoxaluria type 1, plasma oxalate was determined and found extremely elevated. Genetic testing proved diagnosis by showing a disease causing homozygous mutation (AGXT-gene: c.971_972delT). The patient was put on pyridoxine treatment and aggressive dialysis programme. In conclusion; progressive renal failure in infancy with massive nephrocalcinosis, especially if accompanied by consanguinity and family history, should always raise the suspicion of PH type 1. Increased awareness of the disease would help physicians in both treating the patients and guiding the families who have diseased children and plan to have further pregnancies.
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PMID:Primary Hyperoxaluria Type 1: A Cause for Infantile Renal Failure and Massive Nephrocalcinosis. 2609 Sep 95

Primary hyperoxaluria type 1 (PH1), an inherited rare disease of glyoxylate metabolism, arises from mutations in the enzyme alanine-glyoxylate aminotransferase. The resulting deficiency in this enzyme leads to abnormally high oxalate production resulting in calcium oxalate crystal formation and deposition in the kidney and many other tissues, with systemic oxalosis and ESRD being a common outcome. Although a small subset of patients manages the disease with vitamin B6 treatments, the only effective treatment for most is a combined liver-kidney transplant, which requires life-long immune suppression and carries significant mortality risk. In this report, we discuss the development of ALN-GO1, an investigational RNA interference (RNAi) therapeutic targeting glycolate oxidase, to deplete the substrate for oxalate synthesis. Subcutaneous administration of ALN-GO1 resulted in potent, dose-dependent, and durable silencing of the mRNA encoding glycolate oxidase and increased serum glycolate concentrations in wild-type mice, rats, and nonhuman primates. ALN-GO1 also increased urinary glycolate concentrations in normal nonhuman primates and in a genetic mouse model of PH1. Notably, ALN-GO1 reduced urinary oxalate concentration up to 50% after a single dose in the genetic mouse model of PH1, and up to 98% after multiple doses in a rat model of hyperoxaluria. These data demonstrate the ability of ALN-GO1 to reduce oxalate production in preclinical models of PH1 across multiple species and provide a clear rationale for clinical trials with this compound.
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PMID:An Investigational RNAi Therapeutic Targeting Glycolate Oxidase Reduces Oxalate Production in Models of Primary Hyperoxaluria. 2953 12

Oxalate (Ox) is an end-product of metabolism, important for poor solubility of its calcium salt in biological fluids. Ox can therefore be found in about 70% of urinary calculi. Hyperoxaluria (HOx) defined as Ox exceeding 0.5 mmol)/day, may cause nephrolithiasis/nephrocalcinosis and may be classified as dietary (DH), enteric (EH) or primary (PH). Fractional intestinal absorption of Ox is less than 10%, but increases to over 20% at calcium intakes below 200 mg/day. DH is often related to low-calcium diets. EH is caused by non-absorbed fatty acids which bind to calcium and lower its concentration in the intestinal lumen. Ox forms more soluble complexes with other cations and results in HOx. Similar mechanisms may cause HOx following bariatric surgery. PHs are the most severe causes of HOx. Three types have so far been described, all being autosomic recessive. PH1 is due to mutations of AGXT gene encoding liver alanine-glyoxylate aminotransferase, PH2 is caused by mutations of GR-HPR gene encoding glyoxylate reductase and PH3 by mutations of HOGA1 encoding for hydroxyl-oxoglutarate aldolase. HOx results from deficient detoxification from glyoxylate, which is oxidized to Ox. The three PHs have different severity, though not always clinically distinguishable. They are identified through genetics and, in PH1, good genotype/phenotype correlations have been established. Thanks to early biochemical and genetic diagnosis, which are crucial to either prevent progression to ESRF or choose adequate transplantation strategies, the outlook of PH patients has dramatically improved in the last decades and will furtherly do in view of new therapeutic strategies.
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PMID:[The Hyperoxalurias]. 2796 20

This perspective focuses on how the gut microbiota can impact urinary oxalate excretion in the context of hyperoxaluria, a major risk factor in kidney stone disease. In the genetic disease of Primary Hyperoxaluria Type 1 (PH1), an increased endogenous production of oxalate, due to a deficiency of the liver enzyme alanine-glyoxylate aminotransferase (AGT), results in hyperoxaluria and oxalate kidney stones. The constant elevation in urinary oxalate in PH1 patients ultimately leads to tissue deposition of oxalate, renal failure and death and the only known cure for PH1 is a liver or liver-kidney transplant. The potential impact of a probiotic/therapeutic approach may be clinically significant in PH1 and could also extend to a much larger population of idiopathic oxalate stone formers who comprise ~12% of Americans, individuals with enteric hyperoxaluria, and an emerging population of hyperoxaluric patients who have undergone bariatric surgery and develop kidney stone disease as a consequence.
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PMID:Gut microbiota and oxalate homeostasis. 2821 1

Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder characterized by a defect in the liver-specific peroxisomal enzyme alanine-glyoxylate and serine-pyruvate aminotransferase (AGT). This disorder results in hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis. Three forms of PH1 have been reported. Data on the infantile form of PH1 are currently limited in literature. Despite the fact that China is the most populated country in the world, only a few AGXT mutations have been reported in several Chinese PH1 patients. In the present study, we investigated a Chinese family in which two siblings are affected by the infantile form of PH1. Sanger sequencing was carried out on the proband, but the results were misleading. Two novel missense mutations (c.517T > C/p.Cys173Arg and c.667A > C/p.Ser223Arg) of the AGXT gene were successfully detected through whole-exome sequencing. These two mutations occurred in the highly conserved residues of the AGT. Four software programs predicted both mutations as the cause of the disease. A postmortem examination was performed and revealed the occurrence of global nephrocalcinosis on both kidneys. The crystals were collected and analyzed as calcium oxalate monohydrate. This study extends the knowledge on the clinical phenotype-genotype correlation of the AGXT mutation. That is, (i) two novel missense mutations were identified for the infantile form of PH1 and (ii) the same AGXT genotype caused the same infantile form of PH1 within the family.
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PMID:Two Novel AGXT Mutations Cause the Infantile Form of Primary Hyperoxaluria Type I in a Chinese Family: Research on Missed Mutation. 3078 79


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