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Advances in Nephrology From the Necker... 1989In normal adults the urinary excretion of oxalate rarely exceeds 0.5 mmol/24 hours-1 despite dietary and seasonal fluctuations of intake and absorption. Hyperoxaluria... (Review)
Review
In normal adults the urinary excretion of oxalate rarely exceeds 0.5 mmol/24 hours-1 despite dietary and seasonal fluctuations of intake and absorption. Hyperoxaluria may be encountered in a number of disease states because of increased absorption of dietary oxalate or derangements of metabolism (Table 1). More unusually, hyperoxaluria may arise from one of three inborn errors of metabolism, i.e., the primary hyperoxalurias. The most common, primary hyperoxaluria type I (PHI), is recessively inherited; it will be discussed in detail in this paper. Primary hyperoxaluria type II, caused by a deficiency of D-glycerate dehydrogenase (EC 1.1.1.29), has a similar clinical pattern of disease, but has been described in only a very few families. More recently, another idiopathic form of hyperoxaluria has been defined (type III). It is likely that this form results from a primary defect in oxalate absorption in the absence of any morphologically or functionally definable intestinal disease; a satisfactory response to dietary restriction of oxalate, along with the use of thiazide diuretics, has been described.
Topics: Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Transplantation; Liver Transplantation
PubMed: 2493726
DOI: No ID Found -
Nephrology, Dialysis, Transplantation :... Jan 2022
Topics: Humans; Hyperoxaluria; Hyperoxaluria, Primary; Retina
PubMed: 32582926
DOI: 10.1093/ndt/gfaa101 -
Kidney International Mar 2024Primary hyperoxaluria type 1 (PH1) is a childhood-onset autosomal recessive disease, characterized by nephrocalcinosis, multiple recurrent urinary calcium oxalate...
Primary hyperoxaluria type 1 (PH1) is a childhood-onset autosomal recessive disease, characterized by nephrocalcinosis, multiple recurrent urinary calcium oxalate stones, and a high risk of progressive kidney damage. PH1 is caused by inherent genetic defects of the alanine glyoxylate aminotransferase (AGXT) gene. The in vivo repair of disease-causing genes was exceedingly inefficient before the invention of base editors which can efficiently introduce precisely targeted base alterations without double-strand DNA breaks. Adenine base editor (ABE) can precisely convert A·T to G·C with the assistance of specific guide RNA. Here, we demonstrated that systemic delivery of dual adeno-associated virus encoding a split-ABE8e could artificially repair 13% of the pathogenic allele in Agxt rats, a model of PH1, alleviating the disease phenotype. Specifically, ABE treatment partially restored the expression of alanine-glyoxylate-aminotransferase (AGT), reduced endogenous oxalate synthesis and alleviated calcium oxalate crystal deposition. Western blot and immunohistochemistry confirmed that ABE8e treatment restored AGT protein expression in hepatocytes. Moreover, the precise editing efficiency in the liver remained stable six months after treatment. Thus, our findings provided a prospect of in vivo base editing as a personalized and precise medicine for PH1 by directly correcting the mutant Agxt gene.
Topics: Humans; Rats; Animals; Child; Calcium Oxalate; Gene Editing; RNA, Guide, CRISPR-Cas Systems; Hyperoxaluria, Primary; Transaminases; Alanine; Hyperoxaluria; Mutation
PubMed: 38142039
DOI: 10.1016/j.kint.2023.11.029 -
Nephrology, Dialysis, Transplantation :... 1995Most cases of primary hyperoxaluria are due to deficiency of hepatic peroxisomal alanine:glyoxylate aminotransferase [i.e. primary hyperoxaluria type 1 (PH1), McKusick...
Most cases of primary hyperoxaluria are due to deficiency of hepatic peroxisomal alanine:glyoxylate aminotransferase [i.e. primary hyperoxaluria type 1 (PH1), McKusick 259900] and several hundred examples have been described since the original report in 1925. By contrast, primary hyperoxaluria type 2 (PH2, McKusick 260000) is very rare indeed with only 22 patients recorded since the original description in 1968. PH2 is characterized by hyperoxaluria and L-glyceric aciduria and is caused by deficiency of D-glycerate dehydrogenase/glyoxylate reductase. In comparison with PH1 much less is known about PH2 and considerable uncertainties remain about its frequency, clinical course and optimum management.
Topics: Adult; Carbohydrate Dehydrogenases; Child, Preschool; Female; Glyceric Acids; Humans; Hyperoxaluria, Primary; Infant; Kidney Transplantation; Male
PubMed: 8592629
DOI: 10.1093/ndt/10.supp8.58 -
Journal of the Medical Association of... Aug 2007A 5-month-old female infant who had chronic diarrhea and acute renal failure was referred to Chulalongkorn Hospital for further investigation and management. Laboratory...
A 5-month-old female infant who had chronic diarrhea and acute renal failure was referred to Chulalongkorn Hospital for further investigation and management. Laboratory investigation revealed elevated blood urea nitrogen and creatinine level, hypocalcemia, hyperphosphatemia, and hyponatremia. Ultrasonography of the kidneys showed normal size with bilateral hyperechoic kidneys. Eyes examination was compatible with oxalosis maculopathy. Urine organic acid analysis revealed peak of oxalate and glycolate. Clinical impression concluded acute renal failure from hyperoxaluria. The patient underwent continuous venovenous hemodiafiltration (CVVH-DF) with regional citrate anticoagulation and expired on day 13 after admission. Pathological examination of kidney necropsy revealed diffuse intraluminal deposition of oxalate crystals within the renal parenchyma. Primary hyperoxaluria is a very rare disease and has rarely been reported in Thailand. In the presented case, the diagnosis was delayed due to uncommon presentation and unavailability of diagnostic laboratory.
Topics: Acute Kidney Injury; Female; Humans; Hyperoxaluria, Primary; Infant; Kidney
PubMed: 17927001
DOI: No ID Found -
Expert Reviews in Molecular Medicine Jan 2004The primary hyperoxalurias type 1 (PH1) and type 2 (PH2) are autosomal recessive calcium oxalate kidney stone diseases caused by deficiencies of the metabolic enzymes... (Review)
Review
The primary hyperoxalurias type 1 (PH1) and type 2 (PH2) are autosomal recessive calcium oxalate kidney stone diseases caused by deficiencies of the metabolic enzymes alanine:glyoxylate aminotransferase (AGT) and glyoxylate/hydroxypyruvate reductase (GR/HPR), respectively. Over 50 mutations have been identified in the AGXT gene (encoding AGT) in PH1, associated with a wide variety of effects on AGT, including loss of catalytic activity, aggregation, accelerated degradation, and peroxisome-to-mitochondrion mistargeting. Some of these mutations segregate and interact synergistically with a common polymorphism. Over a dozen mutations have been found in the GRHPR gene (encoding GR/HPR) in PH2, all associated with complete loss of glyoxylate reductase enzyme activity and immunoreactive protein. The crystal structure of human AGT, but not human GR/HPR, has been solved, allowing the effects of many of the mutations in PH1 to be rationalised in structural terms. Detailed analysis of the molecular aetiology of PH1 and PH2 has led to significant improvements in all aspects of their clinical management. Enzyme replacement therapy by liver transplantation can provide a metabolic cure for PH1, but it has yet to be tried for PH2. New treatments that aim to counter the effects of specific mutations on the properties of the enzymes could be feasible in the not-too-distant future.
Topics: Alcohol Oxidoreductases; Animals; Calcium Oxalate; Cell Line; Genotype; Humans; Hydroxypyruvate Reductase; Hyperoxaluria, Primary; Models, Molecular; Mutation; Phenotype; Polymorphism, Genetic; Protein Conformation; Transaminases
PubMed: 14987413
DOI: 10.1017/S1462399404007203 -
QJM : Monthly Journal of the... Oct 2021
Topics: Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney
PubMed: 33576401
DOI: 10.1093/qjmed/hcab027 -
Nephrology, Dialysis, Transplantation :... Feb 1999
Review
Topics: Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Pyridoxine
PubMed: 10069180
DOI: 10.1093/ndt/14.2.301 -
Experimental and Clinical... May 2021Primary hyperoxaluria type 1 is an autosomal recessive disorder that causes overproduction and urinary excretion of oxalate. Liver transplant has been suggested as a...
OBJECTIVES
Primary hyperoxaluria type 1 is an autosomal recessive disorder that causes overproduction and urinary excretion of oxalate. Liver transplant has been suggested as a treatment for primary hyperoxaluria type 1 since the defective enzyme is expressed in the liver. This study aimed to investigate results of combined liver and kidney, sequential, and preemptive livertransplantin patients with primary hyperoxaluria type 1.
MATERIALS AND METHODS
In this cohort study, we followed patients with primary hyperoxaluria type 1 who underwent liver transplant at our centerin Shiraz, Iran. Clinical and laboratory data of patients were gathered, and major outcomes, including renal failure after liver transplant, rejection, and mortality were recorded. Survival of patients was analyzed by the Kaplan-Meier method.
RESULTS
Our study included 24 patients. There were 16 male (66.6%) and 8 female (33.33%) patients. Thirteen patients were in the pediatric age group (age < 18 y), and 11 patients were adults (age ≥ 18 y). Thirteen patients underwent sequential transplant, 8 patients underwent combined liver and kidney transplant, and 3 patients underwent preemptive transplant. All patients received organs from deceased donors. There were no statistically significant differences in mortality, rejection, and hemodialysis after transplant between those with sequential transplant and those with combined liver and kidney transplant (P > .05).
CONCLUSIONS
Liver transplant can be considered a treatment for patients with primary hyperoxaluria type 1. Combined liver and kidney transplant and preemptive liver transplant could be proper options for these patients.
Topics: Adult; Child; Cohort Studies; Female; Humans; Hyperoxaluria, Primary; Kidney; Kidney Transplantation; Liver; Liver Transplantation; Male
PubMed: 31580236
DOI: 10.6002/ect.2019.0150 -
Pediatric Transplantation Aug 2000
Review
Topics: Child; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation
PubMed: 10933312
DOI: 10.1034/j.1399-3046.2000.00119.x