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Kidney International Jun 2009The primary hyperoxalurias (PHs) are rare disorders of glyoxylate metabolism in which specific hepatic enzyme deficiencies result in overproduction of oxalate. Due to... (Review)
Review
The primary hyperoxalurias (PHs) are rare disorders of glyoxylate metabolism in which specific hepatic enzyme deficiencies result in overproduction of oxalate. Due to the resulting severe hyperoxaluria, recurrent urolithiasis or progressive nephrocalcinosis are principal manifestations. End stage renal failure frequently occurs and is followed by systemic oxalate deposition along with its devastating effects. Due to the lack of familiarity with PHs and their heterogeneous clinical expressions, the diagnosis is often delayed until there is advanced disease. In recent years, improvements in medical management have been associated with better patient outcomes. Although there are several therapeutic options that can help prevent early kidney failure, the only curative treatment to date is combined liver-kidney transplantation in patients with type I PH. Promising areas of investigation are being identified. Knowledge of the spectrum of disease expression, early diagnosis, and initiation of treatment before renal failure are essential to realize a benefit for patients.
Topics: Alcohol Oxidoreductases; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Mutation; Pyridoxine; Renal Replacement Therapy; Transaminases
PubMed: 19225556
DOI: 10.1038/ki.2009.32 -
Biochimica Et Biophysica Acta.... Jan 2021The Primary Hyperoxalurias (PH) are rare disorders of metabolism leading to excessive endogenous synthesis of oxalate and recurring calcium oxalate kidney stones....
The Primary Hyperoxalurias (PH) are rare disorders of metabolism leading to excessive endogenous synthesis of oxalate and recurring calcium oxalate kidney stones. Alanine glyoxylate aminotransferase (AGT), deficient in PH type 1, is a key enzyme in limiting glyoxylate oxidation to oxalate. The affinity of AGT for its co-substrate, alanine, is low suggesting that its metabolic activity could be sub-optimal in vivo. To test this hypothesis, we examined the effect of L-alanine supplementation on oxalate synthesis in cell culture and in mouse models of Primary Hyperoxaluria Type 1 (Agxt KO), Type 2 (Grhpr KO) and in wild-type mice. Our results demonstrated that increasing L-alanine in cells decreased synthesis of oxalate and increased viability of cells expressing GO and AGT when incubated with glycolate. In both wild type and Grhpr KO male and female mice, supplementation with 10% dietary L-alanine significantly decreased urinary oxalate excretion ~30% compared to baseline levels. This study demonstrates that increasing the availability of L-alanine can increase the metabolic efficiency of AGT and reduce oxalate synthesis.
Topics: Alanine; Alcohol Oxidoreductases; Animals; CHO Cells; Cricetulus; Hyperoxaluria, Primary; Mice; Mice, Knockout; Oxalates; Transaminases
PubMed: 33002578
DOI: 10.1016/j.bbadis.2020.165981 -
International Journal of Nephrology and... 2022Primary hyperoxaluria (PH) is a rare genetic disease caused by excessive hepatic production and elevated urinary excretion of oxalate that leads to recurrent... (Review)
Review
Primary hyperoxaluria (PH) is a rare genetic disease caused by excessive hepatic production and elevated urinary excretion of oxalate that leads to recurrent nephrolithiasis, nephrocalcinosis and, eventually, kidney failure. As glomerular filtration rate declines, oxalate accumulates leading to systemic oxalosis, a debilitating condition with high morbidity and mortality. Although PH is usually diagnosed during infancy, it can present at any age with different phenotypes, ranging from mild symptoms to extremely debilitating manifestations. PH is an autosomal recessive disorder and, to date, three types have been identified: PH1, PH2 and PH3. PH1 is the most common and most aggressive type, accounting for almost 80% of primary hyperoxaluria diagnoses. Until 2020, general treatment for PH1 consisted mainly in high fluid intake, urine alkalization, surgical management of recurrent nephrolithiasis and eventually, if and when kidney failure occurred, intensive dialysis regimens and transplantation strategies (simultaneous or sequential liver-kidney transplant or isolated liver/kidney transplant in carefully selected patients). Specific treatment did and still consists in administration of pyridoxine hydrochloride, although it is only effective in a subset of PH1 patients. Lumasiran, a novel biological drug based on mRNA interference that has been recently approved in the US and European Union, showed promising results and is set to be a turning point in the management of PH1. This literature review aims to summarize the available evidence on PH1 treatment with lumasiran, in order to provide both pediatric and adult nephrologists and clinicians with the knowledge for the identification and management of PH1 patients suitable for treatment.
PubMed: 35747094
DOI: 10.2147/IJNRD.S293682 -
BMC Nephrology Jun 2019Primary hyperoxaluria (PH) is a rare inborn disorder of the metabolism of glyoxylate, which causes the hallmark production oxalate and forms insoluble calcium oxalate... (Review)
Review
BACKGROUND
Primary hyperoxaluria (PH) is a rare inborn disorder of the metabolism of glyoxylate, which causes the hallmark production oxalate and forms insoluble calcium oxalate crystals that accumulate in the kidney and other organs. Since the manifestation of PH varies from recurrent nephrolithiasis, nephrocalcinosis, and end-stage renal disease with age at onset of symptoms ranging from infancy to the sixth decade, the disease remains undiagnosed until after kidney transplantation in some cases.
CASE PRESENTATION
Herein, we report 3 cases of PH diagnosed after kidney transplantation failure, providing the comprehensive clinical course, the ultrasonic image of renal graft and pathologic image of the biopsy, highlighting the relevance of biopsy findings and the results of molecular genetic testing. We also focus on the treatment and the unfavorable outcome of the patients. Meanwhile, we review the literature and show the additional 10 reported cases of PH diagnosed after kidney transplantation. Additionally, we discuss the progressive molecular understanding of the mechanisms involved in PH and molecular therapy.
CONCLUSIONS
Overall, the necessity of preoperative screening of PH in all patients even with a minor history of nephrolithiasis and the importance of proper treatment are the lessons we learn from the 3 cases, which prompt us to avoid tragedies.
Topics: Adult; Humans; Hyperoxaluria, Primary; Kidney Transplantation; Male; Postoperative Complications; Treatment Failure
PubMed: 31215412
DOI: 10.1186/s12882-019-1402-2 -
The Biochemical Journal Mar 1971
Topics: Adolescent; Adult; Alcohol Oxidoreductases; Child; Glycolates; Glyoxylates; Humans; Kidney; Ligases; Liver; Metabolism, Inborn Errors; Nephrocalcinosis; Oxalates; Oxidoreductases; Urinary Calculi; Vitamin B 6 Deficiency; Xanthine Oxidase
PubMed: 5124818
DOI: 10.1042/bj1220007p -
Indian Journal of Urology : IJU :... Jan 2007
PubMed: 19675772
DOI: 10.4103/0970-1591.30276 -
Annals of Laboratory Medicine May 2024Plasma oxalate measurements can be used for the screening and therapeutic monitoring of primary hyperoxaluria. We developed a gas chromatography-mass spectrometry...
BACKGROUND
Plasma oxalate measurements can be used for the screening and therapeutic monitoring of primary hyperoxaluria. We developed a gas chromatography-mass spectrometry (GC-MS) assay for plasma oxalate measurements with high sensitivity and suitable testing volumes for pediatric populations.
METHODS
Plasma oxalate was extracted, derivatized, and analyzed by GC-MS. We measured the ion at m/z 261.10 to quantify oxalate and the C-oxalate ion (m/z: 263.15) as the internal standard. Method validation included determination of the linear range, limit of blank, limit of detection, lower limit of quantification, precision, recovery, carryover, interference, and dilution effect. The cut-off value between primary and non-primary hyperoxaluria in a pediatric population was analyzed.
RESULTS
The detection limit was 0.78 μmol/L, and the linear range was up to 80.0 μmol/L. The between-day precision was 5.7% at 41.3 μmol/L and 13.1% at 1.6 μmol/L. The carryover was <0.2%. The recovery rate ranged from 90% to 110%. Interference analysis showed that Hb did not interfere with plasma oxalate quantification, whereas intralipids and bilirubin caused false elevation of oxalate concentrations. A cut-off of 13.9 μmol/L showed 63% specificity and 77% sensitivity, whereas a cut-off of 4.15 μmol/L showed 100% specificity and 20% sensitivity. The minimum required sample volume was 250 μL. The detected oxalate concentrations showed interference from instrument conditioning, sample preparation procedures, medications, and various clinical conditions.
CONCLUSIONS
GC-MS is a sensitive assay for quantifying plasma oxalate and is suitable for pediatric patients. Plasma oxalate concentrations should be interpreted in a clinical context.
Topics: Humans; Child; Gas Chromatography-Mass Spectrometry; Oxalates; Hyperoxaluria, Primary
PubMed: 37904578
DOI: 10.3343/alm.2023.0178 -
Revue Medicale de Liege Jul 2022Primary hyperoxaluria type 1 is a rare autosomal recessive disorder leading to oxalate overproduction by deficiency in the liver-specific enzyme alanine-glyoxylate...
Primary hyperoxaluria type 1 is a rare autosomal recessive disorder leading to oxalate overproduction by deficiency in the liver-specific enzyme alanine-glyoxylate transaminase (AGT). Oxalate is a poorly soluble molecule that binds calcium and deposits in the entire organism leading to oxalosis. Its elimination is mainly carried out by kidneys. Hence the first manifestations are frequently of urinary concern and whitout any early care, progression of the disease to end-stage renal failure cannot be avoided. The only etiological treatment has long been combined liver-kidney transplantation because it restaures enzymatic function and replaces pathological kidneys. However, for a few years now, numerous studies are carried out on this subject and promising results have already been published with a new drug, lumasiran. From a clinical case, we describe the different options for the therapeutic management of primary hyperoxaluria type 1.
Topics: Humans; Hyperoxaluria, Primary; Nephrocalcinosis; Oxalates; RNA, Small Interfering
PubMed: 35924494
DOI: No ID Found -
Postgraduate Medical Journal Oct 1994
Review
Topics: Crystallization; Female; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Calculi; Male; Oxalates; Oxalic Acid
PubMed: 7831162
DOI: 10.1136/pgmj.70.828.695 -
CEN Case Reports May 2023Infantile primary hyperoxaluria type 1 (PH1) is the most devastating primary hyperoxaluria (PH) subtype as it leads to early end-stage kidney disease (ESKD) associated... (Review)
Review
Infantile primary hyperoxaluria type 1 (PH1) is the most devastating primary hyperoxaluria (PH) subtype as it leads to early end-stage kidney disease (ESKD) associated with high mortality. We report a case of a three-month-old female Chinese infant who was diagnosed with PH1 by renal biopsy and genetic studies. She carried two heterozygous mutations in the alanine-glyoxylate and serine pyruvate aminotransferase (AGXT) gene, one of which has never been previously reported. The patient had multiple organ failures caused by kidney failure, which was improved by extracorporeal membrane oxygenation and continuous renal replacement therapy. However, her primary disease responded poorly to conservative treatment. Fortunately, after waiting for four months, the patient underwent a successful combined liver-kidney transplantation and has progressed well so far. This case highlights the importance of suspecting PH in infant patients with ESKD of uncertain etiology, as early initiation of therapy prevents poor outcomes.
Topics: Infant; Humans; Female; Hyperoxaluria, Primary; Kidney; Kidney Transplantation; Kidney Failure, Chronic
PubMed: 36194362
DOI: 10.1007/s13730-022-00740-z