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Frontiers in Pediatrics 2024Primary hyperoxaluria type 1 is characterized by hepatic oxalate overproduction, leading to nephrocalcinosis, kidney stones, kidney failure and systemic oxalosis,...
BACKGROUND
Primary hyperoxaluria type 1 is characterized by hepatic oxalate overproduction, leading to nephrocalcinosis, kidney stones, kidney failure and systemic oxalosis, including oxalate osteopathy. Combined liver-kidney transplantation (CLKT) and kidney after liver transplantation (KALT) were established therapeutic options to stop the devastating consequences of oxalate bone disease.
METHODS
We describe a retrospective cohort of 10 children with PH1who were referred to our hospital from different countries for combined transplantation. Demographic and clinical data were collected and symptoms of bone disease, conventional radiological examinations, plasma oxalate levels and other determinants of calcium-phosphate metabolism were compared pre and post transplantation.
RESULTS
Ten patients (7 male, median age 5.8 years, median follow-up time 8.1 years) were included in this study. Seven patients were diagnosed with infantile oxalosis and 9 patients received an intensified dialysis regime prior to transplantation. In one patient the transplanted kidney never achieved primary function and the boy remained on HD. All other patients remained without graft failure and retained stable kidney and liver function. Prior to transplantation, seven patients suffered from severe skeletal pain and three children presented with 1-3 series of pathological fractures. Pathological fractures did no longer occur in children who underwent successful CLKT or KALT. Plasma oxalate levels dropped within 6 months following Tx. Determinants of calcium-phosphorus metabolism did not differ significantly in comparison to other HD children. Seven of ten children showed a restricted growth at the time of transplantation and presented a moderate catch-up-growth at the time of last follow-up.
CONCLUSIONS
Patients with PH1 suffer from severe consequences of a disturbed bone metabolism. However, bone health and growth can partially improve following CLKT/KALT.
PubMed: 38455394
DOI: 10.3389/fped.2024.1353880 -
La Tunisie Medicale Jul 2023There are three types of primary hyperoxaluria, with type 1 considered the most severe.
INTRODUCTION
There are three types of primary hyperoxaluria, with type 1 considered the most severe.
AIM
To analyze the clinical, genetic, and evolutionary characteristics of type 1 primary hyperoxaluria with pediatric onset.
METHODS
This was a retrospective, descriptive study that included Tunisian children under the age of 18 at the time of diagnosis over a period of 25 years (January 1, 1996, to December 31, 2022).
RESULTS
Thirty-five patients were included, with a mean age of 4.1 years. The most common presenting circumstances of the disease were nephrolithiasis and end-stage renal failure. The average serum creatinine level was 225.42 µmol/l. Five mutations were identified, with the p.Ile244Thr mutation being the most prevalent. Nephrocalcinosis, surgical intervention, and a creatinine level ≥57 µmol/l were predictive of progression to end-stage renal failure. The infantile form was predictive of mortality.
CONCLUSIONS
Screening for the disease would improve the prognosis of this condition.
Topics: Child; Humans; Child, Preschool; Adult; Hyperoxaluria, Primary; Retrospective Studies; Kidney Failure, Chronic; Mutation
PubMed: 38445424
DOI: No ID Found -
Pharmaceuticals (Basel, Switzerland) Feb 2024A total of nine TIDES (pepTIDES and oligonucleoTIDES) were approved by the FDA during 2023. The four approved oligonucleotides are indicated for various types of... (Review)
Review
A total of nine TIDES (pepTIDES and oligonucleoTIDES) were approved by the FDA during 2023. The four approved oligonucleotides are indicated for various types of disorders, including amyotrophic lateral sclerosis, geographic atrophy, primary hyperoxaluria type 1, and polyneuropathy of hereditary transthyretin-mediated amyloidosis. All oligonucleotides show chemically modified structures to enhance their stability and therapeutic effectiveness as antisense or aptamer oligomers. Some of them demonstrate various types of conjugation to driving ligands. The approved peptides comprise various structures, including linear, cyclic, and lipopeptides, and have diverse applications. Interestingly, the FDA has granted its first orphan drug designation for a peptide-based drug as a highly selective chemokine antagonist. Furthermore, Rett syndrome has found its first-ever core symptoms treatment, which is also peptide-based. Here, we analyze the TIDES approved in 2023 on the basis of their chemical structure, medical target, mode of action, administration route, and common adverse effects.
PubMed: 38399458
DOI: 10.3390/ph17020243 -
Kidney International Mar 2024The study by Chen et al. is the first to apply the revolutionary genetic engineering tool, base editing, in a rat model for the treatment of primary hyperoxaluria type...
The study by Chen et al. is the first to apply the revolutionary genetic engineering tool, base editing, in a rat model for the treatment of primary hyperoxaluria type 1, a disease that originates in the liver but in which the kidney is the main organ affected. This commentary contextualizes and describes the gene-editing technology applied by the authors, provides an interpretation and opinion of their results, and indicates possible future applications.
Topics: Rats; Animals; Gene Editing; CRISPR-Cas Systems; Genetic Engineering; Kidney Diseases; Kidney
PubMed: 38388140
DOI: 10.1016/j.kint.2024.01.004 -
Progress in Molecular Biology and... 2024The excretory system is responsible for removing wastes from the human body, which plays a crucial role in our lives. Current treatments for diseases related to this...
The excretory system is responsible for removing wastes from the human body, which plays a crucial role in our lives. Current treatments for diseases related to this system have shown several limitations; therefore, there is a rising need for novel methods. In this circumstance, RNA-based therapeutics have rapidly emerged as new and promising candidates. In fact, to date, a handful of potential drugs have passed the development step and entered the clinical pipeline. Among them, one drug received FDA approval to enter the global market, which is Oxlumo (Lumasiran) for the treatment of primary hyperoxaluria type 1. For other excretory diseases, such as paroxysmal nocturnal hemoglobinuria, urothelial cancer or renal cancer, RNA-based candidates are also being tested under clinical trials. Currently, the most potential types of RNA therapeutics to treat disorders of the excretory system are those based on small interfering RNA (siRNA), antisense oligonucleotides (ASO) and messenger RNA (mRNA), Among them, siRNA therapeutics seem to be the most promising, including Oxlumo and two other developing drug candidates. This chapter will provide a general overview on the application of RNA therapeutics in disorders of the excretory system.
Topics: Humans; RNA, Small Interfering; Oligonucleotides, Antisense; RNA, Messenger
PubMed: 38360001
DOI: 10.1016/bs.pmbts.2023.12.011 -
Progress in Molecular Biology and... 2024The prevalence of metabolic disorders is increasing exponentially and has recently reached epidemic levels. Over the decades, a large number of therapeutic options have...
The prevalence of metabolic disorders is increasing exponentially and has recently reached epidemic levels. Over the decades, a large number of therapeutic options have been proposed to manage these diseases but still show several limitations. In this circumstance, RNA therapeutics have rapidly emerged as a new hope for patients with metabolic diseases. 57 years have elapsed from the discovery of mRNA, a large number of RNA-based drug candidates have been evaluated for their therapeutic effectiveness and clinical safety under clinical studies. To date, there are seven RNA drugs for treating metabolic disorders receiving official approval and entering the global market. Their targets include hereditary transthyretin-mediated amyloidosis (hATTR), familial chylomicronemia syndrome, acute hepatic porphyria, primary hyperoxaluria type 1 and hypercholesterolemia, which are all related to liver proteins. All of these seven RNA drugs are antisense oligonucleotides (ASO) and small interfering RNA (siRNA). These two types of treatment are both based on oligonucleotides complementary to target RNA through Watson-Crick base-pairing, but their mechanisms of action include different nucleases. Such treatments show greatest potential among all types of RNA therapeutics due to consecutive achievements in chemical modifications. Another method, mRNA therapeutics also promise a brighter future for patients with a handful of drug candidates currently under development.
Topics: Humans; Oligonucleotides; Oligonucleotides, Antisense; RNA, Small Interfering; RNA, Messenger; Amyloid Neuropathies, Familial
PubMed: 38359998
DOI: 10.1016/bs.pmbts.2023.12.014 -
Jornal Brasileiro de Nefrologia 2024
Topics: Humans; Hyperoxaluria, Primary; X-Rays; Radiography, Abdominal; Kidney Calculi
PubMed: 38358912
DOI: 10.1590/2175-8239-JBN-2023-0032en -
Annales de Pathologie Feb 2024
PubMed: 38341314
DOI: 10.1016/j.annpat.2024.01.011