What is hydroxy(vitamin B6, hydroxocobalamin)?

From the Guidelines

Hydrox, in the context of primary hyperoxaluria, refers to the management and treatment of the condition, particularly with RNA interference therapy, as outlined in the recent expert consensus statement from ERKNet and OxalEurope 1. The management of primary hyperoxaluria (PH) involves various strategies, including dietary modifications, hydration, and pharmacological interventions.

• The recent study published in Nature Reviews Nephrology 1 provides clinical practice recommendations for primary hyperoxaluria, including the use of RNA interference therapy.
• The study categorizes patients into different groups based on their responsiveness to vitamin B6 therapy, estimated glomerular filtration rate (eGFR), and clinical phenotype.
• For example, Group A patients, who are non-responsive to vitamin B6 therapy and have an eGFR >30 ml/min/1.73m2, are recommended to start RNA interference therapy 1.
• The study also provides cessation criteria for RNA interference therapy, including a decrease in plasma oxalate levels <20% from baseline or deterioration of clinical condition, as well as severe adverse events (SAEs) potentially related to the therapy 1. In contrast, the evidence from the Journal of Hepatology 1 focuses on nutrition in chronic liver disease and does not provide relevant information for the management of primary hyperoxaluria.
• Therefore, the recommendations for Hydrox management should be based on the most recent and highest-quality study, which is the expert consensus statement from ERKNet and OxalEurope 1.
• The use of RNA interference therapy, such as lumasiran, is recommended for patients with primary hyperoxaluria, particularly those who are non-responsive to vitamin B6 therapy and have an eGFR >30 ml/min/1.73m2, as outlined in the recent expert consensus statement 1.

From the Research

Hydroxychloroquine Uses and Effects

• Hydroxychloroquine (HCQ) is an antimalarial drug that has been used to treat and prevent malaria, as well as to manage autoimmune and rheumatic diseases such as systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, and primary Sjögren's syndrome 2, 3, 4.
• HCQ has been shown to be effective in suppressing rheumatoid arthritis, with a superior benefit to risk ratio, and is indicated for active rheumatoid arthritis not optimally controlled with nonsteroidal anti-inflammatory drugs 5.
• The drug has also been found to be beneficial in slowing the disease progression in RA patients and enhancing the effects of methotrexate in treating RA 6.

Safety and Adverse Effects

• HCQ is generally considered safe, but adverse reactions have been reported, and clinicians should carefully monitor patients with rheumatism when prescribing these drugs 2, 4.
• The most significant adverse effect associated with HCQ is retinopathy, which can be minimized by strict adherence to daily dosage limits and regular ocular examinations 5, 6.
• Other adverse effects, such as cardiomyopathy and conduction defects, have been reported, but are rare 4.

Mechanisms of Action

• HCQ affects various cellular and molecular pathways through different mechanisms, including the inhibition of lysosomal antigen processing, MHC-II antigen presentation, and TLR functions 3, 4.
• The drug has been found to reduce pro-inflammatory cytokine production and release, which is a key symptom of rheumatic autoimmune disorders 3.