Vitamin D deficiency may increase amphotericin B-related kidney toxicity

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Do you take vitamin D supplements over winter?

Current NHS/PHE guidelines say that all adults should consider taking vitamin D supplements between October and March, or all year round if they are at risk of deficiency (e.g. people who have darker skin, or spend most of their time indoors or covered up).

But a new study suggests it might be even more important for people living with aspergillosis. Ferreira et al 2019 found that mice with a vitamin D deficiency experienced more kidney toxicity when given amphotericin B (lipid formulation). Click here to read more here.

If you haven’t had your levels tested recently, it might be worth getting your doctor to check them.

When taking vitamin D supplements:

  •  For best absorption, take it with a meal containing fat and calcium
  •  Check the label for the dosage – it should be 10-25 mcg per day, or 400-1000 IU (don’t rely on % RDA/NRV)
  •  There are two forms: D3 (cholecalciferol) is more effective than D2 (ergocalciferol)

For more information on Vitamin D guidelines:

Aspirin may reduce harmful effects of air pollution on lungs

A recent study by Dr Xu Gao and colleagues has looked at the relationship between lung function and the use of non-steroidal anti-inflammatory drugs (which include aspirin) in 2,280 veterans. The researchers then compared this with air pollution data from the previous month in their hometown of greater Boston. Other factors, including whether or not the participant was a smoker were also taken into consideration.

The study found that NSAIDs nearly halved the effect of particulate matter (all solid and liquid particles suspended in air) on lung function. The mechanism by which this protection happens is unknown, but may be due to NSAIDS reducing inflammation in the lung caused by pollution. As most of the participants in the study were taking aspirin, this effect was deemed to be predominantly due to aspirin, but the effect of other NSAIDs would be useful to study.

These results show that aspirin may be useful in the short-term protection of lungs against air pollution. However, air pollution contributes to a number of other harmful bodily effects so it is still important to minimise overall exposure.

To check air pollution in your area, click here


Fungal biofilm structure and its indications in invasive aspergillosis

Example of increased furrowing and white, non-sporing edges at lower oxygen levels (Kowalski et al., 2019)

Microorganisms can group together on a surface to form collections of cells called biofilms; one example of this is dental plaque. Grouping together as a community protects these cells from environments which they may not be able to survive alone, such as the wrong pH or a lack of water or oxygen. Biofilms may be made up of many different species of microorganism and these species may be varied further by strain. In a recent paper, Caitlin Kowalski and colleagues at the Geisel School of Medicine at Dartmouth, USA, studied the ability of Aspergillus fumigatus biofilms to grow in low oxygen environments and cause invasive aspergillosis in mice.  

Kowalski and colleagues exposed A. fumigatus to low levels of oxygen, which reflect the levels found in the lesions where the fungus grows in the lung, in order to identify genes and mechanisms involved in allowing the pathogen to grow under these conditions. They then discovered a specific mutation which allowed the strain to both grow better in low oxygen, but also cause disease better under these conditions. It remains to be discovered how this particular mutation allows the strain to grow more successfully and be more virulent in low oxygen. However in other fungal biofilms, for example the yeast Candida albicans, the colony can form wrinkles which improve oxygen penetration. Understanding how the structure of biofilm colony growth reflects advantages in the ability of the fungus to cause disease may allow clinicians and scientists to better predict the progression of disease and improve patient care.

Find out more:

Side effects of long-term azole therapy

Azole antifungals are the first-line of treatment or prophylaxis for many fungal infections. They are often administered long-term (weeks to months), which can be associated with a number of adverse effects. In patients receiving several medications, it can be difficult to identify whether antifungals are contributing to, or causing particular symptoms; recognition of common side effects, leading to treatment discontinuation or management, is therefore key to reducing symptoms and reversing toxicity.  A recent review by Dr Lydia Benitez and Dr Peggy Carver summarises these effects and their frequency:

Key points the authors highlight:

  • Liver toxicity, generally reversible, is common with all azoles.
  • Hormone-related adverse effects are observed with select azoles; these include hair loss, breast enlargement, decreased libido, impotence, and (rarely) adrenal insufficiency (beware drug interactions with inhaled and oral steroids).
  • Patients with fair skin on voriconazole should use liberal amounts of broad spectrum UV protectants and wear sun protective clothing, avoid excess sunlight, and undergo frequent monitoring of skin as phototoxic reactions progressing to development of skin cancer has been associated with long-term use.
  • Therapeutic drug monitoring may be utilized to minimise neuropathies in specific patient populations on voriconazole, as neuropathies are more common with higher concentrations and doses. Its role in preventing other long-term toxicities is less clear.

Azoles are a valuable resource in the treatment and prophylaxis for fungal infections. Despite being associated with a number of adverse effects, they are safer and more active than alternatives. Thorough knowledge of the side effects they may cause is therefore important, so that they can be recognised and managed promptly.

Read the paper here: Benitez, L.L. & Carver, P.L. Drugs (2019) 79: 833

Vitamin D deficiency may increase the risk of Amphotericin B-related kidney toxicity

Amphotericin B (AmB) is the drug of choice for the treatment of many fungal infections.  Despite this, the drug can cause several serious side effects, one of which being nephrotoxicity (toxicity to the kidneys). Conventional AmB can be adapted into a lipid emulsion preparation, which can reduce the risk of nephrotoxicity, while preserving its efficacy and remaining a lower cost option. Unfortunately this does not solve the problem, and nephrotoxicity remains an issue for many patients.

Vitamin D deficiency has been found to be a major problem worldwide, and can increase the risk of kidney-related disease, including drug-induced nephrotoxicity. A recent study by Daniela Ferreira and colleagues at the University of Sao Paulo looked at standard and vitamin D-deficient rats and found that the deficient rats treated with AmB presented with impaired renal function. This suggests that vitamin D deficiency may play a key role in the development of AmB-induced nephrotoxicity. Therefore, the authors state that it is essential to monitor levels of vitamin D in patients treated with both conventional and lipid formulations of AmB, in order to reduce the development of kidney disease.

Read the full paper here

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