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Kidney diseases and COVID-19 – probably helped by Vitamin D etc. – Jan 19, 2021

Kidney diseases and COVID-19 infection: causes and effect, supportive therapeutics and nutritional perspectives

Heliyon, 19 Jan 2021, 7(1) DOI: 10.1016/j.heliyon.2021.e06008
Askari H1, Sanadgol N2, Azarnezhad A3, Tajbakhsh A4, Rafiei H5, Safarpour AR1, Gheibihayat SM6, Raeis-Abdollahi E7, Savardashtaki A4, Ghanbariasad A8, Omidifar N9

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Recently, the novel coronavirus disease 2019 (COVID-19), has attracted the attention of scientists where it has a high mortality rate among older adults and individuals suffering from chronic diseases, such as chronic kidney diseases (CKD). It is important to elucidate molecular mechanisms by which COVID-19 affects the kidneys and accordingly develop proper nutritional and pharmacological strategies. Although numerous studies have recently recommended several approaches for the management of COVID-19 in CKD, its impact on patients with renal diseases remains the biggest challenge worldwide. In this paper, we review the most recent evidence regarding causality, potential nutritional supplements, therapeutic options, and management of COVID-19 infection in vulnerable individuals and patients with CKD.
To date, there is no effective treatment for COVID-19-induced kidney dysfunction, and current treatments are yet limited to anti-inflammatory (e.g. ibuprofen) and anti-viral medications (e.g. Remdesivir, and Chloroquine/Hydroxychloroquine) that may increase the chance of treatment.
In conclusion, the knowledge about kidney damage in COVID-19 is very limited, and this review improves our ability to introduce novel approaches for future clinical trials for this contiguous disease.


8.3. Vitamin D (Clipped from the PDF)

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Once vitamin D is produced either in the skin from 7-DHC or absorbed from the diet, it must be activated first to 25OHD and then to its active form 1,25(OH)2D in a multistage liver and kidney metabolisms. The production of vitamin D is not enzymatic but depends on UVB [97]. Vitamin D is a fat-soluble essential vitamin that has a substantial role in promoting innate immune responses and suppressing adaptive immune responses (Figure 4) [98]. Multiple cross-sectional studies have shown that vitamin D deficiency is associated with increased susceptibility to serious viral respiratory tract infections [98]. The beneficial effects of vitamin D on protective immunity are partly due to crosstalk between vitamin D metabolism, VDR signaling, and innate immunity, where TLR binding leads to increased expression of both 1-a-hydroxylase and VDR. This results in the binding of the 1,25 D-VDR-RXR heterodimer to the VDREs of the genes for cathelicidin and beta-defensin 4 and subsequent transcription of these proteins [99]. Immune responses may be enhanced by cathelicidin and some p-defensins that not only act against microbes, but also have chemoattractant capabilities, leading to recruitment of neutrophils, monocytes, and other immune cell molecules to the site of infection (Figure 4). Vitamin D substantially exerts a modulatory role in the adaptive immune system. Recently, studies evaluating 157 potential mechanisms showed that vitamin D plays a pivotal inhibitory role in the innate immune sensing of respiratory viral infections, e.g., influenza A and B, parainfluenza 1 and 2, and respiratory syncytial virus (RSV). A systematic review which that included 39 studies on the function of vitamin D in the prevention of respiratory tract infections showed a statistically significant association between low vitamin D status and increased risk of either upper and lower respiratory tract infections [100]. However, several RCTs revealed conflicting findings regarding this association, possibly due to regimens heterogeneity and baseline serum vitamin D level [100]. An RCT evaluating the effect of high-dose (2000 IU) each day versus standard-dose (400 IU) each day vitamin D supplementation showed no significant difference between the two groups on viral upper respiratory tract infections [101]. However, a recent report on the effect of vitamin D supplements on influenza vaccine response among vitamin D deficient elderly individuals exert a lymphocyte polarization into a tolerogenic immune response, where it promoted a higher TGFp plasma level without ameliorating antibody production [102]. Furthermore, researchers suggest that, a monthly supplementation with high-dose (100,000 IU) per month versus standard-dose group (12,000 IU) per month vitamin D reduced the incidence of acute respiratory infections [103]. It has been shown that the protective effect of vitamin D on antiviral immunity against respiratory infections is presumably dependent on the vitamin D level of the subject in which vitamin D-deficient individuals would benefit more. Given the higher mortality rate from COVID-19 in some countries compared to others, comparing data across nations is complicated. Vitamin D status of populations is one mostly overlooked factor that could be related to the outcome of COVID-19.
A growing body of circumstantial evidence has now specifically linked outcomes of COVID-19 with vitamin D status [104]. The role of vitamin D in the response to COVID-19 infection could be two-fold.

  • First, antimicrobial peptides (AMPs) production in the respiratory epithelium is supported with vitamin D, making infection with the virus and progression ofCOVID-19 signs less likely.
  • Second, vitamin D might help to reduce the inflammatory response to infection with SARS-CoV-2 [98]. Cytokine storm, organ system interaction, and systemic effects are the possible mechanisms of renal injury in patients with Covid-19.

The main function of the kidneys is to remove wastes and excess water from the body. It is reported that patients with kidney disease often have low levels of vitamin D in their blood [105, 106]. Furthermore, people with reduced kidney function develop alterations levels of phosphorus and calcium in the blood. Gradual loss of kidney function leading to the inability to get rid of phosphorus into tubules and inactivation of vitamin D, to maintain normal levels of calcium. These changes are sensed by the parathyroid gland and calcium is increased through the elevating production and release of parathyroid hormone. Accordingly, bone metabolism is altered by these metabolic changes to release calcium and accordingly lead to bone abnormalities and, therefore bone deformation, bone pain, and altered risks of fracture may occur [107]. A recent report indicated that even short-term acute vitamin D deficiency could directly lead to hypertension and impacts on renin-angiotensin system components that result in kidney injury. In cases with CKD, vitamin D deficiency has frequently been associated with proteinuria, albuminuria, progression to end-stage renal disease (ESRD) and increased risk for all-cause mortality (Figure 4)[109].

Attached files

ID Name Comment Uploaded Size Downloads
14994 Kidney vitamin D.jpg admin 06 Feb, 2021 01:52 91.72 Kb 75
14993 Kidney disease nutrients for COVID-19.jpg admin 06 Feb, 2021 01:40 23.41 Kb 94
14992 Kidney diseases and COVID-19 Jan 19.pdf PDF 2021 admin 06 Feb, 2021 01:38 1.97 Mb 63
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