The Role of Vitamin D in SARS-CoV-2 Infection and Acute Kidney Injury

Hsieh, Ming-Chun; Hsiao, Po-Jen; Liao, Min-Tser; Hou, Yi‐Chou; Chang, Ya-Chieh; Chiang, Wei Fan; Wu, Kunlin; Chan, Jenq-Shyong; Lu, Kuo‐Cheng

doi:10.3390/ijms23137368

Cited by 15 publications

(10 citation statements)

References 128 publications

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“…To interpret another reason, we can point to the effect of vitamin D in the hampering of leukocytes' adhesion to the endothelium (16). In one review article, Hsieh et al explained the role of vitamin D in the AKI and COVID-19 and supported our hypothesis (10).…”

Section: Discussionsupporting

confidence: 57%

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The association between vitamin D3 deficiency and acute kidney injury in COVID-19 patients

et al. 2023

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Introduction: Vitamin D deficiency is a common clinical finding in the general population and hospitalized patients, including patients in the intensive care unit (ICU). Acute kidney injury (AKI) occurs in more than 50% in ICU admitted patients. Objectives: There are few studies regarding AKI in COVID-19 patients, therefore we investigated the relationship between vitamin D3 deficiency and the occurrence of AKI in COVID-19 patients. Patients and Methods: This cross-sectional study was conducted on 69 COVID-19 patients who were hospitalized in the ward for 12 months. Their serum vitamin D3 levels were measured in the first 24 hours of hospitalization in the ward. Patients were divided into three groups based on the serum levels of vitamin D3: >50 ng/mL as normal, 20-50 ng/mL as insufficient and <20 ng/mL as deficiency status. The patients were studied until the occurrence of acute renal injury or the occurrence of death. Results: Out of 69 hospitalized patients in the ward with COVID-19, there were 39 patients in group vitamin D3<20 ng/mL, 21 patients in group vitamin D3 of 20-50ng/mL and 9 patients in group of vitamin D3>50 ng/mL. The frequencies of AKI in groups of vitamin D3<20 ng/mL, 20-50 ng/mL, and >50 ng/mL were 46%, 28%, and 23%, respectively. A significant relationship was observed between AKI and our study groups (P=0.011). Furthermore, there was a significant association between our study groups and mortality (P=0.014), ICU admission (P=0.041) and hospital length of stay (P=0.017). In another division in patients with different levels of vitamin D3 in the presence or absence of AKI, there were significant associations between patients with vitamin D3<20 ng/mL and the presence of AKI and also with mortality (P=0.042), ICU admission (P=0.024) and additionally with hospital length of stay (P=0.027). Conclusion: Our study showed significant association between vitamin D deficiency and AKI in ICU-admitted COVID-19 patients. Moreover, there were relationships between vitamin D deficiency and mortality, ICU admission and hospital length of stay. These results suggest the correction of vitamin D deficiency may be beneficial to reduce AKI in patient with COVID-19.

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Section: Discussionsupporting

confidence: 57%

“…To the best of our knowledge, few studies examined the relationship between vitamin D deficiency and AKI in COVID-19 patients, and their results were inconsistent (10,11). The current study aimed to assess whether the vitamin D3 level at the beginning of hospitalization in COVID-19 patients was correlated to AKI.…”

Section: Discussionmentioning

confidence: 96%

The association between vitamin D3 deficiency and acute kidney injury in COVID-19 patients

et al. 2023

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“…A recent casecontrol study revealed that severe COVID-19 can be associated with ED in healthy individuals as a complication, even after their recovery [29]. The long-term consequences on erectile function in men with COVID- 19 are not yet well understood [30]. To the best of our knowledge, only one study showed the presence of viral particles in perivascular erectile tissue, as well as lower protein expression for eNOS in comparison to specimens from men without COVID-19.…”

Section: Discussionmentioning

confidence: 97%

Serum from Men with the Severe Form of COVID-19 Impairs the Nitric Oxide Signaling Pathway in Isolated Corpus Cavernosum from Mice: An In Vitro Study

et al. 2023

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Introduction. Erectile dysfunction (ED) is characterized by the inability to achieve and/or maintain an erection during sexual activity. Vascular-related diseases such as obesity, diabetes, aging, and hypertension are known risk factors that increase the prevalence of ED. The viral infection caused by SARS-CoV-2, the etiological agent of COVID-19, can evolve into mild to severe forms. Patients with comorbidities such as diabetes and obesity present a more severe state of the disease. The cytokine storm and reactive oxygen species associated with COVID-19 can lead to progressive systemic inflammation and vascular dysfunction. This study is aimed at assessing the in vitro effects of serum obtained from unvaccinated men who had the severe form of COVID-19 in isolated corpus cavernosum (CC) from healthy mice. Methods. Concentration-response curves to endothelium-dependent and endothelium-independent substances were carried out in isolated CC from mice after being incubated (3 hours) with serum obtained from patients with and without (control group) the severe form of COVID-19. qRT-PCR and western blotting were also carried out. Results. The relaxing responses induced by acetylcholine (ACh), a nitric oxide donor (sodium nitroprusside), soluble guanylate cyclase (sGC) stimulator (BAY 63-2521), and phosphodiesterase type 5 (PDE5) inhibitor (tadalafil) were significantly reduced in CC incubated with COVID-19 serum when compared with CC incubated with the control serum. Nonetheless, the relaxation induced by the sGC activator BAY 58-2667 was unaffected in CC stimulated with the COVID-19 serum. The coincubation of control or COVID-19 serum with a free radical scavenger (PEG-SOD; 150 UI/mL, 3 hours) significantly improved the relaxation induced by ACh. On the other hand, catalase did not improve ACh-induced relaxation in CC incubated with the sera. The gene expression for PDE5 and NADPH oxidase type 4 was increased in CC stimulated with COVID-19 serum in comparison to tissues stimulated with the control serum. The protein expression for sGC subunits was similar in both groups. Conclusion. Serum obtained from unvaccinated men who presented the severe form of COVID-19 impaired the relaxation induced by cyclic guanosine monophosphate-accumulating substances in CC from mice.

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“…Current evidence suggests that high levels of suPAR are probably a risk factor for AKI in patients with COVID-19 [18] and this AKI may be related to vitamin D status [168]. Clinically, higher levels of suPAR are linked to a rapid deterioration of renal function in children with CKD [169].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, vitamin D is comparatively inexpensive, safe, and widely available. Therefore, supplementation could be considered in these high-risk groups, especially in patients with AKI [53,168]. However, well-designed research is needed to better explore the possible linkage between vitamin D deficiency and COVID-19 morbidity and mortality, and to assess whether the correction of this deficiency can avoid or lessen the severity of COVID-19-related AKI.…”

Section: Discussionmentioning

confidence: 99%

The Perspective of Vitamin D on suPAR-Related AKI in COVID-19

Liao

et al. 2022

IJMS

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The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of millions of people around the world. Severe vitamin D deficiency can increase the risk of death in people with COVID-19. There is growing evidence that acute kidney injury (AKI) is common in COVID-19 patients and is associated with poorer clinical outcomes. The kidney effects of SARS-CoV-2 are directly mediated by angiotensin 2-converting enzyme (ACE2) receptors. AKI is also caused by indirect causes such as the hypercoagulable state and microvascular thrombosis. The increased release of soluble urokinase-type plasminogen activator receptor (suPAR) from immature myeloid cells reduces plasminogen activation by the competitive inhibition of urokinase-type plasminogen activator, which results in low plasmin levels and a fibrinolytic state in COVID-19. Frequent hypercoagulability in critically ill patients with COVID-19 may exacerbate the severity of thrombosis. Versican expression in proximal tubular cells leads to the proliferation of interstitial fibroblasts through the C3a and suPAR pathways. Vitamin D attenuates the local expression of podocyte uPAR and decreases elevated circulating suPAR levels caused by systemic inflammation. This decrease preserves the function and structure of the glomerular barrier, thereby maintaining renal function. The attenuated hyperinflammatory state reduces complement activation, resulting in lower serum C3a levels. Vitamin D can also protect against COVID-19 by modulating innate and adaptive immunity, increasing ACE2 expression, and inhibiting the renin–angiotensin–aldosterone system. We hypothesized that by reducing suPAR levels, appropriate vitamin D supplementation could prevent the progression and reduce the severity of AKI in COVID-19 patients, although the data available require further elucidation.

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The Role of Vitamin D in SARS-CoV-2 Infection and Acute Kidney Injury

Cited by 15 publications

References 128 publications

The association between vitamin D3 deficiency and acute kidney injury in COVID-19 patients

The association between vitamin D3 deficiency and acute kidney injury in COVID-19 patients

Serum from Men with the Severe Form of COVID-19 Impairs the Nitric Oxide Signaling Pathway in Isolated Corpus Cavernosum from Mice: An In Vitro Study

The Perspective of Vitamin D on suPAR-Related AKI in COVID-19

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