Cholecalciferol decreases inflammation and improves vitamin D regulatory enzymes in lymphocytes in the uremic environment: A randomized controlled pilot trial

Carvalho, José Tarcísio Giffoni de; Schneider, Marion; Cuppari, Lílian; Grabulosa, Caren Cristina; Aoike, Danilo Takashi; Redublo, Beata Marie Quinto; Batista, Marcelo C.; Cendoroglo, Miguel; Moysés, Rosa Maria Affonso; Dalboni, Maria Aparecida

doi:10.1371/journal.pone.0179540

Cited by 43 publications

(27 citation statements)

References 38 publications

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“…In support with our suggestion above, VD 3 in our study resulted in significant alleviations in renal and testicular tissue injuries observed in animals exposed to Pb-only. VD 3 also restored and/or preserved the expression of its cellular endogenous molecules compared with positive controls, suggesting a positive feedback regulation, a common phenomenon previously reported by many studies following treatment with VD 49 – 51 .…”

Section: Discussionsupporting

confidence: 75%

Vitamin D alleviates lead induced renal and testicular injuries by immunomodulatory and antioxidant mechanisms in rats

BaSalamah

Abdelghany

El‐Boshy

et al. 2018

Sci Rep

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This study measured the effects of vitamin D (VD) supplementation on the underlying molecular pathways involved in renal and testicular damage induced by lead (Pb) toxicity. Thirty two adult male Wistar rats were divided equally into four groups that were treated individually or simultaneously, except the negative control, for four weeks with lead acetate in drinking water (1,000 mg/L) and/or intramuscular VD (1,000 IU/kg; 3 days/week). Pb toxicity markedly reduced serum VD and Ca2+, induced substantial renal and testicular injuries with concomitant significant alterations in the expression of VD metabolising enzymes, its receptor and binding protein, and the calcium sensing receptor. Pb also significantly promoted lipid peroxidation and pro-inflammatory cytokines (IL-4 and TNF-α) in the organs of interest concomitantly with declines in several anti-oxidative markers (glutathione, glutathione peroxidase and catalase) and the anti-inflammatory cytokine, IL-10. The co-administration of VD with Pb markedly mitigated renal and testicular injuries compared with positive controls. This was associated with restoration of the expression of VD related molecules, promotion of anti-oxidative and anti-inflammatory markers, but tissue Pb concentrations were unaffected. In conclusion, this report is the first to reveal potential protective effects for VD against Pb-induced renal and testicular injuries via anti-inflammatory and anti-oxidative mechanisms.

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Section: Discussionsupporting

confidence: 75%

Vitamin D alleviates lead induced renal and testicular injuries by immunomodulatory and antioxidant mechanisms in rats

BaSalamah

Abdelghany

El‐Boshy

et al. 2018

Sci Rep

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“…Cholecalciferol supplementation reduces inflammation and, subsequently, the C-reactive protein level [21,22]. The findings from a randomized placebo-controlled clinical trial showed that cholecalciferol supplementation had an anti-inflammatory effect and it increased the expression of the intracellular vitamin D regulatory enzymes within lymphocytes in a uremic environment [23]. In the present study, the association between vitamin D and mortality persisted, even after the model was adjusted for the C-reactive protein levels.…”

Section: Discussionsupporting

confidence: 43%

Association between vitamin D levels and mortality in hemodialysis patients: a cohort study

et al. 2020

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Introduction: Low vitamin D levels are associated with mortality in hemodialysis (HD) patients; however, the serum vitamin D thresholds are unclear. This study aimed to identify the vitamin D level below which mortality increases in HD patients. Methods: A cohort of HD patients enrolled from January 2014 to January 2017 was evaluated. The variables were analyzed according to the season, namely, summer, winter, and annual average, mortality was the primary outcome. The patients were assigned to vitamin D quintiles, and multivariate Cox regression analysis adjusted for age, ethnicity, gender, body mass index (BMI), inhibitors of the renin-angiotensin system, statin, calcitriol, and antiplatelet drugs use, hemodialysis vintage, hypertension, diabetes mellitus, atherosclerotic disease, and C-reactive protein was performed. Results: There were studied 306 patients. Vitamin D levels of 18.0-23.6 ng/mL (hazard ratio [HR] ¼ 4.30; 95% confidence interval [CI] 1.60-11.54, p ¼ 0.004) and <18.0 ng/mL (HR ¼ 3.83; 95% CI: 1.42-10.35, p ¼ 0.008) in summer and vitamin D levels of 21.5-27.1 ng/mL (HR ¼ 3.70; 95% CI: 1.50-9.11, p ¼ 0.004) and 17.5 ng/mL (HR ¼ 2.84; 95% CI: 1.13-7.13, p ¼ 0.026) in winter were associated with mortality. The average annual values of vitamin D associated with all-cause mortality were <17.7 ng/dL (adjusted HR ¼ 4.25, 95% CI: 1.57-11.48, p ¼ 0.004), and between >17.7 ng/dL and 23.1 ng/dL (adjusted HR ¼ 3.91, 95% CI: 1.47-10.42, p ¼ 0.006). Conclusions: Annual average vitamin D levels <23.1 ng/mL were associated with higher all-cause mortality, regardless of the confounding variables evaluated.

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“…These data have been confirmed in a recent randomized controlled trial showing increased circulating klotho and total antioxidant capacity after 12 weeks of cholecalciferol treatment compared to the placebo group [95]. Human ex vivo studies indicate that vitamin D exerts anti-inflammatory effects on uremic lymphocytes under renal replacement therapy (RRT) [96]. Meta-analyses demonstrating reduced circulating markers of inflammation in mostly non-CKD subjects on vitamin D supplementation [97,98], further supporting a significant role of vitamin D on the hallmarks of ageing.…”

Section: The Endocrine Phosphate-fgf-23-klotho Axis and Premature Agementioning

confidence: 77%

Inflammation and Premature Ageing in Chronic Kidney Disease

Ebert

Pawelzik

Witasp

et al. 2020

Toxins

162

122

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Persistent low-grade inflammation and premature ageing are hallmarks of the uremic phenotype and contribute to impaired health status, reduced quality of life, and premature mortality in chronic kidney disease (CKD). Because there is a huge global burden of disease due to CKD, treatment strategies targeting inflammation and premature ageing in CKD are of particular interest. Several distinct features of the uremic phenotype may represent potential treatment options to attenuate the risk of progression and poor outcome in CKD. The nuclear factor erythroid 2-related factor 2 (NRF2)–kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1 (KEAP1) signaling pathway, the endocrine phosphate-fibroblast growth factor-23–klotho axis, increased cellular senescence, and impaired mitochondrial biogenesis are currently the most promising candidates, and different pharmaceutical compounds are already under evaluation. If studies in humans show beneficial effects, carefully phenotyped patients with CKD can benefit from them.

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Cholecalciferol decreases inflammation and improves vitamin D regulatory enzymes in lymphocytes in the uremic environment: A randomized controlled pilot trial

Cited by 43 publications

References 38 publications

Vitamin D alleviates lead induced renal and testicular injuries by immunomodulatory and antioxidant mechanisms in rats

Vitamin D alleviates lead induced renal and testicular injuries by immunomodulatory and antioxidant mechanisms in rats

Association between vitamin D levels and mortality in hemodialysis patients: a cohort study

Inflammation and Premature Ageing in Chronic Kidney Disease

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