-
Heliyon Aug 2022Exposure to air pollution can interfere with the vitamin D endocrine system. This study investigated the effects of airborne particulate matter (PM) on renal tubular...
BACKGROUND
Exposure to air pollution can interfere with the vitamin D endocrine system. This study investigated the effects of airborne particulate matter (PM) on renal tubular cell injury and explored the underlying mechanisms.
METHODS
HK-2 human renal proximal tubule cells were treated with PM with or without 1,25(OH)D analog, 19-Nor-1,25(OH)D (paricalcitol, 10 nM) for 48 h. The dose- and time-dependent cytotoxicity of PM with or without paricalcitol was determined via cell counting kit-8 assay. Cellular oxidative stress was assessed using commercially available enzyme-linked immunosorbent assay kits. The protein expression of vitamin D receptor (VDR), cytochrome P450(CYP)27B1, CYP24A1, renin, angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1), nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor-kB (NF-kB), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 was determined.
RESULTS
PM exposure decreased HK-2 cell viability in a dose- and time-dependent manner. The activities of superoxide dismutase and malondialdehyde in HK-2 cells increased significantly in the group exposed to PM. PM exposure decreased VDR and Nrf2, while increasing CYP27B1, renin, ACE, AT1, NF-kB, TNF-α, and IL-6. The expression of VDR, CYP27B1, renin, ACE, AT1, and TNF-α was reversed by paricalcitol treatment. Paricalcitol also restored the cell viability of PM-exposed HK-2 cells.
CONCLUSION
Our findings indicate that exposure to PM induces renal proximal tubular cell injury, concomitant with alteration of vitamin D endocrine system and renin angiotensin system. Vitamin D could attenuate renal tubular cell damage following PM exposure by suppressing the renin-angiotensin system and by partially inhibiting the inflammatory response.
PubMed: 36033312
DOI: 10.1016/j.heliyon.2022.e10184 -
Journal of Acute Medicine Mar 2024Sepsis is a potentially fatal organ failure produced by the host's immune response to infection. It is critical to identify risk factors associated with a poor prognosis...
Sepsis is a potentially fatal organ failure produced by the host's immune response to infection. It is critical to identify risk factors associated with a poor prognosis in septic patients in order to develop new therapy options. Vitamin D deficiency (25-hydroxyvitamin cholecalciferol < 20 ng/mL) is common in critical and septic patients. Serum vitamin D concentrations are associated with an increased incidence of mortality in critically ill adult patients. In critically ill patients, vitamin D supplementation (a very high vitamin D or cholecalciferol loading dosage as a single bolus dose ranging from 400,000 to 540,000 IU) is feasible and safe. Some of the trials and their post-hoc analyses evaluating vitamin D supplementation in severely sick individuals, including septic patients, suggested possible benefits in mortality (reduced 28-day mortality in the range of 8.1%-17.5%), and other outcomes (reduction in hospital length in the range from 9 to 18 days, and decrease in duration of mechanical ventilation in the range from 5 to 10 days). Despite the fact that many studies support the provision of vitamin D to septic patients, there are still many studies that contradict this opinion, and there is still debate about the recommendation to use vitamin D in sepsis. A pragmatic clinical approach in severe sepsis could be supplementation of vitamin D if serum levels are diminished (< 30 ng/mL). It appears that a single ultrahigh dose of vitamin D (cholecalciferol) could be administered to the septic patient via an enteral tube, followed by daily or monthly maintenance doses. Parenteral administration might be reserved for a subgroup of septic patients with gastrointestinal, hepatic, or renal dysfunction. Future clinical trials designed exclusively for septic patients are required to assess the potential advantages of vitamin D. Possible impacts of selective activators of vitamin D receptors, such as paricalcitol, should be elucidated in sepsis. This emphasizes the requirement for more study and confirmation of any potential beneficial effects of vitamin D in sepsis.
PubMed: 38487755
DOI: 10.6705/j.jacme.202403_14(1).0001 -
Frontiers in Clinical Diabetes and... 2021Previous studies have shown that vitamin D analogs (such as paricalcitol) can reduce albuminuria in patients with diabetes mellitus and retard the progression of...
INTRODUCTION
Previous studies have shown that vitamin D analogs (such as paricalcitol) can reduce albuminuria in patients with diabetes mellitus and retard the progression of diabetic kidney disease (DKD). A recent systematic review reported significant improvement of renal function in patients with DKD who received vitamin D or its analogs. Study-driven data about their use in improving DKD outcomes have continued to accumulate over the years.
AIM
This paper aims to systematically review the contemporary evidence about the effectiveness of vitamin D analogs in retarding the onset or progression of DKD.
METHODS
With appropriate descriptors, two electronic databases (PubMed and Google Scholar) were searched for articles published between 2015 and 2021 in the English language. Primary studies that fulfilled the inclusion criteria were selected; their titles and abstracts were screened, and duplicates were removed. Relevant data were retrieved from the final selected studies using a preconceived data-extraction form.
RESULTS
A total of eight studies (three randomized-controlled trials, one prospective study, and four cross-sectional studies) were reviewed. A total of 6,243 participants were investigated in the eight studies and comprised young adults, middle-aged adults, and the elderly with a male-gender predominance. One randomized controlled trial reported that paricalcitol significantly improved renal function in type 1 diabetes patients with renal impairment when combined with renin-angiotensin-aldosterone system (RAAS) blockers. A strong correlation between vitamin D deficiency and DKD risk was noted in the majority of the cross-sectional studies. High doses of cholecalciferol (4,000 or 10,000 IU/day), given early in DKD, significantly reduced disease prevalence.
CONCLUSION
Paricalcitol may retard the onset or progression of DKD, especially if administered in combination with RAAS blockers. The association of vitamin D deficiency with DKD risk also supports this therapeutic effect. Future systematic reviews are still needed to strengthen the current evidence on therapeutic benefit of vitamin D or its analogs in DKD.
PubMed: 36994344
DOI: 10.3389/fcdhc.2021.763844 -
Laboratory Investigation; a Journal of... Dec 2019Liver cirrhosis is a life-threatening consequence of liver fibrosis. The aim of this study was to investigate the antifibrotic potential of clinically available vitamin... (Comparative Study)
Comparative Study
Liver cirrhosis is a life-threatening consequence of liver fibrosis. The aim of this study was to investigate the antifibrotic potential of clinically available vitamin D analogs compared to that of calcitriol in vitro and in vivo. Murine hepatic stellate cells, Kupffer cells, and human LX-2 cells were treated with vitamin D analogs, and the profibrotic behavior of these cells was studied. In vivo liver fibrosis was induced using CCl until measurable fibrosis was established. Animals were then treated with calcitriol and paricalcitol. Vitamin D and its analogs showed antifibrotic effects in vitro. Treatment with active vitamin D (calcitriol, CAL) and its analogs reduced the protein expression of α-smooth muscle actin (α-SMA) in mHSC. In human LX-2 cells alfacalcidol reduced transforming growth factor-β (TGF-β) induced platelet-derived growth factor receptor-β protein expression and contractility while paricalcitol (PCT), in its equipotent dose to CAL, reduced TGF-β induced α-SMA protein expression, and ACTA2 and TGF-β mRNA expression. No effects of a treatment with vitamin D and its analogs were observed in Kupffer cells. In vivo, PCT-treated mice had significantly lower calcium levels than CAL-treated mice. CAL and PCT reduced the hepatic infiltration of CD11b-positive cells and alanine transaminase levels, while PCT but not CAL significantly inhibited fibrosis progression, with a favorable side effect profile in the CCl model. We conclude that hypocalcemic vitamin D analogs should be considered in future studies investigating vitamin D for the treatment of liver fibrosis.
Topics: Animals; Calcitriol; Calcium; Carbon Tetrachloride; Cell Line; Drug Evaluation, Preclinical; Ergocalciferols; Hepatic Stellate Cells; Humans; Kupffer Cells; Liver Cirrhosis; Male; Mice, Inbred C57BL; Primary Cell Culture; Transforming Growth Factor beta; Vitamin D
PubMed: 31467426
DOI: 10.1038/s41374-019-0310-1 -
Nutrition, Metabolism, and... Jan 2024The effect of increased vitamin D levels on vascular function in patients with chronic kidney disease (CKD) is controversial. This meta-analysis aimed to assess the... (Meta-Analysis)
Meta-Analysis
AIM
The effect of increased vitamin D levels on vascular function in patients with chronic kidney disease (CKD) is controversial. This meta-analysis aimed to assess the effect of regulated vitamin D increase on vascular markers in patients with CKD.
DATA SYNTHESIS
We searched PubMed, Web of Science, Embase and ClinicalTrials.gov from database inception up until July 21, 2023. We included randomized controlled trials assessing the effects of using vitamin D and its analogues on vascular function in patients with CKD. Fixed-effects and random-effects model analyses were performed using weighted mean difference effects for each trial by heterogeneity (I2) assessment. Primary outcomes encompassed blood flow-mediated dilation (FMD)、pulse wave velocity (PWV) and augmentation index (AIx).
FINDINGS
From 1964 records we selected 12 trials, 5 (n = 331) on FMD, 8 (n = 626) on PWV and 4 (n = 393) on AIx. Vitamin D and VDRA supplementation failed to significantly improve FMD (WMD 1.68%; 95% CI -0.18 to 3.53; P = 0.08; I = 88%)、PWV (WMD -0.41 m/s; 95%CI -0.95 to 0.13; P = 0.14; I = 57%)and AIx (WMD -0.53%; 95%CI -1.69 to 0.63; P = 0.37; I = 0%). Subgroup analysis revealed that 2 μg paricalcitol significantly improved FMD (WMD 2.09%; 95%CI 1.28 to 2.90; P < 0.00001); I = 0%), as did cholecalciferol (WMD 5.49%; 95% CI 4.35 to 6.63; P < 0.00001).
CONCLUSION
Supplementation vitamin D and VDRA are associated with improved vascular function as measured by FMD, but not arterial stiffness as measured by PWV and AIx, tentatively suggesting that regulating the increase of vitamin D could not potentially reduce the incidence of cardiovascular disease.
Topics: Humans; Vitamin D; Pulse Wave Analysis; Randomized Controlled Trials as Topic; Vitamins; Vascular Stiffness; Renal Insufficiency, Chronic
PubMed: 38000993
DOI: 10.1016/j.numecd.2023.09.015 -
International Journal of Nephrology and... 2019In a high percentage of patients with chronic kidney disease (CKD) low levels of vitamin D are detected. The purpose of this study was to evaluate if the native vitamin...
UNLABELLED
In a high percentage of patients with chronic kidney disease (CKD) low levels of vitamin D are detected. The purpose of this study was to evaluate if the native vitamin D therapy (cholecalciferol) in the patients with stage 3 and hypovitaminosis D allows to modify markers of bone and mineral metabolism once normal serum levels have been achieved.
MATERIALS AND METHODS
From an initial base of 297 patients with CKD and hypovitaminosis D, those with normal or high levels of PTH were chosen for therapy with native vitamin D. The initial administered dose was 1000 IU/day, with adjustments every 4 months of 1000 IU (maximum 4000 IU/day, according to RDA and IOM), until achieving serum levels of 25 hydroxyvitamin D greater than 30 ng/mL and lower than 80 ng/mL. The variables calcium, phosphorus, intact parathormone (iPTH), creatinine and glomerular filtration rate (GFR) were also evaluated every 4 months.
RESULTS
The total number of patients included in this study was 170. Seventy-three patients were excluded along the follow-up: 17 non-responders (never achieved the projected serum levels of vitamin D), and 56 for not completing one year of follow-up. A total of 97 patients were finally included. In 82 patients, follow-up was achieved for 12 months (G1) and in 38 patients for 24 months (G2). In 15 patients despite achieving satisfactory levels of vitamin D at 12 months, it was not possible to obtain adequate levels of iPTH for their GFR according to K/DOQI 2003 guidelines and they were called refractory to therapy (G3). In both groups 1 and 2, a non-significant tendency to increase calcium and serum phosphorus was observed. iPTH decreased significantly at 12 and 24 months follow-up. In group 3, we opted at 12 months for conversion to calcitriol, with a significant reduction in iPTH values. In this group, the initial value of GFR was close to 30 mL/min, and its fall in time more significant than the other two groups to CKD stage 4.
CONCLUSION
Cholecalciferol with adjustment in its dose, and obtaining normal serum levels is an excellent therapeutic alternative for the treatment of patients with CKD stage 3, and hypovitaminosis D. In the group of patients with GFR close to 30 mL/min, or lower values (stage 4), and with the presence of secondary hyperparathyroidism, the use of active form of vitamin D (calcitriol, paricalcitol) is recommended as the first therapeutic alternative.
PubMed: 31827333
DOI: 10.2147/IJNRD.S214194 -
Journal of Cardiovascular Development... Oct 2021Vitamin D secosteroids are intranuclear regulators of cellular growth and suppress the renin-angiotensin system. The aim of this study was to test the hypothesis that...
Vitamin D secosteroids are intranuclear regulators of cellular growth and suppress the renin-angiotensin system. The aim of this study was to test the hypothesis that the vitamin D receptor agonist, paricalcitol (PC), either alone or with enalapril (E) (an angiotensin-converting enzyme inhibitor), reduces the progression of polycystic kidney disease. Preventative treatment of Lewis polycystic kidney (LPK) and Lewis control rats with PC (0.2 μg/kg i.p. 5 days/week) or vehicle from postnatal weeks 3 to 10 did not alter kidney enlargement. To evaluate the efficacy in established disease, LPK rats received either PC (0.8 μg/kg i.p; 3 days/week), vehicle, E (50 mg/L in water) or the combination of PC + E from weeks 10 to 20. In established disease, PC also did not alter the progression of kidney enlargement, kidney cyst growth or decline in renal function in LPK rats. Moreover, the higher dose of PC was associated with increased serum calcium and weight loss. However, in established disease, the combination of PC + E reduced systolic blood pressure and heart-body weight ratio compared to vehicle and E alone ( < 0.05). In conclusion, the combination of PC + E attenuated cardiovascular disease but caused hypercalcaemia and did not alter kidney cyst growth in LPK rats.
PubMed: 34821697
DOI: 10.3390/jcdd8110144 -
Calcified Tissue International Aug 2021A large proportion of patients with chronic kidney disease (CKD) are vitamin D deficient (plasma 25-hydroxyvitamin D (25(OH)D) < 25 or 30 nmol/L per UK and US... (Meta-Analysis)
Meta-Analysis
Vitamin D Supplementation for Patients with Chronic Kidney Disease: A Systematic Review and Meta-analyses of Trials Investigating the Response to Supplementation and an Overview of Guidelines.
A large proportion of patients with chronic kidney disease (CKD) are vitamin D deficient (plasma 25-hydroxyvitamin D (25(OH)D) < 25 or 30 nmol/L per UK and US population guidelines) and this contributes to the development of CKD-mineral bone disease (CKD-MBD). Gaps in the evidence-base for the management of vitamin D status in relation to CKD-MBD are hindering the formulation of comprehensive guidelines. We conducted a systemic review of 22 RCTs with different forms of vitamin D or analogues with CKD-MBD related outcomes and meta-analyses for parathyroid hormone (PTH). We provide a comprehensive overview of current guidelines for the management of vitamin D status for pre-dialysis CKD patients. Vitamin D supplementation had an inconsistent effect on PTH concentrations and meta-analysis showed non- significant reduction (P = 0.08) whereas calcifediol, calcitriol and paricalcitol consistently reduced PTH. An increase in Fibroblast Growth Factor 23 (FGF23) with analogue administration was found in all 3 studies reporting FGF23, but was unaltered in 4 studies with vitamin D or calcifediol. Few RCTS reported markers of bone metabolism and variations in the range of markers prevented direct comparisons. Guidelines for CKD stages G1-G3a follow general population recommendations. For the correction of deficiency general or CKD-specific patient guidelines provide recommendations. Calcitriol or analogues administration is restricted to stages G3b-G5 and depends on patient characteristics. In conclusion, the effect of vitamin D supplementation in CKD patients was inconsistent between studies. Calcifediol and analogues consistently suppressed PTH, but the increase in FGF23 with calcitriol analogues warrants caution.
Topics: Dietary Supplements; Fibroblast Growth Factor-23; Humans; Parathyroid Hormone; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency
PubMed: 33895867
DOI: 10.1007/s00223-021-00844-1 -
Cellular and Molecular Gastroenterology... 2023Observational epidemiologic studies have associated vitamin D deficiency with cholestasis. We reported previously that activation of the vitamin D/vitamin D receptor...
BACKGROUND & AIMS
Observational epidemiologic studies have associated vitamin D deficiency with cholestasis. We reported previously that activation of the vitamin D/vitamin D receptor (VDR) axis in cholangiocytes mitigates cholestatic liver injury by remodeling the damaged bile duct. However, the function of VDR in hepatocytes during cholestasis remains unclear.
METHODS
Paricalcitol (VDR agonist, 200 ng/kg) was injected intraperitoneally into bile duct-ligated mice every other day for 5 days. Primary hepatocytes and HepG2 hepatoma cells were transfected with Vdr short hairpin RNA, control short hairpin RNA, Vdr plasmid, control vector, Atg5 small interfering RNA (siRNA), and control siRNA. Liver histology, cell proliferation, and autophagy were evaluated.
RESULTS
Treatment with the VDR agonist paricalcitol improved liver injury in bile duct-ligated mice by up-regulating VDR expression in hepatocytes, which in turn reduced hepatocyte apoptosis by inhibiting reactive oxygen species (ROS) generation via suppressing the Ras-related C3 botulinum toxin substrate 1/reduced nicotinamide adenine dinucleotide phosphate oxidase 1 pathway. Mechanistically, upon exposure to an ROS-inducing compound, Vdr siRNA contributed to apoptosis, whereas the Vdr overexpression caused resistance to apoptosis. Interestingly, up-regulated VDR expression also increased the generation of autophagosomes and macroautophagic/autophagic flux, which was the underlying mechanism for reduced apoptosis following VDR activation. Autophagy depletion impaired the positive effects of VDR overexpression, whereas autophagy induction was synergystic with VDR overexpression. Importantly, up-regulation of VDR promoted autophagy activation by suppressing the activation of the extracellular signal-regulated kinase (ERK)/p38 mitogen-activated protein kinase (p38MAPK) pathway. Thus, a p38MAPK inhibitor abrogated the Vdr siRNA-induced decrease in autophagy and the Vdr siRNA-induced increase in apoptosis. In contrast, a Mitogen-activated protein kinase kinase (MEK)/ERK activator prevented the enhancement of autophagy and decreased apoptosis following Vdr overexpression. Moreover, the ROS inhibitor N-acetylcystein (NAC) blocked Vdr siRNA-enhanced activation of the ERK/p38MAPK pathway.
CONCLUSIONS
VDR activation mitigated liver cholestatic injury by reducing autophagy-dependent hepatocyte apoptosis and suppressing the activation of the ROS-dependent ERK/p38MAPK pathway. Thus, VDR activation may be a potential target for the treatment of cholestatic liver disease.
Topics: Mice; Animals; Reactive Oxygen Species; Receptors, Calcitriol; Hepatocytes; Apoptosis; Extracellular Signal-Regulated MAP Kinases; Cholestasis; Autophagy; Mitogen-Activated Protein Kinase Kinases; RNA, Small Interfering
PubMed: 36280140
DOI: 10.1016/j.jcmgh.2022.10.011 -
Nefrologia 2020
Topics: Aged; Ankle; Bone Density Conservation Agents; Calciphylaxis; Calcium-Regulating Hormones and Agents; Cinacalcet; Ergocalciferols; Female; Humans; Hyperparathyroidism, Secondary; Iron Overload; Leg Ulcer; Renal Insufficiency, Chronic
PubMed: 31255363
DOI: 10.1016/j.nefro.2019.03.015