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Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics.
Arenas Jimenez, MD, González-Parra, E, Riera, M, Rincón Bello, A, López-Herradón, A, Cao, H, Hurtado, S, Collado, S, Ribera, L, Barbosa, F, et al
Nutrients. 2021;(8)
Abstract
BACKGROUND In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. METHODS A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain. RESULTS The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6-27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97-1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival. CONCLUSIONS Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.
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Vitamin D Status and Pregnancy Complications: Serum 1,25-di-hydroxyl-Vitamin D and its Ratio to 25-hydroxy-Vitamin D are Superior Biomarkers than 25-hydroxy-Vitamin D.
Albahlol, IA, Almaeen, AH, Alduraywish, AA, Dar, UF, El-Metwally, TH
International journal of medical sciences. 2020;(18):3039-3048
Abstract
Vitamin D (VitD) deficiency during pregnancy has been associated with adverse neonatal outcomes and increased risk of late pregnancy complications. We planned to correlate serum VitD biomarkers; 25-hydroxyvitamin D (25-OH-VitD) and 1,25-dihydroxyvitamin D (1,25-diOH-VitD) levels; and their ratio with the frequency of feto-maternal pregnancy complications. A prospective cross-sectional case-control study was conducted at Aljouf Maternity and Children Hospital, Sakaka, Saudi Arabia, during the period of September 1, 2017 to September 30, 2019. 322 pregnant women were stratified into 2 groups: controls (110 cases) and complicated group (212 cases). The later comprised severe preeclamptic toxemia associated with intrauterine growth restriction (58 cases), gestational diabetes mellitus (GDM; 82 cases), abortion (26 cases), undisturbed ectopic pregnancy (16 cases), premature rupture of membranes (PROM; 14 cases), and, inevitable preterm labour (16 cases). After clinical assessment, peripheral blood samples were collected. Serum biomarkers were measured using specific immunoassays. The direct 1,25-diOH-VitD/25-OH-VitD ratio was calculated. Serum 25-OH-VitD indicated widely spreading VitD deficiency among participants with significantly higher levels in controls vs. GDM subgroup only. 1,25-diOH-VitD levels and the ratio were markedly reduced in the six complicated subgroups vs. controls, with non-significant differences amongst the complicated subgroups. ROC analysis showed very high sensitivity and specificity, to differentiate patients from controls, only for 1,25-diOH-VitD (AUC = 0.965; 0.947 - 0.983, p <0.001) followed by the ratio but not 25-OH-VitD. In conclusions, 25-OH-VitD did not show significant changes except for GDM. 1,25-diOH-VitD levels and the ratio showed strong associations with pregnancy complications. Serum 1,25-di-OH-VitD and its ratio to 25-OH-VitD are more reliable and physiologically relevant biomarkers for VitD status in pregnancy.
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Parathyroid hormone - reference values and association with other bone metabolism markers in very low birth weight infants - pilot study.
Matejek, T, Navratilova, M, Zaloudkova, L, Malakova, J, Maly, J, Skalova, S, Palicka, V
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(17):2860-2867
Abstract
Purpose: The aim of this pilot study was to estimate physiological parathyroid hormone (PTH) levels and their relationship with bone metabolism parameters in otherwise healthy preterm newborns with birth weight 1000-1500 g. Methods: PTH, 25(OH)D, S-Ca, S-P, and ALP were analysed from blood samples obtained from 20 preterm infants once a week up to the 36th gestational week. Results: Of the total 134 examined serum samples for PTH levels, the estimated range was 1.6-9.3 pmol/l (15.1-87.7 pg/ml). No statistically significant correlation of PTH level with that of S-Ca, S-P, or ALP was observed, except for the 56th day of life (p = .03; Rho = 0.76; n = 8). From the second month of life, there was a statistically significant relationship only between PTH and 25(OH)D (Rho = -0.71, p ≤ .0001). In our cohort, vitamin D deficiency (20 ng/ml) occurred in 75% at birth and at 30% in the 36th gestational week. Conclusions: The physiological range indicated by the measurements was close to the reference limits for adults (1-7 pmol/l; 9.4-66 pg/ml). PTH level above this range can be considered as hyperparathyroidism in preterm neonates.
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Parathyroid hormone, calcidiol, calcitriol and adverse events in the acute coronary syndrome.
Ramos Ruiz, P, Jaulent Huertas, L, Castañeda Sancirilo, M, Martínez Díaz, JJ, Clavel Ruipérez, G, García de Guadiana Romualdo, L, Wasniewski, S, Merelo Nicolás, M, García Escribano, I, Soria Arcos, F, et al
Medicina intensiva. 2018;(2):73-81
Abstract
OBJECTIVE To know the clinical profile as well as the prognostic significance of elevated levels of parathyroid hormone (PTH) in patients admitted for acute coronary syndrome (ACS). DESIGN AND SETTING Observational and prospective study of patients admitted for ACS in a single Spanish center during a period of six months. INTERVENTION AND VARIABLES OF INTEREST The circulating concentrations of PTH, calcidiol, calcitriol, NT-proBNP, C-reactive protein, cystatinC and fibrinogen were determined within the first 48h at admission. We performed adjusted models to predict death or re-entry for ACS after hospital discharge. RESULTS A total of 161 patients were recruited (age 67±14 years, 75.2% were men). Forty-one (25.5%) patients had elevated PTH values. During follow-up for a period of 275 person-years, 50 adverse events were recorded. Patients with elevated PTH levels were proportionally more women (21.2 vs. 39.0%) and older (63.3 vs. 77.8 years, both P<.05). Likewise, they presented significantly more cardiovascular risk and a worse prognosis during follow-up (incidence rate ratio 2.64 CI 95%: 1.5-4.6). However, in an adjusted model by the GRACE score, PTH levels were not shown to be an independent risk factor (hazard ratio=1.1; 95% CI: 0.6-2.2), neither other components of the panel. CONCLUSIONS The proportion of patients with elevated levels of PTH admitted for ACS was high. The presence of high PTH levels was associated with an unfavorable clinical profile and a worse outcome during the follow-up, although it was not an independent predictor of poor prognosis.
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Serum Calcitriol Concentrations and Kidney Function Decline, Heart Failure, and Mortality in Elderly Community-Living Adults: The Health, Aging, and Body Composition Study.
Selamet, U, Katz, R, Ginsberg, C, Rifkin, DE, Fried, LF, Kritchevsky, SB, Hoofnagle, AN, Bibbins-Domingo, K, Drew, D, Harris, T, et al
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2018;(3):419-428
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Abstract
RATIONALE & OBJECTIVES Lower 25-hydroxyvitamin D concentrations have been associated with risk for kidney function decline, heart failure, and mortality. However, 25-hydroxyvitamin D requires conversion to its active metabolite, calcitriol, for most biological effects. The associations of calcitriol concentrations with clinical events have not been well explored. STUDY DESIGN Case-cohort study. SETTING & PARTICIPANTS Well-functioning community-living older adults aged 70 to 79 years at inception who participated in the Health, Aging, and Body Composition (Health ABC) Study. PREDICTOR Serum calcitriol measured using positive ion electrospray ionization-tandem mass spectrometry. OUTCOMES Major kidney function decline (≥30% decline in estimated glomerular filtration rate from baseline), incident heart failure (HF), and all-cause mortality during 10 years of follow-up. ANALYTIC APPROACH Baseline calcitriol concentrations were measured in a random subcohort of 479 participants and also in cases with major kidney function decline [n=397]) and incident HF (n=207) during 10 years of follow-up. Associations of serum calcitriol concentrations with these end points were evaluated using weighted Cox regression to account for the case-cohort design, while associations with mortality were assessed in the subcohort alone using unweighted Cox regression. RESULTS During 8.6 years of mean follow-up, 212 (44%) subcohort participants died. In fully adjusted models, each 1-standard deviation lower calcitriol concentration was associated with 30% higher risk for major kidney function decline (95% CI, 1.03-1.65; P=0.03). Calcitriol was not significantly associated with incident HF (HR, 1.16; 95% CI, 0.94-1.47) or mortality (HR, 1.01; 95% CI, 0.81-1.26). We observed no significant interactions between calcitriol concentrations and chronic kidney disease status, baseline intact parathyroid or fibroblast factor 23 concentrations. LIMITATIONS Observational study design, calcitriol measurements at a single time point, selective study population of older adults only of white or black race. CONCLUSIONS Lower calcitriol concentrations are independently associated with kidney function decline in community-living older adults. Future studies will be needed to clarify whether these associations reflect lower calcitriol concentrations resulting from abnormal kidney tubule dysfunction or direct mechanisms relating lower calcitriol concentrations to more rapid loss of kidney function.
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Effect of Cinacalcet Combined with Calcitriol on the Clinical Outcome and Bone Metabolism in Patients on Hemodialysis with Severe Secondary Hyperparathyroidism.
Yuan, F, Chen, X, Wang, C, Li, Z, Liu, H
Blood purification. 2018;(1-3):73-78
Abstract
OBJECTIVE To observe the clinical outcome and the effect of bone metabolism of cinacalcet combined with calcitriol in maintenance hemodialysis (MHD) patients with severe secondary hyperparathyroidism (SHPT). METHODS Thirty MHD patients with SHPT were enrolled into the study. All patients were given cinacalcet 25-75 mg and 0.5 μg calcitriol daily. Serum Ca, P, intact parathyroid hormone (iPTH), and bone metabolic markers were measured. The clinical symptoms and their changes were investigated. RESULTS The baseline levels of iPTH, Ca, and P were 1,787.3 ± 1,321 pg/mL, 2.54 ± 0.19 mmol/L, and 2.06 ± 0.15 mmol/L respectively. After 3 months treatment, iPTH decreased by 70%. Serum Ca and P fell to 2.39 ± 0.17 and 1.56 ± 0.50 mmol/L (p < 0.05), respectively. After 6 months, the bone-specific alkaline phosphatase, osteocalcin, and β-cross levels were decreased by 50, 37, and 49% respectively compared with corresponding values before treatment. A decline in the bone density patients was inhibited. CONCLUSION Cinacalcet combined with low dose calcitriol can improve high calcium, high phosphorus, and high iPTH in MHD patients with severe SHPT and also improve bone metabolism. It can be used as a favorable choice for SHPT treatment.
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Factors associated with 1,25-dihydroxyvitamin D3 concentrations in liver transplant recipients: a prospective observational longitudinal study.
Prytuła, A, Walle, JV, Van Vlierberghe, H, Kaufman, JM, Fiers, T, Dehoorne, J, Raes, A
Endocrine. 2016;(1):93-102
Abstract
The aim of the study was to identify factors associated with 1,25(OH)2D3 concentrations in liver transplant recipients with emphasis on the renal function and catabolism. We also tested the hypothesis that tacrolimus increases 1,25(OH)2D3 concentrations. Serum 25(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3 were measured in 41 patients before, at 2 weeks and 3 months after transplantation. Dose-adjusted tacrolimus concentration was used as a surrogate marker of CYP3A4 activity. Factors associated with 1,25(OH)2D3 were identified using multivariate linear regression analysis. The median 1,25(OH)2D3 levels remained stable: 55 versus 46 pg/ml (P = 0.36) despite an increase in 25(OH)D3 from 18 ng/ml at baseline to 26 ng/ml (P = 0.03), serum albumin (34 to 41 g/l, P = 0.02), and comparable eGFR at baseline and month 3 (94 and 92 ml/min, respectively, P = 0.15). At 3 months 19 % of patients had 1,25(OH)2D3 < 25 pg/ml. Low eGFR and a low dose-adjusted tacrolimus concentration were both independently associated with 1,25(OH)2D3 at 3 months. Liver transplant recipients with impaired renal function or a low dose-adjusted tacrolimus concentration suggesting a high CYP3A4 are at risk of low 1,25(OH)2D3 concentrations. The use of tacrolimus does not lead to an increase in 1,25(OH)2D3 concentrations in a clinical setting.
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Low-dose oral cholecalciferol is associated with higher numbers of Helios(+) and total Tregs than oral calcitriol in renal allograft recipients: an observational study.
Aly, MG, Trojan, K, Weimer, R, Morath, C, Opelz, G, Tohamy, MA, Daniel, V
BMC pharmacology & toxicology. 2016;(1):24
Abstract
BACKGROUND Regulatory T cells (Tregs) are a cornerstone of graft acceptance. High numbers of Tregs are associated with better long-term graft survival. Recently, Vitamin D was suggested as an immunomodulator, in addition to its classical role in calcium metabolism. Vitamin D modulates Tregs and might, thereby, promote graft acceptance and long-term graft survival. METHODS One hundred twenty-three renal allograft recipients attending either Heidelberg nephrology or Giessen internal medicine clinic were enrolled in this cross- sectional study. Sixteen healthy controls were studied in addition. Sixty-nine patients were receiving no vitamin D, 38 calcitriol, and 16 cholecalciferol supplementations. We evaluated whether there was a difference in the absolute numbers of Helios(+), Helios(-), CTLA-4(+), IFNg(+), and total Tregs among the patient groups. RESULTS Cholecalciferol supplementation was associated with higher absolute numbers of Helios(+), CTLA-4(+), and total Tregs than calcitriol (p < 0.001, p = 0.004, p = 0.001 respectively). Helios(+) Tregs were also higher in cholecalciferol than no vitamin D supplementation patients (p = 0.001), whereas CTLA-4(+) and total Tregs were similar in both groups (p = NS). Helios(+), Helios(-), CTLA-4(+), IFNg(+), and total Tregs were similar in the cholecalciferol and healthy control groups (p = NS). CONCLUSION Our findings indicate that cholecalciferol, even when administered at low dosages, has a stabilizing effect on Tregs (particularly the Helios + subset), in contrast to calcitriol which showed neither a stabilizing nor a proliferation-inducing effect on the same cell population.
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Differential influence of vitamin D analogs on left ventricular mass index in maintenance hemodialysis patients.
Sezer, S, Tutal, E, Bal, Z, Uyar, ME, Bal, U, Cakir, U, Acar, NO, Haberal, M
The International journal of artificial organs. 2014;(2):118-25
Abstract
PURPOSE Secondary hyperparathyroidism (SHPT) is a common feature in maintenance hemodialysis (MHD) patients. Inadequate treatment of SHPT has been associated with cardiovascular complications, and vitamin D therapy might influence the development of cardiovascular diseases. In the present study, we aimed to evaluate the effects of intravenous paricalcitol and calcitriol treatments on left ventricular mass index changes in MHD patients. METHODS We conducted an observational study with a 12-month follow-up duration to compare the outcomes of intravenous paricalcitol and calcitriol treatments in MHD patients. Eighty patients with moderate to severe SHPT were enrolled in the study. All the patients had normalized total serum Ca concentration <10.5 mg/dL, serum calcium-phosphorus product (Ca × P) <75, and parathyroid hormone level (PTH) level ≥300 pg/mL at the begining of the follow-up period. RESULTS The patients were divided into a paricalcitol group (n = 40) and a calcitriol group (n = 40). The demographic, clinical, and biochemical characteristics of the patients were similar at baseline. We observed significantly superior control of SHPT; lesser frequency of hypercalcemia and hyperphosphatemia, and Ca × P level elevations; and interruption of vitamin D treatment in the paricalcitol group. Moreover, we found no significant change in left ventricular mass index in the paricalcitol group, but found a significantly increased left ventricular mass index in the calcitriol group during the follow-up period (from 136.6 ± 35.2 g/m2 to 132.9 ± 40.4 g/m2 vs. from 137.2 ± 30.1 g/m2 to 149.4 ± 31.0 g/m2; p<0.044). CONCLUSION We observed that, compared with calcitriol therapy, paricalcitol therapy reduced the PTH concentrations more effectively without causing hypercalcemia and hyperphosphatemia and might have a substantial beneficial effect on the development of left ventricular hypertrophy.