Abstract:Background: Renal transplant recipients (RTRs) are often Vitamin D (VitD) depleted as a result of both chronic kidney disease and mandated sun avoidance behaviours. Repleting VitD may be warranted, but how, and for how long, is unknown, as is the impact of seasonality on the success of repletion. We investigated the impact of seasonality on VitD status following VitD repletion in a large cohort of stable, long-term RTRs.
Methods: Serum 25-hydroxyvitamin D [25(OH)D] concentrations and bone biochemistry paramete… Show more
“…The optimization of supplementation however should be guided by serum 25(OH) D and other calcemic parameters because vitamin D excess may lead to hypercalcemia, hyperphosphatemia and hypercalciuria, all of which has inverse relationship with graft function [ 15 ]. A recent study in UK has concluded vitamin D repletion (using a 6 month bolus intermediate dose schedule) to be safe and effective in stable RTRs, however the post-repletion fall in vitamin D status in the absence of maintenance supplementation was intriguing [ 32 ]. Further interventional studies are warranted to explore the implications of low vitamin D status in Nepalese RTR population and whether supplementation is really beneficial and is able to sustain the vitamin D status when coupled with sensible sun exposure.…”
BackgroundVitamin D, apart from being an important part of the “calcium-vitamin D-parathyroid hormone” endocrine axis, has diverse range of “non-calcemic” biological actions. A high prevalence of vitamin D deficiency has been observed in renal transplant recipients (RTRs) worldwide. This study aimed to determine the prevalence of hypovitaminosis D in Nepalese RTRs and interrelations between serum 25-hydroxyvitamin D [25(OH) D] and other biochemical parameters.MethodsA total of 80 adult RTRs visiting a university hospital were enrolled in this cross sectional study. Serum 25(OH) D and intact parathyroid hormone (iPTH) were measured using Enhanced Chemiluminiscent Immunoassay. The RTR population was categorized into recent transplant recipients (≤1 year) and long term recipients (> 1 year). The vitamin D status was defined as per NKF/KDOQI guidelines. SPSS version 20.0 was used to analyze the data. Appropriate statistical tests were applied to compare variables between groups and establish correlation. P < 0.05 was considered to be statistically significant.ResultsThe mean age of the recipients was 38.11 ± 11.47 years (68 males, 85.0%). Chronic glomerulonephritis was the leading cause of CKD. The two RTR groups (recent and long term) didn’t differ in demographic and biochemical characteristics. 83.75% of the recipients had PTH levels above the upper limit of the recommended range for their stage of CKD. 57.5% had hypocalcemia and none of the recipients had hypercalcemia. The median serum 25(OH) D was 24.15 ng/ml (8.00–51.50 ng/ml). Only 27.5% had sufficient vitamin D status whereas 53.8% were vitamin D insufficient and 18.8% were vitamin D deficient, the distribution almost comparable in the 2 transplant group. The serum 25(OH) D was not significantly affected by the time post-transplant, gender and sunlight avoidance. There was a significant negative correlation between serum 25(OH) D and iPTH (Pearson’s r = − 0.35, P = 0.001), but not so with the graft function.ConclusionThere is a high prevalence of vitamin D insufficiency in RTRs. The deficiency status is not corrected despite of nutritional improvement and normalization of GFR post-transplantation and likely exacerbates secondary hyperparathyroidism. Vitamin D supplementation coupled with sensible sun exposure could be important strategies in optimization of the vitamin D status in this population.
“…The optimization of supplementation however should be guided by serum 25(OH) D and other calcemic parameters because vitamin D excess may lead to hypercalcemia, hyperphosphatemia and hypercalciuria, all of which has inverse relationship with graft function [ 15 ]. A recent study in UK has concluded vitamin D repletion (using a 6 month bolus intermediate dose schedule) to be safe and effective in stable RTRs, however the post-repletion fall in vitamin D status in the absence of maintenance supplementation was intriguing [ 32 ]. Further interventional studies are warranted to explore the implications of low vitamin D status in Nepalese RTR population and whether supplementation is really beneficial and is able to sustain the vitamin D status when coupled with sensible sun exposure.…”
BackgroundVitamin D, apart from being an important part of the “calcium-vitamin D-parathyroid hormone” endocrine axis, has diverse range of “non-calcemic” biological actions. A high prevalence of vitamin D deficiency has been observed in renal transplant recipients (RTRs) worldwide. This study aimed to determine the prevalence of hypovitaminosis D in Nepalese RTRs and interrelations between serum 25-hydroxyvitamin D [25(OH) D] and other biochemical parameters.MethodsA total of 80 adult RTRs visiting a university hospital were enrolled in this cross sectional study. Serum 25(OH) D and intact parathyroid hormone (iPTH) were measured using Enhanced Chemiluminiscent Immunoassay. The RTR population was categorized into recent transplant recipients (≤1 year) and long term recipients (> 1 year). The vitamin D status was defined as per NKF/KDOQI guidelines. SPSS version 20.0 was used to analyze the data. Appropriate statistical tests were applied to compare variables between groups and establish correlation. P < 0.05 was considered to be statistically significant.ResultsThe mean age of the recipients was 38.11 ± 11.47 years (68 males, 85.0%). Chronic glomerulonephritis was the leading cause of CKD. The two RTR groups (recent and long term) didn’t differ in demographic and biochemical characteristics. 83.75% of the recipients had PTH levels above the upper limit of the recommended range for their stage of CKD. 57.5% had hypocalcemia and none of the recipients had hypercalcemia. The median serum 25(OH) D was 24.15 ng/ml (8.00–51.50 ng/ml). Only 27.5% had sufficient vitamin D status whereas 53.8% were vitamin D insufficient and 18.8% were vitamin D deficient, the distribution almost comparable in the 2 transplant group. The serum 25(OH) D was not significantly affected by the time post-transplant, gender and sunlight avoidance. There was a significant negative correlation between serum 25(OH) D and iPTH (Pearson’s r = − 0.35, P = 0.001), but not so with the graft function.ConclusionThere is a high prevalence of vitamin D insufficiency in RTRs. The deficiency status is not corrected despite of nutritional improvement and normalization of GFR post-transplantation and likely exacerbates secondary hyperparathyroidism. Vitamin D supplementation coupled with sensible sun exposure could be important strategies in optimization of the vitamin D status in this population.
In-vitro studies suggest that vitamin D reduces inflammation by inhibiting nuclear factor kappa-B (NFκB) activity. Yet, no trials have examined the effects of vitamin D supplementation on NFκB activity in-vivo in humans. We conducted a double-blind randomized trial (RCT) examining effects of vitamin D supplementation on inflammatory markers and NFκB activity in peripheral blood mononuclear cells (PBMCs). Sixty-five overweight/obese, vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] ≤ 50 nmol/L) adults were randomized to a single 100,000 IU bolus followed by 4,000 IU daily cholecalciferol or matching placebo for 16 weeks. We measured BMI, % body fat, serum 25(OH)D, high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor (TNF), monocyte chemoattractant protein-1 (MCP-1), interferon-gamma (IFN-γ), several interleukins, and NFκB activity in PBMCs. Fifty-four participants completed the study. Serum 25(OH)D concentrations increased with vitamin D supplementation compared to placebo (p < 0.001). Vitamin D and placebo groups did not differ in any inflammatory markers or NFκB activity (all p > 0.05). Results remained non-significant after adjustment for age, sex, and % body fat, and after further adjustment for sun exposure, physical activity, and dietary vitamin D intake. Although in-vitro studies report anti-inflammatory effects of vitamin D, our RCT data show no effect of vitamin D supplementation on inflammatory markers or NFκB activity in-vivo in humans.
Thousands of observational studies have linked vitamin D deficiency with numerous diseases, but randomised controlled trials (RCTs) often fail to show benefit of supplementation. Population characteristics and trial design have long been suspected to undermine power but were not systematically investigated. We propose a flexible generative model to characterise benefit of vitamin D supplementation at the individual level, and use this to quantify power in RCTs. The model can account for seasonality and population heterogeneity. In a simulated 1-year trial with 1000 participants per arm and assuming a 25-hydroxyvitamin D (25OHD) increase of 20 nmol/L due to the intervention, with baseline 25OHD in the population of 15, 35, 50, 60 and 75 nmol/L, the power to detect intervention effect was 77%, 99%, 95%, 68% and 19%, respectively. The number of participants required per arm to achieve 80% power according to baseline 25OHD of 15–60 nmol/L was 1200, 400, 600 and 1400, respectively. As expected, larger increases in 25OHD due to supplementation improved power in certain scenarios. For a population baseline of 50 nmol/L, with 1500 participants in each arm, there was 100% power to detect a 20 nmol/L 25OHD increase while it was 76% for a 10 nmol/L increase. Population characteristics and trial design, including temporal considerations, have a dramatic impact on power and required sample size in vitamin D RCTs.
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