Native Vitamin Research Articles

Effects of native vitamin D supplementation on vitamin D status and body composition after sleeve gastrectomy: A retrospective study in Japanese patients

IntroductionThe effect of vitamin D status after bariatric surgery on postoperative skeletal muscle condition has not been adequately studied. MethodsClinical data from 83 patients (median age 44 years, BMI 40.4 kg/m2) who underwent sleeve gastrectomy (SG) were collected from medical records and analyzed retrospectively. Of the 83 patients, 37 who received continuous guidance on native vitamin D3 supplementation from before to 12 months after surgery were defined as the vitamin D supplementation (VDS) group, and 46 patients who did not receive such guidance as the control group. Native vitamin D3 supplement was provided by a dietitian at preoperative and postoperative visits. The supplementation dose was prescribed at 3000 IU/day after SG. ResultsIn VDS group, blood 25-hydroxyvitamin D (25OHD) level increased significantly from 18.5 at baseline to 29.7 ng/mL at 3 months after surgery and plateaued, while 25OHD level remained low in the control group. In the analysis that included both groups, change in 25OHD level from baseline to 12 months after surgery correlated significantly with mean vitamin D intake (r = 0.596, p < 0.001) and 12-month post-SG/baseline ratio of percent lower limb skeletal muscle mass (r = 0.469, p < 0.05). Multiple regression analysis identified change in 25OHD level and mean exercise time as significant factors independently associated with 12-month post-SG/baseline ratio of percent lower limb skeletal muscle mass. ConclusionVitamin D3 supplementation after SG is useful for improving vitamin D status that may be associated with prevention of postoperative lower limb skeletal muscle mass loss.

Native vitamin D in CKD and renal transplantation: meaning and rationale for its supplementation.

Chronic kidney disease (CKD) poses a significant epidemiological challenge, necessitating effective patient management strategies. Nutritional intervention, particularly vitamin D supplementation, has garnered attention for its potential therapeutic utility in CKD. Despite widespread acknowledgment of the importance of vitamin D, particularly in bone and mineral metabolism, its supplementation in CKD patients for non-skeletal purposes remains contentious due to limited evidence. Hypovitaminosis D linked with CKD substantially contributes to disturbances in mineral and bone metabolism, increasing the risks of cardiovascular complications and skeletal disorders. Notably, CKD patients experience progressive vitamin D deficiency, exacerbating as the disease progresses. Guidelines recommend monitoring 25-hydroxyvitamin D (25 (OH)-D) levels due to their correlation with mineral metabolism parameters, although robust evidence for recommendingsupplementation is lacking. The primaryaim of this paper is to focus on the main open questions regarding vitamin D supplementation in CKD, reporting the current evidence concerning the role of vitamin D supplementation in CKD and in renal transplant recipients.

Vitamin D in the critically ill - update 2024.

This review aims to summarize the latest publications on vitamin D focused on critically ill patients. Vitamin D deficiency is common in critically ill patients (children and adults) and associated with a higher risk for mortality and morbidity as well as sepsis, acute respiratory failure, acute renal failure and prolonged ICU stay. As it is an inexpensive substance with a wide safety margin, acute treatment in form of a loading dose in addition to ongoing maintenance therapy is an interesting option in the ICU. The potential benefit of acute native (biologically inactive) vitamin D treatment has not fully been answered but even a small survival benefit demonstrable in very large analyses could be relevant to critical care. To date, less than 5000 patients cumulative have been enrolled in randomized controlled trials concerning vitamin D, with substantial heterogeneity in trial design regarding population (with or without deficiency, coronavirus disease 2019, different age groups, underlying illnesses), metabolite, dosing, outcome, and more. More research is needed, but vitamin D supplementation represents a simple intervention with an excellent safety profile. As adequate vitamin D is essential to the health of multiple organ systems, rapid normalization of deficiency states could translate to benefits across the wide range of diagnoses and organ dysfunctions experienced in the ICU setting. As a minimum, we recommend administering the standard daily dose of vitamin D3 in the critically ill patient.

Cystinosis-associated metabolic bone disease across ages and CKD stages 1-5D/T.

The pathophysiology of cystinosis-associated metabolic bone disease is complex. We hypothesized a disturbed interaction between osteoblasts and osteoclasts. Binational cross-sectional multicenter study. Hospital clinics. One hundred and three patients with cystinosis (61% children) with chronic kidney disease (CKD) stages 1-5D/T. Ten key bone markers. Skeletal complications occurred in two-thirds of the patients, with adults having a five-fold increased risk compared to children. Patients with CKD stages 1-3 showed reduced z-scores for serum phosphate and calcium, suppressed fibroblast growth factor 23 (FGF23) and parathyroid hormone levels in conjunction with elevated bone-specific alkaline phosphatase levels. Serum phosphate was associated with estimated glomerular filtration rate, combined phosphate and active vitamin D treatment, and native vitamin D supplementation, while serum calcium was associated with age and dosage of active vitamin D. Sclerostin was generally elevated in children, and associated with age, FGF23 levels, and treatment with active vitamin D and growth hormone. The osteoclast marker tartrate-resistant acid phosphatase 5b was increased, and associated with age and treatment with active vitamin D. The ratio of soluble ligand of receptor activator of nuclear factor-κB (sRANKL) and osteoprotegerin (OPG), a surrogate for the regulation of osteoclastogenesis by osteoblasts, was decreased and associated with phosphate and 1,25(OH)2D3 levels. These changes were only partly corrected after transplantation. Bone health in cystinosis deteriorates with age, which is associated with increased osteoclast activity despite counterregulation of osteoblasts via OPG/RANKL, which in conjunction with elevated sclerostin levels and persistent rickets/osteomalacia may promote progressive bone loss.

#1230 Comparative analysis of vitamin D status between patients with advanced chronic kidney disease and those on dialysis

Abstract Background and Aims Decreased plasma concentration of 1,25-dihydroxy-vitamin D3 or calcitriol, the most active biological form of vitamin D3, in patients with advanced chronic kidney disease (ACKD) and on dialysis, is almost universal. In addition, 25-50% of these patients also have decreased levels of 25-hydroxy-vitamin D3 (calcidiol or calcifediol). The main cause of calcitriol deficiency is decreased hydroxylation in the kidney, both due to intrinsic renal damage and hyperphosphataemia. Calcifediol deficiency is directly related to decreased intake and sun exposure. We already know that this calcifediol deficiency is associated with ACKD, but we do not know if there are differences between ACKD patients and dialysis patients. The aim of this study is to analyse whether there are differences in calcifediol levels between ACKD and dialysis patients. Method An observational, analytical, ambispective, multicentre, analytical study was carried out with the participation of five Centres in Spain, under conditions of routine clinical practice. As study subjects, we included patients with ACKD and on haemodialysis from the University Hospitals of Virgen del Rocío, La Paz and Nuestra Señora de Candelaria, and the dialysis centres: Avericum, Quironsalud Tenerife. We selected demographic variables and also included serum levels of calcifediol, calcium, phosphorus and PTH; treatment with: phosphorus binders, erythropoietin synthesis analogues (ESA), ferrotherapy, calcimimetics, active vitamin D, native vitamin D. Data are organised and analysed with SPSS Statistics v22. In all analyses, the significance level is set for a P value &amp;lt; 0.05. Multivariate logistic regression analysis was also performed. Results A total of 161 patients were included. Both groups were homogeneous in the presence of diabetes, calcium levels and treatment with iron, native vitamin D, active vitamin D and calcimimetics. There were significant differences in sex, age, phosphorus levels, PTH, phosphate binders, ESA treatment. There are no significant differences in calcifediol levels or vitamin D status between the two comparison groups. Conclusion In our study, within a general context of hypovitaminosis D, patients with ACKD have a vitamin D status similar to dialysis patients.

#108 Mineral and bone disorders during chronic kidney disease

Abstract Background and Aims The objectives of our work were to describe mineral and bone disorders in patients with chronic kidney disease (CKD) not yet at the dialysis stage and to assess the compliance of phosphocalcic balance indicators with international KDIGO recommendations Method It was a retrospective study conducted over a 10-month period (01 November 2018 to 31 August 2019) in the nephrology and haemodialysis department of the Renaissance University Hospital in Ndjamena. We have included all patients followed up in the unit for non-dialysis CKD, aged over 18 years and consenting to participate to this study. Results A total of 387 patients files were collected, 82 of which have been taken on. The average age of the patients was 52.7 (± 15.8) years, with a male predominance (67.1%). The comorbidities were arterial hypertension (71.9%) and diabetes (24.4%). CKD has predominated in stage V (55%), followed by stage III (23%). Clinical signs were mainly diffuse bone pain (37.8%), pruritus (8.5%), muscle pain (7.3%) and insomnia (8.5%). Disorders in phosphocalcic metabolism have been noticed in stage IV (11.9% and 10.7%) and stage V (40.5% and 34.5%) for hypocalcaemia and hyperphosphataemia. Secondary hyperparathyroidism and 25 OH vitamin D deficiency were respectively 28.8% and 40.5% in stage V CKD. Compliance with international KDIGO recommendations was 59.7%, 53.7% and 37% respectively for serum calcium, serum phosphorus and parathyroid hormone. Radiological fractures were observed in 4.9% of patients. The management of these disorders has focused on calcium carbonate (52.4%), native vitamin D (64.6%) and Cinacalcet (6.1%) administration. Hypocalcaemia (p = 0.005) and hyperphosphataemia (p = 0.0001) were higher in stage V patients, with a significant difference. Conclusion The treatment of mineral and bone disorders has way to go for the majority of patients, due to lack of resources and the exorbitant cost of treatment. Prevention of mineral and bone disorders is a fundamental pillar of CKD treatment for our patients.

Development of a premix based on micellar casein for fortification of meat systems with vitamin A

A novel approach to the protection of unstable fat-soluble vitamins, using retinol as an example, is presented in this work. This method is based on introducing vitamin A molecules into casein micelles. Protective properties of micellar casein towards different forms of retinol (native vitamin and palmitic acid ester) in vitro and in emulsion-type meat products are investigated. A technology of the introduction using micellar casein concentrate (MCC) has been developed. Conditions similar to those in which vitamin molecules can be in meat emulsions during heat treatment are simulated in vitro. The optimal time of “encapsulation” (2 hours) and the need for additional surfactant (tween-80) are identified. The use of the casein micelles protection made it possible to increase the number of retinol molecules that did not undergo decomposition under model conditions (in vitro) from ~30% to ~80%. Using the vitamin premix the degree of degradation of vitamin molecules does not exceed 4% after heat treatment. Data received allowed us to determine the efficiency of the protection properties of casein micelles for unstable vitamin A molecules.

The daily calcium profile in patients with chronic hypoparathyroidism depending on different 25(OH) vitamin D level

BACKGROUND: Chronic hypoparathyroidism is a relatively rare disease, which usually treated active forms of vitamin D and oral calcium supplements. Supplementation with native vitamin D can be useful both for achieving «non-skeletal» effects of vitamin D and for a more stable serum calcium profile.AIM: The aim of this study was to estimate the daily serum calcium and 24-hour urine calcium levels depending on different 25(OH) vitamin D values in patients with chronic hypoparathyroidism on treatment of active forms of vitamin D and calcium supplements.MATERIALS AND METHODS: Forty patients with chronic hypoparathyroidism were involved in the study. All patients were divided in two groups, matched on sex and age, according to the median level of 25(OH) vitamin D in the total group.RESULTS: There were no significant differences between groups by total, albumin-adjusted serum calcium levels and urine calcium excretion. Patients with serum 25(ОН) vitamin D level ≥ 35 ng/ml had significant tendency to achieve more often the target levels of total serum calcium during the day (128 vs. 149 measurements during the day, p=0.049, χ2). However, this tendency disappeared for albumin-adjusted serum calcium levels (p=0.517, χ2). There frequency of hypercalcemia by albumin-adjusted serum calcium in the group of patients with 25(ОН) vitamin D ≥ 35 ng/ml (p=0.006, χ2) was significantly lower, but not for total serum calcium (a trend, p=0.042, χ2). As regards hypocalcemia, there were no significant differences by albumin-adjusted serum calcium (p=0.581, χ2) and it tends to lower frequency by total serum calcium (p=0.023, χ2).CONCLUSION: The additional administration of native vitamin D in patients with chronic hypoparathyroidism may have some advantages, related to the general concept of worldwide vitamin D deficiency and better disease control.

The role of native vitamin D treatment in the clinical assessment of osteoporosis in patients with chronic kidney disease

The prevalence of vitamin D deficiency is high in patients with chronic kidney disease (CKD). Vitamin D deficiency is associated with various bone disorders such as osteoporosis by affecting bone mineralization. Current international guidelines recommend vitamin D supplementation in CKD as well as in the general population. However, the effect of various forms of vitamin D on bone health in CKD remains unclear. Few randomized controlled studies have evaluated the effects of vitamin D supplementation on bone mineral density and bone turnover markers; however, the findings of these studies are heterogeneous. This review aimed to present comprehensive and current findings on the effects of native vitamin D supplementation on bone biomarkers and bone mineral density in CKD. We infered that native vitamin D treatment could improve some bone biomarkers, particularly in predialysis CKD patients with severe vitamin D deficiency. Our findings also draw attention to the fact that vitamin D is an important factor in treatment. However, it is essential to design better-quality and comprehensive controlled studies to obtain clear findings.

Does Native Vitamin D Supplementation Have Pleiotropic Effects in Patients with End-Stage Kidney Disease? A Systematic Review of Randomized Trials.

Vitamin D has been shown to have multiple pleiotropic effects beyond bone and mineral metabolism, with purported roles in cardiovascular disease, cancer, and host immunity. Vitamin D deficiency is common in patients with end-stage kidney disease (ESKD); however, current clinical practice has favored the use of the active hormone. Whether vitamin D deficiency should be corrected in patients with ESKD remains unclear, as few randomized trials have been conducted. In this systematic review, we summarize the current evidence examining whether vitamin D supplementation improves outcomes, beyond mineral metabolism, in patients with ESKD. Data from randomized controlled trials of adults with ESKD were obtained by searching Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Web of Science Core Collection from inception to February 2023. Twenty-three trials composed of 2489 participants were identified for inclusion. Data were synthesized by two independent reviewers and summarized in tables organized by outcome. Outcomes included measures of mortality, cardiovascular disease, inflammation, muscle strength/function, nutrition, patient well-being, and outcomes specific to ESKD including erythropoietin usage, pruritus, and dialysis access maturation. The Cochrane risk of Bias Tool (RoB 2, 2019) was used to assess study quality. Overall, our findings indicate a minimal and varied benefit of native vitamin D supplementation. From the largest studies included, we determine that vitamin D has no demonstrated effect on patient-reported measures of well-being or utilization of erythropoietin, nor does it change levels of the inflammation biomarker C-reactive protein. Included trials were heterogeneous with regards to outcomes, and the majority studied small participant populations with a relatively short follow-up. We conclude that vitamin D supplementation corrects vitamin D deficiency and is safe and well-tolerated in humans with ESKD. However, it is not clear from clinical trials conducted to date that a causal pathway exists between 25(OH)D and pleiotropic effects that is responsive to vitamin D treatment.

Improved quantitative LC-MS/MS analysis of vitamin D metabolites in serum after one-pot double derivatization

In this study, we report a one-pot double derivatization scheme, which used acetylation after a Diels-Alder reaction using 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) to improve separation efficiency and provide baseline separations of the five vitamin D metabolites 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), 3β-25-hydroxyvitamin D3 (3β-25(OH)D3), 3α-25-hydroxyvitamin D3 (3α-25(OH)D3) and vitamin D3 on a C-18 stationary phase. Vitamin D metabolites are often very challenging to measure quantitatively using mass spectrometry, due to their low serum concentration levels and low ionization efficiencies. Moreover, some of these species are isomers with virtually identical mass spectral dissociation behavior. To overcome the low ionization efficiency and unspecific fragmentation behavior, derivatization using Diels-Alder reactions with Cookson-type reagents such as PTAD are common. These derivatization reactions generally result in more complicated liquid chromatography separations, because both 6R- and 6S-isomers are formed during Diels-Alder reactions. It has been shown that separations have been particularly challenging for the 3α-25(OH)D3 and 3β-25(OH)D3 epimers. Here, we optimized the PTAD derivatization and the esterification using acetic anhydride. By utilizing the esterification catalyst 4-dimethylaminopyridine, we avoided quenching and evaporation between the two derivatization steps, but were also able to perform the esterification at room temperature without heating. The optimized one-pot double derivatization LC-MS/MS assay was validated with respect to inter/intra-day precision, accuracy, recovery and linear dynamic range and applied to metabolic fingerprinting of vitamin D3 metabolites in serum samples. The metabolites 3α-25(OH)D3, 3β-25(OH)D3 and 24,25(OH)2D3, were readily quantified in all investigated samples. The method was, in principle, also fit for purpose for quantification of the native vitamin D3 species; the relatively high blank concentration of the commercial vitamin D-depleted serum used for calibration, however, limited the limits of quantification for this metabolite. The method provided insufficient limits of quantification for serum levels of 1,25(OH)2D3.

Diagnosis and management of mineral and bone disorders in infants with CKD: clinical practice points from the ESPN CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce.

Infants with chronic kidney disease (CKD) form a vulnerable population who are highly prone to mineral and bone disorders (MBD) including biochemical abnormalities, growth retardation, bone deformities, and fractures. We present a position paper on the diagnosis and management of CKD-MBD in infants based on available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce. PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and relevant literature searches performed covering a population of infants below 2years of age with CKD stages 2-5 or on dialysis. Clinical practice points (CPPs) were developed and leveled using the American Academy of Pediatrics grading matrix. A Delphi consensus approach was followed. We present 34 CPPs for diagnosis and management of CKD-MBD in infants, including dietary control of calcium and phosphate, and medications to prevent and treat CKD-MBD (native and active vitamin D, calcium supplementation, phosphate binders). As there are few high-quality studies in this field, the strength of most statements is weak to moderate, and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested. A higher resolution version of the Graphical abstract is available as Supplementary information.

Are There Any Pleiotropic Benefits of Vitamin D in Patients With Diabetic Kidney Disease? A Systematic Review of Randomized Controlled Trials.

Type 2 diabetes (T2D) and kidney disease are risk factors for vitamin D deficiency. Native forms of vitamin D have a lower risk of hypercalcemia than calcitriol, the active hormone. The enzyme responsible for activating native vitamin D is now known to be expressed throughout the body; therefore, native vitamin D may have clinically relevant effects in many body systems. The objective of this systematic review was to examine the effect of native vitamin D supplementation on clinical outcomes and surrogate laboratory measures in patients with T2D and diabetic kidney disease (DKD). Systematic review. Randomized controlled trials (RCTs) conducted in any country. Adults with T2D and DKD receiving supplementation with any form of native vitamin D (eg, ergocalciferol, cholecalciferol, calcifediol). Clinical outcomes and surrogate clinical and laboratory measures reported in each of the trials were included in this review. The following databases were searched from inception to January 31, 2023: Embase, MEDLINE, Cochrane CENTRAL, Web of Science, ProQuest Dissertations and Theses, and medRxiv. Only RCTs examining supplementation with a native vitamin D form with a control or placebo comparison group were included. We excluded studies reporting only vitamin D status or mineral metabolism parameters, without any other outcomes of clinical relevance or surrogate laboratory measures. Study quality was evaluated using the Cochrane risk-of-bias tool (RoB2). Results were synthesized in summary tables for each type of outcome with the P values from the original studies displayed. Nine publications were included, corresponding to 5 separate RCTs (377 participants total). Mean age ranged from 40 to 63. All trials administered vitamin D3. Intervention groups experienced improvements in vitamin D status and a reduction in proteinuria in 4 of the 5 included RCTs. There was a decrease in low-density lipoprotein and total cholesterol in the 2 trials in which they were measured. Improvements in bone mass, flow-mediated dilation, and inflammation were also reported, but each was only measured in 1 RCT. Effects on glucose metabolism, high-density lipoprotein, triglycerides, blood pressure, oxidative stress, and kidney function were mixed. No serious adverse effects were reported. Limitations include the small number of RCTs and lack of information on the use of drugs that affect measured outcomes (eg, proteinuria-lowering renin-angiotensin-aldosterone system inhibitors and lipid-lowering medication) in most studies. Our study is also limited by the absence of a prestudy protocol and registration. Native vitamin D is a safe treatment that improves vitamin D status in patients with DKD. Vitamin D may modify proteinuria and lipid metabolism in DKD, but further well-designed trials that include well-established treatments are necessary. Overall, there is limited evidence for beneficial pleiotropic effects of vitamin D in patients with DKD.

Development of nanoluciferase-based sensing system that can specifically detect 1α,25-dihydroxyvitamin D in living cells

Previously, we reported a FLucN-LXXLL+LBD-FLucC system that detects VDR ligands using split firefly luciferase techniques, ligand binding domain (LBD) of VDR, and LXXLL sequences that interact with LBD after VDR ligand binding. In vivo, 25-hydroxyvitamin D3 (25(OH)D3) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) act as VDR ligands that bind to VDR, and regulate bone-related gene expression. Therefore, the amount of 25(OH)D3 and 1α,25(OH)2D3 are indicators of bone-related diseases such as rickets and osteoporosis. In this study, we have developed a novel LgBiT-LXXLL+LBD-SmBiT system using NanoLuc Binary Technology (NanoBiT), which has an emission intensity several times higher than that of the split-type firefly luciferase. Furthermore, by using genetic engineering techniques, we attempted to construct a novel system that can specifically detect 1α,25(OH)2D3. Because histidine residues at positions 305 and 397 play important roles in forming a hydrogen bond with a hydroxyl group at position C25 of 25(OH)D3 and 1α,25(OH)2D3, His305 and His397 were each substituted by other amino acids. Consequently, the three mutant VDRs, H305D, H397N, and H397E were equally useful to detect 1α,25(OH)2D3 specifically. In addition, among the 58 variants of the LXXLL sequences, LPYEGSLLLKLLRAPVEE showed the greatest increase in luminescence upon the addition of 25(OH)D3 or 1α,25(OH)2D3. Thus, our novel system using NanoBiT appear to be useful for detecting native vitamin D or its derivatives.

Monitoring 25-OH and 1,25-OH vitamin D levels in hemodialysis patients after starting therapy: Does it make sense?

Background and aimsIn hemodialysis patients, monitoring 25-hydroxyvitamin D (25(OH)D) levels is recommended. It is however unclear if monitoring 1,25-dihydroxyvitamin D (1,25(OH)2D) levels is interesting. Materials and methodsWe repeatedly measured 1,25(OH)2D (DiaSorin Liaison analyser) and 25(OH)D (LCMS/MS) concentrations in patients newly treated by active or native vitamin D to study the impact of such treatments on serum concentrations. ResultsTen patients were included in the native and 12 in the active vitamin D group. In the native group, a significant increase was observed between the baseline and the last 25(OH)D concentrations available (21.65[17.39;25.26] versus 33.49[28.60;40.30] ng/mL, p = 0.0059). The baseline and last available 1,25(OH)2D concentrations were not different (12.15[4.25;15.40] versus 11.35[9.72;21.85] pg/mL, p = 0.5566). In the active group, no difference was observed between the baseline and the last 25(OH)D concentrations (51.70[42.97;63.95] versus 50.89[42.02;64.49] ng/mL, p = 0.5186). The same observation was made for 1,25 (OH)2D concentrations (25.65[17.05;41.85] versus 28.70[23.36;43.73] pg/mL, p = 0.6221). Using a linear mixed model, a significant change over time was only observed in 25(OH)D serum levels for patients treated by with native vitamin D. ConclusionMeasuring 1,25(OH)2D levels in patients newly treated by active vitamin D does not seem useful in monitoring active vitamin D therapy.

Évolution de l’incidence et des résultats à 12 mois de la parathyroïdectomie : 40 ans d’expérience dans un centre de dialyse avec deux services de chirurgie successifs

IntroductionSecondary hyperparathyroidism remains the main complication of mineral and bone metabolism in patients with chronic kidney disease. In case of resistance to medical treatment (native and active vitamin D, calcium and calcimimetics), surgical parathyroidectomy is indicated. The aim of this retrospective study is to show the evolution of the incidence and results of surgical parathyroidectomy in our center between 1980 and 2020 as patient characteristics, diagnostic and therapeutic strategies have changed. Patients and methodsWe collected data from dialysis patients who had a first surgical parathyroidectomy between 2000 and 2020 (period 2) in the same surgical department and compared them with historical data between 1980 and 1999 (period 1) operated in one other center. ResultsIn period 1, 53 surgical parathyroidectomy were performed (2.78/year, 0 to 5, 8.5/1000 patients-year) vs.56 surgical parathyroidectomy in period 2 (2.8/year, 0 to 9, 8/1000 patients-year). The patients of the 2 periods were comparable except for the higher dialysis vintage in period 1 (149±170 vs.89±94 months; P=0.02). In comparison with dialysis patients not requiring surgical parathyroidectomy during the same period, patients who had surgical parathyroidectomy were younger, had higher dialysis vintage and lower diabetes prevalence, but more frequently carriers of glomerulopathy or polycystosis. Systematically performed in period 2, cervical ultrasound identified at least one visible gland in 78.6% of cases while the scintigraphy, performed only in 66% of cases, found at least one gland in 81% of cases. Twelve months after surgery, PTH > 300 pg/mL (marker of secondary hyperparathyroidism recurrence or surgery failure) was present in 30% of patients in period 1 vs. 5.3% in period 2. Hypoparathyroidism was also more frequently observed in period 2 (35.7 vs. 18.8%). Surgical complications were also higher in period 1. ConclusionDespite therapeutic and strategic advances, severe secondary hyperparathyroidism is still as common as ever. It is favored by excessively high PTH targets, by suboptimal prevention before dialysis and poor tolerance of calcimimetics. The surgical parathyroidectomy is effective and safe in the hands of a specialized team with an ultrasound and scintigraphic preoperative assessment.

The clinical relevance of native vitamin D in pediatric kidney disease.

Hypovitaminosis D has been reported to be common in chronic kidney disease (CKD) as well as in proteinuric disorders. We reviewed available evidence to assess clinically relevant effects of low vitamin D status and native vitamin D (NVD) therapy, in pediatric renal diseases. Online medical databases were searched for articles related to vitamin D status, associations of hypovitaminosis D and effects of NVD therapy in kidney disease.Hypovitaminosis D was associated with worse skeletal, cardiovascular, inflammatory, and renal survival outcomes in CKD. Low serum 25 hydroxy-vitamin D (25[OH]D) levels correlated positively with glomerular filtration rate and negatively with serum parathyroid (PTH) levels. However, to date, evidence of benefit of NVD supplementation is restricted mainly to improvements in serum PTH, and biochemical 25[OH]D targets form the basis of clinical practice recommendations for NVD therapy.In nephrotic syndrome (NS) relapse, studies indicate loss of 25[OH]D along with vitamin D binding protein in urine, and serum total 25[OH]D levels are low. Preliminary evidence indicates that free 25[OH]D may be a better guide to the biologically active fraction. NVD therapy in NS does not show consistent results in improving skeletal outcomes and hypercalciuria has been reported when total 25[OH]D levels were considered as indication for therapy.NVD formulations should be regularised, and therapy monitored adequately to avoid adverse effects.

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

Vitamin D has been described as an essential nutrient and hormone, which can cause nuclear, non-genomic, and mitochondrial effects. Vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences the cell metabolism and maintenance specific nuclear programs. Given its broad spectrum of activity and multiple molecular targets, a deficiency of vitamin D can be involved in many pathologies. Vitamin D deficiency also influences mortality and multiple outcomes in chronic kidney disease (CKD). Active and native vitamin D serum levels are also decreased in critically ill patients and are associated with acute kidney injury (AKI) and in-hospital mortality. In addition to regulating calcium and phosphate homeostasis, vitamin D-related mechanisms regulate adaptive and innate immunity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have a role in excessive proinflammatory cell recruitment and cytokine release, which contribute to alveolar and full-body endothelial damage. AKI is one of the most common extrapulmonary manifestations of severe coronavirus disease 2019 (COVID-19). There are also some correlations between the vitamin D level and COVID-19 severity via several pathways. Proper vitamin D supplementation may be an attractive therapeutic strategy for AKI and has the benefits of low cost and low risk of toxicity and side effects.

The effect of prescribing vitamin D analogues and serum vitamin D status on both contracting COVID-19 and clinical outcomes in kidney dialysis patients'.

AimsVitamin D plays a role in innate immune system activation, and deficiency increases susceptibility to respiratory infections and disease severity including COVID‐19. We determined whether vitamin D levels and medications were associated with contracting COVID‐19, and disease severity defined by hospitalisation and dialysis patient mortality.MethodsWe reviewed serum vitamin D levels, and prescription of cholecalciferol and alfacalcidol along with corresponding medical records of adult dialysis patients from a United Kingdom tertiary centre between March 2020 and May 2021. COVID‐19 infection was determined by polymerase chain reaction (PCR) results.Results362 (35%) of 1035 dialysis patients tested PCR positive for COVID‐19. COVID‐19 positive patients had lower native median vitamin D (65 (39–95) versus 74 (40.5–101) nmol/L (p = .009) despite greater prescription of cholecalciferol (median 20 000 (20000‐20 000) versus 20 000 (0–20 000) IU/week), p < .001, but lower prescription of alfacalcidol 0 (0–3.0) versus 2.0 (0.–5.0) ug/week, p < .001. On multivariate logistic regression COVID‐19 infection was associated with haemodialysis versus peritoneal dialysis (p < .001), cholecalciferol dose (p < .001) and negatively with alfacalcidol (p < .001). However, serum vitamin D levels and alfacalcidol dosages were not significantly different for those requiring hospitalisation compared to those managed at home, although those who died were prescribed lower alfacalcidol dosages.ConclusionDialysis patients who contracted COVID‐19 had lower levels of native vitamin D prior to COVID‐19 and were prescribed lower dosages of alfacalcidol. However, there was no association between vitamin D status and disease severity. This retrospective observational analysis supports a potential role for vitamin D and susceptibility to COVID‐19 infection in dialysis patients.

Vitamin D metabolism in living kidney donors before and after organ donation.

Living kidney donors provide a unique setting to study functional and metabolic consequences after organ donation. Since the lack of data of the homoeostasis of numerous vitamin D metabolites in these healthy subjects, the aim of this study was to assess the vitamin D metabolism before and after kidney donation. We investigated the 25-dihydroxyvitamin D2 (25[OH]D2), 25-dihydroxyvitamin D3 (25[OH]D3), 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), 24,25-dihydroxyvitamin D3 (24,25[OH]2D3), 25,26-dihydroxyvitamin D3 (25,26[OH]2D3), and the native vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) in a well characterized study cohort of 32 healthy living kidney donors before and after organ donation. Thirty-two healthy subjects after kidney donation had significantly lower median (interquartile range) 1,25(OH)2D3 serum concentrations (88.6 [62.6-118.8] vs. 138.0 [102.6-152.4]pmol/L, p<0.001) and significantly higher median 25(OH)D2 serum levels (1.80 [1.19-2.19] vs. 1.11 [0.74-1.59]nmol/L, p=0.019) than before donation. Similar serum concentrations of 25(OH)D3 and 25,26(OH)2D3 were observed before and after donation. The 24,25(OH)2D3 blood levels distinctly decreased after organ donation (4.1 [2.3-5.3] vs. 5.3 [2.2-6.9]nmol/L, p=0.153). Native vitamin D2 (0.10 [0.08-0.14] vs. 0.08 [0.06-0.12]nmol/L, p=0.275) was slightly increased and vitamin D3 (1.6 [0.6-7.2] vs. 2.5[0.9-8.6]nmol/L, p=0.957) decreased after kidney donation. Living kidney donors were found with decreased 1,25(OH)2D3 and 24,25(OH)2D3, increased 25(OH)D2 and consistent 25(OH)D3 and 25,26(OH)2D3 serum concentrations after organ donation. The current study advances the understanding on vitamin D metabolism suggesting that altered hydroxylase-activities after donation is accompanied by compensatory elevated dietary-related 25(OH)D2 blood concentrations.