The Role of Vitamin K in CKD-MBD.

PURPOSE OF REVIEW: We describe the mechanism of action of vitamin K, and its implication in cardiovascular disease, bone fractures, and inflammation to underline its protective role, especially in chronic kidney disease (CKD). RECENT FINDINGS: Vitamin K acts as a coenzyme of y-glutamyl carboxylase, transforming undercarboxylated in carboxylated vitamin K-dependent proteins. Furthermore, through the binding of the nuclear steroid and xenobiotic receptor, it activates the expression of genes that encode proteins involved in the maintenance of bone quality and bone remodeling. There are three main types of K vitamers: phylloquinone, menaquinones, and menadione. CKD patients, for several conditions typical of the disease, are characterized by lower levels of vitamin K than the general populations, with a resulting higher prevalence of bone fractures, vascular calcifications, and mortality. Therefore, the definition of vitamin K dosage is an important issue, potentially leading to reduced bone fractures and improved vascular calcifications in the general population and CKD patients.

Phosphate and bone fracture risk in chronic kidney disease patients.

In chronic kidney disease (CKD), phosphate homoeostasis plays a central role in the development of mineral and bone disorder (MBD) together with decreased serum calcium and elevated serum parathyroid hormone, fibroblast growth factor 23 and sclerostin levels. Today there are only a few data exploring the direct role of abnormal phosphate homoeostasis and hyperphosphataemia in the development of CKD-MBD. On the other hand, several studies have looked at the link between hyperphosphataemia and cardiovascular morbidity and mortality in CKD, but there is a lack of evidence to indicate that lowering phosphate levels improves cardiovascular outcomes in this population. Furthermore, the impact of liberalizing phosphate targets on CKD-MBD progression and bone fracture is currently not known. In this review we discuss the central role of phosphate in the pathogenesis of CKD-MBD and how it may be associated with fracture risk, both in hyper- and hypophosphataemia.

Overweight-obesity is associated with decreased vitamin K2 levels in hemodialysis patients.

OBJECTIVES: Obesity is an important risk factor for morbidity and mortality. Vitamin K2 is involved in the production of bone and matrix amino acid g-carboxy-glutamic acid (Gla) proteins (vitamin K-dependent proteins [VKDPs]), regulating bone and vascular calcification (VC). Bone Gla protein (BGP) is involved both in bone mineralization and VCs. We assessed the relationships between vitamin K levels and body mass index (BMI) according to the hypothesis that the impact of BMI on mortality is partly driven by low vitamin K levels. METHODS: The Vitamin K Italian (VIKI) study included 387 hemodialysis patients from 18 dialysis centers in Italy. We determined plasma levels of bone markers: vitamin K levels, VKDPs, vitamin 25(OH)D, alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium (Ca), phosphorus (P) and routine biochemistry. BMI was classified into the following categories: underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2) and obese (BMI ≥ 30 kg/m2). RESULTS: 45.2% of patients were overweight or obese. Stratification by BMI demonstrated lower median menaquinone-7 (MK7)/triglycerides levels in obese patients (0.42 ng/mg [0.19, 0.87], p = 0.005). BGP levels were lower in overweight and obese patients (152 mcg/L [83.2, 251] and 104 mcg/L [62.7, 230], p = <0.001). Furthermore, there was an inverse correlation between MK7/triglycerides levels and BMI (regression coefficient ß = -0.159; p = 0.003). In multiple linear regression, there was an inverse relationship between BGP levels and BMI (ß = - 0.119; p = 0.012). CONCLUSIONS: These data are the first to report an inverse relationship between Vitamin K2 levels and BMI in hemodialysis patients. Further studies are needed to confirm these findings and to determine if lower levels of Vitamin K are related to greater morbidity and mortality in this at-risk population.

Efficacy of weekly administration of cholecalciferol on parathyroid hormone in stable kidney-transplanted patients with CKD stage 1-3.

Objectives: Kidney transplant (KTx) recipients frequently have deficient or insufficient levels of serum vitamin D. Few studies have investigated the effect of cholecalciferol in these patients. We evaluated the efficacy of weekly cholecalciferol administration on parathyroid hormone (PTH) levels in stable KTx patients with chronic kidney disease stage 1-3. Methods: In this retrospective cohort study, 48 stable KTx recipients (37 males, 11 females, aged 52 ± 11 years and 26 months post-transplantation) were treated weekly with oral cholecalciferol (7500-8750 IU) for 12 months and compared to 44 untreated age- and gender-matched recipients. Changes in levels of PTH, 25(OH) vitamin D (25[OH]D), serum calcium, phosphate, creatinine and estimated glomerular filtration rate (eGFR) were measured at baseline, 6 and 12 months. Results: At baseline, clinical characteristics were similar between treated and untreated patients. Considering the entire cohort, 87 (94.6%) were deficient in vitamin D and 64 (69.6%) had PTH ≥130 pg/mL. Serum calcium, phosphate, creatinine and eGFR did not differ between groups over the follow-up period. However, 25(OH)D levels were significantly higher at both 6 (63.5 vs. 30.3 nmol/L, p < 0.001) and 12 months (69.4 vs. 30 nmol/L, p < 0.001) in treated vs. untreated patients, corresponding with a significant reduction in PTH at both 6 (112 vs. 161 pg/mL) and 12 months (109 vs. 154 pg/mL) in treated vs. untreated patients, respectively (p < 0.001 for both). Conclusions: Weekly administration of cholecalciferol can significantly and stably reduce PTH levels, without any adverse effects on serum calcium and renal function.

Vitamin K plasma levels determination in human health.

Vitamin K (phylloquinone or vitamin K1 and menaquinones or vitamin K2) plays an important role as a cofactor in the synthesis of hepatic blood coagulation proteins, but recently has also aroused an increasing interest for its action in extra-hepatic tissues, in particular in the regulation of bone and vascular metabolism. The accurate measurement of vitamin K status in humans is still a critical issue. Along with indirect assays, such as the undercarboxylated fractions of vitamin K-dependent proteins [prothrombin, osteocalcin (OC), and matrix gla protein], the direct analysis of blood levels of phylloquinone and menaquinones forms might be considered a more informative and direct method for assessing vitamin K status. Different methods for direct quantification of vitamin K serum levels are available. High-performance liquid chromatography (HPLC) methods coupled with post-column reduction procedures and fluorimetric or electrochemical detection are commonly used for food and blood analysis of phylloquinone, but they show some limitations when applied to the analysis of serum menaquinones because of interferences from triglycerides. Recent advancements include liquid chromatography tandem mass spectrometry (LCMS/MS) detection, which assures higher specificity. The optimization and standardization of these methods requires specialized laboratories. The variability of results observed in the available studies suggests the need for further investigations to obtain more accurate analytical results.

Vitamin K and bone.

Vitamin K is mainly known as an agent involved in blood coagulation, maintaining the activity of coagulation factors in the liver. In addition, epidemiological studies suggested that a lack of vitamin K is associated with several diseases, including osteoporosis and vascular calcification. There are two main kinds of vitamin K: Phylloquinone (or PK) and Menaquinones (MKn), both act as co-enzyme of y-glutamyl carboxylase (GGCX) transforming under-carboxylated in carboxylated vitamin K dependent proteins, such as Bone Gla Protein (or Osteocalcin) and Matrix Gla Protein. Recently, Vitamin K was also identified as a ligand of the nuclear steroid and xenobiotic receptor (SXR) (in murine species Pregnane X Receptor: PXR), expressed in osteoblasts. The purpose of this literature review is to evaluate the protective role of Vitamin K in bone and vascular health.

Respiratory exchange ratio overshoot during exercise recovery: a promising prognostic marker in HFrEF.

BACKGROUND AND AIMS: Transient increases (overshoot) in respiratory gas analyses have been observed during exercise recovery, but their clinical significance is not clearly understood. An overshoot phenomenon of the respiratory exchange ratio (RER) is commonly observed during recovery from maximal cardiopulmonary exercise testing (CPET), but it has been found reduced in patients with heart failure with reduced ejection fraction (HFrEF). The aim of the study was to analyze the clinical significance of these RER recovery parameters and to understand if these may improve the risk stratification of patients with HFrEF. METHODS: This cross-sectional study includes HFrEF patients who underwent functional evaluation with maximal CPET for the heart transplant checklist at our Sports and Exercise Medicine Division. RER recovery parameters, including RER overshoot as the percentual increase of RER during recovery (RER mag), have been evaluated after CPET with assessment of hard clinical long-term endpoints (MACEs/deaths and transplant/LVAD-free survival). RESULTS: A total of 190 patients with HFrEF and 103 controls were included (54.6 ± 11.9 years; 73% male). RER recovery parameters were significantly lower in patients with HFrEF compared to healthy subjects (RER mag 24.8 ± 14.5% vs 31.4 ± 13.0%), and they showed significant correlations with prognostically relevant CPET parameters. Thirty-three patients with HFrEF did not present a RER overshoot, showing worse cardiorespiratory fitness and efficiency when compared with those patients who showed a detectable overshoot (VO2 peak: 11.0 ± 3.1 vs 15.9 ± 5.1 ml/kg/min; VE/VCO2 slope: 41.5 ± 8.7 vs 32.9 ± 7.9; ΔPETCO2: 2.75 ± 1.83 vs 4.45 ± 2.69 mmHg, respectively). The presence of RER overshoot was associated with a lower risk of cardiovascular events and longer transplant-free survival. CONCLUSION: RER overshoot represents a meaningful cardiorespiratory index to monitor during exercise gas exchange evaluation; it is an easily detectable parameter that could support clinicians to comprehensively interpreting patients' functional impairment and prognosis. CPET recovery analyses should be implemented in the clinical decision-making of advanced HF.

Comparison of Cardiorespiratory Fitness Prediction Equations and Generation of New Predictive Model for Patients with Obesity.

PURPOSE: Cardiorespiratory fitness (CRF) is a critical marker of overall health and a key predictor of morbidity and mortality, but the existing prediction equations for CRF are primarily derived from general populations and may not be suitable for patients with obesity. METHODS: Predicted CRF from different non-exercise prediction equations was compared with measured CRF of patients with obesity who underwent maximal cardiopulmonary exercise testing (CPET). Multiple linear regression was used to develop a population-specific non-exercise CRF prediction model for treadmill exercise including age, sex, weight, height and physical activity level as determinants. RESULTS: 660 patients underwent CPET during the study period. Within the entire cohort, R2 values had a range of 0.24-0.46. Predicted CRF was statistically different from measured CRF for 19 included equations. Only 50% of patients were correctly classified into the measured CRF categories according to predicted CRF. A multiple model for CRF prediction (ml/min) was generated (R2 = 0.78) and validated using two cross-validation methods. CONCLUSIONS: Most used equations provide inaccurate estimates of CRF in patients with obesity, particularly in cases of severe obesity and low CRF. Therefore, a new prediction equation was developed and validated specifically for patients with obesity, offering a more precise tool for clinical CPET interpretation and risk stratification in this population.

Serial cardiopulmonary exercise testing in young patients after one-and-half ventricle repair and Fontan procedure: a comparative study.

BACKGROUND: The Fontan procedure is the palliative surgical treatment for different congenital heart diseases (CHD) with a univentricular heart, but it has been associated with decreased exercise capacity, cardiovascular morbidity, and premature mortality. The one-and-half ventricle repair (1.5VR) was introduced as an alternative to the Fontan procedure, specifically for selected patients with borderline hypoplastic right ventricle (HRV), aiming for a more physiological circulation. Despite these efforts, the benefit of 1.5VR over Fontan circulation comparison on clinical and functional outcomes remains unclear. The aim of this study was to investigate and compare young patients with HRV after 1.5VR with those with functional single right or left ventricles (FSRV or FSLV) after Fontan palliation over a 10-year follow-up period. METHODS: In this retrospective observational study, serial cardiopulmonary exercise tests (CPETs) performed in patients with 1.5VR and Fontan circulation between September 2002 and March 2024 have been analyzed. Only patients with at least 10 years of follow-up were considered. RESULTS: A total of 41 patients were included (age at baseline 8.6 ± 2.6 years): 21 with FSLV, 12 with FSRV, and 10 with 1.5VR. No differences in cardiorespiratory fitness and efficiency were shown at the first CPET assessment among the three groups. At 10-year follow-up, 1.5VR had higher cardiorespiratory fitness and efficiency compared to FSLV and FSRV patients. CONCLUSIONS: These findings suggest that the 1.5VR may provide superior long-term functional outcomes than the Fontan procedure in patients with borderline HRV. Further studies are needed to evaluate the impact on hard clinical endpoints.

Real-world usage of Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD) biomarkers in nephrology practices.

Background: Chronic kidney disease mineral bone disorder (CKD-MBD) is a condition characterized by alterations of calcium, phosphate, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF-23) metabolism that in turn promote bone disorders, vascular calcifications, and increase cardiovascular (CV) risk. Nephrologists' awareness of diagnostic, prognostic, and therapeutic tools to manage CKD-MBD plays a primary role in adequately preventing and managing this condition in clinical practice. Methods: A national survey (composed of 15 closed questions) was launched to inquire about the use of bone biomarkers in the management of CKD-MBD patients by nephrologists and to gain knowledge about the implementation of guideline recommendations in clinical practice. Results: One hundred and six Italian nephrologists participated in the survey for an overall response rate of about 10%. Nephrologists indicated that the laboratories of their hospitals were able to satisfy request of ionized calcium levels, 105 (99.1%) of both PTH and alkaline phosphatase (ALP), 100 (94.3%) of 25(OH)D, and 61 (57.5%) of 1.25(OH)2D; while most laboratories did not support the requests of biomarkers such as FGF-23 (intact: 88.7% and c-terminal: 93.4%), Klotho (95.3%; soluble form: 97.2%), tartrate-resistant acid phosphatase 5b (TRAP-5b) (92.5%), C-terminal telopeptide (CTX) (71.7%), and pro-collagen type 1 N-terminal pro-peptide (P1NP) (88.7%). As interesting data regarding Italian nephrologists' behavior to start treatment of secondary hyperparathyroidism (sHPT), the majority of clinicians used KDOQI guidelines (n = 55, 51.9%). In contrast, only 40 nephrologists (37.7%) relied on KDIGO guidelines, which recommended referring to values of PTH between two and nine times the upper limit of the normal range. Conclusion: Results point out a marked heterogeneity in the management of CKD-MBD by clinicians as well as a suboptimal implementation of guidelines in Italian clinical practice.

The impact of the COVID-19 pandemic on functional capacity in a population of young athletes: should we expect long-time consequences?

BACKGROUND: From 2020, most countries all over the world have implemented strategies aimed at limiting contagion of COVID-19. The pandemic caused a reduction in physical activity (PA) and sports at all levels. The aim of the present study was to analyze and quantify the related impact of imposed PA restrictions on functional capacity in young athletes. METHODS: This observational cohort study evaluated annually the exercise capacity of a sample of young athletes (N.=344) referred for the pre-participation screening at our Sports and Exercise Medicine Division (2017-2021). Standardized maximal exercise testing was performed on treadmill and linear mixed models analyzed metabolic equivalent of tasks (METs) and exercise time as dependent variables. RESULTS: METs and exercise time showed a reduction in the year 2020 and a subsequent increase in 2021, with males revealing a faster recovery in exercise capacity. Athletes who maintained >250 annual training hours were less affected by the pandemic. CONCLUSIONS: These data suggest a significant impact of forced physical inactivity on a cohort of apparently healthy young athletes. The COVID-19-related experience should lead to strategies to avoid negative effects and long-term consequences of containment measures.

Selective Functional Movement Assessment (SFMA) Reliability and Proposal of Its Use in Sports.

INTRODUCTION: The Selective Functional Movement Assessment (SFMA) is a functional movement assessment method to observe movement restrictions in individuals with known musculoskeletal disorders, although it has also been used to evaluate healthy athletes of different sports. AIM: The present paper aimed to evaluate the applicability of SFMA in a clinical setting and to verify whether a student can correctly perform it. METHODS: An introductory and explanatory email was sent to the subjects, containing the instructions needed to produce a video with SFMA evaluation movements. SFMA methodology was then used to analyze the received videos. The results between interobserver and intraobserver agreement were compared to the literature, considered the gold standard methods. RESULTS: Twenty-eight subjects (17.71 ± 1.96 years aged) were rated. The functional non-painful scenario (FN) has been assigned more frequently by all raters. The student's intra-rater reliability proved to be moderate (Kappa coefficient 0.49). Results for inter-rater reliability showed that the reliability degree between the senior physiotherapist and student before and after their educational path is good (Kappa coefficient 0.60 and 0.62, respectively). CONCLUSIONS: The results of this study showed SFMA intra-rater reliability to be moderate, while inter-rater reliability can be considered good. These characteristics make it a valuable tool for sport's needs, even when used by students.

A Novel Quantitative Computer-Assisted Score Can Improve Repeatability in the Estimate of Vascular Calcifications at the Abdominal Aorta.

In CKD and in the elderly, Vascular Calcifications (VC) are associated to cardiovascular events and bone fractures. VC scores at the abdominal aorta (AA) from lateral spine radiographs are widely applied (the 0-24 semiquantitative discrete visual score (SV) being the most used). We hypothesised that a novel continuum score based on quantitative computer-assisted tracking of calcifications (QC score) can improve the precision of the SV score. This study tested the repeatability and reproducibility of QC score and SV score. In forty-four patients with VC from an earlier study, five experts from four specialties evaluated the data twice using a dedicated software. Test-retest was performed on eight subjects. QC results were reported in a 0-24 scale to readily compare with SV. The QC score showed higher intra-operator repeatability: the 95% CI of Bland-Altman differences was almost halved in QC; intra-operator R2 improved from 0.67 for SV to 0.79 for QC. Inter-observer repeatability was higher for QC score in the first (Intraclass Correlation Coefficient 0.78 vs. 0.64), but not in the second evaluation (0.84 vs. 0.82), indicating a possible heavier learning artefact for SV. The Minimum Detectable Difference (MDD) was smaller for QC (2.98 vs. 4 for SV, in the 0-24 range). Both scores were insensitive to test-retest procedure. Notably, QC and SV scores were discordant: SV showed generally higher values, and an increasing trend of differences with VC severity. In summary, the new QC score improved the precision of lateral spine radiograph scores in estimating VC. We reported for the first time an estimate of MDD in VC assessment that was 25% lower for the new QC score with respect to the usual SV score. An ongoing study will determine whether this lower MDD may reduce follow-up times to check for VC progression.

Time for Revival of Bone Biopsy with Histomorphometric Analysis in Chronic Kidney Disease (CKD): Moving from Skepticism to Pragmatism.

Bone Biopsy (BB) with histomorphometric analysis still represents the gold standard for the diagnosis and classification of different forms of renal osteodystrophy. Bone biopsy is the only technique able to provide comprehensive information on all bone parameters, measuring static and dynamic parameters of turnover, cortical and trabecular microarchitecture, and mineralization defects. In nephrological practice, bone biopsy yields relevant indications to support therapeutic choices in CKD, heavily impacting the management and prognosis of uremic patients. Unfortunately, the use of bone biopsy has decreased; a lack of expertise in performing and interpreting, perceived procedure invasiveness and pain, and reimbursement issues have all contributed to this decline. Nevertheless, both bone biomarkers and instrumental images cannot be considered reliable surrogates for histological findings, being insufficiently accurate to properly evaluate underlying mineral and bone disorders. This is a multidisciplinary position paper from the Nephrology and Osteoporosis Italian Scientific Societies with the purpose of restating the role of bone biopsy in CKD patient management and of providing strong solutions to allow diffusion of this technique in Italy, but potentially also in other countries. The Italian approach through the optimization and standardization of bone biopsy procedure, the construction of the Italian Hub and Spoke network, and a request for adjustment and national homogenization of reimbursement to the Italian Health Ministry has led the way to implement bone biopsy and to improve CKD patient management and prognosis.

Effectiveness of In-Hospital Cholecalciferol Use on Clinical Outcomes in Comorbid COVID-19 Patients: A Hypothesis-Generating Study.

Little information is available on the beneficial effects of cholecalciferol treatment in comorbid patients hospitalized for COVID-19. The aim of this study was to retrospectively examine the clinical outcome of patients receiving in-hospital high-dose bolus cholecalciferol. Patients with a positive diagnosis of SARS-CoV-2 and overt COVID-19, hospitalized from 15 March to 20 April 2020, were considered. Based on clinical characteristics, they were supplemented (or not) with 400,000 IU bolus oral cholecalciferol (200,000 IU administered in two consecutive days) and the composite outcome (transfer to intensive care unit; ICU and/or death) was recorded. Ninety-one patients (aged 74 ± 13 years) with COVID-19 were included in this retrospective study. Fifty (54.9%) patients presented with two or more comorbid diseases. Based on the decision of the referring physician, 36 (39.6%) patients were treated with vitamin D. Receiver operating characteristic curve analysis revealed a significant predictive power of the four variables: (a) low (<50 nmol/L) 25(OH) vitamin D levels, (b) current cigarette smoking, (c) elevated D-dimer levels (d) and the presence of comorbid diseases, to explain the decision to administer vitamin D (area under the curve = 0.77, 95% CI: 0.67-0.87, p < 0.0001). Over the follow-up period (14 ± 10 days), 27 (29.7%) patients were transferred to the ICU and 22 (24.2%) died (16 prior to ICU and six in ICU). Overall, 43 (47.3%) patients experienced the combined endpoint of transfer to ICU and/or death. Logistic regression analyses revealed that the comorbidity burden significantly modified the effect of vitamin D treatment on the study outcome, both in crude (p = 0.033) and propensity score-adjusted analyses (p = 0.039), so the positive effect of high-dose cholecalciferol on the combined endpoint was significantly amplified with increasing comorbidity burden. This hypothesis-generating study warrants the formal evaluation (i.e., clinical trial) of the potential benefit that cholecalciferol can offer in these comorbid COVID-19 patients.

The Vessels-Bone Axis: Iliac Artery Calcifications, Vertebral Fractures and Vitamin K from VIKI Study.

Vascular calcification and fragility fractures are associated with high morbidity and mortality, especially in end-stage renal disease. We evaluated the relationship of iliac arteries calcifications (IACs) and abdominal aortic calcifications (AACs) with the risk for vertebral fractures (VFs) in hemodialysis patients. The VIKI study was a multicenter cross-sectional study involving 387 hemodialysis patients. The biochemical data included bone health markers, such as vitamin K levels, vitamin K-dependent proteins, vitamin 25(OH)D, alkaline phosphatase, parathormone, calcium, and phosphate. VF, IACs and AACs was determined through standardized spine radiograms. VF was defined as >20% reduction of vertebral body height, and VC were quantified by measuring the length of calcium deposits along the arteries. The prevalence of IACs and AACs were 56.1% and 80.6%, respectively. After adjusting for confounding variables, the presence of IACs was associated with 73% higher odds of VF (p = 0.028), whereas we found no association (p = 0.294) for AACs. IACs were associated with VF irrespective of calcification severity. Patients with IACs had lower levels of vitamin K2 and menaquinone 7 (0.99 vs. 1.15 ng/mL; p = 0.003), and this deficiency became greater with adjustment for triglycerides (0.57 vs. 0.87 ng/mL; p < 0.001). IACs, regardless of their extent, are a clinically relevant risk factor for VFs. The association is enhanced by adjusting for vitamin K, a main player in bone and vascular health. To our knowledge these results are the first in the literature. Prospective studies are needed to confirm these findings both in chronic kidney disease and in the general population.

Oral Calcitriol Use, Vertebral Fractures, and Vitamin K in Hemodialysis Patients: A Cross-Sectional Study.

Fractures and vascular calcifications (VCs) are common in patients with chronic kidney disease (CKD). They are related to abnormalities in vitamin D metabolism, calcium, phosphorus, parathyroid hormone, and fibroblast growth factor 23 (FGF23)/Klotho that occur with CKD. Impaired vitamin D metabolism and abnormal levels of calcium, phosphate, parathyroid hormone (PTH), and FGF23/Klotho drive bone and vascular changes in CKD. It is unclear if oral calcitriol safely mitigates fracture risk without increasing the burden of calcifications. Therefore, we investigated whether treatment with calcitriol affected the prevalence of fractures and VC progression in hemodialysis (HD) patients. This report is a secondary analysis of the Vitamin K Italian (VIKI) study, a cross-sectional study involving 387 HD patients. We assessed vitamin 25(OH)D, alkaline phosphatase, PTH, calcium, phosphate, osteocalcin or bone Gla protein, matrix Gla protein, and vitamin K levels. Vertebral fractures (VFs) and VCs were determined by spine radiograph. A reduction of >20% of vertebral body height was considered a VF. VCs were quantified by the length of calcific lesions along the arteries. The patients treated with oral calcitriol were 177 of 387 patients (45.7%). The prevalence of VF was lower in patients receiving oral calcitriol than in those untreated (48.6% versus 61.0%, p = 0.015), whereas the presence of aortic and iliac calcifications was similar (aortic: 81.9% versus 79.5%, respectively, p = 0.552; iliac: 52.0% and 59.5%, respectively, p = 0.167). In multivariable logistic regression analysis, oral calcitriol was associated with a 40.2% reduced odds of fracture (OR 0.598; 95% confidence interval [CI], 0.363-0.985; p = 0.043). In conclusion, we found a significant association between oral calcitriol and lower VF in HD patients without an increase in the burden of VC. Further prospective and interventional studies are needed to confirm these findings. © 2021 American Society for Bone and Mineral Research (ASBMR).

Sevelamer Use, Vitamin K Levels, Vascular Calcifications, and Vertebral Fractures in Hemodialysis Patients: Results from the VIKI Study.

Hyperphosphatemia is a risk factor for vascular calcifications (VCs), which are part of the chronic kidney disease-mineral and bone disorders (CKD-MBD). Vitamin K-dependent proteins such as matrix Gla protein (MGP) and bone Gla proteins (BGP, or osteocalcin) can inhibit VCs and regulate bone mineralization. In this analysis of the Vitamin K Italian (VIKI) study, the relationship between vitamin K status, vertebral fractures (VFs) and VCs in 387 hemodialysis (HD) patients with (N = 163; 42.1%) or without N = 224; 57.9%) sevelamer was evaluated. Levels of vitamin K vitamers K1 and K2 or menaquinones (MK; MK4-7), total and undercarboxylated (uc) forms for both BGP and MGP were determined. Although no differences in clinical characteristics were noted, lower levels of MK4 (0.45 versus 0.6 ng/mL, p = .01) and a greater MK4 deficiency was observed in sevelamer-treated patients (13.5% versus 5.4%, p = .005). Multivariate logistic regression revealed that MK4 deficiency was associated with sevelamer use (odds ratio [OR] = 2.64, 95% confidence interval [CI] 1.25-5.58, p = .011) and aortic calcification (OR = 8.04, 95% CI 1.07-60.26, p = .04). In the same logistic model, sevelamer amplified the effect of total BGP levels on the odds of VFs in patients with total BGP <150 µg/L compared with those with total BGP ≥150 µg/L (OR = 3.15, 95% CI 1.46-6.76, p = .003). In contrast, there was no such effect in those untreated (total BGP <150 µg/L versus total BGP ≥150 µg/L: OR = 1.21, 95% CI 0.66-2.23, p = .54]; p = .049 for effect modification by sevelamer). Sevelamer may interfere with MK4 levels in HD patients and interact with low BGP levels to increase bone fractures in CKD patients. © 2020 American Society for Bone and Mineral Research (ASBMR).

Vitamin K and Kidney Transplantation.

The assessment of the vitamin K status and its effects on clinical outcomes in kidney transplantation (KT) patients has sparked interest, but it is still largely unfulfilled. In part, this is due to difficulties in laboratory measurements of vitamin K, especially K2 vitamers. Vitamin K status is currently best assessed by measuring undercarboxylated vitamin-K-dependent proteins. The relative contribution of vitamin K1 and K2 to the health status of the general population and CKD (chronic kidney disease) patients, including KT patients, is also poorly studied. Through a complete and first review of the existing literature, we summarize the current knowledge of vitamin K pathophysiology and its potential role in preventing KT complications and improving organ survival. A specific focus is placed on cardiovascular complications, bone fractures, and the relationship between vitamin K and cancer. Vitamin K deficiency could determine adverse outcomes, and KT patients should be better studied for vitamin K assessment and modalities of effective therapeutic approaches.