Vitamin K effects in human health: new insights beyond bone and cardiovascular health

Vitamin K is a cofactor for the function of the enzyme \u3b3-glutamyl carboxylase, necessary for the activation of multiple vitamin K dependent-proteins. Vitamin K dependent-proteins (VKDPs) have important roles in bone health, vascular health, metabolism, reproduction as well as in cancer progression. Vitamin K deficiency is common in different conditions, including kidney disease, and it may influence the activity of VKDPs. This review discusses vitamin K status in human health and the physiologic and pathologic roles of VKDPs, beyond the established effects in skeletal and cardiovascular health

Persistent Deficits in Bone Quality in Treated Acromegaly: Evidence From Assessments of Microstructure.

Fractures are increased in patients with acromegaly, both before and after successful acromegaly treatment. Abnormalities of bone microstructure, which may underlie this fragility, are present in active acromegaly but to what extent these improve with acromegaly treatment or persist despite biochemical remission remains unclear. To examine these questions, we studied the effects of acromegaly treatment and remission on bone quality. Sixty-five women and men with acromegaly were studied. Subgroups underwent assessments of areal bone mineral density by dual x-ray absorptiometry, trabecular bone score (TBS), and volumetric bone mineral density, microarchitecture, stiffness and failure load of the distal radius and tibia by high-resolution peripheral quantitative tomography in a longitudinal study before and after acromegaly treatment and in a cross-sectional study in which patients were compared to sex-, age-, and body mass index-matched healthy controls. In the longitudinal study, significant increases in total, cortical, and trabecular densities at the radius and tibia and increased stiffness and failure load of the tibia occurred with acromegaly treatment. In the cross-sectional study, patients in biochemical remission after surgery had larger bones, lower trabecular and cortical volumetric density, and disrupted trabecular microarchitecture compared to controls. TBS did not change with acromegaly treatment but correlated with some microstructural parameters. We show, for the first time, that volumetric bone mineral density and microarchitecture of the peripheral skeleton improve with acromegaly treatment but remain abnormal in patients in remission after surgery compared to controls. These abnormalities, known to be associated with fractures in other populations, may play a role in the pathogenesis of persistent fragility in treated acromegaly

Osteocalcin (bone GLA protein) levels, vascular calcifications, vertebral fractures and mortality in hemodialysis patients with diabetes mellitus

Background and aims: Diabetes mellitus is recognized as one of the major causes of end stage kidney disease. Bone Gla protein (BGP) is a vitamin K-dependent protein involved in bone mineralization and vascular calcifications (VC). Our goal was to characterize BGP and undercarboxylated BGP (ucBGP) in DM patients on HD, compared to HD patients without DM, and their association with vascular and bone disease. Methods: 387 HD patients from 18 dialysis centers in Italy. Associations of DM, levels of BGP, vitamin D and VC were evaluated. Time-to-event analysis for all-cause mortality was performed by the Kaplan\u2013Meier. Results: Patients with DM had lower levels of total BGP (139.00 vs. 202.50 mcg/L, p < 0.001), 25(OH)D (23.4 vs. 30.2 ng/ml, p < 0.001), and ucBGP (9.24 vs. 11.32 mcg/L, p = 0.022). In regression models, the geometric means of total BGP and ucBGP were 19% (p = 0.009) and 26% (p = 0.034) lower in diabetic patients. In univariate Cox regression analysis, DM patients had a higher risk of all-cause mortality (HR:1.83, 95% CI 1.13\u20132.96, p = 0.014). Adjustment for confounders confirmed the significant DM-mortality link. We included VC and warfarin into the Cox model, the DM-mortality link was no longer significant, suggesting a role of these risk factors as causal mediators leading to increased mortality in dialysis patients. Conclusions: HD patients have an increased mortality risk associated with DM. Furthermore, we found an association between DM and decreased BGP levels. Although our study does not support the notion that BGP levels act as mediator in the DM-mortality link, to our knowledge this is the first study in HD patients suggesting a potential protective role of BGP in the bone, endocrine and vascular pathway

Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes

In established acute kidney injury (AKI), serum creatinine poorly differentiates prerenal from intrinsic AKI. In this study, we tested whether urinary neutrophil gelatinase-associated lipocalin (NGAL) distinguishes between intrinsic and prerenal AKI, and tested its performance in predicting a composite outcome that included progression to a higher RIFLE (Risk, Injury, Failure, Loss of function, End stage renal disease) class, dialysis, or death. Urinary NGAL was measured using a standardized clinical platform in 161 hospitalized patients with established AKI. Sixteen patients were excluded because of postrenal obstruction or insufficient clinical information. Of the remaining 145 patients, 75 had intrinsic AKI, 32 had prerenal AKI, and 38 patients could not be classified. Urinary NGAL levels effectively discriminated between intrinsic and prerenal AKI (area under the receiver-operating characteristic curve 0.87). An NGAL level over 104 μg/l indicated intrinsic AKI (likelihood ratio 5.97), whereas an NGAL level <47 μg/l made intrinsic AKI unlikely (likelihood ratio 0.2). Patients experiencing the composite outcome had significantly higher median urinary NGAL levels on inclusion. In logistic regression analysis, NGAL independently predicted the composite outcome when corrected for demographics, comorbidities, creatinine, and RIFLE class. Hence, urinary NGAL is useful in classifying and stratifying patients with established AKI

Urine neutrophil gelatinase-associated lipocalin identifies unilateral and bilateral urinary tract obstruction

BACKGROUND: Urinary tract obstruction (UTO) is a common problem that can lead to permanent loss of kidney function. Unilateral UTO may be difficult to diagnose. Urinary neutrophil gelatinase-associated Lipocalin (uNGAL) may identify unilateral and bilateral UTO. METHODS: Retrospective case-control study of patients undergoing hospital admission at three sites. UTO was determined by review of medical records and cases were matched to control patients. uNGAL was measured by immunoblot. RESULTS: Twenty-four unilateral UTO and 15 bilateral UTO cases were identified. Admission serum creatinine (sCr) (milligram per decilitre) was significantly higher in bilateral UTO, 2.0 (1.1-5.3), but not unilateral UTO, 1.1 (0.8-1.5), compared to controls, 0.9 (0.8-1.2). uNGAL (nanogram per millilitre) was significantly higher both in patients with bilateral UTO, 140 (40-450), and unilateral UTO, 50 (20-100), compared to controls, 20 (10-45). Discussion: uNGAL identifies kidney injury in unilateral and bilateral UTO even in the absence of an elevated sCr

The association between a mediterranean-style diet and kidney function in the northern manhattan study cohort

Background and objectives Various dietary strategies have been investigated to slow kidney function decline. However, it is unknownwhether aMediterranean diet,which has been associatedwith improved cardiovascular risk, is associated with change in kidney function Design, setting, participants, &amp;amp; measurements This study used the Northern Manhattan Study, a prospective, multiethnic, observational cohort of participants who were stroke free at baseline. Data were collected between 1993 and 2008. Serum creatinine measurements were taken a mean 6.9 years apart. A baseline dietary questionnairewas extrapolated into a previously used 9-point scoring system(MeDi). The primary outcomewas incident eGFR,60 ml/min per 1.73 m2using the Modification of Diet in Renal Disease formula. A secondary outcome was the upper quartile of annualized eGFR decline (≥2.5 ml/min per 1.73 m2 per year). Conditional logistic regression models adjusted for demographics and baseline vascular risk factors. Results Mean baseline age was 64 years, with 59% women and 65% Hispanics (N=900); mean baseline eGFR was 83.1 ml/min per 1.73 m2. Incident eGFR,60 ml/min per 1.73 m2 developed in 14%. In adjusted models, every 1-point increase in the MeDi score, indicating increasing adherence to a Mediterranean diet, was associated with decreased odds of incident eGFR,60 ml/min per 1.73 m2 (odds ratio, 0.83; 95% confidence interval, 0.71 to 0.96) and decreased odds of being in the upper quartile of eGFR decline (odds ratio, 0.88; 95% confidence interval, 0.79 to 0.98). Conclusions A Mediterranean diet was associated with a reduced incidence of eGFR,60 ml/min per 1.73m2 and upper quartile of eGFR decline in a multiethnic cohort. © 2014 by the American Society of Nephrology

The trabecular bone score: Relationships with trabecular and cortical microarchitecture measured by HR-pQCT and histomorphometry in patients with chronic kidney disease.

The trabecular bone score (TBS) is a novel tool using grayscale variograms of the lumbar spine bone mineral density (BMD) to assess trabecular bone microarchitecture. Studies in patients with chronic kidney disease (CKD) suggest it may be helpful in assessing fracture risk. However, TBS has not been validated as a measure of trabecular architecture against transiliac bone biopsy with histomorphometry in CKD patients. We hypothesized that TBS would reflect trabecular architecture at the iliac crest in CKD patients. We obtained tetracycline double labeled transiliac crest bone biopsy, areal BMD of the spine, total hip, femoral neck (FN) and spine TBS by dual energy X-ray absorptiometry (DXA), and cortical and trabecular volumetric density and microarchitecture by high resolution peripheral quantitative computed tomography (HR-pQCT) in CKD patients from two centers: twenty-two patients from Columbia University Medical Center, USA and thirty patients from Hospital das Clinicas - Universidade de São Paulo, Brazil. Two patients were excluded for outlier status. Univariate and multivariate relationships between TBS and measures from DXA, HR-pQCT and histomorphometry were determined. Patients were 50.2 ± 15.8 years old, 23 (46%) were men, and 33 (66%) were on dialysis. TBS was &lt;1.31 in 21 (42%) patients and 22%, 14% and 10% had T-scores ≤ -2.5 at spine, FN and total hip respectively. In univariate regression, TBS was significantly associated with trabecular bone volume (BV/TV), trabecular width (Tb.Wi), trabecular spacing, cortical width but not with trabecular number or cortical porosity. FN Z-score and height were also associated with cancellous BV/TV and Tb.Wi, In multivariate analysis, TBS remained an independent predictor of BV/TV and Tb.Wi. There were no relationships between TBS and dynamic parameters from histomorphometry. These data suggest that TBS reflected trabecular microarchitecture and cortical width measured by bone biopsy in CKD patients. Future studies should address its utility in the identification of CKD patients who may benefit from fracture prevention strategies

Spine Trabecular Bone Score as an Indicator of Bone Microarchitecture at the Peripheral Skeleton in Kidney Transplant Recipients.

Studies using high-resolution peripheral quantitative computed tomography showed progressive abnormalities in cortical and trabecular microarchitecture and biomechanical competence over the first year after kidney transplantation. However, high-resolution peripheral computed tomography is a research tool lacking wide availability. In contrast, the trabecular bone score is a novel and widely available tool that uses gray-scale variograms of the spine image from dual-energy x-ray absorptiometry to assess trabecular quality. There are no studies assessing whether trabecular bone score characterizes bone quality in kidney transplant recipients. Between 2009 and 2010, we conducted a study to assess changes in peripheral skeletal microarchitecture, measured by high-resolution peripheral computed tomography, during the first year after transplantation in 47 patients managed with early corticosteroid-withdrawal immunosuppression. All adult first-time transplant candidates were eligible. Patients underwent imaging with high-resolution peripheral computed tomography and dual-energy x-ray absorptiometry pretransplantation and 3, 6, and 12 months post-transplantation. We now test if, during the first year after transplantation, trabecular bone score assesses the evolution of bone microarchitecture and biomechanical competence as determined by high-resolution peripheral computed tomography. At baseline and follow-up, among the 72% and 78%, respectively, of patients having normal bone mineral density by dual-energy x-ray absorptiometry, 53% and 50%, respectively, were classified by trabecular bone score as having high fracture risk. At baseline, trabecular bone score correlated with spine, hip, and ultradistal radius bone mineral density by dual-energy x-ray absorptiometry and cortical area, density, thickness, and porosity; trabecular density, thickness, separation, and heterogeneity; and stiffness and failure load by high-resolution peripheral computed tomography. Longitudinally, each percentage increase in trabecular bone score was associated with increases in trabecular number (0.35%±1.4%); decreases in trabecular thickness (-0.45%±0.15%), separation (-0.40%±0.15%), and network heterogeneity (-0.48%±0.20%); and increases in failure load (0.22%±0.09%) by high-resolution peripheral computed tomography (all P&lt;0.05). Trabecular bone score may be a useful method to assess and monitor bone quality and strength and classify fracture risk in kidney transplant recipients