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ABSTRACT Background Disparities in aspects of chronic kidney disease progression and management exist for patients from culturally and linguistically diverse (CALD) backgrounds, including with treatment and outcomes for kidney transplantation. Objective This study aimed to explore factors that impact kidney transplant outcomes from the perspective of kidney transplant recipients (KTRs) from CALD backgrounds and their family caregivers. Methods A descriptive qualitative design was utilised. Participants were recruited from two tertiary hospitals in Victoria, Australia. Semi‐structured interviews were conducted with KTRs who were born overseas in countries where English is not the primary language. Interviews were also conducted with family caregivers. Analysis was guided by the Framework Method, and emergent subcategories were mapped into the categories identified in Andersen's Health Service Utilisation Model. Results Data from 21 KTRs and five caregivers were grouped under the categories of Population Characteristics, Environment, Health Behaviour and Outcomes. KTRs believed that neither culture nor religious beliefs impacted how they managed their transplant or healthcare utilisation. KTRs expressed satisfaction with their care, felt no inequity with how they were treated by health professionals and expressed gratitude for the Australian healthcare system. Language did not necessarily impact transplant outcomes, but there was a reliance on interpreters for non‐English‐speaking patients as most written information was in English. Caregivers were instrumental in providing support but discussed the challenges involved. Conclusion This study explored factors influencing kidney transplantation for KTRs from a CALD background. The study provided insight into how to deliver quality healthcare to these patients, highlighting the importance of health services providing information that is written in the patient's own language and respectively asking KTRs about their health beliefs or customs. Caregivers were instrumental in supporting KTRs, but there is a need to better prepare them for this role. Patient or Public Contribution Patient and public involvement was integrated into the design and delivery of the study. KTRs from CALD backgrounds assisted with framing the research questions and offering advice on the recruitment and data collection process.

Background Cardiovascular calcification, characterized by deposition of calcium phosphate in the arterial wall and heart valves, is associated with cardiovascular morbidity and mortality and is commonly seen in aging, diabetes, and chronic kidney disease. Whether evidence‐based interventions could significantly attenuate cardiovascular calcification progression remains uncertain. Methods and Results We conducted a systematic review of randomized controlled trials involving interventions, compared with placebo, another comparator, or standard of care, to attenuate cardiovascular calcification. Included clinical trials involved participants without chronic kidney disease, and the outcome was cardiovascular calcification measured using radiological methods. Quality of evidence was determined by the Cochrane risk of bias and Grading of Recommendations, Assessment, Development, and Evaluations assessment. Forty‐nine randomized controlled trials involving 9901 participants (median participants 104, median duration 12 months) were eligible for inclusion. Trials involving aged garlic extract (n=6 studies) consistently showed attenuation of cardiovascular calcification. Trials involving 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (n=14), other lipid‐lowering agents (n=2), hormone replacement therapies (n=3), vitamin K (n=5), lifestyle measures (n=4), and omega‐3 fatty acids (n=2) consistently showed no attenuation of cardiovascular calcification with these therapies. Trials involving antiresorptive (n=2), antihypertensive (n=2), antithrombotic (n=4), and hypoglycemic agents (n=3) showed mixed results. Singleton studies involving salsalate, folate with vitamin B6 and 12, and dalcetrapib showed no attenuation of cardiovascular calcification. Overall, Cochrane risk of bias was moderate, and the Grading of Recommendations, Assessment, Development, and Evaluations assessment for a majority of analyses was moderate certainty of evidence. Conclusions Currently, there are insufficient or conflicting data for interventions evaluated in clinical trials for mitigation of cardiovascular calcification. Therapy involving aged garlic extract appears most promising, but evaluable studies were small and of short duration.

Management of atrial fibrillation (AF) is a clinical conundrum in people with kidney failure. Stroke risk is disproportionately high, but clinicians have a limited armamentarium to improve outcomes in this population in whom there is a concurrently high bleeding risk. Direct oral anticoagulants may have a superior benefit–risk profile compared with vitamin K antagonists in people on hemodialysis. Although research has predominantly focused on identifying a safe and effective oral anticoagulation option to reduce stroke risk in people with kidney failure (and predominantly those on hemodialysis), it remains uncertain how clinicians discriminate between people who would derive net clinical benefit as opposed to net harm. The recommended CHA2DS2-VASc score cutoffs provide poor discriminatory value, and there is an urgent need to identify robust markers of thromboembolic risk in kidney failure.There is increasing data to challenge the prior dogma of risk equivalence across AF type, and the American Heart Association highlights moving beyond AF as a binary entity to consider the prognostic significance of AF burden. Implantable cardiac monitor studies reveal high rates and varied burden of subclinical and paroxysmal AF in people on hemodialysis. The association between AF burden and the proarrhythmic environment of hemodialysis with cyclical volume loading, offloading, and electrolyte changes is not well studied. We review the significance of AF burden as a contributor to thromboembolic risk, its potential as the missing link in risk assessment, and updated evidence for anticoagulation in people with kidney failure.

Abstract Plasma approaches metastability with respect to its calcium and phosphate content, with only minor perturbations in ionic activity needed to sustain crystal growth once nucleated. Physiologically, calcium and phosphate are intermittently absorbed from the diet each day, yet plasma concentrations of these ions deviate minimally post-prandially. This implies the existence of a blood-borne mineral buffer system to sequester calcium phosphates and minimise the risk of deposition in the soft tissues. Calciprotein particles (CPP), endogenous mineral-protein colloids containing the plasma protein fetuin-A, may fulfill this function but definitive evidence linking dietary mineral loading with their formation is lacking. Here we demonstrate that CPP are formed as a normal physiological response to feeding in healthy adults and that this occurs despite minimal change in conventional serum mineral markers. Further, in individuals with Chronic Kidney Disease (CKD), in whom mineral handling is impaired, we show that both fasting and post-prandial levels of CPP precursors are markedly augmented and strongly inversely correlated with kidney function. This study highlights the important, but often neglected, contribution of colloidal biochemistry to mineral homeostasis and provides novel insight into the dysregulation of mineral metabolism in CKD.

Background. The fracture pathophysiology associated with type 2 diabetes and chronic kidney disease (CKD) is incompletely understood. We examined individual fracture predictors and prediction sets based on different pathophysiological hypotheses, testing whether any of the sets improved prediction beyond that based on traditional osteoporotic risk factors. Methods. Within the CREDENCE cohort with adjudicated fracture outcomes, we assessed the association of individual factors with fracture using Cox regression models. We used the Akaike information criteria (AIC) and Schwartz Bayes Criterion (SBC) to assess six separate variable sets based on hypothesized associations with fracture, namely, traditional osteoporosis, exploratory general population findings, cardiovascular risk, CKD-mineral and bone disorder, diabetic osteodystrophy, and an all-inclusive set containing all variables. Results. Fracture occurred in 135 (3.1%) participants over a median 2.35 [1.88–2.93] years. Independent fracture predictors were older age (hazard ratio [HR] 1.04, confidence interval [CI] 1.01–1.06), female sex (HR 2.49, CI 1.70–3.65), previous fracture (HR 2.30, CI 1.58–3.34), Asian race (HR 1.74, CI 1.09–2.78), vitamin D therapy requirement (HR 2.05, CI 1.31–3.21), HbA1c (HR 1.14, CI 1.00–1.32), prior cardiovascular event (HR 1.60, CI 1.10–2.33), and serum albumin (HR 0.41, CI 0.23–0.74) (lower albumin associated with greater risk). The goodness of fit of the various hypothesis sets was similar (AIC range 1870.92–1849.51, SBC range 1875.60–1948.04). Conclusion. Independent predictors of fracture were identified in the CREDENCE participants with type 2 diabetes and CKD. Fracture prediction was not improved by models built on alternative pathophysiology hypotheses compared with traditional osteoporosis predictors.

Introduction: Calciprotein particles (CPPs) are potentially modifiable mediators of phosphate toxicity in patients with kidney disease. We compared the effects of calcium carbonate (CC) and the non–calcium-based phosphate binder sevelamer on CPP levels in patients undergoing hemodialysis (HD). We hypothesized that treatment with sevelamer would achieve greater reductions in amorphous calcium phosphate–containing CPP (CPP-1) and hydroxyapatite-containing CPP (CPP-2) owing to reduced calcium loading and anti-inflammatory pleiotropic effects. Methods: We conducted an open-label, randomized controlled trial (RCT) in which 31 stable prevalent HD patients were allocated to receive either sevelamer hydrochloride (SH), sevelamer carbonate (SC), or CC for 24 weeks. Dual primary endpoints were the between groups differences in serum CPP-1 and CPP-2 levels at 24 weeks in SH + SC–treated versus CC-treated patients. Effects on aortic pulse wave velocity (aPWV), inflammatory cytokines (interleukin-6 and -8), and effects across individual treatment arms were also assessed. Results: Serum CPP-1, but not CPP-2, levels were lower in those randomly assigned to the sevelamer (SH + SC) group compared with the CC group at 24 weeks (–70%, 95% confidence interval [CI] –90% to –15%, P = 0.02). In subgroup analysis, this effect was confined to those receiving SC (–83.4%, 95% CI –95.7% to –36.8%, P = 0.01). aPWV and interleukin-8 levels were also lower in those who received sevelamer compared with CC at 24 weeks (–2.0 m/s, 95% CI –2.9 to –1.1; –57%, 95% CI –73% to –30%, respectively, both P = 0.01). Conventional markers of mineral metabolism remained stable across all treatment groups. Discussion: Compared with treatment with CC, use of sevelamer for 24 weeks was associated with lower serum CPP-1 levels and a reduction in aPWV and systemic inflammation.

Abstract Background Vascular calcification (VC) is well described in large- and medium-sized vessels in patients with chronic kidney disease (CKD), especially in those with end-stage kidney disease (ESKD) on dialysis. Medial calcification is particularly prevalent in this population and contributes to arterial stiffness and increased cardiovascular mortality and morbidity. Apart from in the setting of calciphylaxis, few studies have assessed skin and subcutaneous calcification and associations with abnormalities of bone and mineral metabolism in patients with CKD. Methods We performed a single-centre observational study to evaluate incisional skin tissue samples from three anatomical sites in patients with different stages of CKD undergoing elective surgery. We compared these samples to skin samples of a control cohort without CKD. Staining for calcification was performed with von Kossa method. A subgroup of skin samples were assessed by RT-PCR for upregulation of pro-calcific gene transcripts for tissue non-specific alkaline phosphatase (TNAP) and Runt-related transcription factor 2 (RUNX2). Results Forty-five patients were evaluated, 34 with CKD (including ESKD) and 11 control patients. VC was identified in 15 skin samples (13 CKD/ESKD and 2 controls). VC was present in the dermal and subcutaneous tissues of the neck, abdomen and arm samples. Two different histological types of VC were identified: speckled medial calcification and internal elastic lamina calcification. Presence of perieccrine calcification was identified in 14 samples, 10 with concurrent VC. There were no significant differences in serum parathyroid hormone, phosphate or calcium in patients with or without VC. Expression of TNAP or RUNX2 was not increased in samples from patients with ESKD or those with histological evidence of calcification. Conclusion This study reports the novel finding of dermal and subcutaneous calcification in multiple anatomical locations in 38% of patients with advanced CKD/ESKD undergoing elective surgery but free from calciphylaxis.

Background: Secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) has a significant effect on bone, affecting both trabecular and cortical compartments. Although parathyroidectomy results in biochemical improvement in mineral metabolism, changes in bone microarchitecture as evaluated by high-resolution imaging modalities are not known. Magnetic resonance imaging (MRI) provides in-depth three-dimensional assessment of bone microarchitecture, as well as determination of mechanical bone strength determined by finite element analysis (FEA). Methods: We conducted a single-centre longitudinal study to evaluate changes in bone microarchitecture with MRI in patients with SHPT undergoing parathyroidectomy. MRI was performed at the distal tibia at baseline (time of parathyroidectomy) and at least 12 months following surgery. Trabecular and cortical topological parameters as well as bone mechanical competence using FEA were assessed. Results: Fifteen patients with CKD (12 male, 3 female) underwent both MRI scans at the time of surgery and at least 12 months post-surgery. At baseline, 13 patients were on dialysis, one had a functioning kidney transplant, and one was pre-dialysis with stage 5 CKD. Seven patients received a kidney transplant following parathyroidectomy prior to follow-up MRI. MRI parameters in patients at follow up were consistent with loss in trabecular and cortical bone thickness (p = 0.006 and 0.03 respectively). Patients who underwent a kidney transplant in the follow-up period had reduction in trabecular thickness (p = 0.05), whereas those who continued on dialysis had reduction in cortical thickness (p = 0.04) and mechanical bone strength on FEA (p = 0.03). Conclusion: Patients with severe SHPT requiring parathyroidectomy have persistent changes in bone microarchitecture at least 12 months following surgery with evidence of ongoing decline in trabecular and cortical thickness.

Abstract Background Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) is a significant cause of morbidity among haemodialysis patients and is associated with pathological changes in phosphate, calcium and parathyroid hormone (PTH). In the ACTIVE Dialysis study, extended hours dialysis reduced serum phosphate but did not cause important changes in PTH or serum calcium. This secondary analysis aimed to determine if changes in associated therapies may have influenced these findings and to identify differences between patient subgroups. Methods The ACTIVE Dialysis study randomised 200 participants to extended hours haemodialysis (≥24 h/week) or conventional haemodialysis (≤18 h/week) for 12 months. Mean differences between treatment arms in serum phosphate, calcium and PTH; and among key subgroups (high vs. low baseline phosphate/PTH, region, time on dialysis, dialysis setting and frequency) were examined using mixed linear regression. Results Phosphate binder use was reduced with extended hours (− 0.83 tablets per day [95% CI -1.61, − 0.04; p = 0.04]), but no differences in type of phosphate binder, use of vitamin D, dose of cinacalcet or dialysate calcium were observed. In adjusted analysis, extended hours were associated with lower phosphate (− 0.219 mmol/L [− 0.314, − 0.124; P

Abstract Resources to support long-term medication adherence in kidney transplantation are limited. This study aimed to determine the efficacy of an intervention designed for kidney transplant recipients to enhance medication adherence. A single-blind, multi-site, 12-month pilot randomised controlled trial was conducted at all five public hospitals providing adult kidney transplantation in Victoria, Australia. Participants were recruited at 4 to 6 weeks post-transplantation. Thirty-five participants were randomly assigned to a 3-month intervention, involving a face-to-face meeting (a medication review and a consumer-centred video) and health coaching every two weeks. Thirty-six were randomised to receive usual care. All participants were followed for nine months post-intervention. There were no differences in adherence between groups measured by Medication Event Monitoring System (MEMS), however, it was underutilised by 42% of participants. Based on the self-reported Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS©) score, the percentage of adherent participants decreased significantly between baseline and 3 to 12 months in the control group (p-values

Excess sodium intake is a leading but modifiable risk factor for mortality, with implications on hypertension, inflammation, cardiovascular disease, and chronic kidney disease (CKD). This review will focus mainly on the limitations of current measurement methods of sodium balance particularly in patients with CKD who have complex sodium physiology. The suboptimal accuracy of sodium intake and excretion measurement is seemingly more marked with the evolving understanding of tissue (skin and muscle) sodium. Tissue sodium represents an extrarenal influence on sodium homeostasis with demonstrated clinical associations of hypertension and inflammation. Measurement of tissue sodium has been largely unexplored in patients with CKD. Development and adoption of more comprehensive and dynamic assessment of body sodium balance is needed to better understand sodium physiology in the human body and explore therapeutic strategies to improve the clinical outcomes in the CKD population.

Background: Secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) leads to complex bone disease, affecting both trabecular and cortical bone, and increased fracture risk. Optimal assessment of bone in patients with CKD is yet to be determined. High-resolution magnetic resonance imaging (MRI) can provide three-dimensional assessment of bone microarchitecture, as well as determination of mechanical strength with finite element analysis (FEA). Methods: We conducted a single-centre, cross-sectional study to determine bone microarchitecture with MRI in CKD patients with SHPT undergoing parathyroidectomy. Within two weeks of surgery, MRI was performed at the distal tibia and biochemical markers of SHPT (parathyroid hormone [PTH] and alkaline phosphatase [ALP]) were collected. Trabecular and cortical topological parameters as well as bone mechanical competence using FEA were assessed. Correlation of MRI findings of bone was made with biochemical markers. Results: Twenty patients with CKD (15 male, 5 female) underwent MRI at the time of parathyroidectomy (16 on dialysis, 3 with functioning kidney transplant, one pre-dialysis with CKD stage 5). Median PTH at the time of surgery was 138.5 pmol/L [39.6–186.7 pmol/L]. MRI parameters in patients were consistent with trabecular deterioration, with erosion index (EI) 1.01 ± 0.3, and trabecular bone volume (BV/TV) 10.8 ± 2.9%, as well as poor trabecular network integrity with surface-to-curve ratio (S/C) 5.4 ± 2.3. There was also evidence of reduced cortical thickness, with CTh 2.698 ± 0.630 mm, and FEA demonstrated overall poor bone mechanical strength with mean elastic modulus of 2.07 ± 0.44. Conclusion: Patients with severe SHPT requiring parathyroidectomy have evidence of significant changes in bone microarchitecture with trabecular deterioration, low trabecular and cortical bone volume, and reduced mechanical competence of bone.

Abstract Background The calcimimetic agent cinacalcet is effective for the management of secondary hyperparathyroidism (SHPT) in dialysis patients. Changes to reimbursement of cinacalcet in Australia provided an opportunity to assess effects of medication cessation on biochemical and clinical outcomes in dialysis patients, including changes to novel biomarkers such as calciprotein particles (CPP). CPP are nanoparticles of mineral and protein in the circulation associated with increased vascular calcification in patients with chronic kidney disease. Methods Dialysis patients from a single center who ceased cinacalcet between August 2015 and March 2016 were included in a prospective observational study. Bloods were taken at the time of cessation of cinacalcet and at 1, 6 and 12 months. Clinical and biochemical outcomes were compared with an age- and gender-matched cohort of cinacalcet-naïve dialysis patients. Results Sixty-two patients participated in the study. Mean age was 69.6 ± 13.2 years. Biochemical changes over 12 months following cessation of cinacalcet included an increase in serum parathyroid hormone (PTH) (42.2 [IQR 27.8–94.6] pmol/L to 114.8 [83.9–159.1] pmol/L [p

Abstract Background Arterial stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease (CKD). There are limited prospective data however on progression of arterial stiffness in CKD, including evaluating associations with bone mineral markers such as fibroblast growth factor 23 (FGF23) and soluble α-klotho (sKl). Methods In this prospective, single-center, observational study, arterial stiffness [measured by pulse wave velocity (PWV)] and hormones influencing mineral homeostasis, including serum FGF23 and sKl, were compared between non-dialysis CKD stages 4/5 and healthy controls at baseline and 12 months (12 m). Abdominal aortic calcification (AAC) was quantitated using lateral lumbar radiography at baseline. Results Forty patients with CKD [mean estimated glomerular filtration rate (eGFR) 19.5 ± 6.7 mL/min/1.73m2] and 42 controls (mean eGFR 88.6 ± 12.9 mL/min/1.73m2) completed follow-up. There were no differences in age, gender and body mass index between groups. A significant increase in FGF23 [240.6 (141.9–1129.8) to 396.8 (160.3–997.7) pg/mL, p = 0.001] was observed in the CKD group but serum phosphate, corrected calcium, parathyroid hormone and sKl did not change significantly over 12 m. At baseline, CKD subjects had higher AAC prevalence [83.8% versus (vs.) 43.6%, p = 0.002] and higher aortic PWV [9.7(7.6–11.7) vs. 8.1 (7.2–9.7) m/s, p = 0.047] compared to controls. At 12 m, aortic PWV increased by 1.3 m/s (95% confidence interval, 0.56 to 2.08, p 10 m/s). Serum FGF23 was associated with AAC, abnormal PWV and progression of PWV at 12 m. Conclusions Arterial stiffness and serum FGF23, both of which are associated with increased cardiovascular risk, increased over one year in individuals with CKD. Additionally, a significant association was found between serum FGF23 and arterial calcification and stiffness. Larger clinical studies and further experimental work are warranted to delineate the temporal relationship as well as the pathological mechanisms linking FGF23 and vascular disease.

Chronic kidney disease (CKD) is associated with excess cardiovascular mortality, resulting from both traditional and nontraditional, CKD-specific, cardiovascular risk factors. Nontraditional risk factors include the entity Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) which is characterised by disorders of bone and mineral metabolism, including biochemical abnormalities of hyperphosphatemia and hyperparathyroidism, renal osteodystrophy, and vascular calcification. Increased arterial stiffness in the CKD population can be attributed amongst other influences to progression of vascular calcification, with significant resultant contribution to the cardiovascular disease burden. Pulse wave velocity (PWV) measured over the carotid-femoral arterial segments is the noninvasive gold-standard technique for measurement of aortic stiffness and has been suggested as a surrogate cardiovascular end-point. A PWV value of 10 m/s or greater has been recommended as a suitable cut-off for an increased risk of cardiovascular mortality. CKD is a risk factor for an excessive rate of increase in aortic stiffness, reflected by increases in PWV, and increased aortic PWV in CKD shows faster progression than for individuals with normal kidney function. Patients with varying stages of CKD, as well as those on dialysis or with a kidney transplant, have different biological milieu which influence aortic stiffness and associated changes in PWV. This review discusses the pathophysiology of arterial stiffness with CKD and outlines the literature on PWV across the spectrum of CKD, highlighting that determination of arterial stiffness using aortic PWV can be a useful diagnostic and prognostic tool for assessing cardiovascular disease in the CKD population.

Background. Vascular calcification (VC), precipitated by calcium and phosphate imbalance, is a major contributor to cardiovascular disease (CVD) in chronic kidney disease (CKD). Electron-beam computed tomography (EBCT) quantitatively assesses coronary artery calcification (CAC), with VC scores predictive of atherosclerosis and cardiac events in the general and CKD population. EBCT is not readily available but spiral CT can also provide quantitative assessment of the extent of VC. CT fistulograms can be used as initial investigation for arterio-venous fistula (AVF) problems in haemodialysis (HD). The images obtained include thoracic aorta, brachio-cephalic, subclavian and common carotid arteries which allow assessment of the extent of VC in these vessels. No study to date has combined the CT fistulogram with concurrent determination of VC.Methods. We hypothesize that a single investigation for AVF management may also provide information on VC. We retrospectively analysed CT fistulograms on 28 HD patients determining VC scores (in Hounsfield units) in AVF, subclavian and carotid arteries and aorta. We correlated these scores with patient demographics, serum markers of mineral metabolism (time averaged for the period 6 months prior to CT) and calcium-based phosphate binders.Results. Patients (60.7% male) had a median age of 59 years and 46.4% were diabetic. The mean duration of dialysis was 17.5 months. CT fistulograms showed predominantly aortic (75% of patients) and subclavian (75%) calcifications, with only 21.4% having carotid VC and minimal VC at the level of AVF. Median VC scores were 619.8 (0–1481.4) for aorta and 521.7 (0–1139.6) for subclavian (scores of >400 indicate severe atherosclerotic disease), but there was no significant correlation with serum markers or duration of HD. Increasing age correlated significantly with greater VC in aortic (R = 0.53, P = 0.003) and subclavian (R = 0.40, P = 0.03) vessels, as well as with the number of VC sites involved. CAC was present in most patients (89.3%) but CAC scores were not able to be determined because of cardiac movement.Conclusion. Concurrent determination of the degree of calcification in certain vessels may be possible from CT studies assessing AVF structure. VC scores provided by CT fistulograms could contribute to HD patient CVD risk assessment but studies with larger patient numbers are required to determine their relevance. [ABSTRACT FROM AUTHOR]

Background. Vascular calcification (VC) and arterial stiffness are major contributors to cardiovascular (CV) disease in chronic kidney disease (CKD). Both are independent predictors of CV mortality and are inversely correlated with bone mineral density (BMD). Few studies have addressed the extent of VC in the pre-dialysis CKD population, with associated measurements of BMD and arterial compliance. Methods. We report cross-sectional data on 48 patients with CKD (GFR 17–55 ml/min) assessing the prevalence of VC and its associations. All patients had computed tomography (CT) scans through abdominal aorta and superficial femoral arteries (SFAs) to determine VC, pulse wave velocity (PWV) using SphygmoCor device (AtCor PWV Inc., Westmead, Australia) measuring arterial stiffness, and dual-energy X-ray absorptiometry (DEXA) scans to determine BMD, as well as serum markers of renal function and mineral metabolism. Results. Patients, 71% male, 54% diabetic, had a median age 64.5 years. Mean estimated GFR was 35.1 ± 10 ml/min. Mean PWV was 10.0 ± 4.5 m/s and mean aortic VC score was 421.5 ± 244 Hounsfield units, with 90% of subjects having some aortic VC present. In univariate linear regression analysis, aortic VC correlated positively with age (r 0.50, P r 0.47, P = 0.002) and PWV (r 0.33, P = 0.03). There was also greater VC with declining renal function (r −0.28, P = 0.05). There was no significant association between VC and serum markers of mineral metabolism, however phosphate and Ca × P correlated positively with PWV (r 0.35, P = 0.02, r 0.36, P = 0.02, respectively). There was also a positive association between PWV and triglycerides (P = 0.008), and a trend towards greater PWV with increasing age (P = 0.09). In multivariate regression analysis only increasing age and triglyceride levels were significantly associated with aortic VC and PWV. Mean spine and femoral T-scores on DEXA were 0.48 and −1.31 respectively, with 13% of subjects having femoral T-score r −0.43, P = 0.004); however, there was a positive (likely false) association between spine T-scores and aortic VC (r 0.37, P = 0.01), related to the limitation of vertebral DEXA in CKD. Conclusion. There is a high prevalence of VC in pre-dialysis CKD patients, worse with increasing age, triglycerides and reducing renal function. Correlation exists between VC and PWV and determination of one or both may be useful for CKD patient CV risk assessment. Femoral BMD is inversely associated with SFA VC, but measurement of vertebral BMD by DEXA is unreliable in CKD patients with aortic VC. [ABSTRACT FROM AUTHOR]

ABSTRACT Patients with chronic inflammatory diseases (CID) experience accelerated loss of bone mineral density, which is often accompanied by increased vascular calcification. These disturbances can be attenuated by therapies for inflammation, such as the tumor necrosis factor inhibitor infliximab. Calciprotein particles (CPP) are circulating colloidal aggregates of calcium and phosphate together with the mineral‐binding protein fetuin‐A, which have emerged as potential mediators of vascular calcification. The precise origins of serum CPP are unclear, but bone turnover may be an important source. In this longitudinal observational study, we studied patients with CID undergoing treatment with infliximab to assess the temporal relationship between bone turnover and circulating CPP. Ten patients with active CID receiving infliximab induction therapy and an additional 3 patients with quiescent CID on maintenance infliximab therapy were studied for 8 weeks with repeated measures of bone turnover markers as well as CPP (calciprotein monomers [CPM], primary CPP [CPP‐I], and secondary CPP [CPP‐II]). Therapeutic response was appraised using validated disease activity scores. At baseline, those with active CID had elevated markers of bone resorption and suppressed bone formation markers as well as higher CPM and CPP‐I compared with those with quiescent CID. In responders, there was an early but transient reduction in resorption markers by week 1, but a more sustained increase in bone formation markers compared with non‐responders at week 8. This was accompanied by reductions in CPM (β = −6.5 × 103 AU [95% CI −11.1, −1.8], p = 0.006) and CPP‐I (β = −23.4 × 104 particles/mL [95% CI −34.8, −11.9], p

The recently discovered klotho proteins have roles in a diverse range of metabolic processes with the oldest protein, α-klotho, implicated in various cellular pathways in energy, glucose, and phosphate metabolism. Circulating soluble klotho (sKl), derived from membrane α-klotho cleavage, not only has effects on ion channels and insulin signaling pathways, but is inversely associated with mortality. Effects of physical exercise on sKl have not been well studied. The effect of a single high-intensity standardized exercise on sKl and serum phosphate (sPi) levels in healthy adults was investigated. A standard Bruce protocol treadmill exercise was undertaken by 10 fasting healthy volunteers. sKl, sPi, and blood glucose levels were measured in samples collected 1-week prior, immediately pre ( T pre ), 0 ( T post ), 30 ( T 30 ), 240 ( T 240 ) min, and 1-week after exercise. Median (interquartile range) age of participants was 47.5 (44–51) years; five (50%) were male. All study participants achieved at least 90% predicted maximum heart rate (MHR). sKl increased acutely after exercise ( T pre median 448 pg/mL vs. T post median 576 pg/mL; p < 0.01). There was a nonsignificant sPi decline at T 30 ( T pre 0.94 ± 0.12 mmol/L vs. T 30 0.83 ± 0.22 mmol/L). Exercise led to a reduction in blood glucose by T 240 with median glucose levels at T pre , T post , T 30 , and T 240 of 6.0, 6.5, 6.3, and 5.7 mmol/L, respectively. In conclusion, a single high-intensity exercise session is associated with a transient increase in sKl, a delayed reduction in blood glucose, and a nonsignificant decrease in sPi levels in healthy adults. The evaluation of long-term effects of cardiovascular fitness programs on sKl and sPi in healthy individuals and disease cohorts are required to identify potential lifestyle modifications to help improve chronic disease management and long-term outcomes.