The concept of chronic kidney disease-mineral bone disorder (CKD-MBD) does not appear to fulfil the requirements for a syndrome at first glance, but its definition has brought some clear-cut benefits for clinicians and patients, including wider and more complex diagnostic and therapeutic approaches to the management of this challenging set of issues. Admittedly, not all components of CKD-MBD are present in all patients at all times, but these are highly interrelated, involving mineral and bone laboratory abnormalities, clinical and histological bone disease and finally, cardiovascular disease. The presence of typical biological bone ossification processes in an ectopic anatomical location in CKD has helped to define the existence of an unprecedented bone-vascular relationship, extending its interest even to other medical specialities. For now, we believe that CKD-MBD does not reach full criteria to be defined as a syndrome. However, this novel concept has clearly influenced current clinical guidelines. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF/KDOQI™) guidelines in 2003 for instance recommended that calcium-based phosphate binders should be avoided to treat hyperphosphataemia in the presence of cardiovascular calcifications. In 2009, the KDIGO and other guidelines reinforced and extended this recommendation by stating that it is reasonable to choose oral phosphate binder therapy by taking into consideration other components of CKD-MBD. Similarly, it is also considered reasonable to use information on vascular/valvular calcification to guide the management of CKD-MBD. Our current assumption as a working group 'CKD-MBD' is that CKD-MBD has the potential to be defined a true syndrome, such as a constellation of concurrent signs and symptoms that suggest a common underlying mechanism for these components as opposed to the term disease. The term 'syndrome' also implies that in any patient at risk due to the presence of one or a few components of the entire syndrome, the screening for additional components is highly recommended. However, it has not currently been demonstrated that there is an additive predictive value, which can be derived from identifying individual components. Despite all we have learned about this putative syndrome, we have been left with only a hypothetical framework about how to treat patients. So while we agree that the concept of CKD-MBD has influenced, and continues to influence, our current clinical hypotheses, definitive proof of a benefit of interventions in CKD-MBD is still lacking and a global-multiple therapeutic approach to treat simultaneously several components of CKD-MBD should be tested by well-designed new randomized controlled trials.

Although vitamin D was initially considered a nutrient, it has been recognized that the molecules derived from vitamin D metabolism are best considered as a complex endocrine system. In this review article we summarize the basic concepts regarding vitamin D metabolism, transport, and genomic activity through the vitamin D receptor, facilitating activation or suppression of target genes. We also examine non-genomic actions, biological responses to vitamin D in classic target organs (intestine, bone, kidneys, and parathyroid glands), and in organs and tissues not related to mineral homeostasis.

Differential effects of 19-nor-1,25-(OH) 2 D 2 and 1␣-hydroxy-Secondary hyperparathyroidism is a common complicavitamin D 2 on calcium and phosphorus in normal and uremic tion in patients with chronic renal failure. 1,25-(OH) 2 D 3 , rats.the most active metabolite of vitamin D, controls para-Background. Calcitriol, 1,25-(OH) 2 D 3 (1,25D), the most ac-

Peritoneal dialysis (PD) is a well-established renal replacement therapy for end-stage renal disease patients. Nonetheless, on an annual basis, at least 10% of patients shift from PD to hemodialysis for a variety of reasons. Thus the issue of vascular access creation needs to be addressed for this small but significant group of patients. Despite the relatively consistent number of dropouts, the creation of an arteriovenous fistula prior to transfer remains suboptimal, and variable from center to center. Literature for this specific area is poor and dated. Guidelines seem to suggest vascular access creation in high-risk failure patients, but they have no detailed criteria to select patients that would likely fail PD and therefore take advantage of a backup access. There is a need to better understand and predict patients that require conversion to hemodialysis to develop a plan that focuses on wellness and maximum quality of life in the lifecycle of PD patients. This review addresses the issue of vascular access planning in adult PD patients, presents the available literature on the topic and the current guidelines and recommendations, and describes a research agenda to guide decision making in clinical practice.

Background About 300,000 patients in the United States with Chronic Kidney Failure (CKF) are of working age, but up to 70% lose their job within the first year of renal replacement therapy. No study has examined how work ability and perceived health are influenced by the subjects’ adjustment to their job. We assessed the association of occupational stress (Effort-Reward Imbalance, ERI), work ability (WAI) and health-related quality of life (QoL) in hemodialysis. Methods 40 employed hemodialysis patients completed a self-administered questionnaire. Associations between ERI, Short Form 12 (SF-12), Short Form - 6 Dimensions (SF-6D), Kidney Disease QOL - 36 (KDQOL-36) and WAI were tested with partial Spearman's correlation adjusted for age, income, and comorbidity burden. Results Study subjects were mainly low-income (82%), African-American (73%), men (75%); 16 were manual laborers and 9 worked in the industrial sector. Study subjects reported low levels of Occupational Stress: ERI scores indicated an imbalance between Job Efforts and Rewards in only 3 subjects. Nevertheless, ERI scores were inversely and strongly associated with WAI (ρ=-0.41, p<0.012) and all QoL scales even after adjustment for known confounders. Conclusion Our study suggests that psychosocial workplace factors may play a substantial role in modulating patients’ health perception and ability to continue working. The causal relationship between Occupational Stress, perceived health, and work ability should be further investigated. Occupational Health professionals and nephrologists should closely collaborate to meet the needs of occupationally active hemodialysis patients.

BACKGROUND: Hyperphosphatemia is a risk factor for vascular calcifications (VCs) and VCs belong to mineral bone disorders (MBD) in chronic kidney disease (CKD) patients. Vitamin Kdependent proteins such as Matrix Gla Protein (MGP) and Bone Gla Proteins (BGP or osteocalcin) can inhibit VCs and regulate bone mineralization. OBJECTIVE: To evaluate whether the phosphate binder, sevelamer, could influence vitamin K levels in hemodialysis (HD) patients. METHODS: In a secondary analysis of the VItamin K Italian (VIKI) study, we evaluated the relationship between vitamin K status, VFs and VCs in 387 HD patients with/without sevelamer. Levels of serum vitamin 25(OH)D, alkaline phosphatase (ALP), vitamin k vitamers: K1 and K2 or menaquinone (MK, including: MK4, MK5, MK6 and MK7), total and undercarboxylated (uc) forms for both BGP and MGP were determined. RESULTS: No significant differences were observed between sevelamer-treated and untreated patients for main clinical characteristics. Lower MK4 levels (0.45 vs. 0.6 ng/mL, p=0.01) and a higher MK4 deficiency was observed in sevelamer-treated patients (13.5% vs. 5.4%, p=0.005). Multivariate logistic regression revealed that MK4 deficiency was associated with sevelamer use (Odds Ratio; OR: 2.64, 95% CI: 1.25-5.58, p=0.011) and aortic calcification (OR: 8.04, 95% CI: 1.07-60.26, p=0.04). In the same multivariate logistic regression model, sevelamer significantly amplified the effect of total BGP levels on the odds of fractures so that in sevelamer-treated patients, the OR of VFs was about 3 times higher in patients with total BGP <150 µg/L compared to those with total BGP ≥150 µg/L (OR: 3.15, 95% CI: 1.46-6.76, p=0.003), whereas no such effect was found in those untreated (total BGP <150 µg/L vs. total BGP ≥150 µg/L: OR: 1.21, 95% CI: 0.66-2.23, p=0.54] (p=0.049 for effect modification by sevelamer). CONCLUSION: These data suggest that sevelamer could interfere with MK4 levels in HD patients and its use in patients with low BGP levels (<150 µg/L) could increase bone fragility in CKD patients.

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Internal jugular vein cannulation has become a routine and clinically important aspect of medical care of critically ill patients. The landmark guided technique usually affords rapid and easy vascular access, but is not always successful and may be complicated by arterial puncture, hematoma, or pneumothorax. Some categories of patients, in particular patients with no external landmarks and patients with coagulopathies, appear to be at an increased risk of complications. We report the experience of internal jugular vein cannulation by a single operator with the external landmark technique in 10 patients and with ultrasound guidance in 31 patients, including 12 high risk patients. These patients had severe coagulopathies due to hepatic failure, HELLP syndrome, excess of anticoagulation treatment, or they had no external anatomic landmarks because of anasarca or obesity, were unable to maintain the horizontal position, or were external landmark catheterization failures. With the availability of the ultrasound device, success and complication rates improved markedly, suggesting that the ultrasound technique is easy to learn and rapidly produces an improvement over the external landmark method. In particular the 13 cannulations performed in 12 high risk patients were all successful at the first attempt, with no complications. In the overall population successful cannulations improved from 80% to 100%, first attempt success from 20% to 87% and carotid punctures decreased from 33% to 3.2%. Our results confirm that ultrasound guided cannulation of the internal jugular vein allows safer operation in high risk patients or when access problems are anticipated.