Vitamin D. a dynamic molecule. how relevant might the dynamism for a vitamin be

Cholecalciferol, the precursor of Vitamin D3, is a very old, highly conserved, molecule. Its presence is evident in non-mineralized 750 million-year-old living species, such as plankton. The more active metabolites, a receptor and a D binding protein, appear later, along with the increasing complexity of animal species living in the sea. In the sea, however, the biological function of vitamin D is unlikely to be linked with mineral metabolism, and we can hypothesize a relationship with an immune response. It is in terrestrial animals exhibiting cellular bone that the complexity of vitamin D increases. At this stage of evolution, we see the appearance of bone cells that are capable of producing hormones that regulate and are regulated by vitamin D. This interaction starts a sophisticated metabolic system that modulates both mineral and energy metabolism for the requirements of the musculoskeletal system. Among the so-called pleiotropic effects of vitamin D, those resulting from the inhibitory effect on the renin-angiotensin system are of particular interest for nephrologists. Intriguingly, however, more than for anti-hypertensive effects, this interaction could be relevant for anti-inflammatory actions, possibly representative of a residual ancestral role of vitamin D. In addition, this evolutionary dynamism of the vitamin D system should not be separated from the chemical dynamism that characterizes the ligand molecule and its specific receptor. Both are capable of significant tridimensional modifications that contribute to an increase in the variability and the partial predictability of their final biological effect. A dynamic overview of this system that takes into account its evolutionary and adaptive aspects may be helpful to understand its biological complexity and to envisage why using vitamin D metabolites for therapeutic purposes is still a matter of debate

Oxygen Extraction Ratio (OER) as a Measurement of Hemodialysis (HD) Induced Tissue Hypoxia: A Pilot Study

HD tissue hypoxia associates with organ dysfunctions. OER, the ratio between SaO2and central-venous-oxygen-saturation, could estimate oxygen requirements during sessions, but no data are available. We evaluated OER behavior in 20 HD patients with permanent central venous catheter (CVC) as vascular access. Pre-HD OER (33.6 ± 1.4%; M ± SE) was higher than normal (range 20-30%). HD sessions increased OER to 39.2 ± 1.5% (M ± SE; p 40%. In HD patients with CVC as vascular access, OER is a cheap, easily measurable and repeatable parameter useful to assess intradialytic hypoxia, and a potential biomarker of HD related stress and morbidity, helpful to recognize patients at increased risk of mortality

A new technique for measuring fistula flow using venous blood gas oxygen saturation in patients with a central venous catheter

Background. Doppler ultrasound (DU) monitoring early after arteriovenous fistula (AVF) creation allows the identification of low blood flow (Qa) requiring prompt revision, but it is costly (needs skilled operators and technical instruments) and is not available in all dialysis units. Therefore alternative first-line methods to measure Qa would be welcomed.We reasoned that once an AVF is created, an increment in central venous oxygen saturation (ScvO2) is predictable and proportional to Qa. Methods. Accordingly, in patients receiving dialysis through a central venous catheter (CVC) in whom an AVF was created, we measured, by means of blood gas analysis, the ScvO2 increment before and after manual compression of the arteriovenous shunt and verified its correlation with DU-measured Qa. Results. We sampled blood gas in 18 patients with CVC and AVF before and after 30 s manual compression of the AVF. ScvO2 averaged 70.563% before and 65.263% after AVF closure, with an average drop of 5.163% (range 1–12). AVF Qa, which was measured within 24h by means of DU, averaged 6356349 mL/min (range 50–1300) and was strictly and positively correlated with DScvO2 (r ¼ 0.954, P<0.0001). Conclusions. Therefore we suggest that in patients with CVC and a newly created AVF, it is possible to monitor AVF Qa without DU by simply measuring blood gas and DScvO2. This technique is simple, cheap, repeatable, non-invasive and operator independent and represents a new useful screening test to detect delayed AVF access maturation deserving prompt DU measurement and surgical revision. It helps to quickly identify patients in urgent need of DU verification and possible surgical revision. Regrettably, it is applicable only in patients with CVC

Positioning novel biologicals in CKD-mineral and bone disorders

Renal osteodystrophy (ROD), the histologic bone lesions of chronic kidney disease (CKD), is now included in a wider syndrome with laboratory abnormalities of mineral metabolism and extra-skeletal calcifications or CKD-mineral and bone disorders (CKD-MBD), to highlight the increased burden of mortality. Aging people, frequently identified as early CKD, could suffer from either the classical age-related osteoporosis (OP) or ROD. Distinguishing between these two bone diseases may not be easy without bone biopsy. In any case, besides classical therapies for ROD, nephrologists are now challenged by the possibility of using new drugs developed for OP. Importantly, while therapies for ROD mostly aim at controlling parathyroid secretion with bone effects regarded as indirect, new drugs for OP directly modulate bone cells activity. Thus, their action could be useful in specific types of ROD. Parathyroid hormone therapy, which is anabolic in OP, could be useful in renal patients with low turnover bone disease. Denosumab, the monoclonal antibody against receptor activator of NF-κB ligand (RANK-L) that inhibits osteoclast activity and proliferation, could be beneficial in cases with high turnover bone. Use of romosozumab, the monoclonal antibody against sclerostin, which both stimulates osteoblasts and inhibits osteoclasts, could allow both anabolic and anti-resorptive effects. However, we should not forget the systemic role now attributed to CKD-MBD. In fact, therapies targeting bone cells activity could also result in unpredicted extra-bone effects and affect cardiovascular outcomes. In conclusion, the new biologicals established for OP could be useful in renal patients with either OP or ROD. In addition, their potential non-bone effects warrant investigation

Interactions of sclerostin with FGF23, soluble klotho and vitamin D in renal transplantation

Relationships of Sclerostin, a bone anti-anabolic protein, with biomarkers of mineral bone disorders in chronic kidney disease are still unsettled, in particular in kidney transplant (KTR). In 80 KTR patients (31F/49M, 54.7±10.3 years) we studied the relationships of serum Sclerostin with eGFR, Calcium, Phosphate, Alkaline Phosphatase (AP), intact Parathyroid hormone (iPTH), soluble alpha-Klotho (sKlotho), intact Fibroblast Growth Factor 23 (iFGF23), 25-hydroxyvitamin D(25D) and 1,25-dihydroxyvitamin D (1,25D). Thirty healthy subjects (35.0±12.4 years, eGFR 109.1±14.1 ml /min/1,73m2) served as control for Sclerostin, iFGF23 and sKlotho. With a median eGFR of 46.3 mL/min/1.73m2 (IQR, 36.2-58.3) our KTR had median Sclerostin levels of 23.7 pmol/L (IQR: 20.8-32.8), not different from controls (26.6 pmol/L, IQR: 22.0-32.2; p = n.s). Sclerostin correlated negatively with AP (r = -.251; p = 0.023) and positively with iFGF23 (r = .227; p = 0.017) and 25D (r = .214; p = 0.025). Age-adjusted multiple regression analysis identified AP and 1,25D as negative and 25D and sKlotho as positive best predictors of Sclerostin. No correlation was evident with eGFR. The negative correlation with AP confirms the direct anti-anabolic role of Sclerostin. The associations either negative or positive with iFGF23, sKlotho, and vitamin D metabolites suggest also a modulatory role in mineral homeostasis. In particular, the associations with iFGF23 (positive) and 1,25D (negative) underline the relevant inhibitory action of Sclerostin on vitamin D activation. In conclusion, Sclerostin levels in KTR are normal and influenced more by bone turnover than by eGFR. Its involvement with other hormones of mineral homeostasis (FGF23/Klotho and Vitamin D) is part of the sophisticated cross-talk between bone and the kidney

Elevated cerebral spinal fluid biomarkers in children with mucopolysaccharidosis I-H.

Mucopolysaccharidosis (MPS) type-IH is a lysosomal storage disease that results from mutations in the IDUA gene causing the accumulation of glycosaminoglycans (GAGs). Historically, children with the severe phenotype, MPS-IH (Hurler syndrome) develop progressive neurodegeneration with death in the first decade due to cardio-pulmonary complications. New data suggest that inflammation may play a role in MPS pathophysiology. To date there is almost no information on the pathophysiologic changes within the cerebral spinal fluid (CSF) of these patients. We evaluated the CSF of 25 consecutive patients with MPS-IH. While CSF glucose and total protein were within the normal range, we found a significantly mean elevated CSF opening pressure at 24 cm H2O (range 14-37 cm H2O). We observed a 3-fold elevation in CSF heparan sulfate and a 3-8 fold increase in MPS-IH specific non-reducing ends, I0S0 and I0S6. Cytokine analyses in CSF of children with MPS-IH showed significantly elevated inflammatory markers including: MCP-1 SDF-1a, IL-Ra, MIP-1b, IL-8, and VEGF in comparison to unaffected children. This is the largest report of CSF characteristics in children with MPS-IH. Identification of key biomarkers may provide further insight into the inflammatory-mediated mechanisms related to MPS diseases and perhaps lead to improved targeted therapies

Osteodistrofia renale vs Osteoporosi

Abstract non disponibil

La malattia ossea post-trapianto

Abstract non disponibil

CAP/ACMG proficiency testing for biochemical genetics laboratories: a summary of performance

Testing for inborn errors of metabolism is performed by clinical laboratories worldwide, each utilizing laboratory-developed procedures. We sought to summarize performance in the College of American Pathologists’ (CAP) proficiency testing (PT) program and identify opportunities for improving laboratory quality. When evaluating PT data, we focused on a subset of laboratories that have participated in at least one survey since 2010