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Montero N.,Hospital Universitari Bellvitge | Pascual J.,Hospital Del Mar | Pascual J.,Red Of Investigacion Renal Redinren Instituto Carlos Iii | Pascual J.,Institute Mar dInvestigacions Mediques
Current Diabetes Reviews | Year: 2015

Background: Post-transplant diabetes mellitus is a significant risk factor for cardiovascular disease in solid organ transplantation. The main underlying pathophysiological mechanism of PTDM is pancreatic beta cell dysfunction in the context of insulin resistance, but the relative importance of each of these important components of glycemic metabolism is under intense debate. Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials to January 15, 2015. We selected systematic reviews and meta-analyses and randomized clinical trials. When no such reports were found for a given topic or drug, observational studies were included in the assessment. Results: There are agents with known diabetogenic effects: corticosteroids, calcineurin inhibitors including tacrolimus and cyclosporine, as well as the mammalian target of rapamycin inhibitors (sirolimus and everolimus). The association between the use of induction agents and PTDM is very scarce. No diabetogenic effects have been found with the use of azathioprine, mycophenolate mofetil and its derivatives. Conclusion: Immunosuppression is the major modifiable risk factor for development of PTDM but risk versus benefit analysis is required to balance risk of developing PTDM versus rejection. Caution is advisable in immunosuppressant adjustments in the event that PTDM develops based on current evidence. Physicians should choose and use immunosuppression regimens shown to have the best outcome for patient and graft survival, irrespective of PTDM risk. © 2015, Bentham Science Publishers.

Perez-Saez M.J.,Hospital Del Mar | Prieto-Alhambra D.,Institute Mar dInvestigacions Mediques | Prieto-Alhambra D.,Autonomous University of Barcelona | Prieto-Alhambra D.,University of Oxford | And 7 more authors.
Bone | Year: 2015

Background: Many studies have shown a correlation between chronic kidney disease (CKD) and fracture. However, increased mortality in CKD patients is a competing risk scenario not accounted for in previous studies. Our aim was to investigate the true impact of CKD on hip fracture after accounting for a competing risk with death. Methods: We conducted a population-based cohort study to determine the impact of CKD on hip fractures in individuals aged ≥50years old registered in the SIDIAPQ database (representative of 1.9 million people in Catalonia, Spain). Cox regression was used to estimate hazard ratio (HR) for death and hip fracture according to CKD status. A competing risk (Fine and Gray) model was fitted to estimate sub-HR for hip fracture in CKD or CKD-free patients accounting for differential mortality. Results: A total of 873,073 (32,934 (3.8%) CKD) patients were observed for 3. years. During follow-up, 4,823 (14.6%) CKD and 36,328 (4.3%) CKD-free participants died (HR, 1.83 [95% CI, 1.78-1.89]), whilst 522 (1.59%) and 6,292 (0.75%) sustained hip fractures, respectively. Adjusted Cox models showed a significantly increased risk of hip fractures for the CKD group (HR, 1.16 [1.06-1.27]), but this association was attenuated in competing risk models accounting for mortality (SHR, 1.14 [1.03-1.27]). Conclusions: Both death and hip fracture rates are increased (by 83% and 16%, respectively) in CKD patients. However, the association between CKD and hip fractures is attenuated when an excess of mortality is taken into account. A competing risk with death must be considered in future analyses of association between CKD and any health outcomes. © 2014 Elsevier Inc.

Fallon M.,Institute Mar dInvestigacions Mediques | Fallon M.,Universtitat Autonoma Of Barcelona | Pazos M.,Institute Mar dInvestigacions Mediques | Pazos M.,Universtitat Autonoma Of Barcelona | And 12 more authors.
Archivos de la Sociedad Espanola de Oftalmologia | Year: 2015

Objective To evaluate morphological parameters of optic disc and retinal nerve fiber layer (RNFL) examined with confocal laser tomography (HRT3) and laser polarimetry (GDx-VCC) in a normal population, and analyze correlations of these parameters with demographic variables. Patients and methods Cross-sectional study in the context of a glaucoma screening campaign in the primary care center of Barcelona. The individuals selected were non-hypertensive Mediterranean Caucasians with risk for glaucoma development (individuals ≥ 60 years old or ≥ 40 years old with family history of glaucoma or intraocular pressure or myopia > 3 diopter). All subjects underwent a complete ophthalmic examination, confocal laser tomography (HRT3) and scanning laser polarimetry (GDX-VCC), subjects with results within normal limits only being included. Structural parameters were analyzed along with age, refraction, and pachymetry based on the Spearman rank correlation test. Results A total of 224 subjects included, with a mean age of 63.4 ± 11.1 years. Disc areas, excavation and ring area were 2.14 ± 0.52 mm2, 0.44 ± 0.34 mm 2 and 1.69 ± 0.38 mm2, respectively. The mean RNFL (GDX) was 55.9 ± 6.9 μm. Age was correlated with lower ring volume, highest rate of cup shape measure, largest mean and maximum cup depth, lower nerve fiber index (NFI) and RNFL (all p-values below.05). Conclusion The mean values and distribution of several parameters of the papilla and the RNFL in normal Mediterranean Caucasians population are presented. A loss of thickness of the RNFL, ring thinning, and enlarged cup was observed with increased age. © 2014 Sociedad Española de Oftalmología.

Vuckovic F.,Genos Ltd | Kristic J.,Genos Ltd | Gudelj I.,Genos Ltd | Teruel M.,University of Granada | And 28 more authors.
Arthritis and Rheumatology | Year: 2015

Objective Glycans attached to the Fc portion of IgG are important modulators of IgG effector functions. Interindividual differences in IgG glycome composition are large and they associate strongly with different inflammatory and autoimmune diseases. IKZF1, HLA-DQ2A/B, and BACH2 genetic loci that affect IgG glycome composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a potentially causative role of aberrant IgG glycosylation in SLE. We undertook this large multicenter case-control study to determine whether SLE is associated with altered IgG glycosylation. Methods Using ultra-performance liquid chromatography analysis of released glycans, we analyzed the composition of the IgG glycome in 261 SLE patients and 247 matched controls of Latin American Mestizo origin (the discovery cohort) and in 2 independent replication cohorts of different ethnicity (108 SLE patients and 193 controls from Trinidad, and 106 SLE patients and 105 controls from China). Results Multiple statistically significant differences in IgG glycome composition were observed between patients and controls. The most significant changes included decreased galactosylation and sialylation of IgG (which regulate proinflammatory and antiinflammatory actions of IgG) as well as decreased core fucose and increased bisecting N-acetylglucosamine (which affect antibody-dependent cell-mediated cytotoxicity). Conclusion The IgG glycome in SLE patients is significantly altered in a way that decreases immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the intensity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in SLE. © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Barrios C.,Kings College London | Barrios C.,Institute Mar dInvestigacions Mediques | Beaumont M.,Kings College London | Pallister T.,Kings College London | And 8 more authors.
PLoS ONE | Year: 2015

Introduction: Several circulating metabolites derived from bacterial protein fermentation have been found to be inversely associated with renal function but the timing and disease severity is unclear. The aim of this study is to explore the relationship between indoxyl-sulfate, p-cresyl-sulfate, phenylacetylglutamine and gut-microbial profiles in early renal function decline. Results: Indoxyl-sulfate (Beta(SE) = -2.74(0.24); P = 8.8×10-29), p-cresyl-sulfate (-1.99(0.24), P = 4.6×10-16), and phenylacetylglutamine(-2.73 (0.25), P = 1.2×10-25) were inversely associated with eGFR in a large population base cohort (TwinsUK, n = 4439) with minimal renal function decline. In a sub-sample of 855 individuals, we analysed metabolite associations with 16S gut microbiome profiles (909 profiles, QIIME 1.7.0). Three Operational Taxonomic Units (OTUs) were significantly associated with indoxyl-sulfate and 52 with phenylacetylglutamine after multiple testing; while one OTU was nominally associated with p-cresyl sulfate. All 56 microbial members belong to the order Clostridiales and are represented by anaerobic Gram-positive families Christensenellaceae, Ruminococcaceae and Lachnospiraceae. Within these, three microbes were also associated with eGFR. Conclusions: Our data suggest that indoxyl-sulfate, p-cresyl-sulfate and phenylacetylglutamine are early markers of renal function decline. Changes in the intestinal flora associated with these metabolites are detectable in early kidney disease. Future efforts should dissect this relationship to improve early diagnostics and therapeutics strategies. © 2015 Barrios et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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