Advanced glycation end-products, a pathophysiological pathway in the cardiorenal syndrome

The prevalence of heart failure (HF) is increasing. A distinction is made between diastolic HF (preserved left ventricular ejection fraction (LVEF)) and systolic HF (reduced LVEF). Advanced glycation end-products (AGEs) are crystallized proteins that accumulate during ageing, but are particularly increased in patients with diabetes mellitus and in patients with renal failure. Through the formation of collagen crosslinks, and by interaction with the AGE-receptor, which impairs calcium handling and increases fibrosis, AGE-accumulation has pathophysiologically been associated with the development of diastolic and renal dysfunction. Interestingly, diastolic dysfunction is a frequent finding in elderly patients, diabetic patients and in patients with renal failure. Taken together, this suggests that AGEs are related to the development and progression of diastolic HF and renal failure. In this review, the role of AGEs as a possible pathophysiological factor that link the development and progression of heart and renal failure, is discussed. Finally, the role of AGE intervention as a possible treatment in HF patients will be discussed

Good Clinical Teachers Likely to be Specialist Role Models: Results from a Multicenter Cross-Sectional Survey

Medical educational reform includes enhancing role modelling of clinical teachers. This requires faculty being aware of their role model status and performance. We developed the System for Evaluation of Teaching Qualities (SETQ) to generate individualized feedback on previously defined teaching qualities and role model status for faculty in (non) academic hospitals.(i) To examine whether teaching qualities of faculty were associated with their being seen as a specialist role model by residents, and (ii) to investigate whether those associations differed across residency years and specialties.Cross-sectional questionnaire survey amongst 549 Residents of 36 teaching programs in 15 hospitals in the Netherlands. The main outcome measure was faculty being seen as specialist role models by residents. Statistical analyses included (i) Pearson's correlation coefficients and (ii) multivariable logistic generalized estimating equations to assess the (adjusted) associations between each of five teaching qualities and 'being seen as a role model'.407 residents completed a total of 4123 evaluations of 662 faculty. All teaching qualities were positively correlated with 'being seen as a role model' with correlation coefficients ranging from 0.49 for 'evaluation of residents' to 0.64 for 'learning climate' (P<0.001). Faculty most likely to be seen as good role models were those rated highly on 'feedback' (odds ratio 2.91, 95% CI: 2.41-3.51), 'a professional attitude towards residents' (OR 2.70, 95% CI: 2.34-3.10) and 'creating a positive learning climate' (OR 2.45, 95% CI: 1.97-3.04). Results did not seem to vary much across residency years. The relative strength of associations between teaching qualities and being seen as a role model were more distinct when comparing specialties.Good clinical educators are more likely to be seen as specialist role models for most residents

P2Y12 platelet inhibition in clinical practice

Platelet adhesion, activation and aggregation play a pivotal role in atherothrombosis. Intracoronary atherothrombosis is the most common cause of the development of acute coronary syndrome (ACS), and plays a central role in complications occurring around percutaneous coronary intervention (PCI) including recurrent ACS, procedure-related myocardial infarction or stent thrombosis. Inhibition of platelet aggregation by medical treatment impairs formation and progression of thrombotic processes and is therefore of great importance in the prevention of complications after an ACS or around PCI. An essential part in the platelet activation process is the interaction of adenosine diphosphate (ADP) with the platelet P2Y12 receptor. The P2Y12 receptor is the predominant receptor involved in the ADP-stimulated activation of the glycoprotein IIb/IIIa receptor. Activation of the glycoprotein IIb/IIIa receptor results in enhanced platelet degranulation and thromboxane production, and prolonged platelet aggregation. The objectives of this review are to discuss the pharmacological limitations of the P2Y12 inhibitor clopidogrel, and describe the novel alternative P2Y12 inhibitors prasugrel and ticagrelor and the clinical implications of the introduction of these new medicines

Increased renal C5a receptor expression and systemic complement activation in brain dead donors

Nephrolog

<it>UMOD</it> as a susceptibility gene for end-stage renal disease

Abstract Background In recent genetic association studies, common variants including rs12917707 in the UMOD locus have shown strong evidence of association with eGFR, prevalent and incident chronic kidney disease and uromodulin urinary concentration in general population cohorts. The association of rs12917707 with end-stage renal disease (ESRD) in a recent case-control study was only nominally significant. Methods To investigate whether rs12917707 associates with ESRD, graft failure (GF) and urinary uromodulin levels in an independent cohort, we genotyped 1142 ESRD patients receiving a renal transplantation and 1184 kidney donors as controls. After transplantation, 1066 renal transplant recipients were followed up for GF. Urinary uromodulin concentration was measured at median [IQR] 4.2 [2.2-6.1] yrs after kidney transplantation. Results The rs12917707 minor allele showed association with lower risk of ESRD (OR 0.89 [0.76-1.03], p = 0.04) consistent in effect size and direction with the previous report (Böger et al, PLoS Genet 2011). Meta-analysis of these findings showed significant association of rs12917707 with ESRD (OR 0.91 [0.85-98], p = 0.008). In contrast, rs12917707 was not associated with incidence of GF. Urinary uromodulin concentration was lower in recipients-carriers of the donor rs12917707 minor allele as compared to non-carriers, again consistent with previous observations in general population cohorts. Conclusions Our study thus corroborates earlier evidence and independently confirms the association between UMOD and ESRD.</p