Blood pressure management in patients with chronic kidney disease:an appraisal and summary of existing guidelines

Background: Hypertension is a prevalent problem with huge impact on health and health care budgets. Several guidelines on how to manage blood pressure have been published, and it is unclear which one should be preferred. Methods: Eight guidelines dealing with blood pressure management of chronic kidney disease patients were evaluated for methodological quality by the AGREE II instrument by 4 appraisers. They were also analysed for consistency in their recommendations. Results: Most problematic domains were "applicability", "stakeholder involvement" and "editorial independence". Three guidelines scored below 50% for 5, and one for 4 of the 6 AGREE II domains. The guideline produced by Canadian Hypertension Education Program was preferred most, followed by KDIGO. There were discrepancies between the different guidelines with regard to blood pressure targets and thresholds, with the best and most recent advocating 140/90 mmHg. There was a consensus on the use of ACE-I/ARB's in patients with but not for those without proteinuria. However, only two guidelines specify a second line treatment (thiazides), whereas other do not, although it is well known that most patients need more than one drug to control their blood pressure. Three out of eight guidelines did not provide guidance on life-style modification. Those who did, advocated different levels of sodium restriction,, weight control, and physical activity. Remarkably, 5 out of 8 guidelines did not specify how exactly blood pressure should be measured. Conclusion: Blood pressure guidelines seem to be of low methodological quality, with clear improvements for the ones produced the latest. Especially the "applicability" domain, evaluating how the guideline can be put into practice, seems problematic, with as biggest hurdles that it is unclear what should be second or third line treatments, and how blood pressure should be measured or defined. The most recent guidelines advocate an office blood pressure of 140/90 mmHg for patients with chronic kidney disease

WASP is activated by phosphatidylinositol-4,5-bisphosphate to restrict synapse growth in a pathway parallel to bone morphogenetic protein signaling

Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] is a membrane lipid involved in several signaling pathways. However, the role of this lipid in the regulation of synapse growth is ill-defined. Here we identify PI(4,5)P2 as a gatekeeper of neuromuscular junction (NMJ) size. We show that PI(4,5)P2 levels in neurons are critical in restricting synaptic growth by localizing and activating presynaptic Wiscott-Aldrich syndrome protein/WASP (WSP). This function of WSP is independent of bone morphogenetic protein (BMP) signaling but is dependent on Tweek, a neuronally expressed protein. Loss of PI(4,5)P2-mediated WSP activation results in increased formation of membrane-organizing extension spike protein (Moesin)-GFP patches that concentrate at sites of bouton growth. Based on pharmacological and genetic studies, Moesin patches mark polymerized actin accumulations and correlate well with NMJ size. We propose a model in which PI(4,5)P2- and WSP-mediated signaling at presynaptic termini controls actin-dependent synapse growth in a pathway at least in part in parallel to synaptic BMP signaling

Evaluation and management of recurrent urinary tract infections in children: state of the art

Urinary tract infections (UTIs) represent an important cause of febrile illness in young children and can lead to renal scarring and kidney failure. However, diagnosis and treatment of recurrent UTI in children is an area of some controversy. Guidelines from the American Academy of Pediatrics, National Institute for Health and Clinical Excellence and European Society of Paediatric Radiology differ from each other in terms of the diagnostic algorithm to be followed. Treatment of vesicoureteral reflux and antibiotic prophylaxis for prevention of recurrent UTI are also areas of considerable debate. In this review, we collate and appraise recently published literature in order to formulate evidence-based guidance for the diagnosis and treatment of recurrent UTI in children