The increased risk of AKI among patients AZD 9272 taking these medications has been recognised by the UK National Institute for Health and Clinical Excellence and the international organisation Kidney Disease: Improving Global Outcomes, both of which recommend that patients with chronic kidney disease should stop taking them if they become acutely unwell. There are many evidence based indications for use of ACE inhibitors and ARAs and national guidelines recommend treatment with them for a number of chronic conditions including hypertension, chronic kidney disease with proteinuria, and heart failure with left ventricular dysfunction. The result is that these medicines are the second most commonly prescribed in English primary care, accounting for 6% of all prescriptions. Due to increasing prevalence of chronic comorbidities in older people they are commonly used in the elderly: in Belgium, 7.3% of the population were AH 6809 treated with long-term ACE inhibitors or ARAs and this rose to 36% for people aged 80 years or more. However, despite their frequent use, it is not known to what extent increasing use of these medications has contributed to the increasing incidence of AKI on a population level. This is in part because observational studies on this topic are confounded by indication. The conditions for which ACE inhibitors and ARAs are indicated are themselves associated with increased risk of AKI. Therefore increasing incidence of AKI may reflect increasing prevalence of comorbidities, independently of medications used. We hypothesised that if these medications were playing a causal role, changes in prescribing would be associated with changes in hospital admission with AKI within general practices. We therefore conducted a longitudinal ecological analysis using routinely-collected national hospital administrative data to determine whether hospital admission rates with AKI in England are associated with increased prescribing of ACE inhibitor and ARA therapy. All data used in this study relates to the period 1st April 2007 to 31st March 2011. We used prescribing data from the English National Health Service Prescription Services�� Prescribing Database. This provides data for each English general practice for the total number of prescriptions that were prescribed and subsequently dispensed, although information about the quantity of medication provided is not captured. We obtained the numbers of ACE inhibitor and ARA prescriptions from all general practices in England during the study period. The number of prescriptions for ACE inhibitors and ARAs issued by a general practice will be related to the age and sex demographic of the practice population. Therefore we controlled for differences in general practice populations by expressing prescribing as rates where the denominator is Age, Sex, and Temporary Resident Originated Prescribing Units. Because prescribing is generally higher in women and older people, ASTRO-PUs provide a nationally accepted way of weighting prescribing for the age and sex characteristics of the population of a general practice, and thus facilitating the comparison of prescribing between practices. The numbers of ASTRO-PUs for each general practice are updated regularly and a revision to the values of was carried out in April 2008. Therefore, for consistency we used the pre-2008 weightings, devised in 2001, throughout the entire study period. In this study, on average, each person is represented by 4.3 ASTRO-PUs.
Mutations leading to amino acid substitutions in the target proteins
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