Renal dysfunction in people with cystic fibrosis
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(Published version)
Date
2010
Authors
Soulsby, Natalie
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thesis
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Abstract
Measuring and monitoring renal function in patients with CF is a relatively novel concept. Although aminoglycosides are well known for their renal toxicity profile it has been rarely reported in the CF population. Concerns were first raised in 1987 but there have been very little in the literature until recently. This thesis focuses on what is known about measuring renal function in this patient population and explores whether there are issues that require closer scrutiny. It attempts to identify how best to measure and monitor renal function and to offer suitable therapeutic alternatives to reduce risk. Identification of the lack of consensus regarding how best to measure and monitor renal function, and the lack of vigilance led to a review of what is known in Australia and what CF units have experienced. This was in the form of a survey which aimed at identifying what aminoglycosides are being used, dosing regimens, toxicity monitoring (including investigating potential renal and oto toxicities) and if there had been incidences of toxicity. The results of this survey indicated that although there was consensus in the administration and the need for therapeutic drug monitoring of aminoglycosides there was no agreement as to how to monitor for renal toxicity. This led to a number of questions - "What is the best way to measure and monitor renal function in patients with CF? Is there an alternative to an invasive radioisotope scan? Can creatinine clearance equations be relied upon? Is serum creatinine an adequate marker? Is tobramycin clearance an option? Is there something else that is more specific but no more invasive than a simple blood test?" - A thorough literature review identified very few papers that had researched this issue. However, Al-Aloul et al carried out a study to validate several equations that are used to calculate creatinine clearance as well as looking at creatinine alone. They concluded that none of the simple methods currently avai
are reliable. Methods for measuring renal function were investigated. These included the use of a novel blood test for cystatin C. Cystatin C is a protease inhibitor present in all nucleated cells. It is freely filtered in the glomerulus and this factor theoretically makes it an ideal marker for estimating renal function. Our study has shown that measuring GFR using radioisotopes is the only method that can be relied on. As this is impractical a method should be chosen and then used to closely monitor renal function. Clearly there are a group of patients in whom avoidance of IV tobramycin would be beneficial in order to preserve renal function (and hearing); one specific indication would be in pregnancy where IV tobramycin should be avoided, especially in the first trimester. Logically the use of inhaled tobramycin could be considered. A pilot study was then conducted to investigate the potential use of inhaled tobramycin to treat pulmonary exacerbations. The numbers were small but indicate that there may be potential for using inhaled tobramycin in certain patients with CF.
School/Discipline
University of South Australia School of Health Sciences
Sansom Institute for Health Research
Sansom Institute for Health Research
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Thesis (PhD)--University of South Australia, 2010
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Copyright 2010 Natalie Soulsby
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