Doctoral Degrees (Nuclear Medicine)

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Browsing Doctoral Degrees (Nuclear Medicine) by Author "Holness, Jennifer Lyn"

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    Glomerular filtration rate measurement and estimation : improvement and validation of existing methods
    (Stellenbosch : Stellenbosch University, 2019-12) Holness, Jennifer Lyn; Warwick, James Mathew; Davids, Mogamat Razeen; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.
    ENGLISH SUMMARY : Glomerular filtration rate (GFR) is regarded as the best measure of kidney function. It can either be measured or estimated. This dissertation aims to provide a better understanding of GFR measurement in order to improve its performance and interpretation. It also aims to validate GFR estimation in local populations and to demonstrate the utility of simple adaptations of existing equations to improve estimation. On completion of a GFR measurement, various quality control (QC) checks are performed to ensure the accuracy of the result. However, this requires comparison with clearly defined reference ranges. In a study of healthy, potential kidney donors, reference data for two QC parameters were defined. In a study analysing the effect of measurement errors on GFR, the single-sample method was found to be the most robust technique overall, although for all methods measurement error was generally insignificant compared to expected biological variation in GFR. However, at low GFR values measurement errors were shown to affect all methods significantly. Errors in measurement of the doses were found to have the greatest impact on accuracy. Using nuclear medicine techniques 51Cr-ethylenediaminetetra-acetic acid (51Cr-EDTA) is the most commonly used and widely studied exogenous filtration marker. However, 99mTc-diethylenetriaminepenta-acetic acid (99mTc-DTPA) is gaining favour because of a few technical advantages it has over 51Cr-EDTA, its lower cost, and recent issues with the availability of 51Cr-EDTA. In response to a systematic review suggesting that GFR measurement from the plasma clearance of 99mTc-DTPA was inaccurate, a mini meta-analysis was performed that demonstrated excellent agreement between 51Cr-EDTA and 99mTc-DTPA clearance, thus supporting the use of 99mTc-DTPA as a reliable alternative. Where GFR cannot be routinely measured, it is frequently estimated using a creatinine-based equation. The use of any equation first requires validation in the population in which it will be used. In a study evaluating the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in non-cancer, mixed ancestry adults, both equations were found to perform well. However, in a study that evaluated equations in adults with cancer, the GFR estimates were found to be biased and imprecise. This study highlighted the limitations of using estimated GFR for guiding management decisions in cancer patients. A further study evaluated 11 estimating equations in non-cancer and cancer populations of South African children. The accuracy of all estimates was poor, particularly in the cancer group. Given the extensive use of GFR estimates in South Africa, these findings have profound implications for their use in the management of children and adults with cancer in this country. Developing new equations for a specific population requires large datasets and incurs costs that are impractical in most middle- or low-income countries. A simpler alternative is to adapt existing equations. This work demonstrates the application of a relatively simple approach to adapt existing equations, using modest amounts of data and a readily available Microsoft® Excel-based tool. While this approach is simple and likely to require further refinement, its utility was demonstrated in paediatric and adult cancer populations.