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dc.contributor.advisorO'Seaghda, Conall
dc.contributor.advisorLittle, Mark
dc.contributor.authorCanney, Mark
dc.date.accessioned2017-12-18T16:05:44Z
dc.date.available2017-12-18T16:05:44Z
dc.date.issued2017en
dc.date.submitted2017
dc.identifier.citationCANNEY, MARK, Examining the breadth and burden of chronic kidney disease in community-dwelling older adults, Trinity College Dublin.School of Medicine.CLINICAL MEDICINE, 2017en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/82092
dc.descriptionAPPROVEDen
dc.description.abstractIntroduction: Chronic kidney disease (CKD), characterised by reductions in glomerular filtration rate (GFR), is associated with premature mortality and end stage kidney disease. Older adults have the highest prevalence of CKD, however the relative risks of hard outcomes posed by reductions in GFR are lower in older people. There is a pressing need to better characterise the clinical phenotype of CKD in older age. The aim of this thesis was to investigate the burden of reduced GFR on the health and well-being of older adults by examining the association between GFR and more proximal outcomes. Methods: This thesis uses data from the first three waves of The Irish Longitudinal Study on Ageing (TILDA), a cluster-sampled cohort of Irish community-dwelling adults aged ≥50 years. The distributions of kidney biomarkers as a function of age were flexibly modelled using the Box-Cox Power Exponential distribution. Plots of predicted GFR per year of age were generated, weighted to be representative of the target population. We examined the cross-sectional relationships between GFR and three objective tests of physical performance – gait speed, timed-up-and-go (TUG) and grip strength. These associations were explored further using cubic splines of GFR. The longitudinal associations between GFR and repeated measures of gait speed and TUG were investigated using mixed effects models. The association between GFR and quality of life (QoL) was assessed using the Control Autonomy Self-realisation and Pleasure scale, which encompasses both positive and negative aspects of QoL at older age. We investigated the relationship between GFR and postural blood pressure (BP) responses, captured by beat-to-beat BP measurements during a 2-minute active stand test. Results: The shape of the cystatin C distribution with age was markedly different to that of creatinine, exhibiting a sharp rise beyond the age of 65 years. This contributed to a higher predicted probability of confirming CKD using cystatin C at older age. The prevalence of CKD varied between 14% and 19% depending on the GFR estimating equation, and demonstrated a steep age gradient. Cubic splines of GFR illustrated a non-linear association between creatinine-based GFR and physical function outcomes, likely due to age-related declines in muscle mass. GFR estimated from cystatin C demonstrated more linear associations with all physical performance outcomes, a pattern which became more evident at older ages. Unadjusted mixed effects models suggested that lower levels of GFR were associated with greater declines in TUG and gait speed over time, indicated by a statistically significant time*GFR interaction. This interaction did not retain statistical significance after adjusting for demographic variables. GFR estimated from cystatin C, but not from creatinine, predicted lower QoL scores, especially in participants aged 50-64 years compared to older age categories. The multivariable association between GFR and QoL, while statistically significant, was clinically modest. Participants with lower levels of GFR exhibited greater impairments in BP stabilisation after standing, independent of cardiovascular risk factors and antihypertensive medications. Conclusions: The changing distribution of cystatin C with age, and the high pre-test probability of confirming CKD at older ages, question the utility of cystatin C as a confirmatory test of CKD across the age range. Plots of expected GFR per year of age may prove useful to clinicians, by framing an older person’s GFR result in the context of population-representative data. The findings suggest that GFR is a marker, rather than a driver, of declines in physical performance. A reduced GFR does not appear to substantially affect the QoL of an older person. The granular health measures in TILDA facilitate exploration of novel research questions, such as the relationship between GFR and postural BP behaviour. Future studies will build on the hypotheses generated in this thesis and leverage the rich longitudinal data in TILDA to create a more holistic picture of the CKD phenotype in older people.en
dc.language.isoenen
dc.publisherTrinity College Dublin. School of Medicine. Discipline of Clinical Medicineen
dc.rightsYen
dc.subjectChronic kidney diseaseen
dc.subjectQuality of lifeen
dc.subjectOrthostatic hypotensionen
dc.subjectEpidemiologyen
dc.subjectOlder adultsen
dc.subjectPhysical performanceen
dc.titleExamining the breadth and burden of chronic kidney disease in community-dwelling older adultsen
dc.typeThesisen
dc.contributor.sponsorHealth Research Board (HRB)en
dc.contributor.sponsorIrish Nephrology Societyen
dc.type.supercollectionthesis_dissertationsen
dc.type.supercollectionrefereed_publicationsen
dc.type.qualificationlevelPostgraduate Doctoren
dc.identifier.peoplefinderurlhttp://people.tcd.ie/mcanneyen
dc.identifier.rssinternalid180090en
dc.rights.ecaccessrightsopenAccess


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