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Title:	Effects of CYP3A5*3 polymorphism on clinical outcomes, expenditures and quality of life among chronic kidney disease patients
Authors:	Lee Fei Yee (P102729)
Supervisor:	Farida Islahudin, Assoc. Prof. Dr.
Keywords:	Kidney Diseases Antihypertensive Polymorphism Genetic Universiti Kebangsaan Malaysia -- Dissertations Dissertations, Academic -- Malaysia
Issue Date:	4-Jan-2022
Description:	Multiple comorbidities associated with chronic kidney disease (CKD) renders complex medication regimen among CKD patients. Antihypertensives are vital in CKD management and suboptimal antihypertensive management outcomes may accelerate the rate of CKD progression and increase expenditures associated with advanced CKD. Currently, it is unclear of the susceptibility of antihypertensives due to CYP3A5*3 genetic polymorphisms among CKD patients, an enzyme that plays a vital role in medication metabolism among Asians. The objectives of the study are to identify the clinical outcomes of antihypertensives among CKD patients, to investigate the association of CYP3A5*3 polymorphism with blood pressure control and rapid CKD progression, and to investigate the economical outcomes of CYP3A5*3 polymorphism in CKD patients. Frequent adjustment to antihypertensive drugs, a suboptimal medication management outcome, was found in 32.6% of 671 CKD patients. It was associated with follow-ups in multiple institutions (adjusted Odds Ratio [aOR] 1.244, 95% confidence interval [CI]:1.012, 1.530), use of traditional/complementary medicine (aOR 2.058, 95% CI:1.058, 4.001), poor medication adherence (aOR 1.563, 95% CI:1.037, 2.357), change in estimated glomerular filtration rate (aOR 0.970, 95% CI:0.951, 0.990), and albuminuria categories A2 (aOR 2.173, 95% CI:1.311, 3.603) and A3 (aOR 2.117, 95% CI:1.349, 3.322). The next study investigated the role and impact of CYP3A5*3 to antihypertensive management and CKD. While the CYP3A5*3/*3 polymorphism was not associated with blood pressure control, the polymorphism was associated with rapid CKD progression (aOR 7.385, 95% CI:1.502, 36.301). Other factors of rapid CKD progression were frequent adjustment to antihypertensives (aOR 3.949, 95% CI:1.486, 10.492), absence of renin-angiotensin-aldosterone blockade (aOR 3.957, 95% CI: 1.476, 10.603), Stage 1 CKD (aOR 4.557, 95% CI:1.026, 20.243), Stage 2 CKD (aOR 8.456, 95% CI: 1.905, 37.528), Stage 3a CKD (aOR 10.598, 95% CI; 2.241, 50.109) and smoking (aOR 8.894, 95% CI:1.514, 52.252). The final study analysed the cost-effectiveness and quality of life by CYP3A5*3 polymorphism status. Patients with CYP3A5*3 polymorphism incurred higher costs with less patients achieving target blood pressure than those with CYP3A5*1. The CYP3A5*3 polymorphism had incremental cost-effectiveness ratio above the threshold value in preventing rapid CKD progression. The quality of life measured using KDQOL-36 and EQ-5D-5L scores were not significantly different between CYP3A5 polymorphism status. Overall, findings demonstrated that monitoring of the CYP3A5*3 polymorphism might be potentially useful in identifying those at risk of accelerated CKD progression,Ijazah Sarjana Sains
Pages:	194
Publisher:	UKM, Kuala Lumpur
Appears in Collections:	Faculty of Pharmacy / Fakulti Farmasi

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