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Effects of CYP3A5 Genetic Polymorphism on the Pharmacokinetics of Tacrolimus in Renal Transplant Recipients

Mac Guad R, Zaharan NL, Chik Z, Mohamed Z, Peng NK, Adnan WA

Transplant Proc, 2016 Jan-Feb;48(1):81-7.
PMID: 26915847 DOI: 10.1016/j.transproceed.2016.01.001

BACKGROUND: The aim of this study was to compare the within-patient variability trough levels (Co), dose-adjusted Co, and dose requirements of Prograf and Advograf with CYP3A5 polymorphisms in Malaysia renal transplant recipients.
METHODS: Stable post-renal transplantation patients switched from Prograf to Advograf were retrospectively identified from University Malaya Medical Centre (n = 28). Co and concomitant tacrolimus dose 6 months preconversion and postconversion were examined. CYP3A5 was genotyped using reverse transcriptase polymerase chain reaction. Wilcoxon signed rank test and Mann-Whitney U test were used to compare Co and dose between formulations and according to genotypes.
RESULTS: There was a significant difference in the whole-blood tacrolimus Co between the 2 groups (6.16 ± 1.74 ng/mL vs 4.90 ± 1.06 ng/mL; P = .0001). The mean daily maintenance dose of Prograf was 3.9 ± 2.0 mg/kg (0.06 mg/kg/d), which was reduced to 3.3 ± 1.7 mg/d (0.04 mg/kg/d) with Advograf (P = .01). The mean maintenance dose of tacrolimus required for those with CYP3A5*1/*1 (high-expressive) was significantly higher than those with CYP3A5*1/*3 (intermediate-expressive) and CYP3A5*3/*3 (low-expressive) (P < .01) for both formulations. Comparing those with CYP3A5*1/*1, the average dose-adjusted Co was significantly higher in patients with CYP3A5*3/*3 with Advograf (P < .05).
CONCLUSIONS: The requirement for daily maintenance dose was higher in those with CYP3A5*1/*1 variants in both tacrolimus formulations in the Malaysian patients. Furthermore, those with CYP3A5*3/*3 demonstrated significantly higher dose-adjusted Co with Advograf.
Fulltext Clinical Impact of Education Provision on Determining Advance Care Planning Decisions among End Stage Renal Disease Patients Receiving Regular Hemodialysis in University Malaya Medical Centre

Hing Wong A, Chin LE, Ping TL, Peng NK, Kun LS

Indian J Palliat Care, 2016 Oct-Dec;22(4):437-445.
PMID: 27803566

Advance care planning (ACP) is a process of shared decision-making about future health-care plans between patients, health care providers, and family members, should patients becomes incapable of participating in medical treatment decisions. ACP discussions enhance patient's autonomy, focus on patient's values and treatment preferences, and promote patient-centered care. ACP is integrated as part of clinical practice in Singapore and the United States.
Fulltext Factors Associated with Health Care Professionals' Attitude Toward the Presumed Consent System

Tumin M, Tafran K, Mohd Satar NH, Peng NK, Manikam R, Yoong TL, et al.

Exp Clin Transplant, 2019 02;17(1):1-5.
PMID: 29766774 DOI: 10.6002/ect.2017.0214

OBJECTIVES: This paper explores health care professionals' potential attitude toward organ donation if the presumed consent system were to be implemented in Malaysia, as well as factors associated with this attitude.
MATERIALS AND METHODS: We used self-administered questionnaires to investigate the attitude of 382 health care professionals from the University of Malaya Medical Center between January and February 2014. The responses were analyzed using logistic regression.
RESULTS: Of the 382 respondents, 175 (45.8%) stated that they would officially object to organ donation if the presumed consent system were to be implemented, whereas the remaining 207 (54.2%) stated that they would not object. The logistic regression showed that health care professionals from the Malay ethnic group were more likely to object than those from Chinese (adjusted odds ratio of 0.342; P = .001) and Indian and other (adjusted odds ratio of 0.341; P = .003) ethnic groups. Health care professionals earning 3000 Malaysian Ringgit or below were more likely to object than those earning above 3000 Malaysian Ringgit (adjusted odds ratio of 1.919; P = .006). Moreover, respondents who were initially unwilling to donate organs, regardless of the donation system, were more likely to object under the presumed consent system than those who were initially willing to donate (adjusted odds ratio of 2.765; P < .001).
CONCLUSIONS: Health care professionals in Malaysia have a relatively negative attitude toward the presumed consent system, which does not encourage the implementation of this system in the country at present. To pave the way for a successful implementation of the presumed consent system, efforts should be initiated to enhance the attitude of health care professionals toward this system. In particular, these efforts should at most target the health care professionals who are Malay, earn a low income, and have a negative default attitude toward deceased donation.
Fulltext The experiences of suffering of end-stage renal failure patients in Malaysia: a thematic analysis

Beng TS, Yun LA, Yi LX, Yan LH, Peng NK, Kun LS, et al.

Ann Palliat Med, 2019 Sep;8(4):401-410.
PMID: 30943744 DOI: 10.21037/apm.2019.03.04

BACKGROUND: The population of end-stage renal failure (ESRF) receiving dialysis treatment is increasing worldwide. For most patients with ESRF, dialysis can extend their life. However, treatment can be demanding and time-consuming. Despite dialysis treatment, many patients continue to experience various sufferings.
METHODS: A qualitative study was conducted with semi-structured interviews to explore the experiences of suffering of ESRF patients on maintenance dialysis in Malaysia. The results were thematically analyzed.
RESULTS: Nineteen ESRF patients were interviewed. The themes and subthemes were: (I) physical suffering-physical symptoms and functional limitations, (II) psychological suffering-the emotions and thoughts of suffering, (III) social suffering-healthcare-related suffering and burdening of others and (IV) spiritual suffering-the queries of suffering.
CONCLUSIONS: These findings may help healthcare professionals to fill in the gaps in the delivery of best renal palliative care.
HIV type 1 subtypes in Malaysia, determined with serologic assays: 1992-1996

Beyrer C, Vancott TC, Peng NK, Artenstein A, Duriasamy G, Nagaratnam M, et al.

AIDS Res Hum Retroviruses, 1998 Dec 20;14(18):1687-91.
PMID: 9870323

We investigated the molecular epidemiology of HIV-1 subtypes in Malaysia among injecting drug users (IDUs) and sexual transmission risk groups, using serologic and genetic techniques. Frozen sera collected at a general hospital, a blood bank, several drug treatment centers, and an STD clinic in Kuala Lumpur, between 1992 and 1996, were investigated retrospectively. V3 peptide serotyping and monomeric gp120 capture serotyping were used to study 89 known HIV-1-infected subjects. The methods differentiate subtypes B, E, and C. V3 peptide and gp120 capture results were comparable. No subtype C-specific reactive sera were found; one specimen was dually reactive for subtypes C and B, using the V3 peptide ELISA; and four were durally reactive for subtypes E and C using this assay. Genotypic analysis of HIV-1 gag RNA in serum was done on a subset of subjects and confirmed serologic findings. HIV-1 subtypes differed significantly by risk category: of 53 IDUs, 29 (55%) were infected with subtype B and 19 (36%) were infected with subtype E, 3 (6%) were dually reactive, and 2 (4%) were not typable. Of 36 persons with heterosexual risks, 29 (81%) were infected with subtype E, 5 (14%) were infected with subtype B, and 2 (5%) were not typable. Persons with IDU risks were significantly more likely to be infected with subtype B than were those with sexual risks (OR 5.89; 95% CI, 1.94-18.54; p < 0.001). Subtypes B and E of HIV-1 appear to predominate in Malaysia; subtype B was more prevalent among IDUs; subtype E was more prevalent among all other groups. These results may have important HIV-1 vaccine implications.