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Fulltext Muslims' views on the permissibility of organ donation: The case of Malaysia

Tumin M, Noh A, Mohd Satar N, Tafran K, Abdullah N, Wan Md Adnan WAH, et al.

International e-Journal of Science, Medicine & Education, 2016;10(1):41-46.
MyJurnal

Background: Some argue that Malaysia’s extremely low organ donation rate is attributed to religion, specifically Islam. Testing this argument, this study asked Malaysian Muslims their views regarding various issues on organ donation and examined whether their decisions to donate organs are framed by religious beliefs.
Materials and Methods: This study investigated the perspectives of Malaysian Muslims between October and December 2013 in Kuala Lumpur. Self-administered questionnaires were distributed to 900 people, with 829 responses collected (92% response rate). Respondents’ verbal consent was taken before proceeding with the survey.
Results: The survey found that more than half of respondents felt that organ donation is permitted in
Islam and that it is a communal responsibility. However, the same proportions were unsure on the issues of rewards for organs or on whether Islam permits the procuring of organs from brain dead patients.
Conclusions: Malaysian Muslims are not against organ donation; however, encouraging organ donation requires the state to address public concerns on Islam’s views on this sensitive issue through effective policy tools to help address these gaps in Malaysian Muslims’ understanding of organ donation. The organ donation rate could improve by using Islamic scholars as ambassadors for an organ donation drive to convey the message of Malaysia’s urgent need for organ donation.
Renal Transplant Outcomes in Spousal and Living-Related Donors in Malaysia

Guad RM, Ng KP, Lim SK, Hirayama K, Eng HS, Wan Md Adnan WAH

Ann Acad Med Singap, 2019 Dec;48(12):403-411.
PMID: 32112065

INTRODUCTION: Studies have shown that a compatible human leukocyte antigen (HLA) match can confer a favourable effect on graft outcomes. We examined the outcomes of HLA matching in renal transplant donors in Malaysia.
MATERIALS AND METHODS: A total of 140 patients who had compatible ABO blood type with negative T-cell lymphocytotoxicity crossmatch were included in the study and 25% of them were spousal transplant donors. No remarkable differences in acute rejection rate, graft survival, patient survival and serum creatinine level were observed between the spousal and living-related donor groups.
RESULTS: The spousal donor group had a higher degree of HLA mismatch than the living-related donor group. HLA-A mismatch was associated with increased rejection risk at 6 months (odds ratio [OR], 2.75; P = 0.04), 1 year (OR, 2.54; P = 0.03) and 3 years (OR, 3.69; P = 0.001). It was also observed in the deleterious effects of HLA-B and HLA-DQ loci when the number of antigen mismatches increased. The risk was 7 times higher in patients with ≥1 mismatch at HLA-A, HLA-B and HLA-DR loci than those who did not have a mismatch at these loci at 6 months (P = 0.01), 1 year (P = 0.03) and 3 years (P = 0.003).
CONCLUSION: A good match for HLA-A, HLA-B, HLA-DR and HLA-DQ can prevent acute rejection risk in renal transplant patients. Consequently, spousal donor transplants could be a safe intervention in renal patients.
Low Immunologic Risk Living Related Renal Transplant Using Very Low-Dose Antithymocyte Globulin as Induction Therapy: A Single Tertiary Hospital Experience

Jalalonmuhali M, Ng KP, Ong CS, Lee YW, Wan Md Adnan WAH, Lim SK

Transplant Proc, 2020 05 21;52(6):1709-1714.
PMID: 32448669 DOI: 10.1016/j.transproceed.2020.02.139

The aim of induction therapy in the management of kidney transplant is to reduce the incidence of acute rejection and delayed graft function after kidney transplant. The agent for induction therapy differs depending on the recipient risks. The regimen can be either polyclonal (rabbit antithymocyte globulin [rATG]) or monoclonal antibody (basiliximab). Basiliximab is commonly used in patients with low immunologic risk. However, to date we know that the use of rATG on T cell depletion is dose dependent and more potent antirejection therapy. Therefore, we would like to look at 1-year graft function of very low-dose rATG in low immunologic risk recipients. All low immunologic risk patients who received low-dose rATG (0.5 mg/kg of body weight daily) during transplant (day 0) and on days 1 and 2 were recruited. Their renal function, HLA donor-specific antibodies, lymphocyte counts, protocol biopsy results, and cytomegalovirus (CMV) polymerase chain reaction were monitored as per clinical practice. All 10 patients had immediate graft function. Low-dose rATG caused lymphocyte counts to deplete immediately on day 0, and the effect lasted about 1 month post-transplant. All the patients had stable graft function without any significance episode of rejection. Only one patient had de novo HLA-DQ antibody. It is good to know that without prophylaxis antiviral in CMV+ donor to CMV+ recipient, the incidence of CMV viremia is considerably low in our cohort. Very low-dose rATG is an effective induction immunosuppression in low immunologic risk patients with acceptable infection risk.
Fulltext Biological age for chronic kidney disease patients using index model

Abu Bakar SA, Syed Mohamed Shahruddin SNS, Ismail N, Wan Md Adnan WAH

PeerJ, 2022;10:e13694.
PMID: 35935256 DOI: 10.7717/peerj.13694

The estimation of biological age (BA) is an important asymptomatic measure that can be used to understand the physical changes and the aging process of a living being. Factors that contribute towards profiling the human biological age can be diverse. Therefore, this study focuses on developing a BA model for patients with Chronic Kidney Disease (CKD). The procedure commences with the selection of significant biomarkers using a correlation test. Appropriate weighting is then assigned to each selected biomarker using the indexing method to produce a BA index. The BA index is matched to the age variation within the sample to acquire additional terms for the chronological age leading ultimately to the estimated BA. From a sample of 190 patients (133 trained data and 57 testing data) obtained from the University of Malaya Medical Centre (UMMC), Malaysia, the intensity of the BA is found to be between three to nine years from the chronological age. Visual observations further validate the high similarities between the training and testing data sets.
Fulltext Changes in Kidney Function Among Malaysian Adolescents and Its Determinants

Nawawi FA, Wan Md Adnan WAH, Ismail M, Jalaludin MY, Majid HA

Kidney Int Rep, 2023 Oct;8(10):1965-1977.
PMID: 37850001 DOI: 10.1016/j.ekir.2023.07.028

INTRODUCTION: The health and wellbeing of adolescents are often neglected, including the knowledge of chronic kidney disease (CKD), especially in its early stages.
METHODS: A total of 607 adolescents were recruited from the Malaysian Health and Adolescents Longitudinal Research Team (MyHeART) study, a prospective cohort study conducted from March 2012 to May 2016 that explored the noncommunicable diseases (NCDs) risk factors among 13 to 17 years old students in 3 states of Peninsular Malaysia. Students who participated in all 3 data collection periods in 2012, 2014, and 2016 with kidney function assessment across all 3-time points were included in the current study. The students' estimated glomerular filtration rate (eGFR) was calculated from isotope-dilution mass spectrometry-traceable Schwartz's equation and categorized based on Kidney Disease: Improving Global Outcomes (KDIGO) classification. Changes in kidney function were examined, and the longitudinal relationship between eGFR and multiple NCD risk factors was analyzed using the generalized estimating equation (GEE).
RESULTS: The prevalence of decreased eGFR (60-89 ml/min per 1.73 m2) among the students increased from 6.1% (2012) to 30.0% (2014) and 40.2% (2016). Based on the GEE, the student's eGFR decreased over time, with a steeper decline during early to midadolescence. Males and rural students had lower eGFR compared to their counterparts. Students who are morbidly obese had lower eGFR than those with normal body mass index (BMI). Protein consumption also has a potential moderating effect on eGFR in adolescents.
CONCLUSION: Kidney function changes can be detected as early as adolescence and are likely attributable to multiple NCD risk factors. Therefore, more comprehensive prevention efforts from various stakeholders are needed to identify health issues like CKD.
Fulltext Risk of Preeclampsia and Pregnancy Complications in Women With a History of Acute Kidney Injury

Tangren JS, Wan Md Adnan WAH, Powe CE, Ecker J, Bramham K, Hladunewich MA, et al.

Hypertension, 2018 08;72(2):451-459.
PMID: 29915020 DOI: 10.1161/HYPERTENSIONAHA.118.11161

An episode of clinically recovered acute kidney injury (r-AKI) has been identified as a risk factor for future hypertension and cardiovascular disease. Our objective was to assess whether r-AKI was associated with future preeclampsia and other adverse pregnancy outcomes and to identify whether severity of AKI or time interval between AKI and pregnancy was associated with pregnancy complications. We conducted a retrospective cohort study of women who delivered infants between 1998 and 2016 at Massachusetts General Hospital. AKI was defined using the 2012 Kidney Disease Improving Global Outcomes laboratory criteria with subsequent clinical recovery (estimate glomerular filtration rate, >90 mL/min per 1.73 m2 before conception). AKI was further classified by severity (Kidney Disease Improving Global Outcomes stages 1-3) and time interval between AKI episode and the start of pregnancy. Women with r-AKI had an increased rate of preeclampsia compared with women without previous r-AKI (22% versus 9%; P<0.001). Infants of women with r-AKI were born earlier (gestational age, 38.2±3.0 versus 39.0±2.2 weeks; P<0.001) and were more likely to be small for gestational age (9% versus 5%; P=0.002). Increasing severity of r-AKI was associated with increased risk of preeclampsia for stages 2 and 3 AKI (adjusted odds ratio, 3.5; 95% confidence interval, 2.1-5.7 and adjusted odds ratio, 6.5; 95% confidence interval, 3.5-12.0, respectively), but not for stage 1 (adjusted odds ratio, 1.7; 95% confidence interval, 0.9-3.2). A history of AKI before pregnancy, despite apparent full recovery, was associated with increased risk of pregnancy complications. Severity and timing of the AKI episode modified the risk.
Fulltext Clinical and genetic risk factors for new-onset diabetes mellitus after transplantation (NODAT) in major transplant centres in Malaysia

Guad RM, Taylor-Robinson AW, Wu YS, Gan SH, Zaharan NL, Basu RC, et al.

BMC Nephrol, 2020 09 07;21(1):388.
PMID: 32894076 DOI: 10.1186/s12882-020-02052-9

BACKGROUND: New-onset diabetes after transplantation (NODAT) is associated with reduced patient and graft survival. This study examined the clinical and selected genetic factors associated with NODAT among renal-transplanted Malaysian patients.
METHODS: This study included 168 non-diabetic patients (58% males, 69% of Chinese ethnicity) who received renal transplantation between 1st January 1994 to 31st December 2014, and were followed up in two major renal transplant centres in Malaysia. Fasting blood glucose levels were used to diagnose NODAT in patients who received renal transplantation within 1 year. Two single nucleotide polymorphisms (SNPs), namely; rs1494558 (interleukin-7 receptor, IL-7R) and rs2232365 (mannose-binding leptin-2, MBL2) were selected and genotyped using Sequenom MassArray platform. Cox proportional hazard regression analyses were used to examine the risk of developing NODAT according to the different demographics and clinical covariates, utilizing four time-points (one-month, three-months, six-months, one-year) post-transplant.
RESULTS: Seventeen per cent of patients (n = 29, 55% males, 69% Chinese) were found to have developed NODAT within one-year of renal transplantation based on their fasting blood glucose levels. NODAT patients had renal transplantation at an older age compared to non-NODAT (39.3 ± 13.4 vs 33.9 ± 11.8 years, p = 0.03). In multivariate analysis, renal-transplanted patients who received a higher daily dose of cyclosporine (mg) were associated with increased risk of NODAT (Hazard ratio (HR) =1.01 per mg increase in dose, 95% confidence interval (CI) 1.00-1.01, p = 0.002). Other demographic (gender, ethnicities, age at transplant) and clinical factors (primary kidney disease, type of donor, place of transplant, type of calcineurin inhibitors, duration of dialysis pre-transplant, BMI, creatinine levels, and daily doses of tacrolimus and prednisolone) were not found to be significantly associated with risk of NODAT. GA genotype of rs1494558 (HR = 3.15 95% CI 1.26, 7.86) and AG genotype of rs2232365 (HR = 2.57 95% CI 1.07, 6.18) were associated with increased risk of NODAT as compared to AA genotypes.
CONCLUSION: The daily dose of cyclosporine and SNPs of IL-7R (rs1494558) and MBL2 (rs2232365) genes are significantly associated with the development of NODAT in the Malaysian renal transplant population.
The Effects of Different Induction Regimes on Serial Lymphocyte Subsets in Kidney Transplant Recipients: A Single Tertiary Center Experience

Jalalonmuhali M, Ng KP, Lee YW, Gan CC, Hing Wong A, Wan Md Adnan WAH, et al.

Transplant Proc, 2022 Feb 15.
PMID: 35181166 DOI: 10.1016/j.transproceed.2022.01.004

BACKGROUND: Immunosuppressive therapy is the backbone of kidney transplantation in preventing acute rejection. T-cell depletion after doses of thymoglobulin is dose-dependent, as are their side effects. At the same time, basiliximab and other maintenance immunosuppressive drugs act at different signals on T lymphocytes. Therefore, studying the pattern of lymphocyte subset depletion depending on the induction regime given at transplantation could be an added tool in managing post-transplant recipients.
METHODOLOGY: This prospective observational study recruited kidney transplant recipients from August 2019 through April 2021 at the University of Malaya Medical Centre. Blood tests for lymphocyte subsets were taken at pre-transplant, 1 week, 1 month, 3 months, and 6 months post-transplantation. At transplantation, recipients received either basiliximab, low-dose thymoglobulin (cumulative dose: 1.5 mg/kg), or standard-dose thymoglobulin (cumulative dose: 5 mg/kg).
RESULTS: A total of 39 patients were recruited: 38.5% received basiliximab (15 of 39), 15.4% received low-dose thymoglobulin (6 of 39), and 46.2% received standard-dose thymoglobulin (18 of 39). Absolute lymphocyte counts 1 week post-transplantation were 1.5 ± 0.84 × 109/L for basiliximab, 0.7 ± 0.57 × 109/L for low-dose thymoglobulin, and 0.1 ± 0.08 × 109/L for standard-dose thymoglobulin (P < .001). The CD4+ and CD8+ counts were severely depleted in the standard-dose thymoglobulin group, with a statistically significant differenceup to 6 months post-transplantation. In the low-dose thymoglobulin group, the CD4+ and CD8+ counts were depleted at 1 week post-transplantation and recovered at 1 month post-transplantation. There was no difference in allograft function and incidence of allograft rejection across groups.
CONCLUSIONS: The effects on lymphocyte counts, CD4+ and CD8+, vary depending on the type and dose of induction immunosuppression. This could be a guiding tool in managing immunosuppression post-transplantation depending on the patient's immunologic risk.