Soo Kun Lim

A randomized, controlled trial of everolimus‐based dual immunosuppression versus standard of care in de novo kidney transplant recipients

Kidney transplant recipients receiving calcineurin inhibitor‐based immunosuppression incur increased long‐term risks of cancer and kidney fibrosis. Switch to mammalian target of rapamycin (mTOR) inhibitors may reduce these risks. Steroid or Cyclosporin Removal After Transplant using Everolimus (SOCRATES), a 36‐month, prospective, multinational, open‐label, randomized controlled trial for de novo kidney transplant recipients, assessed whether everolimus switch could enable elimination of mycophenolate plus either steroids or CNI without compromising efficacy. Patients received cyclosporin, mycophenolate and steroids for the first 14 days then everolimus with mycophenolate and CNIwithdrawal (CNI‐WD); everolimus with mycophenolate and steroid withdrawal (steroid‐WD); or cyclosporin, mycophenolate and steroids (control). 126 patients were randomized. The steroid WD arm was terminated prematurely because of excess discontinuations. Mean eGFR at month 12 for CNI‐WD versus control was 65.1 ml/min/1.73 m2 vs. 67.1 ml/min/1.73 m2 by ITT, which met predefined noninferiority criteria (P = 0.026). The CNI‐WD group experienced a higher rate of BPAR(31% vs. control 13%, P = 0.048) and showed a trend towards higher composite treatment failure (BPAR, graft loss, death, loss to follow‐up). The 12 month results from SOCRATES show noninferiority in eGFR, but a significant excess of acute rejection when everolimus was commenced at week 2 to enable a progressive withdrawal of mycophenolate and cyclosporin in kidney transplant recipients.

Association of HLA locus variant in Parkinson's disease.

A variant (rs3129882) in the genome‐wide association study (GWAS)‐linked variant [in the human leukocyte antigen (HLA) gene region] has been reported to associate with an increased risk of Parkinsons disease (PD) in Caucasian population. Studies among Chinese are limited. To address this, we analysed rs3129882 in a total of 1312 subjects of Chinese ethnicity from independent Asian centers comprising of 675 controls and 637 PD cases. The rs3129882 variant was associated with a decreased risk in our ethnic Chinese PD patients. Logistic regression analysis taking into consideration variables of age, gender and race showed that allele A reduced the risk of PD via a dominant model [odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.62, 0.96, p = 0.018]. As HLA is a highly polymorphic region, it is possible that ethnic‐specific effect or environmental agents may modulate the effect of this GWAS‐linked locus in influencing the risk of PD.

Pneumocystis jirovecii pneumonia 13 years post renal transplant following a recurrent cytomegalovirus infection

Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP) is a rare but serious infection that usually occurs within a year after solid organ transplantation. PCP may occur after 1 year post transplantation, but the rate is reported to be very low. Studies have shown an association between cytomegalovirus (CMV) infection in solid organ transplant patients and an increased risk of opportunistic infection. This increased risk is thought to be a result of the immunomodulatory effects of the CMV infection. We present a case of PCP infection occurring 13 years after a renal transplantation. This occurred following a recurrent CMV infection while the patient was on low‐dose immunosuppressants.

Insight into Gene Polymorphisms Involved in Toll-Like Receptor/Interferon Signalling Pathways for Systemic Lupus Erythematosus in South East Asia

Polymorphisms in genes involved in toll-like receptor/interferon signalling pathways have been reported previously to be associated with SLE in many populations. This study aimed to investigate the role of seven single nucleotide polymorphisms within TNFAIP3, STAT4, and IRF5, which are involved in upstream and downstream pathways of type I interferon production, in SLE in the South East Asian populations. Genotyping of 360 Malaysian SLE patients and 430 normal healthy individuals revealed that minor alleles of STAT4 rs7574865 and rs10168266 were associated with elevated risk of SLE in the Chinese and Malay patients, respectively (P = 0.028, odds ratio (OR) = 1.42; P = 0.035, OR = 1.80, respectively). Polymorphisms in TNFAIP3 and IRF5 did not show significant associations with SLE in any of the ethnicities. Combined analysis of the Malays, Chinese, and Indians for each SNP indicated that STAT4 rs10168266 was significantly associated with the Malaysian SLE as a whole (P = 0.014; OR = 1.435). The meta-analysis of STAT4 rs10168266, which combined the data of other studies and this study, further confirmed its importance as the risk factor for SLE by having pooled OR of 1.559 and P value of <0.001.

Glycemic control and antidiabetic drugs in type 2 diabetes mellitus patients with renal complications

Background Good glycemic control can delay the progression of kidney diseases in type 2 diabetes mellitus (T2DM) patients with renal complications. To date, the association between antidiabetic agents and glycemic control in this specific patient population is not well established. Purpose This study aimed to identify antidiabetic regimens as well as other factors that associated with glycemic control in T2DM patients with different stages of chronic kidney disease (CKD). Patients and methods This retrospective, cross-sectional study involved 242 T2DM inpatients and outpatients with renal complications from January 2009 to March 2014 and was conducted in a tertiary teaching hospital in Malaysia. Glycated hemoglobin (A1C) was used as main parameter to assess patients’ glycemic status. Patients were classified to have good (A1C <7%) or poor glycemic control (A1C ≥7%) based on the recommendations of the American Diabetes Association. Results Majority of the patients presented with CKD stage 4 (43.4%). Approximately 55.4% of patients were categorized to have poor glycemic control. Insulin (57.9%) was the most commonly prescribed antidiabetic medication, followed by sulfonylureas (43%). Of all antidiabetic regimens, sulfonylureas monotherapy (P<0.001), insulin therapy (P=0.005), and combination of biguanides with insulin (P=0.038) were found to be significantly associated with glycemic control. Other factors including duration of T2DM (P=0.004), comorbidities such as anemia (P=0.024) and retinopathy (P=0.033), concurrent medications such as erythropoietin therapy (P=0.047), α-blockers (P=0.033), and antigouts (P=0.003) were also correlated with A1C. Conclusion Identification of factors that are associated with glycemic control is important to help in optimization of glucose control in T2DM patients with renal complication.

Resolution of epoetin-induced pure red cell aplasia 2 years later, successful re-challenge with continuous erythropoiesis receptor stimulator.

Epoetin-induced pure red cell aplasia (PRCA) is most commonly associated with epoetin-a; nevertheless, its occurrence has been reported in epoetin-β and darbepoetin-a. We report a young hemodialysis patient who developed PRCA 2 years after receiving intravenous epoetin-β. Epoetin- induced PRCA was confirmed by bone marrow aspiration, associated with markedly elevated anti-erythropoietin antibody. He was treated with prednisolone and cyclophosphamide for 3 months but continued to be transfusion-dependent. 17 months after the development of PRCA, he was started on intravenous continuous erythropoiesis receptor stimulator (CERA) in view of frequent transfusions. He tolerated the CERA injection well and the hemoglobin level stabilized 7 months later. Repeat bone marrow aspiration confirmed complete resolution of PRCA with disappearance of anti-erythropoietin antibody. To date, he maintained a stable hemoglobin level and has been transfusion-independent for the past 1 year. This is the first in the literature that reported the utilization of CERA in epoetin-induced PRCA. Very low or undetectable level of anti-erythropoietin antibody might be the key to the success of re-challenge strategy in cases of epoetininduced PRCA. Thus, routine checking of anti-erythropoietin antibody before the rechallenge with an alternative erythropoietin product is highly recommended.

PARK16 is associated with PD in the Malaysian population.

PARK16 was identified as a risk factor for Parkinsons disease in a Japanese cohort; however, subsequent studies in the other populations including the Chinese, European, Caucasian, and Chilean have shown a protective role instead. To investigate this locus in our Malaysian cohort, 1,144 individuals were screened for five SNPs in the PARK16 locus and logistic regression analysis showed that the A allele of the rs947211 SNP reduced the risk of developing PD via a recessive model (Odds ratio 0.57, P‐value 0.0003). Pooled analysis with other Asian studies showed that A allele of the rs947211 SNP decreased the risk of developing PD via a recessive model (Odds ratio 0.71, P‐value 0.0001). In addition, when meta‐analysis was performed with other Asian population, three SNPs (rs823128, rs823156, and rs11240572) reduced risk of developing PD via a dominant model.

Identification and Characterization of a Rare Fungus, Quambalaria cyanescens, Isolated from the Peritoneal Fluid of a Patient after Nocturnal Intermittent Peritoneal Dialysis.

Peritonitis is the leading complication of peritoneal dialysis, which is primarily caused by bacteria rather than fungi. Peritonitis is responsible for approximately 18% of the infection-related mortality in peritoneal dialysis patients. In this paper, we report the isolation of a rare fungus, Quambalaria cyanescens, from the peritoneal fluid of a man after he switched from continuous ambulatory peritoneal dialysis to nocturnal intermittent peritoneal dialysis. Based on the morphological examination and multigene phylogeny, the clinical isolate was confirmed as Q. cyanescens. This pathogen exhibited low sensitivity to all tested echinocandins and 5-flucytosine. Interestingly, morphological characterization revealed that Q. cyanescens UM 1095 produced different pigments at low temperatures (25°C and 30°C) on various culture media. It is important to monitor the emergence of this rare fungus as a potential human pathogen in the tropics. This study provides insight into Q. cyanescens UM 1095 phenotype profiles using a Biolog phenotypic microarray (PM). Of the 760 nutrient sources tested, Q. cyanescens UM 1095 utilized 42 compounds, and the fungus can adapt to a broad range of osmotic and acidic environments. To our knowledge, this is the first report of the isolation of Q. cyanescens from peritoneal fluid, revealing this rare fungus as a potential human pathogen that may be misidentified using conventional methods. The detailed morphological, molecular and phenotypic characterization of Q. cyanescens UM 1095 provides the basis for future studies on its biology, lifestyle, and potential pathogenicity.

Non-organ donors' attitudes toward incentives

Malaysians indicating that they did not intend to become organ donors upon their death were surveyed regarding interest in non‐fungible financial incentives to be granted to surviving family members. Among the 730 (56% of the total sample of 1311) indicating unwillingness to be donors, 29.6% (216/730) subsequently indicated that they would be willing donors if the government introduced policies that, upon their death, “rewarded your (their) family with incentives for your (their) deeds.” Among the 69% (504/730) who insisted that they would not become organ donor even with incentive, nearly 80% (404/501) of them were able to identify relevant incentives they thought should be provided by the state to those who make organ donations upon death. The majority of both groups preferred the state provide medical benefits to a surviving family member, suggesting this may be an attractive policy option for the state to raise the deceased organ donation pool.

Strategies Targeted at Motivating Unrelated Living Kidney Donation

BACKGROUND This paper aimed to assess the willingness of Malaysians with post-secondary education to be living kidney donors. MATERIAL AND METHODS From the total of 1,310 living kidney donor respondents in Kuala Lumpur and its suburbs, we focused on 688 respondents with post-secondary education. These 688 respondents were asked whether they were willing to become living kidney donors if the government provides a reasonable amount of financial incentive. Those who were not willing to be donors (490) were then asked the reasons for their unwillingness. Six options were given and respondents can choose more than 1 option. RESULTS Malaysians with post-secondary education remain unconvinced to be living donors even when provided with monetized incentives. The main reason cited was they are not convinced that individuals can live with just 1 kidney. CONCLUSIONS There is a need for the government to develop new ways to promote organ donation. These include strengthening government coordination of medical procedures and creating public awareness about the safety of living with 1 kidney. Setting up new institutions such as donor clinics, creating a living donor registry, and having independent donor advocates are also instrumental.