Precision Medicine in Erythropoietin Deficiency and Treatment Resistance: A Novel Approach to Management of Anaemia in Chronic Kidney Disease.

The study of anaemia is a well-developed discipline where the concepts of precision medicine have, in part, been researched extensively. This review discusses the treatment of erythropoietin (EPO) deficiency anaemia and resistance in cases of chronic kidney disease (CKD). Traditionally, erythropoietin-stimulating agents (ESAs) and iron supplementation have been used to manage anaemia in cases of CKD. However, these treatments pose potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron supplementation, and erythropoietin-iron combination therapy. Another novel approach is the use of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). This review highlights the need for precision medicine targeting the genetic components of EPO deficiency anaemia in CKD and discusses individual variability in genes such as the erythropoietin gene (EPO), the interleukin-ß gene (IL-ß), and the hypoxia-inducible factor gene (HIF). Pharmacogenetic testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, thus optimising treatment outcomes and minimising resistance and adverse effects. This article concludes by suggesting that receptor modification has the potential to revolutionise the treatment outcomes of patients with erythropoietin deficiency anaemia through the integration of the mentioned approach.

Metabolic dysfunction-associated fatty liver disease (MAFLD) and advanced liver fibrosis among hemodialysis patients in a multiethnic urban population in Malaysia.

BACKGROUND: Metabolic-dysfunction-associated fatty liver disease (MAFLD) and end stage kidney disease (ESKD) are complications of the metabolic syndrome. Our aim is to study the prevalence of MAFLD and advanced liver fibrosis and the associated factors among hemodialysis patients in a multiracial urban population in Malaysia. METHODS: A cross-sectional study of hemodialysis patients from 10 hemodialysis centers was used. FibroTouch examination was performed on all patients. Fatty liver was diagnosed based on ultrasound attenuation parameter ≥248 dB/m while advanced liver fibrosis was diagnosed based on liver stiffness measurement ≥10 kPa. RESULTS: This study included 447 hemodialysis patients (median age 59 [50-67], male 55%, Chinese 61%, Malay 20%, Indian 18%). Dialysis vintage was 49 (22-93) months. The prevalence of MAFLD was 43.4%. Independent factors associated with MAFLD were elevated waist circumference (aOR = 10.1, 95% CI = 5.3-19.4, p < 0.001), normal platelet count (aOR = 3.1, 95% CI = 1.3-7.3, p < 0.05), low HDL cholesterol (aOR = 2.3, 95% CI = 1.3-4.2, p < 0.01), elevated fasting blood sugar (aOR = 2.3, 95% CI = 1.3-3.8, p < 0.01), elevated hsCRP (aOR = 2.2, 95% CI = 1.2-4.0, p < 0.01), and advanced liver fibrosis (aOR = 3.0, 95% CI = 1.6-5.6, p < 0.001). The prevalence of advanced liver fibrosis was 25.5%. Independent factors associated with advanced liver fibrosis were male gender (aOR = 1.8, 95% CI = 1.0-3.0, p < 0.05), elevated waist circumference (aOR = 2.0, 95% CI = 1.0-4.0, p < 0.05), low platelet count (aOR = 5.4, 95% CI = 2.7-11.0, p < 0.001), elevated GGT (aOR = 5.0, 95% CI = 2.9-8.8, p < 0.001), and MAFLD (aOR = 3.2, 95% CI = 1.7-5.9, p < 0.001). CONCLUSION: A high prevalence of MAFLD and advanced liver fibrosis was observed among hemodialysis patients. Nephrologists should consider a more proactive approach in diagnosing MAFLD and/or advanced liver fibrosis in hemodialysis patients.

Is metabolic-dysfunction-associated fatty liver disease or advanced liver fibrosis associated with erythropoietin stimulating agent hypo-responsiveness among patients with end-stage kidney disease on haemodialysis?

AIM: This study aims to determine if metabolic-dysfunction-associated fatty liver disease (MAFLD) or advanced liver fibrosis is associated with erythropoietin stimulating agent (ESA) hypo-responsiveness in hemodialysis patients. METHODS: In a cross-sectional study of 379 hemodialysis patients, FibroTouch transient elastography was performed on all patients. Erythropoeitin resistance index (ERI) was used to measure the responsiveness to ESA. Patients in the highest tertile of ERI were considered as having ESA hypo-responsiveness. RESULTS: The percentage of patients with ESA hypo-responsiveness who had MAFLD was lower than patients without ESA hypo-responsiveness. FIB-4 index was significantly higher in ESA hypo-responsive patients. In multivariate analysis, female gender (aOR = 3.4, 95% CI = 1.9-6.2, p < 0.001), dialysis duration ≥50 months (aOR = 1.8, 95% CI = 1.1-2.9, p < 0.05), elevated waist circumference (aOR = 0.4, 95% CI = 0.2-0.8, p = 0.005), low platelet (aOR = 2.6, 95% CI 1.3-5.1, p < 0.01), elevated total cholesterol (aOR = 0.5, 95% CI 0.3-0.9, p < 0.05) and low serum iron (aOR = 3.8, 95% CI = 2.3-6.5, p < 0.001) were found to be independent factors associated with ESA hypo-responsiveness. Neither MAFLD nor advanced liver fibrosis was independently associated with ESA hypo-responsiveness. However, every 1 kPA increase in LSM increased the chance of ESA-hyporesponsiveness by 13% (aOR = 1.1, 95% CI = 1.0-1.2, p = 0.002) when UAP and LSM were used instead of presence of MAFLD and advanced liver fibrosis, respectively. CONCLUSION: MAFLD and advanced liver fibrosis were not independently associated with ESA hypo-responsiveness. Nevertheless, higher FIB-4 score in ESA hypo-responsive group and significant association between LSM and ESA hypo-responsiveness suggest that liver fibrosis may be a potential clinical marker of ESA hypo-responsiveness.

Creatinine clearance in selection of living kidney donor among the Malaysian population: is it safe?

BACKGROUND: Assessment of donor renal function is made by the measurement of Glomerular Filtration Rate (GFR). Exogenous markers are preferred over creatinine clearance and are widely used for measuring GFR. However, they are difficult to obtain, costly and laborious. This is a study to look into the safety and accuracy of creatinine clearance for renal assessment among the living kidney donors in the Malaysian population. METHODS: This is a retrospective, single-centre study comprising 105 living kidney donor candidates from the year 2007 to 2020. By comparing against 51-Chromium ethylenediamine-tetraacetic acid (51Cr-EDTA), we analysed creatinine clearance for correlation, bias, precision and accuracy. RESULTS: The study group had a mean age of 45.68 ± 10.97 years with a mean serum creatinine of 64.43 ± 17.68 µmol/L and a urine volume of 2.06 ± 0.83 L. Mean measured GFR from 51Cr-EDTA was 124.37 ± 26.83 ml/min/1.73m2 whereas mean creatinine clearance was 132.35 ± 38.18 ml/min/1.73m2. Creatinine clearance overestimated 51Cr-EDTA significantly with a correlation coefficient of 0.48 (p < 0.001) and an accuracy of 78.10% and 64.0% within 30% and 20% respectively of 51Cr-EDTA. CONCLUSION: Creatinine clearance is an acceptable and affordable alternative for donor renal assessment in the absence of exogenous markers with an emphasis on adequate urine collection followed by using measured GFR in selected cases.

Caring for Patients With Advanced Chronic Kidney Disease: Dietary Options and Conservative Care Instead of Maintenance Dialysis.

An expert advisory board discussed the prevention and treatment of chronic kidney disease (CKD), with a focus on dietary options. This is timely, given the uptake of value based models for kidney care in the United States. Timing of dialysis start is influenced by patients' clinical status and complex patient-clinician interactions. Patients value personal freedom and quality of life and may want to delay dialysis, whilst physicians are sometimes more concerned with clinical outcomes. Kidney-preserving therapy can prolong the dialysis-free period and preserve residual kidney function, thus patients are asked to adjust their lifestyle and diet, to follow a low- or very low-protein diet, with or without ketoacid analogues. Multi-modal approaches include pharmacotherapies, management of symptoms, and a gradual, individualized dialysis transition. Patient empowerment is vital, including CKD education and involvement in decision making. These ideas may help patients, their families, and clinical teams to improve the management of CKD.

Cultural adaptation and validation of the Malay Chronic Kidney Disease Self-management instrument (MCKD-SM).

BACKGROUND: There is growing evidence that self-management behaviour can improve outcomes for patients with chronic kidney disease (CKD). However, no measures are available in Malay to effectively assess the self-management of CKD. The aim of this study was to translate, culturally adapt and validate the Malay Chronic Kidney Disease Self-Management (MCKD-SM) instrument for Malay-speaking health professionals and patients. METHODS: This study was carried out in two phases: the translation and cultural adaptation phase and the validation phase. The instrument was translated from English to Malay and then adapted and validated in a sample of 337 patients with CKD stages 3-4 attending a nephrology clinic in a tertiary hospital in Malaysia. Structural validity was evaluated by exploratory factor analysis. The instrument's reliability was assessed by internal consistency and test-retest reliability. The correlations between the MCKD-SM and kidney disease knowledge and the MCKD-SM and self-efficacy were hypothesised a priori and investigated. RESULTS: The MCKD-SM instrument has 29 items grouped into three factors: 'Understanding and Managing My CKD', 'Seeking Support' and 'Adherence to Recommended Regimen'. The three factors accounted for 56.3% of the total variance. Each factor showed acceptable internal reliability, with Cronbach's α from 0.885 to 0.960. The two-week intra-rater test-retest reliability intraclass correlation coefficient values for all items ranged between 0.938 and 1.000. The MCKD-SM scores significantly correlated with kidney disease knowledge (r = 0.366, p < 0.01) and self-efficacy (r = 0.212, p < 0.01). CONCLUSION: The MCKD-SM was found to be a valid and reliable patient-reported outcome measure of pre-dialysis CKD self-management behaviour in the Malay-speaking population.

Insights from CREDENCE trial indicate an acute drop in estimated glomerular filtration rate during treatment with canagliflozin with implications for clinical practice.

Canagliflozin slows the progression of chronic kidney disease in patients with type 2 diabetes and induces a reversible acute drop in estimated glomerular filtration rate (eGFR), believed to be a hemodynamic effect. Predictors of the initial drop and its association with long-term eGFR trajectories and safety outcomes are unknown. To assess this, we performed a post-hoc analysis of 4289 participants in the CREDENCE trial with type 2 diabetes and chronic kidney disease equally split into treatment and placebo groups who had eGFR measured at both baseline and week three. The eGFR was categorized at week three as greater than a 10% decline; between 0 and 10% decline; and no decline. Long-term eGFR trajectories and safety outcomes were estimated in each category of acute eGFR change by linear mixed effects models and Cox regression after adjustment for baseline characteristics and medications use. Significantly more participants in the canagliflozin (45%) compared to the placebo (21%) group experienced an acute drop in eGFR over 10%. An over 30% drop occurred infrequently (4% of participants with canagliflozin and 2% with placebo). The odds ratio for a drop in eGFR over 10% with canagliflozin compared to placebo was significant at 3.03 (95% confidence interval 2.65, 3.47). Following the initial drop in eGFR, multivariable adjusted long-term eGFR trajectories, as well as overall and kidney safety profiles, in those treated with canagliflozin were similar across eGFR decline categories. Thus, although acute drops in eGFR over 10% occurred in nearly half of all participants following initiation of canagliflozin, the clinical benefit of canagliflozin was observed regardless. Additionally, safety outcomes were similar among subgroups of acute eGFR drop.

Association study of MCCC1/LAMP3 and DGKQ variants with Parkinson's disease in patients of Malay ancestry.

BACKGROUND: Genome-wide association studies (GWAS) have shown that variants in the 3-methylcrotonyl-CoA carboxylase (MCCC1)/lysosome-associated membrane protein 3 (LAMP3) loci (rs10513789, rs12637471, rs12493050) reduce the risk of Parkinson's disease (PD) in Caucasians, Chinese and Ashkenazi-Jews while the rs11248060 variant in the diacylglycerol kinase theta (DGKQ) gene increases the risk of PD in Caucasian and Han Chinese cohorts. However, their roles in Malays are unknown. Therefore, this study aims to investigate the association of these variants with the risk of PD in individuals of Malay ancestry. METHODS: A total of 1114 subjects comprising of 536 PD patients and 578 healthy controls of Malay ancestry were recruited and genotyped using Taqman® allelic discrimination assays. RESULTS: The G allele of rs10513789 (OR = 0.83, p = 0.001) and A allele of rs12637471 (OR = 0.79, p = 0.007) in the MCCC1/LAMP3 locus were associated with a protective effect against developing PD in the Malay population. A recessive model of penetrance showed a protective effect of the GG genotype for rs10513789 and the AA genotype for rs12637471. No association with PD was found with the other MCCC1/LAMP3 rs12493050 variant or with the DGKQ (rs11248060) variant. No significant associations were found between the four variants with the age at PD diagnosis. CONCLUSION: MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population.

Natural-derived compounds and their mechanisms in potential autosomal dominant polycystic kidney disease (ADPKD) treatment.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic kidney disorder that impairs renal functions progressively leading to kidney failure. The disease affects between 1:400 and 1:1000 ratio of the people worldwide. It is caused by the mutated PKD1 and PKD2 genes which encode for the defective polycystins. Polycystins mimic the receptor protein or protein channel and mediate aberrant cell signaling that causes cystic development in the renal parenchyma. The cystic development is driven by the increased cyclic AMP stimulating fluid secretion and infinite cell growth. In recent years, natural product-derived small molecules or drugs targeting specific signaling pathways have caught attention in the drug discovery discipline. The advantages of natural products over synthetic drugs enthusiast researchers to utilize the medicinal benefits in various diseases including ADPKD. CONCLUSION: Overall, this review discusses some of the previously studied and reported natural products and their mechanisms of action which may potentially be redirected into ADPKD.

Recommendations by the Asian Pacific society of nephrology (APSN) on the appropriate use of HIF-PH inhibitors.

Renal anaemia is a common and important complication in patients with chronic kidney disease (CKD). The current standard-of-care treatment for renal anaemia in CKD patients involves ensuring adequate iron stores and administration of erythropoietin stimulating agents (ESA). Hypoxia inducible factor (HIF) is a key transcription factor primarily involved in the cellular regulation and efficiency of oxygen delivery. Manipulation of the HIF pathway by the use of HIF-prolyl hydroxylase inhibitors (HIF-PHI) has emerged as a novel approach for renal anaemia management. Despite it being approved for clinical use in various Asia-Pacific countries, its novelty mandates the need for nephrologists and clinicians generally in the region to well understand potential benefits and harms when prescribing this class of drug. The Asian Pacific society of nephrology HIF-PHI Recommendation Committee, formed by a panel of 11 nephrologists from the Asia-Pacific region who have clinical experience or have been investigators in HIF-PHI studies, reviewed and deliberated on the clinical and preclinical data concerning HIF-PHI. This recommendation summarizes the consensus views of the committee regarding the use of HIF-PHI, taking into account both available data and expert opinion in areas where evidence remains scarce.

A multicentre, multi-national, double-blind, randomised, active-controlled, parallel-group clinical study to assess the safety and efficacy of PDA10 (Epoetin-alpha) vs. Eprex® in patients with anaemia of chronic renal failure.

BACKGROUND: Erythropoietin stimulating agent (ESA) has been standard of care in treating renal anaemia for the past 20 years. Many patients have limited access to ESA in view of long-term costs leading to suboptimal ESA dosage. Biosimilar epoetin is a potential cost-effective alternative to originator for optimal renal anaemia management. OBJECTIVE: To determine efficacy and safety of PDA10 in treating renal anaemia in haemodialysis patients, in comparison to the originator epoetin-α, Eprex®. METHODS: A phase 3, multicentre, multi-national, double-blind, randomised, active-controlled and parallel group study conducted over 40 weeks in Malaysia and Korea. End stage kidney disease patients undergoing regular haemodialysis who were on erythropoietin treatment were recruited. The study has 3 phases, which included a 12-week titration phase, followed by 28-week double-blind treatment phase and 24-week open-label extension phase. RESULTS: The PDA10 and Eprex® were shown to be therapeutically equivalent (p < 0.0001) with mean absolute change in haemoglobin from baseline of - 0.176 (± 0.91) g/dl and - 0.118 (± 1.114) g/dl, respectively. Weekly dose change was 10.01 IU/kg/week in PDA10 group and 10.30 IU/kg/week in Eprex® group, which has no significant difference. There were no significant differences in the safety profile between PDA10 and Eprex® groups. CONCLUSION: This study has confirmed the therapeutic equivalence between PDA10 and Eprex® in terms of efficacy, dosage requirement and safety profile in haemodialysis patients with renal anaemia. TRIAL REGISTRATION: The study was registered with the National Medical Research Register ( NMRR-13-400-16313 ). This study has been registered retrospectively with Clinical Research Information Service ( CRiS ), Republic of Korea on 25 March 2021.

Hepatitis C core antigen testing to diagnose active hepatitis C infection among haemodialysis patients.

BACKGROUND: Hepatitis C virus (HCV) infects more than 71 million people worldwide and chronic HCV infection increases the risk of liver cirrhosis and failure. Haemodialysis (HD) is one of the renal replacement therapies with risk of HCV transmission. Anti-HCV antibodies are the serological screening test for HCV infection that does not detect active phase of infection. Majority HCV infected HD patients in Malaysia do not have further HCV RNA performed due to high cost and thus HCV treatment is less frequently offered. HCV Core Antigen (HCV Ag) can potentially be used to diagnose active HCV infection in HD population in comparison to HCV RNA, at lower cost. METHODS: We conducted a cross-sectional study to assess the correlation between HCV Ag and HCV RNA and to identify the prevalence of active HCV infection among HCV seropositive HD patients from dialysis centres across West Malaysia from July 2019 to May 2020. Pre-dialysis blood was taken and tested for both HCV Ag and HCV RNA tests. HCV Ag was tested with Abbott ARCHITECT HCV Ag test. RESULTS: We recruited 112 seropositive HD patients from 17 centres with mean age of 54.04 ± 11.62 years, HD vintage of 14.1 ± 9.7 years, and male constitute 59.8% (67) of the study population. HCV Ag correlates well with HCV RNA (Spearman test coefficient 0.833, p < 0.001). The sensitivity was 90.7%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 76.5%, and accuracy 92.9%. For HCV RNA level > 3000 IU/mL, HCV Ag had a higher sensitivity of 95.1% and greater correlation (Spearman test coefficient 0.897, p < 0.001). The prevalence of active HCV infection was 76.8% among HCV seropositive HD patients. CONCLUSIONS: Although HCV Ag is less sensitive, it shows an excellent correlation with HCV RNA and has 100% PPV. HCV Ag can be considered as an alternative diagnostic tool for chronic active HCV infection among HD cohort, who can then be considered for HCV treatment. For seropositive HD patient with negative HCV Ag, we recommend to follow-up with HCV RNA test.

Cross cultural adaptation and validation of the Malay Kidney Disease Quality of Life (KDQOL-36™).

BACKGROUND: In Malaysia, the prevalence of chronic kidney disease is high (9.1%). To date, no questionnaire that specifically assesses the health-related quality of life of patients with chronic kidney disease has been validated in Malaysia. Malay is the national language of Malaysia and spoken by the majority of its citizens. Therefore, the aim of our study was to cross-culturally adapt and validate the Malay Kidney Disease Quality of Life-36 (KDQOL-36) among patients with chronic kidney disease. METHODS: The English version of the KDQOL-36 was translated according to international guidelines to Malay. Content validity was verified by an expert panel and piloted in five patients. Our instrument was then administered to patients with chronic kidney disease stage 1-3A and patients on hemodialysis at baseline and 4 weeks later. RESULTS: A total of 181/232 patients agreed to participate (response rate = 78.0%). The majority were male (69.6%) with a median age of 51.0 years. Exploratory factor analysis found that the KDQOL-36 had three domains. All three domains showed low to moderate correlation (Spearman's Rho = 0.297-0.610) with the Europe Quality of Life Five Dimension questionnaire. Patients on hemodialysis (physical component summary = 39.8; mental component summary = 53.1;burden of disease = 37.5; symptoms/burden list = 75.0; effects of kidney disease on daily life = 68.8) had significantly worse quality of life than patients with chronic kidney disease stage 1-3A (physical component summary = 49.9; mental component summary = 52.9; burden of disease = 75.0; symptoms/burden list = 85.4; effects of kidney disease on daily life = 93.8, p < 0.001) except for the mental component summary. This indicates that the Malay KDQOL-36 has achieved adequate known-groups validity. Cronbach alpha ranged from 0.872-0.901, indicating adequate internal consistency. At retest, intraclass correlation coefficient ranged from 0.584-0.902, indicating moderate to good correlation. CONCLUSION: The Malay Kidney Disease Quality of Life-36 was found to be a valid and reliable tool to assess the quality of life in patients with chronic kidney disease. This tool can now be used to assess the health-related quality of life (HRQOL) in patients with chronic kidney disease, as HRQOL is an important independent predictor of patient outcome.

Sleep disturbance among Malaysian patients with end-stage renal disease with pruritus.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) is a well-recognized, frequent and compromising complication among patients on hemodialysis. Despite advancement in basic medical sciences, CKD-aP is still a major complication and a challenge for both physicians and patients to manage. The aim of this study was to estimate the prevalence of CKD-aP among hemodialysis patients in Malaysia, to determine the impact of CKD-aP on sleep quality and any factors associated with CKD-aP. METHOD: A multi-centered, cross-sectional study design was conducted from February 2017 to September 2017 at a tertiary hospital and its affiliated dialysis centers, in Kuala Lumpur, Malaysia. Included were patients > 18 years of age who were undergoing hemodialysis and could understand Malay. Participants were asked to fill the Malay 5D-itch scale and the Malay Pittsburgh sleep quality index (PSQI) upon recruitment. RESULTS: A total of 334/334 patients were recruited (response rate = 100%). The majority were male (59.6%) and Chinese (61.7%). A total of 61.3% had pruritus, of which most patients (63.4%) reported that their pruritus was mild. More than half (54.1%) reported that they slept > 6 h, and 93.2% experienced no sleep disturbances during the night. However; the overall PSQI median score [IQR] was 6.0 [5.0-9.0]. No significant association was found between demographic and clinical characteristics of patients with the severity of pruritus. Patients with moderate to severe pruritus were found to be 5.47 times more likely to experience poor sleep quality as compared to patients with mild or no pruritus. CONCLUSION: In Malaysia, the prevalence of CKD-aP was 61.3%, of which the majority reported that their pruritus was mild. Patients with moderate to severe pruritus were found to be 5.47 times more likely to experience poor sleep quality as compared to patients with mild or no pruritus.

MDRD vs. CKD-EPI in comparison to 51Chromium EDTA: a cross sectional study of Malaysian CKD cohort.

BACKGROUND: Accurate measurement of renal function is important: however, radiolabelled gold standard measurement of GFR is highly expensive and can only be used on a very limited scale. We aim to compare the performance of Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations in the multi-ethnic population attending University Malaya Medical Centre (UMMC). METHODS: This is a cross-sectional study recruiting patients, who attend UMMC Nephrology clinics on voluntary basis. 51-Chromium EDTA (51Cr-EDTA) plasma level was used to measure the reference GFR. The serum creatinine was determined by IDMS reference modified Jaffe kinetic assay (CrJaffe). The predictive capabilities of MDRD and CKD-EPI based equations were calculated. Data was analysed using SPSS version 20 and correlation, bias, precision and accuracy were determined. RESULTS: A total of 113 subjects with mean age of 58.12 ± 14.76 years and BMI of 25.99 ± 4.29 kg/m2 were recruited. The mean reference GFR was 66.98 ± 40.65 ml/min/1.73m2, while the estimated GFR based on MDRD and CKD-EPI formula were 62.17 ± 40.40, and 60.44 ± 34.59, respectively. Both MDRD and CKD-EPI were well-correlated with reference GFR (0.806 and 0.867 respectively) and statistically significant with p < 0.001. In the overall cohort, although MDRD had smaller bias than CKD-EPI (4.81 vs. 6.54), CKD-EPI was more precise (25.22 vs. 20.29) with higher accuracy within 30% of measured GFR (79.65 vs. 86.73%). CONCLUSION: The CKD-EPI equation appeared to be more precise and accurate than the MDRD equation in estimating GFR in our cohort of multi-ethnic populations in Malaysia.

Association between serum 25-hydroxyvitamin D levels and carotid atherosclerosis in chronic kidney disease patients.

BACKGROUND: Epidemiological studies have shown an inverse relationship between vitamin D levels and cardiovascular diseases. However, this does not infer a causal relationship between the two. Chronic kidney disease (CKD) patients have a high prevalence of vitamin D deficiency and carotid atherosclerosis. Therefore, in this study we have aimed to determine the association between serum 25-hydroxyvitamin D levels and carotid atherosclerosis in the CKD population. METHODS: 100 CKD stage 3-4 patients were included in the study. Direct chemiluminesent immunoassay was used to determine the level of serum 25-hydroxyvitamin D. All subjects underwent a carotid ultrasound to measure common carotid artery intima-media thickness (CCA-IMT) and to assess the presence of carotid plaques or significant stenosis (≥50 %). Vitamin D deficiency was defined as serum 25-hydroxyvitamin D < 25 nmol/L. Abnormal CCA-IMT was defined as CCA-IMT ≥ 0.8 mm. Plaque was defined as a focal structure that encroaches into the arterial lumen of ≥ 0.5 mm or 50 % of the surrounding IMT value. Significant stenosis was defined as peak-systolic velocities ≥ 125 cm/s and end-diastolic velocities ≥ 40 cm/s. RESULTS: The vitamin D deficiency and non-deficiency groups did not differ significantly in terms of abnormal CCA-IMT (P = 0.443), carotid plaque (P = 0.349), and carotid stenosis (P = 0.554). No significant correlation between serum 25-hydroxyvitamin D levels and CCA-IMT (P = 0.693) was found. On a backward multiple linear regression model, serum 25-hydroxyvitamin D levels was not associated with CCA-IMT, abnormal CCA-IMT, or plaque presence. CONCLUSIONS: No important association between serum 25-hydroxyvitamin levels and carotid atherosclerosis was found in CKD patients.

PARK16 is associated with PD in the Malaysian population.

PARK16 was identified as a risk factor for Parkinson's 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. © 2016 Wiley Periodicals, Inc.