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.

COVID-19 death and kidney disease in a multiracial Asian country.

INTRODUCTION: COVID-19 infection and kidney disease (KD) carry a considerable risk of mortality. Understanding predictors of death and KD may help improve management and patient outcome. METHODS: This is a prospective multicentre observational study conducted in a multiracial Asian country to identify predictors of death and acute kidney injury (AKI) in hospitalized COVID-19 patients from January to June 2020. RESULTS: A total of 6078 patients were included in this study. Mean age was 37.3 (±16.8) years, 71% were male, 59.4% Malay, 6.7% Chinese, 2.3% Indian and 31.7% other ethnicities. AKI was seen in 3.5% of patients while 1.6% had pre-existing chronic kidney disease (CKD). Overall case fatality rate (CFR) was 1.3%. Patients with KD (AKI and CKD) had CFR of 20%. Many factors were associated with increased risk of death and AKI. However, significant predictors of death after adjustment for covariates were age (>70 years), Chinese ethnicity, diabetes mellitus (DM) and KD. Adjusted predictors of AKI were age (>51 years), DM and severity at presentation. Chinese were 2.58 times more likely to die (p = .036) compared to Malay. Centre capacity to manage, ventilate and dialyze patients significantly influenced death. Among those with AKI, the most common symptoms were fever, cough, and dyspnea. They had lower absolute lymphocyte count, were more likely to be admitted to ICU, required more ventilation and longer hospitalization. CONCLUSION: Patient and centre factors influence death and AKI among COVID-19 patients. This study also demonstrates death disparities across different racial groups and centre capacities in this multiracial Asian country.

Everolimus-facilitated calcineurin inhibitor reduction in Asian de novo kidney transplant recipients: 2-year results from the subgroup analysis of the TRANSFORM study.

OBJECTIVE: We analyzed the efficacy and safety of an everolimus with reduced-exposure calcineurin inhibitor (EVR+rCNI) versus mycophenolic acid with standard-exposure CNI (MPA+sCNI) regimen in Asian patients from the TRANSFORM study. METHODS: In this 24-month, open-label study, de novo kidney transplant recipients (KTxRs) were randomized (1:1) to receive EVR+rCNI or MPA+sCNI, along with induction therapy and corticosteroids. RESULTS: Of the 2037 patients randomized in the TRANSFORM study, 293 were Asian (EVR+rCNI, N = 136; MPA+sCNI, N = 157). At month 24, EVR+rCNI was noninferior to MPA+sCNI for the binary endpoint of estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m2 or treated biopsy-proven acute rejection (27.0% vs. 29.2%, P = .011 for a noninferiority margin of 10%). Graft loss and death were reported for one patient each in both arms. Mean eGFR was higher in EVR+rCNI versus MPA+sCNI (72.2 vs. 66.3 ml/min/1.73 m2 , P = .0414) even after adjusting for donor type and donor age (64.3 vs. 59.3 ml/min/1.73 m2 , P = .0582). Overall incidence of adverse events was comparable. BK virus (4.4% vs. 12.1%) and cytomegalovirus (4.4% vs. 13.4%) infections were significantly lower in the EVR+rCNI arm. CONCLUSION: This subgroup analysis in Asian de novo KTxRs demonstrated that the EVR+rCNI versus MPA+sCNI regimen provides comparable antirejection efficacy, better renal function, and reduced viral infections (NCT01950819).

Hepatic adverse drug reactions in Malaysia: An 18-year review of the national centralized reporting system.

PURPOSE: To determine the incidence, demographic profile, background of reporters, causative agents, severity and clinical outcomes of hepatic adverse drug reaction (ADR) reports in Malaysia using the national ADR reporting database. METHODS: The ADR reports recorded between 2000 and 2017 were retrospectively analysed to identify hepatic ADR reports. The trend and characteristics of hepatic ADR cases were described. Multivariate disproportionality analysis of the causative agents was performed to generate signals of hepatic ADRs. RESULTS: A total of 2090 hepatic ADRs (1.77% of all ADRs) were reported with mortality rate of 12.7% among cases with known clinical outcomes. The incidence of hepatic ADR reporting in Malaysia increased significantly over 18 years from 0.26 to 9.45 per million population (P < .001). Antituberculosis drugs (n = 268, 12.82%) was the most common suspected class of causative agents with a reporting odds ratio (ROR) and 95% CI of 8.39 (7.26-9.70), followed by traditional/complementary medicines or herbal/dietary supplements (TCM/HDS) (n = 235, 11.24%, ROR 3.26 [2.84-3.75]), systemic antibacterials (n = 159, 7.61%, ROR 2.65 [2.25-3.13]), lipid modifying agents (n = 142, 6.79%, ROR 2.21 [1.86-2.63]) and amiodarone (n = 137, 6.56%, ROR 35.25 [28.40-43.75]). Most (72.9%) of the TCM/HDS were not registered with the authorities. CONCLUSIONS: Hepatic ADR cases have increased significantly in Malaysia, with antituberculosis drugs, systemic antibacterials, and TCM/HDS being the most common causative agents reported. Most TCM/HDS reported to be associated with hepatic ADR were not registered with the authorities.

Survival advantage of initiating dialysis in elderly and non-elderly incident end-stage kidney disease patients.

AIM: Many patients, especially the elderly, who require renal replacement therapies (RRT) have delayed or rejected dialysis for various reasons. Current dialysis guidelines may not be relevant for the elderly or frail patients. We aim to determine survival advantage of initiating dialysis in patients deemed to require RRT. METHODS: This was an observational cohort on incident end-stage kidney disease (ESKD) patients from January 1, 2007 to December 31, 2008. The primary outcome was all-cause mortality. Patients contributed person-time from the date of ESKD diagnosis until death, transplant or end of study on December 31, 2014, whichever occurred first. An extended Cox regression model with time-varying exposure to dialysis was used to account for immortal time bias. RESULTS: Of 3990 incident ESKD patients included, 70.2% patients initiated dialysis; 78.8% with haemodialysis (HD) while the remaining 21.2% with peritoneal dialysis (PD). Dialysis reduced hazard of death in both elderly and non-elderly patients even after controlling for comorbidities (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.50, 0.68 and HR 0.76, 95% CI 0.69, 0.85, respectively). HD was protective in both the elderly and non-elderly (HR 0.53, 95% CI 0.45, 0.63 and HR 0.71, 95% CI 0.64, 0.80, respectively). PD significantly reduced risk of death compared to no dialysis in the elderly but not in the non-elderly. CONCLUSION: Dialysis improved survival in all incident ESKD patients. The findings suggested a larger protection offered by HD. Although improvement in survival from initiating dialysis was large, its true benefit should take overall quality of life into account. SUMMARY AT A GLANCE This observational study showed that initiation of dialysis improves the survival of end-stage kidney disease (ESKD) patients of all age groups, but the quality of life is an important aspect that has not been explored.

Pharmacogenotyping of CYP3A5 in predicting dose-adjusted trough levels of tacrolimus among Malaysian kidney-transplant patients.

Tacrolimus (FK506) is a calcineurin inhibitor with a narrow therapeutic index that exhibits large interindividual variation. Seventy-eight kidney transplant patients treated with tacrolimus were recruited to study the correlation of dose adjusted trough level (level/dose; L/D) of tacrolimus with CYP3A5 and ABCB1 genotypes, as well as the mRNA copy number of ABCB1 in blood. Patients were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T) and CYP3A5 (G6986A), while ABCB1 mRNA transcript copy number was determined by absolute quantification (real-time PCR) in 46 patients. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus L/D in kidney-transplant patients. Significantly higher L/D was observed among non-expressors (2.85, 95%: 2.05-3.70 (ng·mL(-1))/(mg·kg(-1))) as compared with the expressors (1.15, 95%: 0.95-1.80 (ng·mL(-1))/(mg·kg(-1))) of CYP3A5 (Mann-Whitney U test; P < 0.001). No correlation was observed between L/D and the ABCB1 genotypes. A significant inverse correlation of blood ABCB1 mRNA level with L/D was demonstrated (Spearman's Rank Order correlation; P = 0.016, rs = -0.348). However, in multiple regression analysis, only CYP3A5*3 genotype groups were found to be significantly correlated with tacrolimus L/D (P < 0.001). These findings highlight the importance of CYP3A5*3 pharmacogenotyping among kidney-transplant patients treated with tacrolimus, and confirm the role of blood cell P-glycoprotein in influencing the L/D for tacrolimus.

The Impact of ABCC2 -24C>T Gene Polymorphism on Graft Survival in Kidney Transplant Recipients.

Personalized medicine in kidney transplantation has the potential to improve outcomes and reduce complications. The aim of this study was to investigate the influence of single nucleotide polymorphisms in genes encoding metabolizing enzymes (CYP3A5) and transporters (ABCC2) on clinical outcomes (acute graft failure and/or acute tubular necrosis (ATN)) in kidney transplant recipients (KTR). This was a multicenter, retrospective cohort study where adult KTR who had undergone kidney transplantation between 2020 and 2021 and received tacrolimus-mycophenolate treatment were enrolled in the study. DNA was extracted from collected blood samples using a commercially available kit. CYP3A5*3, ABCC2 -24C>T and ABCC2 3972C>T SNP were determined by polymerase chain reaction. Of the total 39 patients included, nine (23.1%) KTR had an incidence of acute graft failure and/or ATN. A multiple logistic regression showed wildtype ABCC2 -24C>T C allele had a higher risk of developing acute graft rejection and/or ATN compared to the variant allele carriers (adjusted Odd Ratios [aOR]: 27.675, p = 0.038). Recipients who had delayed graft function (aOR: 49.214, p = 0.012) and a history of CMV infection (aOR: 18.097, p = 0.009) were at 49.2 and 18.1-times increased risk for acute graft failure and/or ATN, respectively. The large aOR was inevitable due to the small sample size and required cautious interpretation. This is the first study to determine the effect of the ABCC2 -24C>T genetic polymorphism on clinical outcomes in Malaysian KTR and forms the basis for further work on ABCC2 -24C>T effects in long-term KTR.

Conversion to enteric-coated mycophenolate sodium from mycophenolate mofetil in stable renal transplant patients: results of an Asia-Pacific study.

AIM: Mycophenolate mofetil has proven efficacy in the prophylaxis of acute rejection in solid organ transplantation; however, gastrointestinal intolerance can risk this efficacy because of associated dose adjustments and discontinued treatment. Enteric-coated mycophenolate sodium has demonstrated improved gastrointestinal tolerability, but the data in Asian subjects are scarce. METHODS: This was a Phase-IIIb, open-label, single-arm, multicentre, prospective 6-month study which investigated safety and graft function in stable maintenance renal transplant recipients of Asian origin, after switching from mycophenolate mofetil to enteric-coated mycophenolate sodium at least 3 months after transplantation. Primary end-points included renal allograft function and safety parameters. RESULTS: The study recruited patients from 16 centres in Asian countries. The intention-to-treat and safety populations both included 122 patients. Graft function remained stable over the course of the study as measured by creatinine clearance and glomerular filtration rate. At 6 months the incidence of any gastrointestinal adverse events was 20.5% (n = 25), none of which required dose adjustments. There were only three cases of biopsy proven acute rejection with no reports of graft loss or death. CONCLUSION: This study demonstrated that enteric-coated mycophenolate sodium is a safe and effective alternative to mycophenolate mofetil in Asian kidney transplant recipients.

Predictive Factors, Treatment, and Outcomes of Coagulase-Negative Staphylococcal Peritonitis in Malaysian Peritoneal Dialysis Patients: A Single-Center Study.

Aims: Coagulase-negative Staphylococci (CoNS) are frequently isolated in peritoneal dialysis (PD)-related peritonitis with a high rate of relapse and repeat peritonitis after initial response to antimicrobials. The optimal treatment regimen for CoNS peritonitis remains debatable. Hence, this study aimed to describe the clinical and microbiologic characteristics of CoNS peritonitis in a PD center and determine predictive factors influencing the outcomes. Methods: All cases of CoNS peritonitis in Selayang Hospital between 2011 and 2019 were reviewed retrospectively. Results: A total of 906 episodes of peritonitis were recorded; 140 episodes (15%) in 98 patients were caused by CoNS. The oxacillin and gentamicin resistance rates were 47% and 46%, respectively. The overall primary response rate was 90%, and the complete cure rate was 79%. Patients with concomitant exit-site infection (odds ratio (OR) 0.06, 95% confidence interval (CI) 0.01 to 0.40, P < 0.01) and history of recent systemic antibiotic use (OR 0.04, 95% CI 0.01 to 0.82, P=0.04) were less likely to achieve primary response. CoNS episodes that were treated with beta-lactam-based or vancomycin-based therapy had a similar primary response rate and complete cure rate. The rates of relapse and repeat were 12% and 16%, respectively. Relapsed episodes (OR 0.35, 95% CI 0.13 to 0.97, P=0.04) had a significantly lower complete cure rate than the first episodes. Conclusion: Relapsed CoNS peritonitis was common and was associated with worse outcomes than the first episode of CoNS peritonitis. Oxacillin resistance was common, but the treatment outcome remained favourable when a beta-lactam-based regimen was used as empirical therapy.

Butyricimonas virosa Peritonitis in Peritoneal Dialysis Patient: A Case Report and Review.

Butyricimonas virosa is a Gram-negative bacillus, which was first discovered in rat faeces in 2009. To date, only seven human infections have been reported in literature. To our knowledge, this is the first reported case of peritoneal dialysis (PD)-related peritonitis due to B. virosa. A 65-year-old Chinese man presented to the hospital with complaints of dizziness and vomiting. On admission, the drained peritoneal dialysate was cloudy. He was empirically treated as a case of PD-related peritonitis with intraperitoneal (IP) cefazolin, ceftazidime, and gentamicin. B. virosa was isolated from peritoneal fluid sample and the antibiotics were changed to IP imipenem and amikacin. Three weeks after completion of the antibiotics, the patient presented again with cloudy peritoneal dialysate and blood stained diarrhoea. IP imipenem and amikacin were recommenced. Multiple peritoneal dialysate samples were sent to the microbiology laboratory, but this time no microorganism was isolated. Colonoscopy examination revealed the presence of extensive rectosigmoidal ulcerations. IP imipenem was replaced with IP piperacillin-tazobactam when the patient developed imipenem-associated neurotoxicity at Day 9 of treatment. The patient recovered fully after completing 3 weeks of IP piperacillin-tazobactam and 2 weeks of IP amikacin. This is the first reported case of PD-related peritonitis due to B. virosa. Susceptibility data for B. virosa are scarce, but a 3-week course of IP piperacillin-tazobactam, imipenem, or meropenem could be potentially useful in treating PD-related peritonitis caused by this organism.

Adverse Drug Reactions of Antihypertensives and CYP3A5*3 Polymorphism Among Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) patients may be more susceptible to adverse drug reactions (ADRs), given their complex medication regimen and altered physiological state driven by a decline in kidney function. This study aimed to describe the relationship between CYP3A5*3 polymorphism and the ADR of antihypertensive drugs in CKD patients. This retrospective, multi-center, observational cohort study was performed among adult CKD patients with a follow-up period of up to 3 years. ADRs were detected through medical records. CYP3A5*3 genotyping was performed using the direct sequencing method. From the 200 patients recruited in this study, 33 (16.5%) were found to have ADRs related to antihypertensive drugs, with 40 ADRs reported. The most frequent ADR recorded was hyperkalemia (n = 8, 20.0%), followed by bradycardia, hypotension, and dizziness, with 6 cases (15.0%) each. The most common suspected agents were angiotensin II receptor blockers (n = 11, 27.5%), followed by angiotensin-converting enzyme inhibitors (n = 9, 22.5%). The CYP3A5*3 polymorphism was not found to be associated with antihypertensive-related ADR across the genetic models tested, despite adjustment for other possible factors through multiple logistic regression (p > 0.05). After adjusting for possible confounding factors, the factors associated with antihypertensive-related ADR were anemia (adjusted odds ratio [aOR] 5.438, 95% confidence interval [CI]: 2.002, 14.288) and poor medication adherence (aOR 3.512, 95% CI: 1.470, 8.388). In conclusion, the CYP3A5*3 polymorphism was not found to be associated with ADRs related to antihypertensives in CKD patients, which requires further verification by larger studies.

Comparison of Clinical Outcomes Among Deceased Donor Kidney Transplant Recipients Before and After Utilizing Estimated Posttransplant Survival Score for Kidneys Allocation in Malaysia.

BACKGROUND: The Malaysian Kidney Allocation System implemented in 2020 includes only kidney transplant candidates with estimated posttransplant survival (EPTS) score of ≤20%, in replacement of Malaysian Organs Sharing System, which was based solely on dialysis vintage. We aim to compare the clinical outcomes of deceased-donor kidney transplant recipients (DDKTRs) with EPTS ≤20% to those with EPTS >20%. METHODS: All DDKTRs between January 1, 2015, and December 29, 2020, were included and categorized into 2 groups: EPTS ≤20% and EPTS >20%. Cox regression was performed to evaluate the association of EPTS score and patient survival. The rate of postoperative complications, graft failure and patient survival were compared between 2 groups. Data were analyzed with SPSS v26 and R v4.0.4. The study complies with the Helsinki Congress and the Istanbul Declaration. RESULTS: We included 159 DDKTRs, with a median follow-up of 25 months (range, 10-60 months). The mean age of those with EPTS ≤20% was 32.2 ± 3.4 years and those with EPTS >20% was 46.0 ± 6.7 years, and the median EPTS score were 16% (range, 12%-18%) and 38% (range, 27%-56.5%), respectively. EPTS score was associated with patient survival (hazard ratio, 1.031; 95% CI 1.010-1.052; P = .003), and the cutoff points of 30% and above were associated with worse survival. It showed good discrimination (C-index, 0.729; 95% CI 0.579-0.878; P = .003) and the optimal cutoff value was 38% (65.5% sensitivity, 68.8% specificity, 17.8% positive predictive value, and 95.8% negative predictive value). Both groups had similar rate of surgical complications (P = .191), graft failure (P = .503), and patient survival (P = .654), but those with EPTS >20% had higher incidence of urinary tract infection (9.3% vs 27.6%, P = .016). CONCLUSIONS: There was no difference in clinical outcomes using an EPTS cutoff point of 20% but worse patient survival if higher cutoff point was used.

Factors associated with the frequency of antihypertensive drug adjustments in chronic kidney disease patients: a multicentre, 2-year retrospective study.

Background Optimum antihypertensive drug effect in chronic kidney disease is important to mitigate disease progression. As frequent adjustments to antihypertensive drugs might lead to problems that may affect their effectiveness, the modifiable factors leading to frequent adjustments of antihypertensive drugs should be identified and addressed. Objective This study aims to identify the factors associated with frequent adjustments to antihypertensive drugs among chronic kidney disease patients receiving routine nephrology care. Setting Nephrology clinics at two Malaysian tertiary hospitals. Method This multi-centre, retrospective cohort study included adult patients under chronic kidney disease clinic follow-up. Demographic data, clinical information, laboratory data and medication characteristics from 2018 to 2020 were collected. Multiple logistic regression was used to identify the factors associated with frequent adjustments to antihypertensive drugs (≥ 1 per year). Main outcome measure Frequent adjustments to antihypertensive drugs. Results From 671 patients included in the study, 219 (32.6%) had frequent adjustments to antihypertensive drugs. Frequent adjustment to antihypertensive drugs was more likely to occur 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), after controlling for confounding factors. Conclusion This work highlights the importance of close monitoring of patients requiring initial adjustments to antihypertensive drugs. Antihypertensive drug adjustments may indicate events that could contribute to poorer outcomes in the future.

Effects of CYP3A5 Polymorphism on Rapid Progression of Chronic Kidney Disease: A Prospective, Multicentre Study.

Personalised medicine is potentially useful to delay the progression of chronic kidney disease (CKD). The aim of this study was to determine the effects of CYP3A5 polymorphism in rapid CKD progression. This multicentre, observational, prospective cohort study was performed among adult CKD patients (≥18 years) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, who had ≥4 outpatient, non-emergency eGFR values during the three-year study period. The blood samples collected were analysed for CYP3A5*3 polymorphism. Rapid CKD progression was defined as eGFR decline of >5 mL/min/1.73 m2/year. Multiple logistic regression was then performed to identify the factors associated with rapid CKD progression. A total of 124 subjects consented to participate. The distribution of the genotypes adhered to the Hardy-Weinberg equilibrium (X2 = 0.237, p = 0.626). After adjusting for potential confounding factors via multiple logistic regression, the factors associated with rapid CKD progression were CYP3A5*3/*3 polymorphism (adjusted Odds Ratio [aOR] 4.190, 95% confidence interval [CI]: 1.268, 13.852), adjustments to antihypertensives, young age, dyslipidaemia, smoking and use of traditional/complementary medicine. CKD patients should be monitored closely for possible factors associated with rapid CKD progression to optimise clinical outcomes. The CYP3A5*3/*3 genotype could potentially be screened among CKD patients to offer more individualised management among these patients.

Muscle Status Response to Oral Nutritional Supplementation in Hemodialysis Patients With Protein Energy Wasting: A Multi-Center Randomized, Open Label-Controlled Trial.

Background: Muscle wasting, observed in patients with end-stage kidney disease and protein energy wasting (PEW), is associated with increased mortality for those on hemodialysis (HD). Oral nutritional supplementation (ONS) and nutrition counseling (NC) are treatment options for PEW but research targeting muscle status, as an outcome metric, is limited. Aim: We compared the effects of combined treatment (ONS + NC) vs. NC alone on muscle status and nutritional parameters in HD patients with PEW. Methods: This multi-center randomized, open label-controlled trial, registered under ClinicalTrials.gov (Identifier no. NCT04789031), recruited 56 HD patients identified with PEW using the International Society of Renal Nutrition and Metabolism criteria. Patients were randomly allocated to intervention (ONS + NC, n = 29) and control (NC, n = 27) groups. The ONS + NC received commercial renal-specific ONS providing 475 kcal and 21.7 g of protein daily for 6 months. Both groups also received standard NC during the study period. Differences in quadriceps muscle status assessed using ultrasound (US) imaging, arm muscle area and circumference, bio-impedance spectroscopy (BIS), and handgrip strength (HGS) methods were analyzed using the generalized linear model for repeated measures. Results: Muscle indices as per US metrics indicated significance (p < 0.001) for group × time interaction only in the ONS + NC group, with increases by 8.3 and 7.7% for quadriceps muscle thickness and 4.5% for cross-sectional area (all p < 0.05). This effect was not observed for arm muscle area and circumference, BIS metrics and HGS in both the groups. ONS + NC compared to NC demonstrated increased dry weight (p = 0.039), mid-thigh girth (p = 0.004), serum prealbumin (p = 0.005), normalized protein catabolic rate (p = 0.025), and dietary intakes (p < 0.001), along with lower malnutrition-inflammation score (MIS) (p = 0.041). At the end of the study, lesser patients in the ONS + NC group were diagnosed with PEW (24.1%, p = 0.008) as they had achieved dietary adequacy with ONS provision. Conclusion: Combination of ONS with NC was effective in treating PEW and contributed to a gain in the muscle status as assessed by the US, suggesting that the treatment for PEW requires nutritional optimization via ONS.

Clinical effectiveness of a Malaysian-manufactured CAPD product: A randomised trial.

BACKGROUND: We compared the clinical effectiveness of a new peritoneal dialysis (PD) product with polyvinyl chloride-containing tubing (Stay Safe Link®, SSL) with the plastic-free alternative (Stay Safe®, STS) in patients on continuous ambulatory peritoneal dialysis (CAPD). METHOD: A multicentre, parallel, randomised, controlled, open-label, non-inferiority trial was conducted. Adult patients receiving CAPD were randomised in a 1:1 ratio to SSL or STS. The primary outcome was the rate of peritonitis after 1 year of follow-up. RESULTS: A total of 472 subjects were randomised (SSL, n = 233; STS, n = 239). One subject in each group was excluded from the analysis as they withdrew consent before the first dialysis dose. Four hundred and seventy subjects (SSL, n = 232; STS, n = 238) were included in the modified intention-to-treat analysis. Non-inferiority between two groups was established as no significant difference was found in peritonitis rate (incident rate ratio: 0.91, 95% CI: 0.65-1.28). No significant difference was detected in weekly Kt/V (p = 0.58) and creatinine clearance (p = 0.55). However, the average ultrafiltration volume was significantly lower in SSL, with a mean difference of 93 ml (p < 0.01). SSL also demonstrated a 2.57-times higher risk of device defect than STS (95% CI: 1.77-3.75). CONCLUSION: SSL was non-inferior in peritonitis rate compared to plastic-free STS over 1 year in patients requiring CAPD. There was no difference in the delivered dialysis dose, but there was a higher rate of device defects with SSL.

A randomized, multicenter, open-label trial to determine peritonitis rate, product defect, and technique survival between ANDY-Disc and UltraBag in patients on CAPD.

BACKGROUND: With the various twin-bag systems available on the market, we decided to conduct a therapeutic equivalence study comparing ANDY-Disc (Fresenius Medical Care, Bad Homburg, Germany) with UltraBag (Baxter, Deerfield, IL) in patients on continuous ambulatory peritoneal dialysis (CAPD) therapy. METHODS: This multicenter, open-label, parallel-group, randomized trial is designed to show the therapeutic equivalence of ANDY-Disc with UltraBag. All CAPD patients from the 6 participating centers who met inclusion/exclusion criteria were enrolled into the trial. They were randomly assigned and converted from the Y-disconnect system (Ultraset; Baxter) to the twin-bag systems. The primary outcome variable is peritonitis, and secondary outcome parameters are technique failure or product defect. RESULTS: From April 2002 to May 2003, a total of 270 patients were recruited for this study. Overall peritonitis rates were 22.9 patient-months/episode for ANDY-Disc and 35.0 patient-months/episode for UltraBag. The overall peritonitis rate for ANDY-Disc was 53% greater compared with UltraBag, but the 95% confidence interval overlaps the prespecified margin of equivalence. There were more product defects reported with ANDY-Disc; 236 product defects compared with 17 with UltraBag. The time series of the number of product defects and peritonitis count on the ANDY-Disc arm suggests a possible cause-and-effect relationship. CONCLUSION: Therapeutic equivalence of ANDY-Disc to UltraBag could not be established with respect to peritonitis. There is a trend toward greater risk for peritonitis on the Andy-Disc arm. There also is a suggestive cause-and-effect relation between the occurrence of product defect and peritonitis on the ANDY-Disc arm during the early part of the trial.

Prevention of renal failure: the Malaysian experience.

Renal replacement therapy in Malaysia has shown exponential growth since 1990. The dialysis acceptance rate for 2003 was 80 per million population, prevalence 391 per million population. There are now more than 10,000 patients on dialysis. This growth is proportional to the growth in gross domestic product (GDP). Improvement in nephrology and urology services with widespread availability of ultrasonography and renal pathology has improved care of renal patients. Proper management of renal stone disease, lupus nephritis, and acute renal failure has decreased these as causes of end-stage renal disease (ESRD) in younger age groups. Older patients are being accepted for dialysis, and 51% of new patients on dialysis were diabetic in 2003. The prevalence of diabetes is rising in the country (presently 7%); glycemic control of such patients is suboptimal. Thirty-three percent of adult Malaysians are hypertensive and blood pressure control is poor (6%). There is a national coordinating committee to oversee the control of diabetes and hypertension in the country. Primary care clinics have been provided with kits to detect microalbuminuria, and ACE inhibitors for the treatment of hypertension and diabetic nephropathy. Prevention of renal failure workshops targeted at primary care doctors have been launched, opportunistic screening at health clinics is being carried out, and public education targeting high-risk groups is ongoing. The challenge in Malaysia is to stem the rising tide of diabetic ESRD.

The Cost and Utility of Renal Transplantation in Malaysia.

UNLABELLED: Kidney transplantation is the optimal therapy for the majority of patients with end-stage renal disease. However, the cost and health outcomes of transplantation have not been assessed in a middle-income nation with a low volume of transplantation, such as Malaysia. AIM AND METHODS: This study used microcosting methods to determine the cost and health outcomes of living and deceased donor kidney transplantation in adult and pediatric recipients. The perspective used was from the Ministry of Health Malaysia. Cost-effectiveness measures were cost per life year (LY) and cost per quality-adjusted LYs. The time horizon was the lifetime of the transplant recipient from transplant to death. RESULTS: Records of 206 KT recipients (118 adults and 88 children) were obtained for microcosting. In adults, discounted cost per LY was US $8609(Malaysian Ringgit [RM]29 482) and US $13 209(RM45 234) for living-donor kidney transplant (LKT) and deceased donor kidney transplant (DKT), respectively, whereas in children, it was US $10 485(RM35 905) and US $14 985(RM51 317), respectively. Cost per quality-adjusted LY in adults was US $8826 (RM30 224) for LKT and US $13 592(RM46 546) for DKT. Total lifetime discounted costs of adult transplants were US $119 702 (RM409 921) for LKT, US $147 152 (RM503 922) for DKT. Total costs for pediatric transplants were US $154 841(RM530 252) and US $159 313(RM545 566) for the 2 categories respectively. CONCLUSIONS: Both LKT and DKT are economically favorable for Malaysian adult and pediatric patients with ESRD and result in improvement in quality of life.