Displaying all 12 publications

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  1. Ismail H, Abdul Manaf MR, Abdul Gafor AH, Mohamad Zaher ZM, Ibrahim AIN
    Kidney Int Rep, 2019 Sep;4(9):1261-1270.
    PMID: 31517145 DOI: 10.1016/j.ekir.2019.05.016
    Introduction: Prevalence of chronic kidney disease (CKD) in Malaysia is 9.07% of the total population, of which 0.36% are at stage 5 CKD or end-stage renal disease (ESRD). Public-private partnership has improved accessibility of renal replacement therapies (RRT), especially dialysis, in Malaysia, but the economic burden of the existing RRT financing mechanism, which is predominantly provided by the public sector, has never been quantified.

    Methods: Primary data were collected through a standardized survey, and secondary data analysis was used to derive estimates of the ESRD expenditure.

    Results: Total annual expenditure of ESRD by the public sector has grown 94% within a span of 7 years, from Malaysian Ringgit [MYR] 572 million (US dollars [USD] 405 million, purchasing power parity [PPP] 2010) in 2010 to MYR 1.12 billion (USD 785 million, PPP 2016) in 2016. The total ESRD expenditure in 2010 constituted 2.95% of the public sector's total health expenditure, whereas in 2016, the proportion has increased to 4.2%. Only 6% of ESRD expenditure was spent on renal transplantation, and the remaining 94% was spent on dialysis.

    Conclusion: The share of ESRD expenditure in total health expenditure for the public sector is considered substantial given only a small proportion of the population is affected by the disease. The rapid increase in expenditure relative to the national total health expenditure should warrant the relevant authorities about sustainability of the existing financing mechanism of ESRD and the importance to institutionalize more drastic preventive measures.

  2. Cooper DJ, Plewes K, Grigg MJ, Patel A, Rajahram GS, William T, et al.
    Kidney Int Rep, 2021 Mar;6(3):645-656.
    PMID: 33732979 DOI: 10.1016/j.ekir.2020.12.020
    Introduction: Classification of acute kidney injury (AKI) requires a premorbid baseline creatinine, often unavailable in studies in acute infection.

    Methods: We evaluated commonly used surrogate and imputed baseline creatinine values against a "reference" creatinine measured during follow-up in an adult clinical trial cohort. Known AKI incidence (Kidney Disease: Improving Global Outcomes [KDIGO] criteria) was compared with AKI incidence classified by (1) back-calculation using the Modification of Diet in Renal Disease (MDRD) equation with and without a Chinese ethnicity correction coefficient; (2) back-calculation using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation; (3) assigning glomerular filtration rate (GFR) from age and sex-standardized reference tables; and (4) lowest measured creatinine during admission. Back-calculated distributions were performed using GFRs of 75 and 100 ml/min.

    Results: All equations using an assumed GFR of 75 ml/min underestimated AKI incidence by more than 50%. Back-calculation with CKD-EPI and GFR of 100 ml/min most accurately predicted AKI but misclassified all AKI stages and had low levels of agreement with true AKI diagnoses. Back-calculation using MDRD and assumed GFR of 100 ml/min, age and sex-reference GFR values adjusted for good health, and lowest creatinine during admission performed similarly, best predicting AKI incidence (area under the receiver operating characteristic curves [AUC ROCs] of 0.85, 0.87, and 0.85, respectively). MDRD back-calculation using a cohort mean GFR showed low total error (22%) and an AUC ROC of 0.85.

    Conclusion: Current methods for estimating baseline creatinine are large sources of potential error in acute infection studies. Preferred alternatives include MDRD equation back-calculation with a population mean GFR, age- and sex-specific GFR values corrected for "good health," or lowest measured creatinine. Studies using surrogate baseline creatinine values should report specific methodology.

  3. Li PK, Bavanandan S, Mohamed R, Szeto CC, Wong VW, Chow KM, et al.
    Kidney Int Rep, 2020 Aug;5(8):1129-1138.
    PMID: 32775812 DOI: 10.1016/j.ekir.2020.05.001
    In 2018, Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). The guideline synthesized recent advances, especially in HCV therapeutics and diagnostics, and provided clinical recommendations and suggestions to aid healthcare providers and improve care for CKD patients with HCV. To gain insight into the extent that the 2018 guideline has been adopted in Asia, KDIGO convened an HCV Implementation Summit in Hong Kong. Participants included nephrologists, hepatologists, and nurse consultants from 8 Southeast Asian countries or regions with comparable high-to-middle economic ranking by the World Bank: mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. Through presentations and discussions, meeting participants described regional practice patterns related to the KDIGO HCV in CKD guideline, identified barriers to implementing the guideline, and developed strategies for overcoming the barriers in Asia and around the world.
  4. Harkness JR, Beaman GM, Teik KW, Sidhu S, Sayer JA, Cordell HJ, et al.
    Kidney Int Rep, 2020 Oct;5(10):1823-1827.
    PMID: 33102976 DOI: 10.1016/j.ekir.2020.07.001
  5. Wang AY, Akizawa T, Bavanandan S, Hamano T, Liew A, Lu KC, et al.
    Kidney Int Rep, 2019 Nov;4(11):1523-1537.
    PMID: 31890994 DOI: 10.1016/j.ekir.2019.09.007
    Improving Global Outcomes (KDIGO) Clinical Practice Guideline on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) 2009 provided recommendations on the detection, evaluation, and treatment of CKD-MBD in patients CKD who are and are not undergoing dialysis. Because of the accumulation of evidence since this initial publication, the CKD-MBD Guideline underwent a selective update in 2017. In April 2018, KDIGO convened a CKD-MBD Guideline Implementation Summit in Japan with the key objective to discuss various barriers to the uptake and implementation of the CKD-MBD Guideline in 8 Asian countries/regions. These countries/regions were comparable according to their high-to-middle economic ranking assigned by the World Bank. The discussion took into account the availability of CKD-MBD medication therapies and government health policies that may influence reimbursement and practice patterns in the region. Most importantly, Summit participants developed a framework of multifaceted strategies aimed at overcoming barriers to guideline implementation. The Summit attendees suggested a shared decision-making approach between clinicians and patients in CKD-MBD management, as well as individualized care based on the treatment risk-benefit ratio. The Summit participants also discussed how KDIGO, as a guideline development organization, may work in partnership with local and national nephrology societies to provide education and facilitate implementation of the guideline by clinicians. The conclusions drawn from this Summit in Asia may serve as an important guide for other regions to follow.
  6. Yu X, Nakayama M, Wu MS, Kim YL, Mushahar L, Szeto CC, et al.
    Kidney Int Rep, 2022 Jan;7(1):15-27.
    PMID: 35005310 DOI: 10.1016/j.ekir.2021.10.019
    The prevalence of kidney failure continues to rise globally. Dialysis is a treatment option for individuals with kidney failure; after the decision to initiate dialysis has been made, it is critical to involve individuals in the decision on which dialysis modality to choose. This review, based on evidence arising from the literature, examines the role of shared decision-making (SDM) in helping those with kidney failure to select a dialysis modality. SDM was found to lead to more people with kidney failure feeling satisfied with their choice of dialysis modality. Individuals with kidney failure must be cognizant that SDM is an active and iterative process, and their participation is essential for success in empowering them to make decisions on dialysis modality. The educational components of SDM must be easy to understand, high quality, unbiased, up to date, and targeted to the linguistic, educational, and cultural needs of the individual. All individuals with kidney failure should be encouraged to participate in SDM and should be involved in the design and implementation of SDM approaches.
  7. Kashani K, Macedo E, Burdmann EA, Hooi LS, Khullar D, Bagga A, et al.
    Kidney Int Rep, 2017 Jul;2(4):519-529.
    PMID: 28845471 DOI: 10.1016/j.ekir.2017.03.014
    The incidence of acute kidney injury (AKI) among acutely ill patients is reportedly very high and has vexing consequences on patient outcomes and health care systems. The risks and impact of AKI differ between developed and developing countries. Among developing countries, AKI occurs in young individuals with no or limited comorbidities, and is usually due to environmental causes, including infectious diseases. Although several risk factors have been identified for AKI in different settings, there is limited information on how risk assessment can be used at population and patient levels to improve care in patients with AKI, particularly in developing countries where significant health disparities may exist. The Acute Disease Quality Initiative consensus conference work group addressed the issue of identifying risk factors for AKI and provided recommendations for developing individualized risk stratification strategies to improve care. We proposed a 5-dimension, evidence-based categorization of AKI risk that allows clinicians and investigators to study, define, and implement individualized risk assessment tools for the region or country where they practice. These dimensions include environmental, socioeconomic and cultural factors, processes of care, exposures, and the inherent risks of AKI. We provide examples of these risks and describe approaches for risk assessments in the developing world. We anticipate that these recommendations will be useful for health care providers to plan and execute interventions to limit the impact of AKI on society and each individual patient. Using a modified Delphi process, this group reached consensus regarding several aspects of AKI risk stratification.
  8. Wang D, Mohammad M, Wang Y, Tan R, Murray LS, Ricardo S, et al.
    Kidney Int Rep, 2017 Jul;2(4):739-748.
    PMID: 29142990 DOI: 10.1016/j.ekir.2017.03.004
    Introduction: X-linked Alport syndrome (OMIM 301050) is caused by COL4A5 missense variants in 40% of families. This study examined the effects of chemical chaperone treatment (sodium 4-phenylbutyrate) on fibroblast cell lines derived from men with missense mutations.

    Methods: Dermal fibroblast cultures were established from 2 affected men and 3 normals. Proliferation rates were examined, the collagen IV α5 chain localized with immunostaining, and levels of the intra- and extracellular chains quantitated with an in-house enzyme-linked immunosorbent assay. COL4A5 mRNA was measured using quantitative reverse transcriptase polymerase chain reaction. Endoplasmic reticulum (ER) size was measured on electron micrographs and after HSP47 immunostaining. Markers of ER stress (ATF6, HSPA5, DDIT3), autophagy (ATG5, BECN1, ATG7), and apoptosis (CASP3, BAD, BCL2) were also quantitated by quantitative reverse transcriptase polymerase chain reaction. Measurements were repeated after 48 hours of incubation with 10 mM sodium 4-phenylbutyrate acid.

    Results: Both COL4A5 missense variants were associated with reduced proliferation rates on day 6 (P = 0.01 and P = 0.03), ER enlargement, and increased mRNA for ER stress and autophagy (all P values < 0.05) when compared with normal. Sodium 4-phenylbutyrate treatment increased COL4A5 transcript levels (P < 0.01), and reduced ER size (P < 0.01 by EM and P < 0.001 by immunostaining), ER stress (p HSPA5 and DDIT3, all P values < 0.01) and autophagy (ATG7, P < 0.01). Extracellular collagen IV α5 chain was increased in the M1 line only (P = 0.06).

    Discussion: Sodium 4-phenylbutyrate increases collagen IV α5 mRNA levels, reduces ER stress and autophagy, and possibly facilitates collagen IV α5 extracellular transport. Whether these actions delay end-stage renal failure in men with X-linked Alport syndrome and missense mutations will only be determined with clinical trials.

  9. 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.

  10. Herrington WG, Harper C, Staplin N, Haynes R, Emberson J, Reith C, et al.
    Kidney Int Rep, 2023 Aug;8(8):1489-1495.
    PMID: 37538810 DOI: 10.1016/j.ekir.2023.05.008
    INTRODUCTION: We aimed to assess opportunities for trial streamlining and the scientific impact of adjudication on kidney and cardiovascular outcomes in CKD.

    METHODS: We analysed the effects of adjudication of ~2100 maintenance kidney replacement therapy (KRT) and ~1300 major atherosclerotic events (MAEs) recorded in SHARP. We first compared outcome classification before versus after adjudication, and then re-ran randomised comparisons using pre-adjudicated follow-up data.

    RESULTS: For maintenance KRT, adjudication had little impact with only 1% of events being refuted (28/2115). Consequently, randomised comparisons using pre-adjudication reports found almost identical results (pre-adjudication: simvastatin/ezetimibe 1038 vs placebo 1077; risk ratio [RR] 0.95, 95%CI 0.88-1.04; post-adjudicated: 1057 vs 1084; RR=0.97, 95%CI 0.89-1.05). For MAEs, about one-quarter of patient reports were refuted (324/1275 [25%]), and reviewing 3538 other potential vascular events and death reports identified only 194 additional MAEs. Nevertheless, randomised analyses using SHARP's pre-adjudicated data alone found similar results to analyses based on adjudicated outcomes (pre-adjudication: 573 vs 702; RR=0.80, 95%CI 0.72-0.89; adjudicated: 526 vs 619; RR=0.83, 95%CI 0.74- 0.94), and also suggested refuted MAEs were likely to represent atherosclerotic disease (RR for refuted MAEs=0.80, 95%CI 0.65-1.00).

    CONCLUSIONS: These analyses provide three key insights. First, they provide a rationale for nephrology trials not to adjudicate maintenance KRT. Secondly, when an event that mimics an atherosclerotic outcome is not expected to be influenced by the treatment under study (e.g. heart failure), the aim of adjudicating atherosclerotic outcomes should be to remove such events. Lastly, restrictive definitions for the remaining suspected atherosclerotic outcomes may reduce statistical power.

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