Automated peritoneal dialysis: Challenge and hope for Indonesia.

Peritoneal dialysis utilisation in Indonesia decreased yearly from 6.6% in 2014 to 1.6% in 2018. Various efforts have been made by the government and the Indonesian Nephrologist Organization (PERNEFRI) through education and regulation to optimise the use of peritoneal dialysis, but have yet to succeed. The simplicity of automated peritoneal dialysis (APD) made it worth considering as another solution to optimise peritoneal dialysis in Indonesia. Several advantages are offered by using APD, such as providing more time for activities compared to continuous ambulatory peritoneal dialysis, cheaper cost than haemodialysis and allowing remote monitoring. The advantages of APD make it a promising kidney replacement therapy (KRT) modality for developing countries like Indonesia, but the application is scarce. Some of the challenges in implementing APD in Indonesia include APD machines and fluids that are not available in the Indonesian market; the price of machines and fluids is still high; health workers are not familiar with APD; patients and their families not knowing APD as one of KRT; and APD machines distribution in archipelagic country is challenging.

Bilateral Pleural Effusion in Continuous Ambulatory Peritoneal Dialysis Managed by Vats Pleurodesis.

Pleuroperitoneal leak as a cause of pleural effusions in peritoneal dialysis is a rare but important complication to consider in continuous ambulatory peritoneal dialysis (CAPD) patients presenting with recurrent progressive dyspnoea. Generally, these effusions are unilateral and right-sided, resulting in shortness of breath and reduced ultrafiltration volume, which are initially managed by peritoneal rest. We describe a case of bilateral pleural effusions in a 57-year-old female on chronic CAPD who developed recurrent progressive dyspnoea but maintained adequate dialysis output. A chest radiograph revealed bilateral pleural effusions with high glucose content, and scintigraphy confirmed the existence of a definite pleuroperitoneal communication. She was managed by temporary substitution to haemodialysis, followed by suturing of the shunt and successful video-assisted thoracoscopic surgery (VATS) pleurodesis with an aldehyde-based surgical glue. Unexplained recurring dyspnoea in chronic CAPD should raise the suspicion of a possible pleuroperitoneal leak, even in patients without an apparent loss of ultrafiltration. Pleurodesis using an aldehyde-based adhesive was effective and tolerated well by our patient and may be considered in managing cases of recurrent pleural effusion. LEARNING POINTS: Recurrent dyspnoea in a chronic peritoneal dialysis patient should raise the diagnosis of a possible pleuroperitoneal leak, even if no apparent loss of ultrafiltration was observed.Minimally invasive surgical pleurodesis using surgical adhesive can be considered in cases of refractory pleuroperitoneal leak.

Peritoneal Dialysis Patient Training Program to Enhance independence and Prevent Complications: A Scoping Review.

Background: Peritoneal dialysis (PD) training is essential to ensure patient independence and prevent life-threatening complications, such as peritonitis. The International Society for Peritoneal Dialysis (ISPD) recommends that every PD unit worldwide implement local PD training programs with the goal of improving self-care capabilities. This scoping review aims to give an overview of recent literature and recommendations on PD training programs aiming to improve the quality of care and outcomes for PD patients. Methods: The literature search was conducted using the PC (Population, Concept) approach. The population of interest in this study is PD patients, and the study concept is the PD training program. Several databases were used to conduct the literature search, including PubMed, Science Direct, and CINAHL. The search process began from July 2022 until January 2023. The inclusion criteria for the search included research articles and recommendations. Results: The search yielded 22 articles recommending training programs lasting from 5-8 days, with 1-3-hour sessions and a nurse-to-patient ratio of 1:1. A cumulative training time of 15 hours or more is recommended to enhance patient independence and reduce peritonitis rates. Home-based or in-unit PD training, conducted by experienced nurses using adult learning strategies, has shown significant value in improving self-care and preventing peritonitis. Evaluating training outcomes should encompass knowledge, skills, and attitudes, and the impact on peritonitis rates. Training programs should be flexible and consider physiological and psychosocial barriers to achieving the best results. Conclusion: There are a variety of strategies for dialysis training concerning duration, session length, patient-to-trainer ratio, timing, methods, location, compliance, and the need for retraining. More evidence is needed to assess the impact of PD patient training programs on self-care capabilities and peritonitis incidence. Future studies should investigate the effects of training programs on compliance, self-efficacy, and patient and nurse perspectives.

Safety and efficacy of dendritic cell vaccine for COVID-19 prevention after 1-Year follow-up: phase I and II clinical trial final result.

Introduction: Interim analysis of phase I and phase II clinical trials of personalized vaccines made from autologous monocyte-derived dendritic cells (DCs) incubated with S-protein of SARS-CoV-2 show that this vaccine is safe and well tolerated. Our previous report also indicates that this vaccine can induce specific T-cell and B cell responses against SARS-CoV-2. Herein, we report the final analysis after 1 year of follow-up regarding its safety and efficacy in subjects of phase I and phase II clinical trials. Methods: Adult subjects (>18 years old) were given autologous DCs derived from peripheral blood monocytes, which were incubated with the S-protein of SARS-CoV-2. The primary outcome is safety in phase I clinical trials. Meanwhile, optimal antigen dosage is determined in phase II clinical trials. Corona Virus Disease 2019 (COVID-19) and Non-COVID-19 adverse events (AEs) were observed for 1 year. Results: A total of 28 subjects in the phase I clinical trial were randomly assigned to nine groups based on antigen and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) dosage. In the phase II clinical trial, 145 subjects were randomly grouped into three groups based on antigen dosage. During the 1-year follow-up period, 35.71% of subjects in phase I and 16.54% in phase II had non-COVID AEs. No subjects in phase I experienced moderate-severe COVID-19. Meanwhile, 4.31% of subjects in phase II had moderate-severe COVID-19. There is no difference in both COVID and non-COVID-19 AEs between groups. Conclusions: After 1 year of follow-up, this vaccine is proven safe and effective for preventing COVID-19. A phase III clinical trial involving more subjects should be conducted to establish its efficacy and see other possible side effects.

Expanded hemodialysis: a new concept of renal replacement therapy.

Expanded hemodialysis (HDx) is an innovation that can increase the effectiveness of hemodialysis. The dialysis process is expected to promote more uremic toxins removal without causing significant hypoalbuminemia using the medium cut-off (MCO) membrane or also known as the high retention onset membrane. Compared with conventional membranes such as those of low-flux hemodialysis, high-flux hemodialysis, and hemodiafiltration, the MCO membrane in HDx is considered to be the closest to the physiology of the glomerular membrane. Several studies have shown the use of the MCO membrane in HDx provides clinical benefits and better outcome although further studies are needed to assess the long-term effect and greater impact for dialysis patients.

Cohort Prospective Study to Evaluate Immunogenicity of Epodion® (Biosimilar Epoetin-a) in Anemia Associated with Chronic Kidney Disease (CKD) Patients.

BACKGROUND: Anemia due to chronic kidney disease (CKD) is often associated with decreased erythropoietin (EPO) levels in the blood. Treatments available are improving blood iron levels and administration of exogenous EPO (rhEPO). This study aims to assess the safety and immunogenicity of Epodion, a biosimilar rhEPO product, in haemodialysis patients with CKD-associated anaemia in three Indonesian hospitals. METHODS: This prospective, open label, single arm, and multicenter study enrolled patients with anemia associated with CKD under hemodialysis treatment. Patient eligibility was assessed within the 4-week screening period. Blood samples for determination of erythropoietin antibody (Anti-Drug Antibody) were taken at week-0, 24, and 52 using a validated and highly sensitive bridging ELISA method. Evaluation of Neutralizing Antibody (NAb) was carried out to confirm the impact of the antibody to pharmacological activity (e.g., antibody-mediated PRCA) when the ADA detection of patients was positive after screening and confirmatory assay. RESULTS: Results from all tested patients show that Epodion could maintain hemoglobin and hematocrit levels. ADA detection using ELISA assay yielded negative results for all plasma samples of week-24 and week-52, so the evaluation of NAb was not carried out. No adverse events were considered relevant to tested product. CONCLUSION: This study proves no immunogenic effect of Epodion on stimulating immune system's antibodies in Indonesian patients with CKD-associated anemia.

Developing dendritic cell for SARS-CoV-2 vaccine: Breakthrough in the pandemic.

Finding a vaccine that can last a long time and effective against viruses with high mutation rates such as SARS-CoV-2 is still a challenge today. The various vaccines that have been available have decreased in effectiveness and require booster administration. As the professional antigen presenting cell, Dendritic Cells can also activate the immune system, especially T cells. This ability makes dendritic cells have been developed as vaccines for some types of diseases. In SARS-CoV-2 infection, T cells play a vital role in eliminating the virus, and their presence can be detected in the long term. Hence, this condition shows that the formation of T cell immunity is essential to prevent and control the course of the disease. The construction of vaccines oriented to induce strong T cells response can be formed by utilizing dendritic cells. In this article, we discuss and illustrate the role of dendritic cells and T cells in the pathogenesis of SARS-CoV-2 infection and summarizing the crucial role of dendritic cells in the formation of T cell immunity. We arrange the basis concept of developing dendritic cells for SARS-CoV-2 vaccines. A dendritic cell-based vaccine for SARS-CoV-2 has the potential to be an effective vaccine that solves existing problems.

A personal COVID-19 dendritic cell vaccine made at point-of-care: Feasibility, safety, and antigen-specific cellular immune responses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a world-wide pandemic. Internationally, because of availability, accessibility, and distribution issues, there is a need for additional vaccines. This study aimed to: establish the feasibility of personal dendritic cell vaccines to the SARS-CoV-2 spike protein, establish the safety of a single subcutaneous vaccine injection, and determine the antigen-specific immune response following vaccination. In Phase 1, 31 subjects were assigned to one of nine formulations of autologous dendritic cells and lymphocytes (DCL) incubated with 0.10, 0.33, or 1.0 µg of recombinant SARS-CoV-2 spike protein, and admixed with saline or 250 or 500 µg of granulocyte-macrophage colony-stimulating factor (GM-CSF) prior to injection, then assessed for safety and humoral response. In Phase 2, 145 subjects were randomized to one of three formulations defined by incubation with the same three quantities of spike protein without GM-CSF, then assessed for safety and cellular response. Vaccines were successfully manufactured for every subject at point-of-care. Approximately 46.4% of subjects had a grade 1 adverse event (AE); 6.5% had a grade 2 AE. Among 169 evaluable subjects, there were no acute allergic, grade 3 or 4, or serious AE. In Phase 1, anti-receptor binding domain antibodies were increased in 70% of subjects on day-28. In Phase 2, in the 127 subjects who did not have high levels of gamma interferon-producing cells at baseline, 94.4% had increased by day 14 and 96.8% by day 28. Point-of-care personal vaccine manufacturing was feasible. Further development of such subject-specific vaccines is warranted.

Dendritic cell vaccine as a potential strategy to end the COVID-19 pandemic. Why should it be Ex Vivo?

INTRODUCTION: Developing a safe and efficacious vaccine that can induce broad and long-term immunity for SARS-CoV-2 infection is the most critical research to date. As the most potent APCs, dendritic cells (DCs) can induce a robust T cell immunity. In addition, DCs also play an essential role in COVID-19 pathogenesis, making them a potential vaccination target. However, the DCs-based vaccine with ex vivo loading has not yet been explored for COVID-19. AREAS COVERED: This review aims to provide the rationale for developing a DCs-based vaccine with ex vivo loading of SARS-CoV-2 antigen. Here, we discuss the role of DCs in immunity and the effect of SARS-CoV-2 infection on DCs. Then, we propose the mechanism of the DCs-based vaccine in inducing immunity and highlight the benefits of ex vivo loading of antigen. EXPERT OPINION: We make the case that an ex vivo loaded DC-based vaccination is appropriate for COVID-19 prevention.

Acute Kidney Injury and Jaundice in a Patient With Concurrent Severe Malaria and Acute Exacerbation of Hepatitis B.

Patients chronically infected with hepatitis B virus (HBV) may travel to areas with high endemicity of malaria. The overlap between malaria and HBV infection can be clinically severe and present a diagnostic challenge as both diseases manifest similar symptoms. This case describes a fatal case of a 43-year-old man with chronic HBV infected with Plasmodium falciparum malaria that presents as acute kidney injury (AKI) and jaundice following a trip to malaria-endemic region. Despite administering antimalarial and 6 courses of renal replacement therapy, the patient's clinical condition did not improve, leading to septic shock, multi-organ dysfunction, and eventually, death. AKI and jaundice are commonly seen in severe P. falciparum malaria, as well as acute exacerbation of chronic HBV. This case emphasizes the importance to consider malarial screening when evaluating sick returning travelers, even in those with underlying chronic HBV. Given the severity of coinfection, prompt identification of this overlap can avert the rapid deterioration of severe malaria by early administration of intravenous artesunate and renal replacement therapy.

Modalities of renal replacement therapy and clinical outcomes of patients with acute kidney injury in a resource-limited setting: Results from a SEA-AKI study.

PURPOSE: To determine the effects of modalities of renal replacement therapy (RRT) on the 30-d mortality and renal recovery in patients with acute kidney injury (AKI). MATERIALS AND METHODS: A multicenter cohort study was conducted in 17 hospitals from Thailand and Indonesia. We recruited patients who were admitted to the Intensive care unit and diagnosed with AKI. Relevant mode of RRT, as intermittent hemodialysis (IHD), continuous renal replacement therapy (CRRT), peritoneal dialysis (PD), or sustained low efficiency dialysis (SLED), was initiated as indicated. RESULTS: From 2844 patients with AKI, 449 cases (8.1%) received RRT. There were no significant differences in the 30-d mortality between those initially treated with CRRT, PD, and SLED compared to those treated with IHD. The renal recovery was similar for each RRT mode. The three independent factors of death were the primary diagnosis of kidney disease, higher APACHE II score, and non-renal SOFA score. Only 48 (10.7%) patients had been switched to another mode of RRT. CONCLUSIONS: All four modes of RRT (IHD, CRRT, PD, and SLED) are acceptable treatments for severe AKI and gave a similar survival rate.

Incidence of acute kidney injury and use of renal replacement therapy in intensive care unit patients in Indonesia.

BACKGROUND: Currently, there is limited epidemiology data on acute kidney injury (AKI) in Indonesia. Therefore, we assessed the incidence of AKI and the utilization of renal replacement therapy (RRT) in Indonesia. METHODS: Demographic and clinical data were collected from 952 ICU participants. The participants were categorized into AKI and non-AKI groups. The participants were further classified according to the 3 different stages of AKI as per the Kidney Disease Improving Global Outcome (KDIGO) criteria. RESULTS: Overall incidence of AKI was 43%. The participants were divided into three groups based on the AKI stages: 18.5% had stage 1, 33% had stage 2, and 48.5% had stage 3. Primary diagnosis of renal disease and high APACHE II score were the risk factors associated with AKI (OR = 4.53, 95% CI: 1.67-12.33, p = 0.003 and OR = 1.14 per 1 unit increase, 95% CI: 1.09-1.20, p < 0.001, respectively). Chronic kidney disease was the risk factor for severe AKI. Sepsis was the leading cause of AKI. Among the AKI participants, 24.6% required RRT. The most common RRT modalities were intermittent hemodialysis (71.7%), followed by slow low-efficiency dialysis (22.8%), continuous renal replacement therapy (4.3%), and peritoneal dialysis (1.1%). CONCLUSIONS: This study showed that AKI was a common problem in the Indonesian ICU. We strongly believe that identification of the risk factors associated with AKI will help us develop a predictive score for AKI so we can prevent and improve AKI outcome in the future.