Biomarkers in acute kidney injury.

Acute kidney injury (AKI) is a multifactorial syndrome with a high risk of short- and long-term complications as well as increased health care costs. The traditional biomarkers of AKI, serum creatinine and urine output, have important limitations. The discovery of new functional and damage/stress biomarkers has enabled a more precise delineation of the aetiology, pathophysiology, site, mechanisms, and severity of injury. This has allowed earlier diagnosis, better prognostication, and the identification of AKI sub-phenotypes. In this review, we summarize the roles and challenges of these new biomarkers in clinical practice and research.

Recommendations for clinical trial design in acute kidney injury from the 31st acute disease quality initiative consensus conference. A consensus statement.

PURPOSE: Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations on endpoints and trial design for studies of AKI prevention and treatment interventions based on existing data and expert consensus. METHODS: At the 31st Acute Disease Quality Initiative (ADQI) meeting, international experts in critical care, nephrology, involving adults and pediatrics, biostatistics and people with lived experience (PWLE) were assembled. We focused on four main areas: (1) patient enrichment strategies, (2) prevention and attenuation studies, (3) treatment studies, and (4) innovative trial designs of studies other than traditional (parallel arm or cluster) randomized controlled trials. Using a modified Delphi process, recommendations and consensus statements were developed based on existing data, with > 90% agreement among panel members required for final adoption. RESULTS: The panel developed 12 consensus statements for clinical trial endpoints, application of enrichment strategies where appropriate, and inclusion of PWLE to inform trial designs. Innovative trial designs were also considered. CONCLUSION: The current lack of specific therapy for prevention or treatment of AKI demands refinement of future clinical trial design. Here we report the consensus findings of the 31st ADQI group meeting which has attempted to address these issues including the use of predictive and prognostic enrichment strategies to enable appropriate patient selection.

A simple nomogram to predict dengue shock syndrome: A study of 4522 south east Asian children.

Dengue shock syndrome (DSS) substantially worsens the prognosis of children with dengue infection. This study aimed to develop a simple clinical tool to predict the risk of DSS. A cohort of 2221 Thai children with a confirmed dengue infection who were admitted to King Chulalongkorn Memorial Hospital between 1987 and 2007 was conducted. Another data set from a previous publication comprising 2,301 Vietnamese children with dengue infection was employed to create a pooled data set, which was randomly split into training (n = 3182), testing (n = 697) and validating (n = 643) datasets. Logistic regression was compared to alternative machine learning algorithms to derive the most predictive model for DSS. 4522 children, including 899 DSS cases (758 Thai and 143 Vietnamese children) with a mean age of 9.8 ± 3.4 years, were analyzed. Among the 12 candidate clinical parameters, the Bayesian Model Averaging algorithm retained the most predictive subset of five covariates, including body weight, history of vomiting, liver size, hematocrit levels, and platelet counts. At an Area Under the Curve (AUC) value of 0.85 (95% CI: 0.81-0.90) in testing data set, logistic regression outperformed random forest, XGBoost and support vector machine algorithms, with AUC values being 0.82 (0.77-0.88), 0.82 (0.76-0.88), and 0.848 (0.81-0.89), respectively. At its optimal threshold, this model had a sensitivity of 0.71 (0.62-0.80), a specificity of 0.84 (0.81-0.88), and an accuracy of 0.82 (0.78-0.85) on validating data set with consistent performance across subgroup analyses by age and gender. A logistic regression-based nomogram was developed to facilitate the application of this model. This work introduces a simple and robust clinical model for DSS prediction that is well-tailored for children in resource-limited settings.

The Role of Early Hemoadsorption in Severe COVID-19 Treatment: A Pilot Randomized Controlled Trial.

INTRODUCTION: Hemoadsorption, an extracorporeal apheresis technique, is reportedly used in severe COVID-19 patients. However, limited evidence from randomized clinical trials supports this practice. METHODS: In this single-center study, severe COVID-19 patients requiring ICU admission were randomly assigned (1:1) to receive HA-330 hemoadsorption in combination with standard treatment or standard therapy alone. Both groups received tocilizumab intravenously if their clinical conditions worsened within 24-48 h. The primary outcome was mortality from any cause within 28 days after randomization. Secondary outcomes included mechanical ventilator-free days, daily C-reactive protein levels, oxygenation (defined by PaO2/FiO2 ratio), daily sequential organ failure assessment score, and severity score of lung infiltration on chest X-rays (CXR RALE score). RESULTS: A total of 28 patients underwent randomization, with 14 (50%) receiving HA-330 hemoadsorption. Only 9 out of 14 patients (64.3%) in the control group experienced clinical worsening and were subsequently administered intravenous tocilizumab. At 28 days, the mortality rate was significantly lower in the intervention group (28.57% vs. 78.57%, p = 0.021), with a hazard ratio of death of 0.26 (95% CI = 0.08-0.81; p = 0.021). All of secondary outcomes were comparable in both groups. CONCLUSION: Based on our pilot randomized trial, the early application of HA-330 hemoadsorption in patients with severe COVID-19 may establish a favorable outcome in term of mortality. These data provide the initial proof of concept for conducting a large-scale study in the future.

Outcomes of continuous renal replacement therapy versus peritoneal dialysis as a renal replacement therapy modality in patients undergoing Venoarterial extracorporeal membrane oxygenation.

INTRODUCTION: The optimal modality for renal replacement therapy (RRT) in patients venoarterial extracorporeal membrane oxygenation (VA-ECMO) remains unclear. This study aimed to compare outcomes between continuous renal replacement therapy (CRRT) and peritoneal dialysis (PD) in VA-ECMO patients. METHODS: This single-center retrospective study included VA-ECMO patients who developed AKI and subsequently required CRRT or PD. Data on patient demographics, comorbidities, clinical characteristics, RRT modality, and outcomes were collected. The primary outcome was in-hospital mortality, with secondary outcomes including length of stays, RRT durations, and complications associated with RRT. RESULTS: A total of 43 patients were included (72.1% male, mean age 58.2 ± 15.7 years). Of these, 21 received CRRT and 22 received PD during ECMO therapy. In-hospital mortality rates did not significantly differ between CRRT and PD groups (80.9% vs 90.9%, p = 0.35). However, PD was associated with a higher incidence of catheter-related complications, including malposition (31.8% vs 4.7%, p = 0.046), infection (22.7% vs 4.7%, p = 0.19), and bleeding (18.2% vs 9.5%, p = 0.66), respectively. CONCLUSION: Among patients receiving VA-ECMO-supported RRT, our study revealed comparable in-hospital mortality rates between CRRT and PD, although PD was associated with a higher incidence of catheter-related complications.

Common arboviruses and the kidney: a review.

Arboviruses are endemic in several countries and represent a worrying public health problem. The most important of these diseases is dengue fever, whose numbers continue to rise and have reached millions of annual cases in Brazil since the last decade. Other arboviruses of public health concern are chikungunya and Zika, both of which have caused recent epidemics, and yellow fever, which has also caused epidemic outbreaks in our country. Like most infectious diseases, arboviruses have the potential to affect the kidneys through several mechanisms. These include the direct action of the viruses, systemic inflammation, hemorrhagic phenomena and other complications, in addition to the toxicity of the drugs used in treatment. In this review article, the epidemiological aspects of the main arboviruses in Brazil and other countries where these diseases are endemic, clinical aspects and the main laboratory changes found, including changes in renal function, are addressed. It also describes how arboviruses behave in kidney transplant patients. The pathophysiological mechanisms of kidney injury associated with arboviruses are described and finally the recommended treatment for each disease and recommendations for kidney support in this context are given.

Outcomes of extracorporeal blood purification with oXiris® membrane in critically ill patients: A systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of the novel oXiris® membrane in critically ill adult patients. METHODS: We systematically searched MEDLINE, EMBASE, and CENTRAL from inception to 01/06/2023 for relevant randomised controlled trials (RCTs) and non-randomised studies of intervention (NRSI). The primary outcome was overall mortality. Random effect meta-analyses were conducted in RevMan 5.4.1. Study quality was evaluated using Cochrane's risk of bias tool. (PROSPERO: CRD42023389198). RESULTS: Ten studies (2 RCTs and 8 NRSIs) with 481 patients were included. None had low risk of bias. Treatment using oXiris® was associated with reduced overall mortality (RR 0.78, 95%CI 0.62-0.98; p = 0.03; 6 NRSI). One RCT reported 28-day mortality, finding no significant difference between groups. Besides, pooled NRSIs results showed significant reductions in SOFA scores, norepinephrine dosage, and several inflammatory biomarkers (C-reactive protein [CRP], lactate, and interleukin-6 [IL-6]) post oXiris® treatment. However, other clinical outcomes (ICU and hospital length of stay, mechanical ventilation duration) were similar between groups. CONCLUSION: In critically ill patients, the use of oXiris® membrane was associated with reduced overall mortality, norepinephrine dosage, CRP, IL-6, lactate levels, along with improved organ function. However, the certainty of evidence was very low, necessitating high-quality RCTs to further evaluate its efficacy in this population.

Dengue virus transmission risk in blood donation: Evidence from Thailand.

Individuals infected with dengue virus (DENV) often show no symptoms, which raises the risk of DENV transfusion transmission (TT-DENV) in areas where the virus is prevalent. This study aimed to determine the evidence of DENV infection in blood donors from different geographic regions of Thailand. A cross-sectional study was conducted on blood donor samples collected from the Thai Red Cross National Blood Center and four regional blood centers between March and September 2020. Screening for DENV nonstructural protein 1 (NS1), anti-DENV immunoglobulin G (IgG), and IgM antibodies was performed on residual blood from 1053 donors using enzyme-linked immunosorbent assay kits. Positive NS1 and IgM samples indicating acute infection were verified using four different techniques, including quantitative real-time (q) RT-PCR, nested PCR, virus isolation in C6/36 cells, and mosquito amplification. DENV IgG seropositivity was identified in 89% (938/1053) of blood donors. Additionally, 0.4% (4/1053) and 2.1% (22/1053) of Thai blood donors tested positive for NS1 and IgM, respectively. The presence of asymptomatic dengue virus infection in healthy blood donors suggests a potential risk of transmission through blood transfusion, posing a concern for blood safety.

Global trends in chronic kidney disease-related mortality: a systematic review protocol.

INTRODUCTION: In recent decades, all-cause mortality has increased among individuals with chronic kidney disease (CKD), influenced by factors such as aetiology, standards of care and access to kidney replacement therapies (dialysis and transplantation). The recent COVID-19 pandemic also affected mortality over the past few years. Here, we outline the protocol for a systematic review to investigate global temporal trends in all-cause mortality among patients with CKD at any stage from 1990 to current. We also aim to assess temporal trends in the mortality rate associated with the COVID-19 pandemic. METHODS AND ANALYSIS: We will conduct a systematic review of studies reporting mortality for patients with CKD following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search electronic databases, national and multiregional kidney registries and grey literature to identify observational studies that reported on mortality associated with any cause for patients with CKD of all ages with any stage of the disease. We will collect data between April and August 2023 to include all studies published from 1990 to August 2023. There will be no language restriction, and clinical trials will be excluded. Primary outcome will be temporal trends in CKD-related mortality. Secondary outcomes include assessing mortality differences before and during the COVID-19 pandemic, exploring causes of death and examining trends across CKD stages, country classifications, income levels and demographics. ETHICS AND DISSEMINATION: A systematic review will analyse existing data from previously published studies and have no direct involvement with patient data. Thus, ethical approval is not required. Our findings will be published in an open-access peer-reviewed journal and presented at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42023416084.

Proceedings of the 6th Asia Dengue Summit, June 2023.

The 6th Asia Dengue Summit (ADS) themed "Road Map to Zero Dengue Death" was held in Thailand from 15th-16th June 2023. The summit was hosted by Tropical Medicine Cluster, Chulalongkorn University, Bangkok, Thailand in conjunction with Queen Saovabha Memorial Institute, The Thai Red Cross Society; Faculty of Tropical Medicine, Mahidol University; and the Ministry of Public Health. The 6th ADS was convened by Asia Dengue Voice and Action (ADVA); Global Dengue and Aedes Transmitted Diseases Consortium (GDAC); Southeast Asian Ministers of Education Tropical Medicine and Public Health Network (SEAMEO TROPMED); Fondation Mérieux (FMx) and the International Society for Neglected Tropical Diseases (ISNTD). Dengue experts from academia and research, and representatives from the Ministries of Health, Regional and Global World Health Organization (WHO) and International Vaccine Institute (IVI) participated in the three-day summit. With more than 51 speakers and 451 delegates from over 24 countries, 10 symposiums, and 2 full days, the 6th ADS highlighted the growing threat of dengue and its antigenic evolution, flagged the urgent need to overcome vaccine hesitancy and misinformation crisis, and focused on dengue control policies, newer diagnostics, therapeutics and vaccines, travel-associated dengue, and strategies to improve community involvement.

A Proposed Predictive Equation for Energy Expenditure Estimation Among Noncritically Ill Patients With Acute Kidney Injury.

OBJECTIVE: The incidence of acute kidney injury (AKI) is identified more frequently in noncritical compared with intensive care settings. The prognosis of malnourished AKI patients is far worse than those with normal nutritional status. However, a method for estimating the optimal amount of energy required to guide nutritional support among noncritically ill AKI patients is yet to be determined. METHODS: We evaluated the performance of weight-based formulas (20-30 kcal/kg/day) with the reference values of energy expenditure (EE) measured by indirect calorimetry (IC) among noncritically ill AKI patients during hospitalization. The statistics for assessing agreement, including total deviation index and accuracy within 10% represent the percentage of estimations falling within the IC value range of ±10%, were tested. Parameters for predicting the EE equation were also developed using a regression analysis model. RESULTS: A total of 40 noncritically ill AKI patients were recruited. The mean age of participants was 62.5 ± 16.5 years with 50% being male. The average IC-derived EE was 1,124.6 ± 278.9 kcal/day with respiratory quotients 0.8-1.3, indicating good validity of the IC test. Receiving dialysis, protein catabolic rate, and age was not significantly associated with measured EE. Nearly all weight-based formulas overestimated measured EE. The magnitude of total deviation index values was broad with the proportion of patients achieving an accuracy of 10% being as low as 20%. The proposed equation to predict EE derived from this study was EE (kcal/day) = 618.27 + (8.98 x weight in kg) + 137.0 if diabetes - 199.7 if female (r2 = 0.68, P < .001). In the validation study with an independent group of noncritically ill AKI patients, predicted EE using the newly derived equation was also significantly correlated with measured EE by IC (r = 0.69, P = .004). CONCLUSION: Estimation of EE by weight-based formulas usually overestimated measured EE among noncritically ill AKI patients. In the absence of IC, the proposed predictive equation, specifically for noncritically ill AKI patients might be useful, in addition to weight-based formulas, for guiding caloric dosing in clinical practice.

Effectiveness of Multidisciplinary Post-Acute Kidney Injury Clinic on Awareness and Knowledge in Acute Kidney Injury Survivors.

INTRODUCTION: Acute kidney injury (AKI) awareness and knowledge among survivors is poor, leading to suboptimal self-management and follow-up care. The purpose of the study was to evaluate the impact of a multidisciplinary post-AKI clinic on AKI awareness and knowledge among survivors. METHODS: We conducted a quasi-experimental study among stage 2-3 AKI survivors who were followed in the multidisciplinary post-AKI clinic, comprising nephrologists, renal nurses, pharmacists, and dietitians. Patients were evaluated before and after entering the clinic during a 3-month follow-up period, using a three-component questionnaire including the following: (1) Do you know of your AKI diagnosis during hospitalization? (yes/no), (2) how do you rate your AKI knowledge? (ranging from 1 or "very low" to 5 or "excellent"), and (3) 25-item objective AKI knowledge survey instrument that covered general knowledge of AKI, nutrition, medication, and symptoms of renal failure. RESULTS: A total of 108 AKI survivors were enrolled, with 37.0%, 41.7%, and 21.3% being stage 2 AKI, stage 3 AKI, and stage 3-dialysis AKI, respectively. Before entering the clinic, 50% of patients were unaware of their AKI during hospitalization. After receiving education from the multidisciplinary post-AKI clinic, all patients became aware they had experienced AKI. The mean perceived knowledge and objective knowledge scores were significantly increased over the 3-month period from 1.6 (0.7) to 3.9 (0.7) out of 5 and 15.4 (3.5) to 21.4 (2.0) out of 25, respectively (p < 0.001 for both). Additionally, reverse transformation of the Likert scale to a percentage format also revealed a significant improvement in mean perceived AKI knowledge scores, transitioning from 13.8 ± 16.8 to 73.0 ± 17.6, p < 0.001. CONCLUSION: The multidisciplinary post-AKI clinic effectively enhanced AKI awareness and knowledge among survivors. These findings highlight the importance of follow-up care and the benefits of a multidisciplinary approach. Further studies are needed to determine the long-term outcomes associated with increased knowledge.

Efficacy of the Cytokine Adsorption Therapy in Patients with Severe COVID-19-Associated Pneumonia: Lesson Learned from a Prospective Observational Study.

INTRODUCTION: Severe COVID-19 pneumonia can activate a cytokine storm. Hemoperfusion can reduce pro-inflammatory cytokines in sepsis but is still debated in the COVID-19 setting. Thus, we sought to investigate the benefits of HA-330 cytokine adsorption through clinical and laboratory outcomes. METHODS: We conducted a single-center prospective observational study in adults with severe COVID-19 pneumonia admitted to the intensive care unit at Chiang Mai University Hospital (Chiang Mai, Thailand). Those with cytokine storms indicated by organ injury, including acute respiratory distress syndrome (ARDS), and high inflammatory markers were included. Patients treated with the HA-330 device were classified as a hemoperfusion group, while those without cytokine adsorption were classified as a control group. We compared the outcomes on day 7 after treatment and evaluated the factors associated with 60-day mortality. RESULTS: A total of 112 patients were enrolled. Thirty-eight patients received hemoperfusion, while 74 patients did not. Baseline cytokine storm parameters were comparable. In univariate analysis, there was an improvement in clinical and laboratory effects from hemoperfusion therapy. In multivariate analysis, APACHE II score, SOFA score, PaO2/FiO2, the number of hemoperfusion sessions, the amount of blood purified, high-sensitivity C-reactive protein, and IL-6 were associated with mortality. Using at least 3 sessions of hemoperfusion could mitigate, the 60-day mortality (adjusted odds ratio 0.25, 95% confidence interval: 0.03-0.33, p = 0.001). By categorizing the amount of blood treated into 3 groups of <1 L/kg, 1-2 L/kg, and ≥2 L/kg, there was a linear dose-response association with survival, which was better in the higher volume purified (mortality 60% vs. 33.3% vs. 0%, respectively, p = 0.015). CONCLUSIONS: The early initiation of HA-330 hemoperfusion could improve the severity score and laboratory outcomes of COVID-19 ARDS. The optimal dose of at least three sessions or the amount of blood purified greater than 1 L/kg was associated with a reduction in 60-day mortality.

Lacosamide dosing in patients receiving continuous renal replacement therapy.

BACKGROUND: Lacosamide is one of the anticonvulsants used in critically ill patients. This study aimed to suggest appropriate lacosamide dosing regimens in critically ill patients receiving continuous renal replacement therapy (CRRT) via Monte Carlo simulations. METHODS: Mathematical models were created using published demographic and pharmacokinetics in adult critically ill patients. CRRT modalities with different effluent rates were added into the models. Lacosamide regimens were evaluated on the probability of target attainment (PTA) using pharmacodynamic targets of trough concentrations and area under the curve within a range of 5-10 mg/L and 80.25-143 and 143-231 mg*h/L for the initial 72 h-therapy, respectively. Optimal regimens were defined from regimens that yielded the highest PTA. Each dosing regimen was tested in a group of different 10,000 virtual patients. RESULTS: Our results revealed the optimal lacosamide dosing regimen of 300-450 mg/day is recommended for adult patients receiving both CRRT modalities with 20-25 effluent rates. The dose of 600 mg/day was suggested in higher effluent rate of 35 mL/kg/h. Moreover, a patient with body weight > 100 kg was less likely to attain the targets. CONCLUSIONS: Volume of distribution, total clearance, CRRT clearance and body weight were significantly contributed to lacosamide dosing. Clinical validation of the finding is strongly indicated.

Standard versus no post-filter ionized calcium monitoring in regional citrate anticoagulation for continuous renal replacement therapy (NPC trial).

Background: Current guidelines recommend monitoring of post-filter ionized calcium (pfCa) when using regional citrate anticoagulation during continuous renal replacement therapy (RCA-CRRT) to determine citrate efficiency for the prevention of filter clotting. However, the reliability of pfCa raises the question of whether routine monitoring is required. Reducing the frequency of pfCa monitoring could potentially reduce costs and workload. Our objective was to test the efficacy and safety of no pfCa monitoring among critically ill patients receiving RCA-CRRT. Methods: This study was a non-inferiority randomized controlled trial conducted between January 2021 and October 2021 at King Chulalongkorn Memorial Hospital, Thailand. Critically ill patients who were treated with RCA-CRRT were randomized to receive either standard pfCa monitoring (aiming pfCa level of 0.25-0.35 mmol/L), or no pfCa monitoring, in which a constant rate of citrate infusion was maintained at pre-determined citrate concentrations of 4 mmol/L with blinding of pfCa levels to treating clinicians. The primary outcome was the filter lifespan. Non-inferiority would be demonstrated if the upper limit of the 95% confidence interval (CI) for the difference in filter lifespan between the groups was less than 20 h. Results: Fifty patients were randomized to the standard pfCa monitoring group (n = 25) or no pfCa monitoring group (n = 25). The mean filter lifespan was 54 ± 20 h in the standard pfCa monitoring group and 47 ± 23 h in the no pfCa monitoring group (absolute difference 7.1 h; 95% CI -5.3, 19.5, P = .25). When restricting the analysis to circuits reaching the maximum duration of circuit lifespan at 72 h and clotted filters, the filter lifespan was 61 ± 17 h in the standard pfCa group vs 60 ± 19 h in the no pfCa monitoring group (absolute difference 0.9 h; 95% CI -11.5, 13.4, P = .88). Compared with the no pfCa monitoring group, the standard pfCa monitoring group had a significantly higher mean citrate concentrations (4.43 ± 0.32 vs 4 mmol/L, P < .001) and a higher rate of severe hypocalcemia (44% vs 20%, P = .13). No statistical differences were found in filter clotting, citrate accumulation, citrate overload and mortality between the two groups. Conclusions: Among critically ill patients receiving RCA-CRRT, no pfCa monitoring by maintaining the citrate concentrations of 4 mmol/L is feasible. Larger randomized controlled trials should be conducted to ensure the efficacy, safety and cost-effectiveness of this strategy. Trial registration: ClinicalTrials.gov: NCT04792424 (registered 11 March 2021).

Practice of dialysis access interventional nephrology procedures in the Asia-Pacific region: Getting lay of the land.

AIM: This cross-sectional survey aimed to determine the prevalence of Interventional Nephrology (IN) practice amongst nephrologists in the Asia-Pacific Region (APR), specifically related to dialysis access (DA). METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey. RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel. CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.

The Role of Erythropoietin Levels in Predicting Long-Term Outcomes following Severe Acute Kidney Injury.

INTRODUCTION: Acute kidney injury (AKI) survivors are at an increased risk of chronic kidney disease, end-stage kidney disease, and mortality. Little is known about the effect of erythropoietin (EPO), a kidney-producing hormone, in post-AKI setting. We aimed to investigate the role of EPO as a predictor of long-term outcomes in post-severe AKI survivors. METHODS: We performed a retrospective analysis of post-AKI cohort conducted between August 2018 and December 2021. Adults who survived severe AKI stages 2-3 were enrolled. Serum EPO was obtained at 1 month after hospital discharge. We explored whether EPO level could predict long-term kidney outcomes at 12 months including mortality, kidney replacement therapy, doubling serum creatinine, and major adverse kidney events at 365 days. RESULTS: One hundred and twelve patients were enrolled. Median EPO level was significantly higher in non-survivors than survivors (28.9 [interquartile range: 16.2-50.7] versus 11.6 mU/mL [7.5-22.3], p = 0.003). The best EPO level cut-off was 16.2 mU/mL (sensitivity 77.8%, specificity 62.1%). Serum EPO predicted 12-month mortality with an area under the curve (AUC) of 0.69. Combining clinical model using age, baseline, and discharge kidney function with serum EPO improved prediction with AUC of 0.74. Multivariable analysis demonstrated that high-level of EPO group had significantly higher mortality compared with low-level EPO group (15.2% vs. 3.0%, p = 0.020). Hematocrit was significantly lower in high-level EPO group compared with low-level EPO group at 12 months (33.4 ± 1.1% vs. 36.0 ± 0.9%, p = 0.038). CONCLUSIONS: Plasma EPO appears to be a useful marker for predicting long-term outcome in post-severe AKI survivors.

The combination of RPA-CRISPR/Cas12a and Leptospira IgM RDT enhances the early detection of leptospirosis.

BACKGROUND: Lack of available sensitive point-of-care testing is one of the primary obstacles to the rapid diagnosis of leptospirosis. The purpose of this study was to test the performance of two point-of-care tests, a clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 12a (CRISPR/Cas12a) fluorescence-based diagnostic assay (FBDA), a Leptospira immunoglobulin M (IgM) rapid diagnostic test (RDT), and the two tests combined. METHODOLOGY/PRINCIPAL FINDINGS: For the diagnosis of 171 clinical samples, a recombinase polymerase amplification (RPA)-CRISPR/Cas12a FBDA for whole blood and Leptospira IgM RDT (Medical Science Public Health, Thailand) for serum were used. The confirmed cases were determined by using any positive qPCR, microscopic agglutination test (MAT), and culture results. Diagnostic accuracy was assessed on the first day of enrollment and stratified by the day after symptom onset. The overall sensitivity of the Leptospira IgM RDT and RPA-CRISPR/Cas12a FBDA was 55.66% and 60.38%, respectively. When the two tests were combined, the sensitivity rose to 84.91%. The specificity of each test was 63.08% and 100%, respectively, and 63.08% when combined. The sensitivity of the Leptospira IgM RDT rose on days 4-6 after the onset of fever, while the RPA-CRISPR/Cas12a FBDA continued to decrease. When the two tests were combined, the sensitivity was over 80% at different days post-onset of fever. CONCLUSIONS/SIGNIFICANCE: The combination of Leptospira IgM RDT and RPA-CRISPR/Cas12 FBDA exhibited significant sensitivity for the detection of leptospires at various days after the onset of fever, thereby reducing the likelihood of misdiagnosis. The combination of these assays may be suitable for early leptospirosis screening in situations with limited resources.

Seroprevalence of leptospirosis among blood donors in an endemic area.

Thailand is known to be endemic for leptospirosis. This bacterium may pose a potential risk to transfusion safety. This study was a cross-sectional study examining the seroprevalence of leptospirosis among Thai blood donors. A total of 1053 serum specimens collected from blood donors residing in 5 regions of Thailand during March to September 2020 were included in this study. All samples were tested for the presence of antibodies to 22 leptospiral serovars using the microscopic agglutination test (MAT) and anti-Leptospira IgG antibodies using commercially available enzyme immunoassay. We found no evidence of recent exposure to Leptospira spp. in sera of healthy Thai blood donors by MAT, including those in higher-risk areas. However, in this same group, we did find small numbers of past exposure (1.7%) to Leptospira spp. by IgG ELISA. According to the findings of this study, there is currently no evidence for implementing new blood banking procedures to identify possible carriers in Thailand, however these should be continually monitored and revised according to the infectious disease burden in each country. It should be noted that there was a difference in the occupation rate between the general population reported in Thailand and blood donors in this study; it may not reflect the actual situation in the country.