Endotoxin Adsorbent Therapy in Severe COVID-19 Pneumonia.

INTRODUCTION: Uncontrolled systemic inflammation may occur in severe coronavirus disease 19 (COVID-19). We have previously shown that endotoxemia, presumably from the gut, may complicate COVID-19. However, the role of endotoxin adsorbent (EA) therapy to mitigate organ dysfunction in COVID-19 has not been explored. METHODS: We conducted a retrospective observational study in COVID-19 patients who received EA therapy at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between March 13 and April 17, 2020. Relevant clinical and laboratory data were collected by inpatient chart review. RESULTS: Among 147 hospitalized COVID-19 patients, 6 patients received EA therapy. All of the 6 patients had severe COVID-19 infection with acute respiratory distress syndrome (ARDS). Among these, 5 of them were mechanically ventilated and 4 had complications of secondary bacterial infection. The endotoxin activity assay (EAA) results of pre-EA therapy ranged from 0.47 to 2.79. The choices of EA therapy were at the discretion of attending physicians. One patient was treated with oXiris® along with continuous renal replacement therapy, and the others received polymyxin B hemoperfusion sessions. All patients have survived and were finally free from the mechanical ventilation as well as had improvement in PaO2/FiO2 ratio and decreased EAA level after EA therapy. CONCLUSIONS: We demonstrated the clinical improvement of severe COVID-19 patients with elevated EAA level upon receiving EA therapy. However, the benefit of EA therapy in COVID-19 ARDS is still unclear and needs to be elucidated with randomized controlled study.

Acute kidney injury in renal transplant recipients undergoing cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is a key risk factor for chronic kidney disease in the general population, but has not been investigated in detail among renal transplant recipients (RTRs). We investigated the incidence, severity and risk factors for AKI following cardiac surgery among RTRs compared with non-RTRs with otherwise similar clinical characteristics. METHODS: We conducted a retrospective cohort study of RTRs (n = 83) and non-RTRs (n = 83) who underwent cardiac surgery at two major academic medical centers. Non-RTRs were matched 1:1 to RTRs by age, preoperative (preop) estimated glomerular filtration rate and type of cardiac surgery. We defined AKI according to Kidney Disease: Improving Global Outcomes criteria. RESULTS: RTRs had a higher rate of AKI following cardiac surgery compared with non-RTRs [46% versus 28%; adjusted odds ratio 2.77 (95% confidence interval 1.36-5.64)]. Among RTRs, deceased donor (DD) versus living donor (LD) status, as well as higher versus lower preop calcineurin inhibitor (CNI) trough levels, were associated with higher rates of AKI (57% versus 33% among DD-RTRs versus LD-RTRs; P = 0.047; 73% versus 36% among RTRs with higher versus lower CNI trough levels, P = 0.02). The combination of both risk factors (DD status and higher CNI trough level) had an additive effect (88% AKI incidence among patients with both risk factors versus 25% incidence among RTRs with neither risk factor, P = 0.004). CONCLUSIONS: RTRs have a higher risk of AKI following cardiac surgery compared with non-RTRs with otherwise similar characteristics. Among RTRs, DD-RTRs and those with higher preop CNI trough levels are at the highest risk.

Comprehensive versus standard care in post-severe acute kidney injury survivors, a randomized controlled trial.

BACKGROUND: Currently, there is a lack of evidence to guide optimal care for acute kidney injury (AKI) survivors. Therefore, post-discharge care by a multidisciplinary care team (MDCT) may improve these outcomes. This study aimed to demonstrate the outcomes of implementing comprehensive care by a MDCT in severe AKI survivors. METHODS: This study was a randomized controlled trial conducted between August 2018 to January 2021. Patients who survived severe AKI stage 2-3 were enrolled and randomized to be followed up with either comprehensive or standard care for 12 months. The comprehensive post-AKI care involved an MDCT (nephrologists, nurses, nutritionists, and pharmacists). The primary outcome was the feasibility outcomes; comprising of the rates of loss to follow up, 3-d dietary record, drug reconciliation, and drug alert rates at 12 months. Secondary outcomes included major adverse kidney events, estimated glomerular filtration rate (eGFR), and the amount of albuminuria at 12 months. RESULTS: Ninety-eight AKI stage 3 survivors were enrolled and randomized into comprehensive care and standard care groups (49 patients in each group). Compared to the standard care group, the comprehensive care group had significantly better feasibility outcomes; 3-d dietary record, drug reconciliation, and drug alerts (p < 0.001). The mean eGFR at 12 months were comparable between the two groups (66.74 vs. 61.12 mL/min/1.73 m2, p = 0.54). The urine albumin: creatinine ratio (UACR) was significantly lower in the comprehensive care group (36.83 vs. 177.70 mg/g, p = 0.036), while the blood pressure control was also better in the comprehensive care group (87.9% vs. 57.5%, p = 0.006). There were no differences in the other renal outcomes between the two groups. CONCLUSIONS: Comprehensive care by an MDCT is feasible and could be implemented for severe AKI survivors. MDCT involvement also yields better reduction of the UACR and better blood pressure control. Trial registration Clinicaltrial.gov: NCT04012008 (First registered July 9, 2019).

Epidemiology and short-term outcomes of acute kidney injury among patients in the intensive care unit in Laos: a nationwide multicenter, prospective, and observational study.

BACKGROUND: Acute kidney injury (AKI) has become a global health issue. Little is known about the disease burden in Laos. We aimed to evaluate the burden and outcomes of AKI as well as assess the availability of AKI treatment in Laos. METHODS: We performed a multicentric prospective observational study in adult patients who had been admitted to 5 intensive care units (ICU) in Laos. The data was serially collected on the first 28 days of ICU admission. Patients were diagnosed by the KDIGO 2012 criteria for AKI. We used AKI occurrence as the primary outcome and explored risk factors on the development and outcomes of AKI. RESULTS: We enrolled 1480 patients from 5 ICU centers across Laos from January to December 2016. After excluding patients with end-stage renal disease and those with incomplete data, AKI occurred in 508 of the 1460 enrolled patients (34.8%). Overall, the rates of maximum AKI staging were 4% for stage 1, 10.3% for stage 2, and 20.5% for stage 3. Risk factors for AKI were older age, obesity, cardiovascular diseases, respiratory diseases, renal diseases, oncologic diseases, and chronic kidney diseases. Only 1.8% of all participants received RRT. The mortality rate was 28.4% in non-AKI patients compared to 44.5% in AKI patients, which increased according to the stage of AKI (stage 1, 4.9%; stage 2, 28.3%; stage 3 66.8%; P < 0.001). There were 13.6% who were discharged against medical advice. CONCLUSIONS: AKI is a huge burden in Laos with under-recognition and poor outcomes.

The epidemiology and characteristics of acute kidney injury in the Southeast Asia intensive care unit: a prospective multicentre study.

BACKGROUND: Etiologies for acute kidney injury (AKI) vary by geographic region and socioeconomic status. While considerable information is now available on AKI in the Americas, Europe and China, large comprehensive epidemiologic studies of AKI from Southeast Asia (SEA) are still lacking. The aim of this study was to investigate the rates and characteristics of AKI among intensive care unit (ICU) patients in Thailand. METHODS: We conducted the largest prospective observational study of AKI in SEA. The data were serially collected on the first 28 days of ICU admission by registration in electronic web-based format. AKI status was defined by full Kidney Disease: Improving Global Outcome criteria. We used AKI occurrence as the clinical outcome and explored the impact of modifiable and non-modifiable risk factors on the development and progression of AKI. RESULTS: We enrolled 5476 patients from 17 ICU centres across Thailand from February 2013 to July 2015. After excluding patients with end-stage renal disease and those with incomplete data, AKI occurred in 2471 of 4668 patients (52.9%). Overall, the maximum AKI stage was Stage 1 in 7.5%, Stage 2 in 16.5% and Stage 3 in 28.9%. In the multivariable adjusted model, we found that older age, female sex, admission to a regional hospital, medical ICU, high body mass index, primary diagnosis of cardiovascular-related disease and infectious disease, higher Acute Physiology and Chronic Health Evaluation II, non-renal Sequential Organ Failure Assessment scores, underlying anemia and use of vasopressors were all independent risk factors for AKI development. CONCLUSIONS: In Thai ICUs, AKI is very common. Identification of risk factors of AKI development will help in the development of a prognostic scoring model for this population and should help in decision making for timely intervention, ultimately leading to better clinical outcomes.

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).

The epidemiology and long-term outcomes of acute kidney disease in a resource-limited setting.

BACKGROUND: The concept of acute kidney disease (AKD) implies kidney damage that results in a significant decrease in glomerular filtration rate, including acute kidney injury (AKI), but that is not persistent enough to meet the criteria of chronic kidney disease (CKD). While a few studies have shown associations between AKD and the risk of adverse outcomes, there is still a lack of evidence from resource-limited settings. METHODS: All hospitalized patients at the study hospital during 2017 were retrospectively reviewed. Diagnosis of AKI, AKD, and CKD was based on the diagnostic algorithm proposed by KDIGO. Patients were followed up for 2 years to determine their risks of mortality, development of CKD, and progression of pre-existing CKD. RESULTS: A total of 9800 patients were included in the analysis, 26.1% of whom had pre-existing CKD, while AKD without AKI was found in 8% and 7% of individuals with and without pre-existing CKD, respectively. Patients with AKD without AKI were associated with higher in-hospital mortality than those without pre-existing CKD [adjusted hazard ratio (aHR) of 2.50; 95% CI 1.43, 4.37] and with pre-existing CKD (aHR 1.79; 95% CI 1.16, 2.76). The incidence of new CKD was higher in the group of AKD without AKI than in the AKI group (34.8 vs. 14.7%). CONCLUSION: In a resource-limited setting, AKD is associated with short- and long-term mortality and CKD progression, especially in individuals with pre-existing CKD.

In-hospital mortality of critically Ill patients with interactions of acute kidney injury and acute respiratory failure in the resource-limited settings: Results from SEA-AKI study.

PURPOSE: Our goal was to describe clinical outcomes and explore the physiological interactions between acute kidney injury (AKI) and acute respiratory failure (ARF) in critically ill patients. MATERIALS AND METHODS: Data were retrieved from the SEA-AKI study, a multinational multicenter database of adult ICUs from Thailand, Laos, and Indonesia. AKI was defined using KDIGO criteria stage 2-3. ARF was defined by being mechanically ventilated. Patients were assigned into 6 patterns based on AKI and ARF sequence: "no AKI/ARF", "ARF alone", "AKI alone", "ARF first", "AKI first", and "Concurrent AKI-ARF". The primary outcome was in-hospital mortality of each pattern. RESULTS: A final cohort of 5468 patients were eligible for the analysis. The "Concurrent AKI-ARF" had the highest in-hospital mortality of 69.6%. The "AKI first" and the "ARF first" had in-hospital mortality of 54.4% and 53%, respectively. Among patients with single organ failure, in-hospital mortality was 14.6% and 31.5% in the "AKI alone" and the "ARF alone", accordingly. In-hospital mortality was 12.4% in patients without AKI and ARF. CONCLUSION: Critically ill patients with ARF and AKI are at higher risk of in-hospital death. Different patterns of AKI and ARF interaction result in unique clinical outcomes as well as risk factors.

Circulating and urinary microRNAs profile for predicting renal recovery from severe acute kidney injury.

BACKGROUND: There is little known about the contribution of microRNAs (miRNAs) in the recovery from acute kidney injury (AKI). This study aimed to discover and validate miRNA profiles for predicting renal recovery from severe AKI. PATIENTS AND METHODS: A prospective observational study was conducted between June 2020 and January 2021. Urine and serum samples of participants with AKI stage 3 were collected from two groups: renal recovery and renal non-recovery. Transcriptomic analysis was performed using nCounter miRNA Expression Assay. Expression levels of candidate miRNAs were validated using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The discovery phase identified 18 and 11 differentially expressed miRNAs that were statistically significant between the two groups in urine and serum specimens, respectively. Top candidate miRNAs selected included miR-556-3p, miR-1915-3p, miR-4284, miR-32-5p, miR-96-5p, and miR-556-5p in urine, and miR-499b-5p, miR-30a-3p, miR-92b-3p and miR-770-5p in serum. This study enrolled 110 participants in the validation phase. The qRT-PCR analysis indicated that urine miR-556-3p was significantly higher in the renal recovery group than in the renal non-recovery group. Urine miR-556-3p alone predicted renal recovery with an area under the curve (AUC) of 0.64 (95%CI 0.52-0.75, p = 0.03). Combining the clinical model with urine miR-556-3p predicted renal recovery with an AUC of 0.83 (95%CI 0.75-0.92, p < 0.01). CONCLUSION: This data provides evidence that microtranscriptome profiles of severe AKI patients with renal recovery differed from the non-recovery group. Urine miR-556-3p had the potential to improve the prediction of renal recovery from severe AKI.

Biomarkers in Acute Kidney Injury.

Biomarkers have become a pillar of precision medicine in acute kidney injury (AKI). Traditional markers for diagnosis of AKI are insensitive and insufficient to provide comprehensive information for prognostication. Several emerging biomarkers have shown promising results in large-scale clinical studies. These novel markers likely will be beneficial for personalized AKI prevention and treatment.

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.

The role of leptospiremia and specific immune response in severe leptospirosis.

Leptospirosis can cause a high mortality rate, especially in severe cases. This multicenter cross-sectional study aimed to examine both host and pathogen factors that might contribute to the disease severity. A total of 217 leptospirosis patients were recruited and divided into two groups of non-severe and severe. Severe leptospirosis was defined by a modified sequential organ failure assessment (mSOFA) score of more than two or needed for mechanical ventilation support or had pulmonary hemorrhage or death. We found that leptospiremia, plasma neutrophil gelatinase-associated lipocalin (pNGAL), and interleukin 6 (IL-6) at the first day of enrollment (day 1) and microscopic agglutination test (MAT) titer at 7 days after enrollment (days 7) were significantly higher in the severe group than in the non-severe group. After adjustment for age, gender, and the days of fever, there were statistically significant associations of baseline leptospiremia level (OR 1.70, 95% CI 1.23-2.34, p = 0.001), pNGAL (OR 9.46, 95% CI 4.20-21.33, p < 0.001), and IL-6 (OR 2.82, 95% CI 1.96-4.07, p < 0.001) with the severity. In conclusion, a high leptospiremia, pNGAL, and IL-6 level at baseline were associated with severe leptospirosis.

The role of serum cystatin C in estimation of renal function in survivors of critical illness.

PURPOSE: Estimating renal function by serum creatinine after critical illness is a challenging problem. However, the role of cystatin C for estimation of the renal function in survivors of critical illness is unknown. We aimed to compare the performance of serum cystatin C- and serum creatinine-based eGFR against a reference GFR using 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) in survivors of critical illness. MATERIAL AND METHODS: Survivors of critical illness with stable hemodynamics and renal functions were recruited. Their serum creatinine and cystatin C levels were measured. eGFR were calculated by using various equations: 1)CKD-EPI SCysC; 2) Thai eGFR SCysC; 3)CKD-EPI SCr; 4)Thai eGFR SCr; 5)MDRD Caucasian SCr; 6)CKD-EPI SCr-SCysC. The 99mTc-DTPA plasma clearance was used as a standard eGFR. RESULTS: Forty-two patients were included. The bias (median percentage difference) between standard GFR and SCysC-based eGFR were 41.97% (95%CI 33.1% to 48.5%) for CKD-EPI SCysC and 31.72% (95%CI 21.1% to 34.9%) for Thai eGFR SCysC. While, the bias between standard GFR and SCr-based eGFR were -11.37 (95%CI -20.9 to 1.6) for CKD-EPI SCr, -18.30 (95%CI -26.3 to -10.6) for Thai eGFR SCr, and -27.17 (-43.7 to -19.1) for MDRD Caucasian SCr. CONCLUSION: In survivors of critical illness, we demonstrated limitations of estimating GFR by both currently available SCysC and SCr-based equations. Therefore, further studies are still needed to develop better eGFR equations.

Diagnostic Challenges of Acute Kidney Injury in Asia.

Early diagnosis of acute kidney injury (AKI) is an important step to improve AKI outcome. In Asia, several distinct conditions of this region such as environment (tropical climate), socioeconomic status (high-resource and low-resource settings), process of care (shortage of nephrologists), exposure factors (specific tropical infections such as leptospirosis, malaria, dengue), and inherent factor (aging) make the diagnosis of AKI in Asia more challenging than in other parts of the world. To improve the diagnosis of AKI, novel tools such as clinical risk scores, AKI alert systems, and telemedicine should be implemented into current clinical practice.

The role of neutrophil chemotaxis activity as an immunologic biomarker to predict mortality in critically-ill patients with severe sepsis.

BACKGROUND: Innate immunity is an important host response to infection. However, the role of innate immunity as a prognostic biomarker in severe sepsis is still unknown. This study is to evaluate the discriminatory characteristics of these biomarkers on clinical outcome. MATERIALS AND METHODS: Retrospective study was conducted in critically ill patients with severe sepsis. Neutrophil function was assessed by neutrophil chemotaxis activity and CD-11b expression. Monocyte function was assessed by measurement of mHLA-DR expression and presepsin level. The primary end point was 28 day-mortality. RESULTS: A total of 136 participants were enrolled. Patients were classified into 2 groups as survivors (n = 63, 46.3%) and non-survivors (n = 73, 53.7%). Neutrophil chemotaxis activity was significantly higher in survivors (46.7% vs. 41.2%, p = .023). There was no difference in the remaining biomarker levels between survivors and non-survivors. Only decreased neutrophil chemotaxis activity was associated with 28-day mortality. Combining neutrophil chemotaxis activity with mHLA-DR, CD-11b expression, presepsin, and SOFA score provided the highest AUC of 0.90 (0.84-0.96) in predicting 28-day mortality. CONCLUSION: Neutrophil chemotaxis activity appears to be a promising novel immunologic biomarker in predicting clinical outcome in patients with severe sepsis.

Endotoxemia and circulating bacteriome in severe COVID-19 patients.

BACKGROUND: When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium is injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19. METHODS: We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on days 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1 → 3)-ß-D-glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome. RESULTS: Of the 19 patients, 13 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime. CONCLUSIONS: Bacterial DNA and toxins were discovered in virtually all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease.

Current practice of diagnosis and management of acute kidney injury in intensive care unit in resource limited settings.

PURPOSE: In a resource limited settings, there is sparse information about the management of acute kidney injury (AKI) based on systemic data collection. This survey aimed to described the current management of AKI in intensive care units (ICUs) across Thailand. MATERIALS AND METHODS: Questionnaires were distributed to 160 physicians involved in the intensive care between January and December 2014 across Thailand. Distribution was done through an online survey platform or telephone interview. RESULTS: The response rate was 80.6% (129 physicians). AKI diagnosis was mostly made by using KDIGO criteria (36.7%). A common diagnostic investigation of AKI was urinalysis (86%). Nephrologists had a major role (86.4%) in deciding the initiation and selection of renal replacement therapy (RRT) modality. Intermittent hemodialysis is the preferable mode of RRT (72.0%), followed by continuous renal replacement therapy (CRRT, 12%), sustained low efficiency dialysis (10.0%) and peritoneal dialysis (6.0%). Catheter insertion was predominantly performed by nephrologist (51.1%) with ultrasound guidance. The right internal jugular vein was the most common site of insertion (70.4%). The most common indication for CRRT was hemodynamic instability. CONCLUSIONS: Amid increasing concern of AKI in the ICU, our study provides the insight into the management of AKI in resource limited settings.