Sepsis-associated acute kidney injury (S-AKI) is a frequent complication of the critically ill patient and is associated with unacceptable morbidity and mortality. Prevention of S-AKI is difficult ...because by the time patients seek medical attention, most have already developed acute kidney injury. Thus, early recognition is crucial to provide supportive treatment and limit further insults. Current diagnostic criteria for acute kidney injury has limited early detection; however, novel biomarkers of kidney stress and damage have been recently validated for risk prediction and early diagnosis of acute kidney injury in the setting of sepsis. Recent evidence shows that microvascular dysfunction, inflammation, and metabolic reprogramming are 3 fundamental mechanisms that may play a role in the development of S-AKI. However, more mechanistic studies are needed to better understand the convoluted pathophysiology of S-AKI and to translate these findings into potential treatment strategies and add to the promising pharmacologic approaches being developed and tested in clinical trials.
Citrate has been proposed as anticoagulation of choice in continuous renal replacement therapy (CRRT). However, little is known about the pharmacokinetics (PK) and metabolism of citrate in liver ...failure patients who require CRRT with regional citrate anticoagulation (RCA). This prospective clinical PK study was conducted at King Chulalongkorn Memorial Hospital between July 2019 to April 2021, evaluating seven acute liver failure (ALF) and seven acute-on-chronic liver failure (ACLF) patients who received CRRT support utilizing RCA as an anticoagulant at a citrate dose of 3 mmol/L. For evaluation of the citrate PK, we delivered citrate for 120 min and then stopped for a further 120 min. Total body clearance of citrate was 152.5 ± 50.9 and 195.6 ± 174.3 mL/min in ALF and ACLF, respectively. The ionized calcium, ionized magnesium, and pH slightly decreased after starting citrate infusion and gradually increased to baseline after stopping citrate infusion. Two of the ACLF patients displayed citrate toxicity during citrate infusion, while, no ALF patient had citrate toxicity. In summary, citrate clearance was significantly decreased in critically ill ALF and ACLF patients receiving CRRT. Citrate use as an anticoagulation in these patients is of concern for the risk of citrate toxicity.
The timing of initiation of renal replacement therapy (RRT) in severe acute kidney injury (AKI) remains controversial, with early initiation resulting in unnecessary therapy for some patients while ...expectant therapy may delay RRT for other patients. The furosemide stress test (FST) has been shown to predict the need for RRT and therefore could be used to exclude low-risk patients from enrollment in trials of RRT timing. We conducted this multicenter pilot study to determine whether FST could be used to screen patients at high risk for RRT and to determine the feasibility of incorporating FST into a trial of early initiation of RRT.
FST was performed using intravenous furosemide (1 mg/kg in furosemide-naive patients or 1.5 mg/kg in previous furosemide users). FST-nonresponsive patients (urine output less than 200 mL in 2 h) were then randomized to early (initiation within 6 h) or standard (initiation by urgent indication) RRT.
FST was completed in all patients (100%). Only 6/44 (13.6%) FST-responsive patients ultimately received RRT while 47/60 (78.3%) nonresponders randomized to standard RRT either received RRT or died (P < 0.001). Among 118 FST-nonresponsive patients, 98.3% in the early RRT arm and 75% in the standard RRT arm received RRT. The adherence to the protocol was 94.8% and 100% in the early and standard RRT group, respectively. We observed no differences in 28-day mortality (62.1 versus 58.3%, P = 0.68), 7-day fluid balance, or RRT dependence at day 28. However, hypophosphatemia occurred more frequently in the early RRT arm (P = 0.002).
The furosemide stress test appears to be feasible and effective in identifying patients for randomization to different RRT initiation times. Our findings should guide implementation of large-scale randomized controlled trials for the timing of RRT initiation.
clinicaltrials.gov, NCT02730117 . Registered 6 April 2016.
Abstract
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.
We aimed to determine whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) can accurately predict persistent AKI, major adverse kidney events at 30 days (MAKE30) and 365 days (MAKE365) ...in hospitalized AKI patients. This is a retrospective study of adult patients who were admitted at King Chulalongkorn Memorial Hospital. We performed multivariable logistic regression for persistent AKI, MAKE30, and MAKE365. We developed equations for predicting MAKE30 and MAKE365 and divided the dataset into derivation and validation cohorts. uNGAL performance and predictive models were assessed using the area under the receiver operating characteristic curve (AROC). Among 1,322 patients with AKI, 76.9%, 45.1%, and 61.7% had persistent AKI, MAKE30, and MAKE365. The AROC were 0.75 (95% confidence intervalCI 0.70-0.80), 0.66 (95%CI 0.61-0.71), and 0.64 (95%CI 0.59-0.70) for prediction of persistent AKI, MAKE30, and MAKE365 by uNGAL. The AROC in the validation dataset combining uNGAL with clinical covariates were 0.74 (95%CI 0.69-0.79) and 0.72 (95%CI 0.67-0.77) for MAKE30 and MAKE365. We demonstrated an association between uNGAL and persistent AKI, MAKE30, and MAKE365. Prediction models combining uNGAL can modestly predict MAKE30 and MAKE365. Therefore, uNGAL is a useful tool for improving AKI risk stratification.
Recent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for ...highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells.
We conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level ≥ 0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28.
Fifty-nine patients were randomized to PMX-HP (n = 29) and non-PMX-HP (n = 30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P = 0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P = 0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups.
PMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression.
ClinicalTrials.gov, NCT02413541 . Registered on 3 March 2015.
Abstract
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 m
2
,
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).
Rapid diagnostic tests (RDTs) have become widely used in low-resource settings for leptospirosis diagnostic. This study aims to evaluate the diagnostic performance of the five commercially available ...RDTs to detect human IgM against Leptospira spp. in Thai population.
Ninety-nine serum samples from Leptospirosis suspicious patients were tested with five RDTs, including Medical Science Public Health, Leptocheck-WB, SD bioline, TRUSTline, and J.Mitra. The case definition was based on MAT, qPCR, and culture results. Diagnostic accuracy was determined based on the first day of enrollment in an overall analysis and stratified according to days post-onset of fever. The five RDTs had overall sensitivity ranging from 1.8% to 75% and specificity ranging from 52.3% to 97.7%. Leptocheck-WB had high sensitivity of 75.0%. The sensitivity of five RDTs increased on days 4-6 post-onset of fever, while the specificity of all tests remained relatively stable at different days post-onset of fever.
The tested RDTs showed low sensitivity. Therefore, based on the present study, five commercially available RDTs might not be an appropriate test for acute leptospirosis screening in the Thai population.
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.
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.
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.
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.
Leptospirosis is one of the most important zoonosis in the tropics. Currently, specific laboratory diagnostic test for leptospirosis such as polymerase chain reaction (PCR) or direct culture cannot ...be applied at the primary care setting especially in the resource- limited countries. Therefore, clinical presentation and laboratory examination are still the primary diagnostic tools for leptospirosis.
To detect clinical factors for predicting leptospirosis in suspected cases, and to create a clinical prediction score (THAI-LEPTO) that is practical and easy to use in general practice while awaiting laboratory results.
We performed a prospective multicenter study with a development and a validation cohort of patients presenting with clinical suspicion of leptospirosis as per the WHO clinical criteria. The development cohort was conducted at 11 centers in 8 provinces around Thailand. The validation cohort was conducted at 4 centers in 1 province from the Northeastern part of Thailand. Leptospirosis confirmed cases were defined if any one of the tests were positive: microscopic agglutination test, direct culture, or PCR technique. Multivariable logistic regression was used to identify predictors of leptospirosis. The clinical prediction score was derived from the regression coefficients (original) or from the odds ratio values (simplified). We used receiver operating characteristic (ROC) curve analysis to evaluate the diagnostic ability of our score and to find the optimal cutoff values of the score. We used a validation cohort to evaluate the accuracy of our methods.
In the development cohort, we enrolled 221 leptospirosis suspected cases and analyzed 211. Among those, 105 (50%) were leptospirosis confirmed cases. In logistic regression adjusted for age, gender, day of fever, and one clinical factor at a time, leptospirosis group had more hypotension OR = 2.76 (95% CI 1.07-7.10), jaundice OR = 3.40 (95%CI 1.48-8.44), muscle pain OR = 2.12 (95%CI 1.06-4.26), acute kidney injury (AKI) OR = 2.90 (95%CI 1.31-6.15), low hemoglobin OR = 3.48 (95%CI 1.72-7.04), and hypokalemia with hyponatremia OR = 3.56 (95%CI 1.17-10.84) than non-leptospirosis group. The abovementioned factors along with neutrophilia and pulmonary opacity were used in the development of the score. The simplified score with 7 variables was the summation of the odds ratio values as follows: hypotension 3, jaundice 2, muscle pain 2, AKI 1.5, low hemoglobin 3, hypokalemia with hyponatremia 3, and neutrophilia 1. The score showed the highest discriminatory power with area under the curve (AUC) 0.82 (95%CI 0.67-0.97) on fever day 3-4. In the validation cohort we enrolled 96 leptospirosis suspected cases and analyzed 92. Of those, 69 (75%) were leptospirosis confirmed cases. The performance of the simplified score with 7 variables at a cutoff of 4 was AUC 0.78 (95%CI 0.68-0.89); sensitivity 73.5; specificity 73.7; positive predictive value 87.8; negative predictive value 58.3.
THAI-LEPTO score is a newly developed diagnostic tool for early presumptive diagnosis of leptospirosis in patients presenting with severe clinical suspicion of the disease. The score can easily be applied at the point of care while awaiting confirmatory laboratory results. Each predictor used has been supported by evidence of clinical and pathophysiological correlation.
PDF
