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 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.

Recovery after AKI: Effects on outcomes over 15 years.

PURPOSE: To examine the effect of kidney recovery on mortality, dialysis and kidney transplantation up to 15 years after AKI. MATERIALS AND METHODS: We studied 29,726 survivors of critical illness and compared these outcomes stratified by AKI and recovery status at hospital discharge. Kidney recovery was defined as a return of serum creatinine to ≤150% of baseline without dialysis prior to hospital discharge. RESULTS: Overall AKI occurred in 59.2% in which two thirds developed stage 2-3 AKI. Recovery rate of AKI at hospital discharge was 80.8%. Patients who did not recover experienced the worst 15-year mortality compared to those who recovered and those without AKI (57.8% vs 45.2% vs 30.3%, p < 0.001). This pattern was also found in subgroups of patients with suspected sepsis-associated (57.1% vs 47.9% vs 36.5%, p < 0.001) and cardiac surgery-associated AKI (60.1% vs 41.8% vs 25.9%, p < 0.001). The rates of dialysis and transplantation at 15 years were low and not associated with recovery status. CONCLUSIONS: Recovery of AKI in critically ill patients at hospital discharge had an effect on long-term mortality for up to 15 years. These results have implications for acute care, follow-up and choice of endpoints for clinical trials.

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.

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.

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.

Citrate pharmacokinetics in critically ill liver failure patients receiving CRRT.

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.

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.

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).

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.

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.

Limiting Acute Kidney Injury Progression In Sepsis: Study Protocol and Trial Simulation.

OBJECTIVES: To describe study design considerations and to simulate a trial of biomarker-guided sepsis management aimed to reduce acute kidney injury (acute kidney injury). Tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7, urinary biomarkers of cell-cycle arrest, and indicators of kidney stress can detect acute kidney injury before clinical manifestations. We sought to determine the event rates for acute kidney injury as a function of serial measurements of urinary (tissue inhibitor of metalloproteinases-2)•(insulin-like growth factor-binding protein 7) in patients at risk of sepsis-associated acute kidney injury, so that an escalating series of kidney-sparing sepsis bundles based on international guidelines could be applied. DESIGN: We described the study protocol of "Limiting acute kidney injury Progression In Sepsis," a phase 4, multicenter, adaptive, randomized controlled trial. We performed simulations to estimate the rates for the trial's primary endpoint using patient-level data from two previous studies (Sapphire and Protocolized Care for Early Septic Shock). SETTING: Academic and community ICUs. PATIENTS: Critically ill patients with sepsis or septic shock, without evidence of stage 2/3 acute kidney injury at enrollment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our primary endpoint is progression of two or more stages of acute kidney injury, death, or dialysis within 72 hours after enrollment. In the Sapphire simulation, 45 of 203 patients (22%) with sepsis met the endpoint. In Protocolized Care for Early Septic Shock, 144 of 607 patients (24%) with septic shock met the endpoint. In both simulations, (tissue inhibitor of metalloproteinases-2)•(insulin-like growth factor-binding protein 7) patterns, suggested by Limiting acute kidney injury Progression In Sepsis protocol, stratified the risk for the endpoint from 6% (three negative tests) to 41% (for patients eligible for the highest level of kidney-sparing sepsis bundle) in Sapphire, and 14% (two negative tests) to 46% (for the highest level of kidney-sparing sepsis bundle) in Protocolized Care for Early Septic Shock. CONCLUSIONS: Findings of our Limiting acute kidney injury Progression In Sepsis trial simulation confirmed that (tissue inhibitor of metalloproteinases-2)•(insulin-like growth factor-binding protein 7) could identify patients with different rates of progression to moderate/severe acute kidney injury, death, or dialysis in 72 hours. The Limiting acute kidney injury Progression In Sepsis protocol algorithm is therefore feasible in terms of identifying suitably high-risk individuals for kidney-sparing sepsis bundle.

A prospective study to evaluate the accuracy of rapid diagnostic tests for diagnosis of human leptospirosis: Result from THAI-LEPTO AKI study.

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

Development and validation of point-of-care testing of albuminuria for early screening of chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) is a significant global health issue. As the prevalence of renal replacement therapy (RRT) in Thailand is increasing, early detection and management of CKD is the most important step to prevent CKD progression and the need for RRT. Current diagnostic tests for CKD are non-specific and expensive. We aimed to develop and validate antibody-based-albumin point-of-care testing (POCT) to detect patients with impaired kidney function at early stage. METHODS: The prototype strip test was developed under the concept of competitive lateral flow immunochromatography assay, or strip test. Monoclonal antibodies (MAbs) to human serum albumin (HSA) were harvested from the hybridomas of spleen cells from immunized mice and mouse myeloma cells. Presence of MAbs was detected by enzyme-linked immunosorbent assay (ELISA). Spot urine was obtained from patients with kidney disease, type I, or type II Diabetes Mellitus upon their visit at King Chulalongkorn Memorial Hospital during 2018-2019. All samples were analyzed for urine albumin with our POCT (CU microalbumin) and the other two commercial POCTs (Microalbu PHAN and MICRAL). The results were validated against standard method for urine microalbumin measurement. A urine microalbumin concentration of less than 20 ug/ml was defined as normal. The sensitivity, specificity, and predictive values were calculated in comparison with the standard laboratory method. RESULT: A total of 100 adult patients were included. CU microalbumin had a sensitivity of 86%, a specificity of 94%, and a positive predictive value of 96%. Our POCT showed good correlation with the laboratory results. CONCLUSION: CU microalbumin correlated well with the standard method for quantitative measurement of urine albumin. Therefore, it has the potential for early screening of CKD, especially in primary health care facilities in resource limited settings.

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.

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.

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 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.

Sepsis-Associated Acute Kidney Disease.

INTRODUCTION: About one-third of critically ill patients with acute kidney injury (AKI) develop persistently decreased kidney function, known as acute kidney disease (AKD), which may progress to chronic kidney disease (CKD). Although sepsis is the most common cause of AKI, little is known about sepsis-associated AKD. METHODS: Using data from a large randomized trial including 1341 patients with septic shock, we studied patients with stage 2 or 3 AKI on day 1 of hospitalization. We defined AKD as a persistently reduced glomerular filtration rate for >7 days. In addition to clinical data, we measured several urinary biomarkers (tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 [TIMP-2∗IGFBP7], neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1], liver-type fatty acid binding protein, and type 4 collagen) at 0, 6, and 24 hours, to predict AKD. RESULTS: Of 598 patients, 119 (19.9%) died within 7 days, 318 (53.2%) had early reversal of AKI within the first 7 days, whereas 161 (26.9%) developed AKD. In patients with early reversal, 45 (14.2%) had relapsed AKI after early reversal, and only about one-third of these recovered. Among patients developing AKD, only 15 (9.3%) recovered renal function prior to discharge. Male sex, African American race, and underlying CKD were more predominant in patients developing AKD. None of the biomarkers tested performed well for prediction of AKD, although NGAL modestly increased the performance of a clinical model. CONCLUSIONS: AKD is common in patients with septic shock, especially among African American males and those with underlying CKD. Existing AKI biomarkers have limited utility for predicting AKD but might be useful together with clinical variables. Novel predictive biomarkers for renal recovery are needed.