Successful Application of a Hemoperfusion Machine in Separated System CRRT: Evaluating Effectiveness and Safety in Critically Ill Patients With AKI in Resource-Limited Settings.

BACKGROUND: It is imperative to note that integrated system continuous renal replacement therapy (CRRT) necessitates a sophisticated and costly apparatus, potentially limiting its availability within resource-limited settings. The introduction of a separated system for continuous veno-venous hemofiltration (CVVH), characterized by uncomplicated setup procedures with a hemoperfusion machine, holds promise as a feasible alternative to CRRT for critically ill patients with acute kidney injury (AKI). METHODS: We aimed to retrospectively analyze the effectiveness and safety of separated CRRT applied from a hemoperfusion machine in critically ill patients with AKI during the January 2015 to December 2021 period. We also examine the in-hospital mortality rate and multivariate logistic regression analysis to uncover the factors that affect mortality. RESULTS: We included a total of 129 critically ill patients who received separated system CRRT. The SOFA score at CRRT initiation was 12.6 ± 3.8. The fluid accumulation at the day of CRRT initiation was 3900 mL (622-8172 mL) All patients received pre- and postdilution CVVH. The mean prescribed CRRT dose was 22.4 ± 3.1 mL/kg/h. We found no serious complications including circuit explosion and air embolism. The in-hospital mortality rate was 68.9%. High SOFA score and positive fluid accumulation at CRRT initiation serve as predictors of survival. CONCLUSIONS: Separated system CRRT using a hemoperfusion machine provides a simplified system to operate and is proven to be effective and safe in real-life practice, especially in resource-limited areas.

Carboxyhemoglobin in Cardiac Surgery Patients and Its Association with Risk Factors and Biomarkers of Hemolysis.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with hemolysis. Yet, there is no easily available and frequently measured marker to monitor this hemolysis. However, carboxyhemoglobin (CO-Hb), formed by the binding of carbon monoxide (a product of heme breakdown) to hemoglobin, may reflect such hemolysis. We hypothesized that CO-Hb might increase after cardiac surgery and show associations with operative risk factors and indirect markers for hemolysis. METHODS: We conducted a retrospective descriptive cohort study of data from on-pump cardiac surgery patients. We analyzed temporal changes in CO-Hb levels and applied a generalized linear model to assess patient characteristics associated with peak CO-Hb levels. Additionally, we examined their relationship with red blood cell (RBC) transfusion and bilirubin levels. RESULTS: We studied 38,487 CO-Hb measurements in 1735 patients. CO-Hb levels increased significantly after cardiac surgery, reaching a peak CO-Hb level 2.1 times higher than baseline (P < .001) at a median of 17 hours after the initiation of surgery. Several factors were independently associated with higher peak CO-Hb, including age (P < .001), preoperative respiratory disease (P = .001), New York Heart Association Class IV (P = .019), the number of packed RBC transfused (P < .001), and the duration of CPB (P = .002). Peak CO-Hb levels also significantly correlated with postoperative total bilirubin levels (Rho = 0.27, P < .001). CONCLUSIONS: CO-Hb may represent a readily obtainable and frequently measured biomarker that has a moderate association with known biomarkers of and risk factors for hemolysis in on-pump cardiac surgery patients. These findings have potential clinical implications and warrant further investigation.

Relative Blood Volume Monitoring during Continuous Renal Replacement Therapy: A Prospective Observational Study.

INTRODUCTION: Hematocrit monitoring during continuous renal replacement therapy (CRRT) allows the continuous estimation of relative blood volume (RBV). This may enable early detection of intravascular volume depletion prior to clinical sequelae. We aimed to investigate the feasibility of extended RBV monitoring and its epidemiology during usual CRRT management by clinicians unaware of RBV. Moreover, we studied the association between changes in RBV and net ultrafiltration (NUF) rates. METHODS: In a cohort of adult intensive care unit patients receiving CRRT, we continuously monitored hematocrit and RBV using a pre-filter noninvasive optical sensor. We analyzed temporal changes in RBV and investigated the association between RBV change and NUF rates, using the classification of NUF rates into low, moderate, or high based on predefined cut-offs. RESULTS: We obtained >60,000 minute-by-minute measurements in >1,000 CRRT hours in 36 patients. The median RBV change was negative (decrease) in 69% of patients and the median peak change in RBV was -9.3% (interquartile range: -3.9% to -14.3%). Moreover, the median RBV decreased from baseline by >5% in 40.2% of measurements and by >10% in 20.6% of measurements. Finally, RBV decreased significantly more when patients received a high NUF rate (>1.75 mL/kg/h) compared to low or moderate NUF rates (5.32% vs. 1.93% or 1.97%, p < 0.001). CONCLUSION: Continuous hematocrit and RBV monitoring during CRRT was feasible. RBV decreased significantly during CRRT, and decreases were greater with higher NUF rates. RBV monitoring may help optimize NUF management and prevent the occurrence of intravascular volume depletion.

A Pilot and Feasibility Study of Continuous Cardiac Output and Blood Pressure Monitoring during Intermittent Hemodialysis.

INTRODUCTION: Hypotension is common during intermittent hemodialysis (IHD) and may be due to a decreased cardiac index (CI). However, no study has simultaneously and continuously measured CI and mean arterial pressure (MAP) to understand the prevalence, severity, and duration of CI decreases or relate them to MAP, blood volume (BV) and net ultrafiltration (NUF) rate. METHODS: In a prospective, pilot and feasibility investigation, we studied 10 chronic IHD patients. We used the ClearSight System™ to continuously monitor CI and MAP; the CRIT-LINE®IV monitor to detect BV changes and collected data on NUF rate. RESULTS: Device tolerance and compliance was 100%. All patients experienced at least ≥ 1 episode of severe CI decrease (> 25% from baseline), with a median duration of 24 minutes [IQR 6-87] and of 68 minutes [14-106] for moderate decreases (>15% but  25% from baseline). Eight patients experienced a low CI state (<2.2 L/min/m2). The lowest CI was 0.9 L/min/m2 with a concomitant MAP of 94 mmHg. When the fall in CI was severe, MAP increased in 58% of cases and remained stable in 28%. Overall, CI decreased by -0.55 L/min/m2 when BV decrease was moderate vs mild (p<0.001) and by -0.8 L/min/m2 when NUF rate was high vs low (p<0.001). CONCLUSION: Continuous CI monitoring is feasible in IHD and shows frequent moderate-severe CI decreases, sometimes to low CI state levels. Such decreases are typically associated with markers of decreased intravascular volume status but not with a decrease in MAP, implying marked vasoconstriction.

Carboxyhemoglobin as Potential Biomarker for Cardiac Surgery Associated Acute Kidney Injury.

OBJECTIVES: Carboxyhemoglobin (CO-Hb) is a marker of hemolysis and inflammation, both risk factors for cardiac surgery-associated AKI (CSA-AKI). However, the association between CO-Hb and CSA-AKI remains unknown. DESIGN: A retrospective cohort study. SETTING: Tertiary university-affiliated metropolitan hospital: single center. PARTICIPANTS: Adult on-pump cardiac surgery patients from July 2014 to June 2022 (N = 1,698). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were stratified into quartiles based on CO-Hb levels at intensive care unit (ICU) admission. A progressive increased risk of CSA-AKI was observed with higher CO-Hb levels at ICU admission. On multivariable logistic regression analysis, the highest quartile (CO-Hb ≥ 1.4%) showed an independent association with the occurrence of CSA-AKI (odds ratio 1.45 compared to the lowest quartile [CO-Hb < 1.0%], 95% CI 1.023-2.071; p = 0.038). Compared to patients with CO-Hb <1.4%, patients with CO-Hb ≥ 1.4% at ICU admission had significantly higher postoperative creatinine (135 vs 116 µmol/L, p < 0.001), higher rates of postoperative RRT (6.7% vs 2.3%, p < 0.001) and AKI (p < 0.001) on univariable analysis and shorter time to event for AKI or death (p < 0.001). CONCLUSIONS: CO-Hb ≥ 1.4% at ICU admission is an independent risk factor for CSA-AKI, which is easily obtainable and available on routine arterial blood gas measurements. Thus, CO-Hb may serve as a practical and biologically logical biomarker for risk stratification and population enrichment in trials of CSA-AKI prevention.

Cost-utility analysis of separated continuous renal replacement therapy systems versus intermittent hemodialysis in critically ill patients with acute kidney injury in a low-resource setting.

BACKGROUND: The aim of this study is to perform a cost-utility analysis of separated continuous renal replacement therapy (CRRT) compared with intermittent hemodialysis (IHD) in critically ill patients with acute kidney injury (AKI). METHODS: Cost and clinical data were gathered from adult patients with AKI who received separated CRRT or IHD at a tertiary hospital in Thailand. We applied a Markov model in this study. Our primary outcome was the incremental cost-effectiveness ratio (ICER). We performed sensitivity analysis to assess the influence of parameter uncertainty. RESULTS: We enrolled 199 critically ill patients with AKI. Of these patients, 129 underwent separated CRRT, and the rest underwent IHD. The mortality rate and dialysis dependence status were not significantly different between the groups. The total costs of separated CRRT were lower than IHD ($73 042.20 vs. $89 244.37). We estimated that separated CRRT increased quality-adjusted life years (QALYs) by 0.21 compared with IHD. The ICER of -74 035.16 USD/QALY gained in the case-based analysis indicated that separated CRRT is superior to IHD due to the lower cost and more cumulative QALYs. After performing sensitivity analysis by varying parameter ranges, separated CRRT remained a cost-saving approach. CONCLUSIONS: Separated CRRT is a cost-saving modality compared with IHD in critically ill patients with AKI. This approach can be applied in resource-limited settings.

Impact of Calcium Phosphate Product on Acute Kidney Injury and Mortality: A Retrospective Cohort Study.

PURPOSE: This study aims to assess the association between admission-corrected serum calcium phosphate (CaPO4) levels and the risks of in-hospital acute kidney injury (AKI) and mortality, hypothesizing a dose-dependent relationship between serum CaPO4 concentrations and the likelihood of developing AKI. METHODS: This large retrospective cohort study analyzed hospitalized adult patients who had serum calcium, phosphate, and albumin levels measured within 24 hours of admission between January 2014 and December 2018. Piecewise regression was employed to identify the optimal CaPO4 cutoff values for predicting in-hospital AKI and mortality. Subsequently, the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the risks of in-hospital AKI and mortality associated with these cutoff values. RESULTS: A total of 2,116 patients were included in the study. The incidence rates of AKI for patients with CaPO4 levels ≤27 and >27 mg2/dL2 were 9.6% and 10.9%, respectively. The bilinear association pattern revealed the lowest risk of AKI at a CaPO4 level of 27 mg2/dL2. Piecewise regression analysis showed that each 1 mg2/dL2 increase in CaPO4 level above the 27 mg2/dL2 cutoff was associated with increased risks of in-hospital AKI and mortality, with OR of 1.048 (95% CI: 1.030-1.065) and 1.048 (95% CI: 1.032-1.065), respectively. CONCLUSION: Our findings indicate a critical relationship between elevated serum CaPO4 levels and increased risks of in-hospital AKI and mortality, with a notable cutoff at CaPO4 >27 mg2/dL2.

Comparison of immediate-start peritoneal dialysis without break-in period and conventional-start peritoneal dialysis: a two-center retrospective audit.

PURPOSE: Immediate-start peritoneal dialysis (PD) has emerged as a strategy for patients in need of urgent dialysis. However, the ideal timing for initiating this procedure remains uncertain. In this study, we aimed to compare complications and outcomes between immediate-start PD and conventional-start PD. METHODS: We performed a two-center retrospective cohort study between 1 January 2015 and 31 May 2020. Patients who underwent PD were divided into immediate-start PD (without break-in period) and conventional-start PD group (break-in period within at least 14 days). The primary outcomes were the incidence of the mechanical complications and infectious complication. The secondary outcomes were technique failure and patient survival. RESULTS: A total of 209 patients (106 in the immediate-start PD group and 103 in the conventional-start PD group) were included. Immediate-start PD had significantly lower catheter malfunction or migration rate compare with conventional-start PD (2.8% vs. 15.5%, p = 0.003) but comparable rates of dialysate leaks, pleuroperitoneal leaks, and hemoperitoneum. Infectious complications (exit-site infection and peritonitis) were similar between groups. Technique survival was comparable (7.5% vs. 4.8%, p = 0.22), while immediate-start PD exhibited lower mortality rates (0.9% vs. 13.6%, p = 0.001). CONCLUSION: Immediate-start PD appears to be a viable option for patients in need of urgent dialysis, with reduced catheter complications and comparable infectious complications and technique survival when compared to conventional-start PD.

Anti-Melanogenic Activity of Ethanolic Extract from Garcinia atroviridis Fruits Using In Vitro Experiments, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Melanin, the pigment responsible for human skin color, increases susceptibility to UV radiation, leading to excessive melanin production and hyperpigmentation disorders. This study investigated the ethanolic extract of Garcinia atroviridis fruits for its phenolic and flavonoid contents, antioxidant activity, and impact on melanogenesis pathways using qRT-PCR and Western blot analysis. Utilizing network pharmacology, molecular docking, and dynamics simulations, researchers explored G. atroviridis fruit extract's active compounds, targets, and pharmacological effects on hyperpigmentation. G. atroviridis fruit extract exhibited antioxidant properties, scavenging DPPH• and ABTS•+ radicals radicals and chelating copper. It inhibited cellular tyrosinase activity and melanin content in stimulated B16F10 cells, downregulating TYR, TRP-1, phosphorylated CREB, CREB, and MITF proteins along with transcription levels of MITF, TYR, and TRP-2. LC-MS analysis identified thirty-three metabolites, with seventeen compounds selected for further investigation. Network pharmacology revealed 41 hyperpigmentation-associated genes and identified significant GO terms and KEGG pathways, including cancer-related pathways. Kaempferol-3-O-α-L-rhamnoside exhibited high binding affinity against MAPK3/ERK1, potentially regulating melanogenesis by inhibiting tyrosinase activity. Stable ligand-protein interactions in molecular dynamics simulations supported these findings. Overall, this study suggests that the ethanolic extract of G. atroviridis fruits possesses significant antioxidant, tyrosinase inhibitory, and anti-melanogenic properties mediated through key molecular targets and pathways.

A Rare Case of Bilateral Renal Abscess from Staphylococcal Infection in a Young Healthy Patient.

Bilateral renal abscess is a rare infectious disease. Most patients have some risk factors for comorbidities, such as diabetes or an abnormal urinary tract, causing abscess formation. The incidence of the disease is infrequent in young healthy adults. Here, we report a case of a previously healthy non-diabetic young man who presented with abdominal pain with a high-grade fever. With clinically persistent abdominal pain, computerized tomography of the whole abdomen was done. The result showed bilateral renal abscess. The culture from the abscess reported Staphylococcus aureus. The patient's clinical abdominal pain and fever resolved after receiving antibiotics for 4 weeks.

Characteristics, Outcomes, and Factors Affecting Mortality in Hospitalized Patients with CAP Due to Different Variants of SARS-CoV-2 and Non-COVID-19 CAP.

The study was conducted from October 2020 to March 2022 in a province in southern Thailand. The inpatients with community-acquired pneumonia (CAP) and more than 18 years old were enrolled. Of the 1511 inpatients with CAP, COVID-19 was the leading cause, accounting for 27%. Among the patients with COVID-19 CAP, mortalities, mechanical ventilators, ICU admissions, ICU stay, and hospital costs were significantly higher than of those with non-COVID-19 CAP. Household and workplace contact with COVID-19, co-morbidities, lymphocytopenia and peripheral infiltration in chest imaging were associated with CAP due to COVID-19. The delta variant yielded the most unfavorable clinical and non-clinical outcomes. While COVID-19 CAP due to B.1.113, Alpha and Omicron variants had relatively similar outcomes. Among those with CAP, COVID-19 infection as well as obesity, a higher Charlson comorbidity index (CCI) and APACHE II score were associated with in-hospital mortality. Among those with COVID-19 CAP, obesity, infection due to the Delta variant, a higher CCI and higher APACHE II score were associated with in-hospital mortality. COVID-19 had a great impact on the epidemiology and outcomes of CAP.

A Rare Case Report of Postoperative Paraneoplastic Glomerulopathy in Kidney Transplant.

Kidney transplant recipients are more likely to develop posttransplant renal cell carcinoma than the general population. Symptoms of renal cell carcinoma are often nonspecific, such as nausea, vomiting, and weight loss, and tend to occur syndrome caused by the release of peptides and hormones by the cancer itself. However, there have been rare case reports of postoperative paraneoplastic glomerulopathy associated with renal cell carcinoma in kidney transplant recipients. Here, we report the case of a 54-year-old male who presented with subnephrotic range proteinuria with a urine protein-to-creatinine ratio of 1.0 within 1 year after a deceased donor kidney transplant without kidney function decline. The transplant team decided to perform a biopsy of the transplanted kidney, and the ultrasonography before intervention revealed a right- side native renal mass. The result of the kidney biopsy revealed focal segmental glomerulosclerosis. At the same time, computed tomography was done to find the cause of the renal mass, and we found that the right native kidney mass had features highly suspicious for renal cell carcinoma. The urologist subsequently performed a right radical nephrectomy. The pathology diagnosis of the kidney mass was renal cell carcinoma. After the cancer had been eliminated, clinical improvement of proteinuria was achieved. Hence, we diagnosed a rare secondary focal segmental glomerulosclerosis from renal cell carcinoma (paraneoplastic glomerulopathy) about which, to our knowledge, there are no previous reports. To date, there is no consensus recommendation for screening postoperative renal cell carcinoma in organ transplant recipients. The potential postoperative diagnosis of paraneoplastic glomerulopathy-associated renal cell carcinoma in kidney transplant recipients must be recognized.

Preemptive Living-Related Kidney Transplantation Is a Cost-Saving Strategy Compared With Post-dialysis Kidney Transplantation in Thailand.

Background: Compared with other kidney replacement therapies, preemptive kidney transplantation (KT) provides better clinical outcomes, reduces mortality, and improves the quality of life of patients with end-stage kidney disease (ESKD). However, evidence related to the cost-effectiveness of preemptive living-related KT (LRKT) is limited, especially in low- and middle-income countries, such as Thailand. This study compared the cost-effectiveness of LRKT with those of non-preemptive KT strategies. Methods: Cost and clinical data were obtained from adult patients who underwent KT at Siriraj Hospital, Mahidol University, Thailand. A decision tree and Markov model were used to evaluate and compare the lifetime costs and health-related outcomes of LRKT with those of 2 KT strategies: non-preemptive LRKT and non-preemptive deceased donor KT (DDKT). The model's input parameters were sourced from the hospital's database and a systematic review. The primary outcome was incremental cost-effectiveness ratios (ICERs). Costs are reported in 2020 United States dollars (USD). One-way and probabilistic sensitivity analyses were performed. Results: Of 140 enrolled KT patients, 40 were preemptive LRKT recipients, 50 were non-preemptive LRKT recipients, and the rest were DDKT recipients. There were no significant differences in the baseline demographic data, complications, or rejection rates of the three groups of patients. The average costs per life year gained were $10,647 (preemptive LRKT), $11,708 (non-preemptive LRKT), and $11,486 (DDKT). The QALY gained of the preemptive option was 0.47 compared with the non-preemptive strategies. Preemptive LRKT was the best-buy strategy. The sensitivity analyses indicated that the model was robust. Within all varied ranges of parameters, preemptive LRKT remained cost-saving. The probability of preemptive LRKT being cost-saving was 79.4%. Compared with non-preemptive DDKT, non-preemptive LRKT was not cost-effective at the current Thai willingness-to-pay threshold of $5113/QALY gained. Conclusions: Preemptive LRKT is a cost-saving strategy compared with non-preemptive KT strategies. Our findings should be considered during evidence-based policy development to promote preemptive LRKT among adults with ESKD in Thailand.