Ceftobiprole and Cefiderocol for Patients on Extracorporeal Membrane Oxygenation: The Role of Therapeutic Drug Monitoring.

INTRODUCTION: Limited data exist on therapeutic ranges for newer antimicrobials in the critically ill, with few pharmacokinetic studies including patients undergoing renal replacement therapy or extracorporeal membrane oxygenation (ECMO). CASE REPRESENTATION: These interventions can potentially alter the pharmacokinetic profile of antibiotics, resulting in therapeutic failures, antimicrobial resistance, or increased toxicity. In this report, we present two ECMO patients treated with cefiderocol and ceftobiprole, where therapeutic drug monitoring (TDM) aided in the successful treatment of severe infections. Antibiotic trough concentrations in both cases were consistent with previously reported therapeutic levels in critically ill and ECMO patients, meeting minimal inhibitory concentrations recommended by the European Committee on Antimicrobial Susceptibility Testing for the respective pathogens. CONCLUSION: Treatment might be suboptimal if doses are not adjusted based on physicochemical properties and extracorporeal support. In an era marked by highly resistant pathogens, these cases highlight the importance of timely access to real-time TDM for optimizing and individualizing antimicrobial treatment.

Quality of life and psychological distress in end-stage renal disease patients undergoing hemodialysis and transplantation.

BACKGROUND: Among diverse profound impacts on patients' quality of life (QoL), end-stage renal disease (ESRD) frequently results in increased levels of depression, anxiety, and stress. Renal replacement therapies such as hemodialysis (HD) and transplantation (TX) are intended to enhance QoL, although their ability to alleviate psychological distress remains uncertain. This research posits the existence of a significant correlation between negative emotional states and QoL among ESRD patients, with varying effects observed in HD and TX patients. AIM: To examine the relationship between QoL and negative emotional states (depression, anxiety, and stress) and predicted QoL in various end-stage renal replacement therapy patients with ESRD. METHODS: This cross-sectional study included HD or TX patients in the Eastern Region of Saudi Arabia. The 36-item Short Form Survey and Depression Anxiety Stress Scale (DASS) was used for data collection, and correlation and regression analyses were performed. RESULTS: The HD and TX transplantation groups showed statistically significant inverse relationships between QoL and DASS scores. HD patients with high anxiety levels and less education scored low on the physical component summary (PCS). In addition, the results of the mental component summary (MCS) were associated with reduced depression. Compared with older transplant patients, TX patients' PCS scores were lower, and depression, stress, and negative working conditions were highly correlated with MCS scores. CONCLUSION: The findings of this study revealed notable connections between well-being and mental turmoil experienced by individuals undergoing HD and TX. The PCS of HD patients is affected by heightened levels of anxiety and lower educational attainment, while the MCS of transplant patients is influenced by advancing age and elevated stress levels. These insights will contribute to a more comprehensive understanding of patient support.

The evolution of public attention in acute kidney injury and continuous renal replacement therapy: trends analysis from 2004 to 2024.

Background: Acute kidney injury (AKI) and the need for Continuous Renal Replacement Therapy (CRRT) are critically important health concerns. This study analyzes global and regional Internet search queries to understand public attention in AKI and CRRT over time. Methods: We used Google Trends™ to analyze search queries for AKI and CRRT from January 2004 to March 2024. The study examined global trends and detailed insights from the United States, including state-by-state breakdowns. We identified patterns, peaks of attention, and temporal trends in public attention, comparing regional variations across the US and top-ranking countries worldwide. Results: Global attention in AKI peaked in October 2022, with Portugal, Zambia, and Spain showing the highest regional attention. Within the United States, peak attention was in February 2008. Tennessee, Pennsylvania, and West Virginia were the top states that paid attention to AKI. Attention in CRRT peaked globally in March 2024. South Korea, Saudi Arabia, and Bahrain have led the global attention to CRRT. In the United States, peak attention was in April 2020. West Virginia, Tennessee, and Kentucky showed the highest state-specific attention in CRRT. Conclusions: This study reveals significant temporal and geographical variations in online search patterns for AKI and CRRT, suggesting evolving public attention to these critical health issues. This knowledge can guide the development of targeted public health initiatives, enhance medical education efforts, and help healthcare systems tailor their approach to improving awareness and outcomes in kidney health across diverse populations.

Protocolized Regional Citrate Anticoagulation during Continuous Renal Replacement Therapy: A Single Center Experience.

Background: Regional citrate anticoagulation (RCA) has emerged as a treatment modality that reduces bleeding risk and filter clotting. With initial experience of using RCA with continuous renal replacement therapy (CRRT), we have formulated a working protocol based on published literature. Objective: The study aimed to evaluate the protocol for routine use of RCA during CRRT requiring anticoagulation and evaluation of filter life. Methodology: It is a single-center, open-label, prospective, non-randomized, non-interventional, single-arm, observational study conducted at a tertiary care hospital between September 2022 and July 2023. All adult patients with acute kidney injury (AKI) or hyperammonemia requiring CRRT and necessitating the use of anticoagulation were enrolled in the study. The study used Prisma Flex M100 AN 69 dialyzer on Prisma Flex (Baxter) CRRT machines during continuous venovenous hemodiafiltration (CVVHDF). The targeted CRRT dose in all the study patients was 25-30 mL/kg/hour. Based on the published literature, we have developed a working protocol (Appendix 1) for managing patients on CRRT using RCA. Results: A total of 159 patients were analyzed for the study. The median [interquartile range (IQR)] filter life using RCA was 30 (12-55) hours. Filter clotting was observed in 33.3% of patients. Citrate accumulation was present in 52.25% of patients, but no CRRT was discontinued as citrate accumulation resolved after following the corrective steps in the protocol. None of the patients had citrate toxicity. Chronic liver disease (CLD) (p ≤ 0.001) and those who were post-living donor liver transplant recipients (p = 0.004) had a statistically significant increase in citrate accumulation. Also, patients who had higher lactate at baseline (6 hours post-CRRT initiation), had a higher chance of citrate accumulation. Conclusion: Our RCA protocol provides a safe approach to regional anticoagulation during CRRT in critically ill patients. How to cite this article: Pachisia AV, Kumar GP, Harne R, Jagadeesh KN, Patel SJ, Pal D, et al. Protocolized Regional Citrate Anticoagulation during Continuous Renal Replacement Therapy: A Single Center Experience. Indian J Crit Care Med 2024;28(9):859-865.

Pharmacokinetic Research in Pediatric Extracorporeal Therapies: Current State and Future Directions.

Extracorporeal life support (ECLS), including extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), are life-saving therapies for critically ill children. Despite this, these modalities carry frustratingly high mortality rates. One driver of mortality may be altered drug disposition due to a combination of underlying illness, patient-circuit interactions, and drug-circuit interactions. Children receiving ECMO and/or CRRT routinely receive 20 or more drugs, and data supporting optimal dosing is lacking for most of these medications. The Pediatric Paracorporeal and Extracorporeal Therapies Summit (PPETS) gathered an international group of experts in the fields of ECMO, CRRT, and other ECLS modalities to discuss the current state of these therapies, disseminate innovative support strategies, share clinical experiences, and foster future collaborations. Here, we summarize the conclusions of PPETS and put forward a pathway to optimize pharmacokinetic (PK) research in this population. We must prioritize specific medications for in-depth study to improve drug use in ECLS and patient outcomes. Based on frequency of use, potential for adverse outcomes if dosed inappropriately, and lack of existing PK data, a list of high priority drugs was compiled for future research. Researchers must additionally reconsider study designs, emphasizing pooling of resources through multi-center studies and the use of innovative PK modeling techniques. Finally, the integration of validated PK models into clinical practice must be streamlined to deliver optimal medication use at the bedside. Focusing on the proposed list of highlighted medications and key methodological considerations will maximize the impact of future research.

The furosemide stress test predicts successful discontinuation of continuous renal replacement therapy in critically ill patients with acute kidney injury.

PURPOSE: There is still no good method for predicting renal recovery and successful discontinuation of continuous renal replacement therapy (CRRT). This study assessed the ability of the furosemide stress test (FST) to predict successful discontinuation of CRRT. MATERIALS AND METHODS: This prospective single-center study included patients with acute kidney injury who underwent an initial attempt at discontinuation of CRRT. Successful discontinuation was defined as alive without renal replacement therapy for 7 days after discontinuation. Furosemide 1.0 mg/kg was administered intravenously within 2 h after discontinuation of CRRT. Urine output was recorded for the next 2 h. Receiver-operating characteristic curve and logistic regression analyses were performed to determine the best discriminative variable and to identify independent risk factors. RESULTS: Discontinuation of CRRT was successful in 30 of 55 patients. The area under the curve for prediction of successful discontinuation was significantly greater for urine output in the 2 h following the FST (0.913) than for 24-h urine output on the previous day (0.739, P = 0.003) and urine neutrophil gelatinase-associated lipocalin (0.725, P = 0.020). A 2-h urine output of 188 mL had optimal sensitivity (0.800) and specificity (0.920). Multivariate analysis showed that 2-h urine output independently predicted successful discontinuation. CONCLUSIONS: A urine output >188 mL in the first 2 h after FST predicted successful discontinuation of CRRT.

A Case Series of Monoclonal Immunoglobulin-Depositing Proliferative Glomerulonephritis.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposition disease (PGNMIDD) is a rare entity. We evaluated the clinicopathological features of PGNMIDD and the effectiveness of different treatment regimens in 13 cases diagnosed using kidney biopsy. Most had chronic kidney disease followed by acute nephritic syndrome, rapidly progressive glomerulonephritis, and nephrotic syndrome. Membranoproliferative glomerulonephritis was the most common pattern of renal injury. Three patients had abnormal bone marrow studies. Different treatment regimens were deployed; >60% had partial remission at the end of six months and 30.7% progressed to end stage renal disease.

Extracorporeal pediatric renal replacement therapy: diversifying application beyond kidney failure.

The utilization of extracorporeal renal replacement therapy (RRT), including continuous renal replacement therapy (CRRT) and hemodialysis (HD), beyond the treatment of volume overload and acute kidney injury (AKI) has witnessed a significant shift, demonstrating the potential to improve patient outcomes for a range of diseases. This comprehensive review explores the non-kidney applications for RRT platforms in critically ill children, focusing on diverse clinical scenarios such as sepsis, inborn errors of metabolism, liver failure, drug overdose, tumor lysis syndrome, and rhabdomyolysis. In the context of sepsis and septic shock, RRT not only facilitates fluid, electrolyte, and acid/base homeostasis, but may offer benefits in cytokine regulation, endotoxin clearance, and immunomodulation which may improve multi-organ dysfunction as well as hemodynamic challenges posed by this life-threatening condition. RRT modalities also have an important role in caring for children with inborn errors of metabolism, liver failure, and tumor lysis syndrome as they can control metabolic derangements with the efficient clearance of endogenous toxins in affected children. In cases of drug overdose, RRT is a crucial tool for rapid extracorporeal clearance of exogenous toxins, mitigating potential organ damage. The intricate interplay between liver failure and kidney function is examined, elucidating the role of RRT and plasma exchange in maintaining fluid and electrolyte balance when hepatic dysfunction complicates the clinical picture. Furthermore, RRT and HD are explored in the context of rhabdomyolysis, highlighting their utility in addressing AKI secondary to traumatic events and crush syndrome.

Vascular Access for Renal Replacement Therapy in Neonates and Infants: A Single Center Experience.

INTRODUCTION: Neonatal renal replacement therapy (RRT) is a treatment modality used for severe kidney failure. Historically, its use has been limited in small infants due to circuits with large extra-corporeal volumes that require large double lumen vascular catheters. We sought to review our institution's experience with vascular access and overall survival in infants who receive RRT. METHODS: A retrospective chart review of infants less than 5 kg (kg) was performed at our free-standing children's hospital from January 2016 to July 2023. We assessed the number of catheters used per patient, location of catheter placements, size of catheter, duration of treatment, reasons for line removal, and mortality. RESULTS: A total of 93 neonatal patients were identified who underwent RRT. Thirty-two patients (34.4%) required more than one catheter, with a total of 145 catheters placed for this cohort. The median (IQR) weight at insertion was 3.3 kg (2.7-4.0). The most common location for placement was the right internal jugular vein (n = 114, 78.6%). Patients required catheters for RRT for a median (IQR) of 16 days (7-39). Six patients underwent catheter placement at a weight of less than 2 kg. Nineteen total patients went on to peritoneal dialysis (20.4%). Fifty-three patients died during their admission (57.0%). CONCLUSION: To our knowledge this is the largest review of catheter use for RRT in infants within an intensive care unit and it reveals the success in treating renal failure in even the smallest infants. LEVEL OF EVIDENCE: IV, Treatment Study.

Distinct phenotyping of critical patients with demand-capacity imbalance initiating acute renal replacement therapy by consensus clustering.

BACKGROUND: Certain patient subpopulations requiring dialysis initiation show varied survival rates and chances of ending renal replacement therapy (RRT). Consensus clustering can help identify these subgroups and their dialysis outcomes. METHODS: The study included patients who were over 18 years old with urine output above 400 ml per day and an estimated glomerular filtration rate over 15 ml/min/1.73 m2. They underwent acute RRT because of systemic demand-capacity imbalance. Using consensus clustering with 33 clinical variables and urea:creatinine ratio (UCR) to the variables to investigate the catabolic demand. Endpoints were all-cause mortality and being dialysis-free at 180-day follow-up after RRT initiation. RESULTS: Of 946 patients (mean 63 ± 17 years and 649 men, 68.6 %) three distinct phenotypes were identified. 509 (53.8%) patients died and 364 (38.5%) patients were weaned off dialysis. Cluster 2 showed better survival (60.23% vs. 53.18% [cluster 1] vs. 45.85% [cluster 3], P < 0.01) and higher possibility to be weaned off RRT (45.24% vs. 38.44% [cluster 1] vs. 31.62% [cluster 3], P < 0.01). High UCR had increased mortality (59.16% vs. 47.75%, P < 0.01) and a lower weaning rates (33.27%; 45.72%, P < .01). UCR with the clustering phenotype improved risk stratification. CONCLUSIONS: Among critical patients undergoing RRT due to systemic demand-capacity imbalance, more than half of the patients died. We identified distinct phenotypes in demand-capacity imbalance in a heterogeneous cohort of patients initializing RRT. Additionally, we found that pre-dialysis UCR as a novel predictor for mortality and the likelihood of being dialysis-free.

Population Pharmacokinetics of Tigecycline for Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

Background: Tigecycline is considered one of the last resorts for treating infections caused by multidrug-resistant bacteria. Continuous renal replacement therapy (CRRT) is widely used in critically ill patients, especially those with acute kidney injury or severe infections. However, pharmacokinetic data for tigecycline in patients receiving CRRT are limited. Methods: This was a single-center prospective clinical study with intensive sampling that included critically ill patients who received tigecycline and CRRT. A population pharmacokinetic (PPK) model was developed and evaluated by goodness-of-fit plots, bootstrap analysis, visual predictive checks, and numerical predictive checks. Pharmacokinetic/pharmacodynamic target attainment and cumulative fraction of response analyses were performed to explore the potential need for dose adjustments of tigecycline in CRRT. Results: In total, 21 patients with 167 concentrations were included. A two-compartment model adequately described the tigecycline concentration-time points, but no covariates were found to adequately explain the viability in the pharmacokinetic parameters of tigecycline. The typical values of CL, Q, V1 and V2 were 4.42 L/h, 34.8 L/h, 30.9 L and 98.7 L, respectively. For most infections, the standard regimen of 50 mg/12 h was deemed appropriate, expect for skin and soft skin tissue infections and community-acquired pneumonia caused by Acinetobacter baumannii and Klebsiella pneumoniae, which required a dosage regimen of 100 mg/12 h or higher. Conclusion: A tigecycline PPK model describing critically ill patients undergoing CRRT was successfully developed. The optimized dosage regimens for various infections are recommended.

Sex-Related Differences in Outcome of Patients Treated With Microaxial Percutaneous Left Ventricular Assist Device for Cardiogenic Shock.

BACKGROUND: The use of microaxial percutaneous left ventricular assist devices (pLVADs) in cardiogenic shock (CS) has increased in recent years, despite limited evidence, and data on sex disparities are particularly scarce. This study aimed to compare short-term outcomes between males and females. METHODS: Data were retrospectively collected from the Dresden Impella Registry, which is a large, prospective, single-centre registry that consecutively enrolled patients who received microaxial pLVAD. Inclusion criteria were CS due to left ventricular failure with serum lactate >4 mM. Patients with pLVAD other than Impella CP were excluded. The primary endpoint was the composite of all-cause mortality at 30 days or requirement of renal replacement therapy (RRT). Secondary endpoints were the components of the primary endpoint alone. Propensity score matched (PSM) analysis was used to adjust for baseline characteristics. RESULTS: A total of 319 male (69 years; body mass index, 26.7 kg/m2) and 113 female patients (74 years; 27.9 kg/m2) were included in the study. The primary composite endpoint occurred less frequently in female patients in the unmatched analysis (♂ 75.9% [n=239] vs ♀ 64.4% [n=72]; p=0.040) but not in the PSM analysis (♂ 81.1% [n=73] vs ♀ 68.9% [n=42]; p=0.056). However, females less frequently required RRT in both analyses (♂ 48.2% [n=126] vs ♀ 25.9% [n=25]; p=0.001; PSM: ♂ 49.1% [n=36] vs ♀ 23.3% [n=12]; p=0.007). All-cause mortality did not differ between the cohorts. CONCLUSIONS: This study showed no differences in all-cause mortality at 30 days between male and female patients receiving microaxial pLVAD in CS. Larger studies are required to confirm whether female sex is associated with reduced requirement of RRT in CS treated with microaxial pLVAD.

Edoxaban pharmacokinetics during in vitro continuous renal replacement therapy.

BACKGROUND: To evaluate the clearance of edoxaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. METHODS: Edoxaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types, flow rates, and point of CVVH replacement fluid dilution. Concentrations of edoxaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma pharmacokinetic parameters for edoxaban were estimated via noncompartmental analysis. Two and three-way analysis of variance (ANOVA) models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLCRRT. Linear regression was utilized to provide dosing estimations across CRRT effluent flow rates from 0.5 to 5 L/h. Optimal edoxaban doses were suggested using CLCRRT and population non-renal clearance (CLNR) to estimate total clearance and match the systemic AUC associated with efficacy in the treatment of venous thromboembolism. RESULTS: Edoxaban clearance from the CRRT circuit occurred primarily via hemofilter adsorption to the HF1400 and M150 filters at 74% and 65%, respectively, while mean percent protein binding was 41%. Multivariate analyses confirmed the lack of influence of CRRT mode, filter type, and point of dilution on the CLCRRT of edoxaban allowing dosing recommendations to be made based on effluent flow rate. Edoxaban doses of 30-45 mg once daily were estimated to achieve target the AUC threshold for flow rates from 0.5 to 5 L/h. CONCLUSION: For CRRT flow rates most employed in clinical practice, an edoxaban dose of 45 mg once daily is predicted to achieve target systemic exposure thresholds for venous thromboembolism treatment. The safety and efficacy of this proposed dosing warrants further investigation in clinical studies.

Transitioning to peritoneal dialysis: it does not matter where you come from / Transição para diálise peritoneal: não importa de onde

Introduction: Patients with end-stage renal disease (ESRD) frequently change renal replacement (RRT) therapy modality due to medical or social reasons. We aimed to evaluate the outcomes of patients under peritoneal dialysis (PD) according to the preceding RRT modality. Methods: We conducted a retrospective observational single-center study in prevalent PD patients from January 1, 2010, to December 31, 2017, who were followed for 60 months or until they dropped out of PD. Patients were divided into three groups according to the preceding RRT: prior hemodialysis (HD), failed kidney transplant (KT), and PD-first. Results: Among 152 patients, 115 were PD-first, 22 transitioned from HD, and 15 from a failing KT. There was a tendency for ultrafiltration failure to occur more in patients transitioning from HD (27.3% vs. 9.6% vs. 6.7%, p = 0.07). Residual renal function was better preserved in the group with no prior RRT (p < 0.001). A tendency towards a higher annual rate of peritonitis was observed in the prior KT group (0.70 peritonitis/year per patient vs. 0.10 vs. 0.21, p = 0.065). Thirteen patients (8.6%) had a major cardiovascular event, 5 of those had been transferred from a failing KT (p = 0.004). There were no differences between PD-first, prior KT, and prior HD in terms of death and technique survival (p = 0.195 and p = 0.917, respectively) and PD efficacy was adequate in all groups. Conclusions: PD is a suitable option for ESRD patients regardless of the previous RRT and should be offered to patients according to their clinical and social status and preferences.

Introdução: Pacientes com doença renal em estágio terminal (DRET) frequentemente mudam de modalidade de terapia renal substitutiva (TRS) por razões médicas ou sociais. Nosso objetivo foi avaliar desfechos de pacientes em diálise peritoneal (DP) segundo a modalidade anterior de TRS. Métodos: Realizamos estudo retrospectivo observacional unicêntrico, em pacientes prevalentes em DP, de 1º de janeiro de 2010 a 31 de dezembro de 2017, acompanhados por 60 meses ou até saírem de DP. Pacientes foram divididos em três grupos de acordo com a TRS anterior: hemodiálise prévia (HD), transplante renal malsucedido (TR) e DP como primeira opção (PD-first). Resultados: Entre 152 pacientes, 115 eram PD-first, 22 transitaram da HD e 15 de TR malsucedido. Houve tendência à maior ocorrência de falência de ultrafiltração em pacientes em transição da HD (27,3% vs. 9,6% vs. 6,7%; p = 0,07). A função renal residual foi melhor preservada no grupo sem TRS prévia (p < 0,001). Observou-se tendência à maior taxa anual de peritonite no grupo TR prévio (0,70 peritonite/ano por paciente vs. 0,10 vs. 0,21; p = 0,065). Treze pacientes (8,6%) tiveram um evento cardiovascular maior, cinco dos quais haviam sido transferidos de um TR malsucedido (p = 0,004). Não houve diferenças entre PD-first, TR prévio e HD prévia em termos de óbito e sobrevida da técnica (p = 0,195 e p = 0,917, respectivamente) e a eficácia da DP foi adequada em todos os grupos. Conclusões: A DP é uma opção adequada para pacientes com DRET, independentemente da TRS anterior, e deve ser oferecida aos pacientes de acordo com seu status clínico e social e suas preferências.

Evaluation of Factors Affecting the Health-Related Quality of Life in End-Stage Renal Disease Patients Receiving Hemodialysis Treatment in Northern Cyprus.

Introduction Health-related quality of life (HR-QoL) is recognized as an important predictor of mortality and morbidity in end-stage renal disease (ESRD) patients receiving hemodialysis (HD). The goal of this study was to obtain HR-QoL scores using the Kidney Disease and Quality of Life questionnaire (KDQOL-36TM) (RAND Corporation, Santa Monica, CA) and to assess the factors affecting HR-QoL in ESRD patients receiving HD. Methods A multicenter cross-sectional study was performed using the KDQOL-36TM for the assessment of HR-QoL of ESRD patients receiving HD in Northern Cypriot state hospitals. Alongside KDQOL-36TM scores for assessing HR-QoL, sociodemographic as well as relevant laboratory data were collected. Spearman Correlations and multiple linear regression analyses using the 'stepwise' method were carried out to identify predictors of HR-QoL. Nonparametric tests were used to determine significantly (p<0.05) associated variables. Ethical approvals were received from the Northern Cypriot Ministry of Health and Eastern Mediterranean University Research and Publication Ethics Boards. Results One hundred and thirty-eight participants were recruited in this study, corresponding to 85.1% of the total study population. Participants had a mean age of 66.49 ± 13.35. 65.2% of the participants were males. Participants had low scores on most dimensions of quality of life, namely, Burden of Disease, Physical Component Summary (PCS), and Mental Component Summary (MCS) subscales. Particularly, females, unemployed patients, and patients with more comorbidities had significantly lower scores (p=0.003, p<0.001, and p=0.005, respectively). Spearman correlation analyses revealed multiple significant moderate correlations between sociodemographic data, laboratory variables, and scores. Furthermore, multiple linear regression analysis identified gender (p=0.006), total number of comorbidities (p=0.005), age (p<0.001), and patient care (p=0.019) as significant predictors of KDQOL-36TM scores. Conclusion This study has shown that the quality of life of hemodialysis patients was highly impaired. Gender, current employment status, and presence of comorbidities were all significant independent factors affecting HR-QoL mean scores. Lastly, further studies regarding the implementation of routine HR-QoL surveillance and targeted interventions are required to better understand their potential therapeutic benefits.

Higher doses of fluconazole are needed to ensure target attainment in critically ill adults on continuous Veno-venous hemodialysis.

BACKGROUND: Critically ill patients undergoing Continuous Renal Replacement Therapy (CRRT) are treated with higher doses of fluconazole based on the literature recommendations. However, clinical follow-up data demonstrating the effectiveness of this approach are lacking. PURPOSE: A retrospective cohort study was conducted to evaluate whether target attainment was achieved with higher doses of fluconazole. Additionally, the study focused on identifying factors that may contribute to variability in fluconazole exposure in these patients. METHODS: Critically ill patients undergoing Continuous Veno-Venous Hemodialysis (CVVHD) who received either standard or higher doses of intravenous fluconazole were included. Evaluation of target attainment was conducted for each dose regimen. RESULTS: Administering higher doses resulted in target attainment in 100 % of the patients, indicating that starting with at least 400 mg twice daily is an adequate dosing guideline. In this study, only the dose of fluconazole was found to significantly influence target attainment (p < 0.001), with no other predefined factors identified as having a significant impact. CONCLUSION: According to the results of the study, increasing the fluconazole dose to at least 400 mg twice daily is sufficient to reach the desired target in critically ill patients undergoing CVVHD.

Aminopeptidasic Enzymes as Early Biomarkers of Cardiac Surgery-Associated Acute Kidney Injury and Long-Term Events.

BACKGROUND: Diagnosis of acute kidney injury (AKI) relies on serum creatinine (SCr) changes. This study investigated if urinary aminopeptidases are early and predictive biomarkers of cardiac surgery-associated AKI (CSA-AKI). METHODS: Glutamyl aminopeptidase (GluAp), alanyl aminopeptidase (AlaAp), dipeptidyl peptidase-4 (DPP4), proteinuria, albuminuria, N-acetyl-ß-D-glucosaminidase (NAG), and neutrophile gelatinase-associated lipocalin (NGAL) were measured in urine samples from 44 patients at arrival in the intensive care unit (ICU) after cardiac surgery. Sensitivity, specificity, and positive and negative predictive value for diagnosis of stages 1, 2, and 3 of AKI were analyzed for the highest quartile of each marker. We also studied the relationship with SCr after surgery, 6- and 12-month glomerular filtration rates (GFRs), and other long-term events over the next 5 years. RESULTS: GluAp diagnosed the maximal number of patients that developed stage 2 or 3 of AKI, increasing diagnostic sensitivity from 0% to 75%. In addition, GluAp and DPP4 were related to the decrease in GFR at 6 or 12 months after surgery. CONCLUSIONS: Urinary aminopeptidases are a potential tool for the early diagnosis of CSA-AKI, with GluAp being the most effective marker for diagnosing stage 2 or 3 of AKI at ICU admission. GluAp and DPP4 serve as predictive biomarkers for a decrease in GFR.

Efficacy of immediate versus delayed renal replacement therapy in septic patients undergoing continuous renal replacement therapy.

OBJECTIVE: To compare the therapeutic efficacy of immediate versus delayed renal replacement therapy (RRT) in septic patients undergoing continuous RRT. METHODS: We retrospectively analyzed 98 septic patients who received continuous RRT between August 2021 and January 2023. Patients were divided into two groups: RRT group (n=50, immediate RRT) and delayed RRT group (n=48), where RRT was delayed by 48 hours in the absence of renal function recovery. Demographic data, comorbidities, vital signs, laboratory results, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, Sequential Organ Failure Assessment (SOFA) scores, and follow-up details were compared between the two groups. RESULTS: The RRT group showed significantly lower serum interleukin-6 and creatinine levels at 1, 3, and 5 days of treatment (P=0.006, P=0.021, P=0.007; P=0.016, P=0.006, P=0.021, respectively) compared with the delayed RRT group. Additionally, the RRT group had shorter ICU stays, reduced duration of mechanical ventilation, and lower total treatment costs (P=0.016, P=0.003, P=0.029). Post-treatment, the RRT group exhibited significantly lower APACHE II and SOFA scores (P=0.031, P=0.018), a shorter average ICU stay (P=0.009), and a lower mortality rate (P=0.018) than the delayed RRT group. CONCLUSION: Immediate RRT in septic patients undergoing continuous RRT significantly reduces inflammatory markers, accelerates patient outcome, and decreases short-term mortality compared to delayed treatment.

Impact of renal replacement therapy modality on coagulation and platelet function in critically ill patients: A prospective observational study.

BACKGROUND: Renal replacement therapy (RRT) may affect coagulation and platelet function in critically ill patients. However, the mechanism and the difference in the impact on coagulation between intermittent hemodialysis (iHD) and continuous renal replacement therapy (CRRT) remains unclear. This study aimed to investigate and compare the impact of iHD and CRRT on coagulation and platelet function. METHODS: Critically ill patients undergoing RRT were classified into the iHD group or the CRRT group. After the first blood sampling, patients underwent either a single session of hemodialysis or 48 h of CRRT, then a second blood sample was taken. Rotational thromboelastometry (ROTEM), platelet aggregometry and conventional coagulation tests were performed. The primary outcome was a change in extrinsically activated ROTEM (EXTEM) clotting time (CT). RESULTS: 60 dialysis sessions from 56 patients were finally included, with 30 dialysis sessions per group. EXTEM CT was prolonged significantly after dialysis in the iHD group (90 [74, 128] vs. 74 [61, 91], p < 0.001), but did not change in the CRRT group (94.4 ± 29.4 vs. 91.6 ± 22.9, p = 0.986). The platelet aggregation did not change after both iHD and CRRT. A change in EXTEM CT was significantly greater in the iHD group compared to the CRRT group (p = 0.006). The difference in the incidence of bleeding events was insignificant between the two groups (p = 0.301). CONCLUSIONS: EXTEM CT was significantly prolonged after iHD, but this change was not shown after CRRT. Platelet function was not affected by both dialysis modalities.

Efficient decellularization of human fetal kidneys through optimized SDS exposure.

Chronic kidney disease poses a significant threat to public health. Renal replacement therapy is the primary treatment option for end-stage kidney disease. However, there is a promising and relatively new method in regenerative medicine for creating a functional organ known as whole kidney decellularization. This method uses the intrinsic vasculature to perfuse the decellularizing agent into the tissue, effectively penetrating and removing cellular material. The regenerated bioscaffolds could serve as a source of organ donation. This study is focused on evaluating the effectiveness of various SDS exposures in decellularizing human fetal kidneys. The study included human fetal kidneys harvested from fetuses terminated before 14 weeks of gestational age. Kidneys were divided into six treatment groups based on SDS concentration and duration of perfusion. Decellularization, scanning electron microscopy, histopathological staining, immunofluorescent staining, and immunohistochemistry staining were performed to evaluate the adequacy of the process. The statistical analysis revealed that the SDS 0.1% treatment group had the highest collagen deposition after 24 h, significantly greater than the SDS 0.5% treatment group at 24 and 48 h. No significant differences were observed among the other treatment groups. The study concludes that the SDS 0.1% treatment group for 24 h was the most effective in terms of ECM content preservation and effective cell removal. This treatment showed better results than the other treatment groups and can be considered for future whole kidney decellularization studies.