This study aimed to explore the role of peritoneal dialysis (PD) in patients with acute kidney injury (AKI) in relation to metabolic and fluid control, outcome and risk factors for death.

We performed a retrospective cohort study collecting data from a large reference Center in Brazil on patient characteristics, hospitalization, PD prescription and delivery, clinical outcomes and laboratory exams. We evaluated all patients who had been consecutively treated by PD between January 2004 and January 2024.

Four hundred eighty-seven patients were included. Median age was 64.02 ± 15 years, most of the patients were hospitalized in the intensive care unit (ICU) and needed vasoactive drugs and mechanical ventilation. Sepsis was the main cause of AKI followed by cardiorenal syndrome type 1. Uremia was the main indication for dialysis, followed by the need to meet metabolic and fluid demands. Blood urea nitrogen and creatinine levels stabilized after a median of four dialysis sessions. Fluid removal increased progressively and stabilized at around 2.320 ± 0.91 ml after four sessions. Mechanical complications occurred in 9.2% and peritonitis in 6.2% of patients. Regarding AKI outcome, 34.9% recovered renal function, 6.8% remained on dialysis for over 30 days, and 55.8% died. Technique failure occurred in 19.9% of the cases and the main cause was a mechanical complication. Age, hepatorenal syndrome, APACHE score and dropout from PD due to insufficient fluid control were identified as risk factors for death, while cardiorenal syndrome, need to meet metabolic and fluid demand as indication of dialysis, and negative fluid balance after 4 sessions of PD were identified as protective factors.

PD may be an effective solution for AKI patients, allowing adequate metabolic and fluid control. Age, APACHE score, hepatorenal syndrome and dropout from PD were associated with death, while cardiorenal syndrome, need to meet metabolic and fluid demands as indication of dialysis, and negative fluid balance were positive prognostic factors.

Sepsis-associated acute kidney injury (SA-AKI) is a prevalent and severe complication in critically ill patients. However, diagnostic and therapeutic advancements have been hindered by the biological heterogeneity underlying the disease. Both transcriptomic endotyping and biomarker profiling have been proposed individually to identify molecular subtypes of sepsis and may enhance risk stratification. This study aimed to evaluate the utility of combining transcriptomic endotyping with protein-based biomarkers for improving risk stratification in SA-AKI.

This secondary analysis of the PredARRT-Sep-Trial included 167 critically ill patients who met Sepsis-3 criteria. Patients were stratified into three transcriptomic endotypes-inflammopathic (IE), adaptive (AE), and coagulopathic (CE)-using a validated whole-blood gene expression classifier. Eight protein-based biomarkers encompassing kidney function, vascular integrity, and immune response were measured. Predictive performance for the primary endpoint kidney replacement therapy or death was assessed using receiver operating characteristic curve analysis and logistic regression models.

Stratification into transcriptomic endotypes assigned 33% of patients to IE, 42% to AE, and 24% to CE. Patients classified as IE exhibited the highest disease severity and were most likely to meet the primary endpoint (30%), compared to AE and CE (17% and 10%, respectively). Kidney function biomarkers showed stepwise increases with AKI severity across all endotypes, whereas non-functional biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], soluble urokinase plasminogen activator receptor [suPAR], and bioactive adrenomedullin [bio-ADM]) exhibited endotype-specific differences independent of AKI severity. NGAL and suPAR levels were disproportionately elevated in the IE group, suggesting a dominant role of innate immune dysregulation in this endotype. In contrast, bio-ADM, a marker of endothelial dysfunction, was the strongest risk-predictor of outcomes in CE. The combination of transcriptomic endotyping with protein-based biomarkers enhanced predictive accuracy for the primary endpoint and 7-day mortality, with the highest area under the receiver operating characteristic curve of 0.80 (95% CI 0.72-0.88) for endotyping + bio-ADM and 0.85 (95% CI 0.78-0.93) for endotyping and suPAR, respectively. Combinations of endotyping with functional and non-functional biomarkers particularly improved mortality-related risk stratification.

Combining transcriptomic endotyping with protein-based biomarker profiling enhances risk-stratification in SA-AKI, offering a promising strategy for personalized treatment and trial enrichment in the future. Further research should validate these findings and explore therapeutic applications.

Acute kidney injury (AKI) is associated with high death rates and unfavorable outcomes. Previous studies evaluating the effect of the timing of CRRT therapy on the prognosis of patients with AKI have shown inconsistent results. Consequently, we aimed to assess the impact of continuous renal replacement therapy (CRRT) initiation on the outcomes of patients with AKI. This meta-analysis identified eligible randomized controlled trials (RCTs) via comprehensive searches of PubMed, Embase, and the Cochrane databases from their creation until June 1, 2024. Outcomes, including 28-, 60-, and 90-day mortality and adverse event incidence, were compared between the early and delayed CRRT groups post-randomization. Twelve RCTs (n = 1,244) were included. Meta-analysis indicated that early initiation of CRRT did not significantly affect 28-day mortality (RR 0.91 [0.79, 1.06]; p =  0.23; I2 =  0). Early CRRT initiation correlated with a shorter length of ICU stay [MD -3.24 (-5.14, -1.35); p = 0.0008; I2 = 36%] but did not significantly affect hospital stay duration [MD -7.00 (-14.60, 0.60); p = 0.07; I2 = 38%]. The early initiation of CRRT was associated with a significant reduction in RRT dependency at discharge [RR 0.57 (0.32, 0.99); P = 0.05; I2 = 0%; P = 0.47]. Compared to delayed CRRT, early CRRT was associated with higher incidence rates of hypotension [RR 1.26 (1.06, 1.50); p = 0.008; I2 = 0%], thrombocytopenia [RR 1.53 (1.11, 2.10); p = 0.009; I2 = 0%], and hypophosphatemia [RR 3.35 (2.18, 5.15); p < 0.00001; I2 = 11%]. Our findings suggest that although early CRRT initiation is associated with short intensive care unit stays and reduced RRT dependence, it has no significant effect on mortality and is in fact associated with higher incidence rates of hypotension, thrombocytopenia, and hypophosphatemia. Therefore, early CRRT should be used clinically with caution and consideration of potential adverse effects.

The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to assist healthcare providers in making appropriate decisions in the treatment of sepsis and septic shock, leading to improved patient outcomes. We aimed to create guidelines that are easy to understand and use for physicians who recognize sepsis and provide initial management, specialized physicians who take over the treatment, and multidisciplinary healthcare providers, including nurses, physical therapists, clinical engineers, and pharmacists. The J-SSCG 2024 covers the following nine areas: diagnosis of sepsis and source control, antimicrobial therapy, initial resuscitation, blood purification, disseminated intravascular coagulation, adjunctive therapy, post-intensive care syndrome, patient and family care, and pediatrics. In these areas, we extracted 78 important clinical issues. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 42 GRADE-based recommendations, 7 good practice statements, and 22 information-to-background questions were created as responses to clinical questions. We also described 12 future research questions.

Among critically ill patients with severe acute kidney injury (AKI) who lack emergent indications for renal replacement therapy (RRT), a strategy of preemptive RRT initiation does not lead to improved outcomes. However, for patients with persistent AKI and without urgent indications for RRT, the safety of prolonged delays in RRT initiation is unclear. We sought to assess the association between progressively longer delays in RRT initiation and clinical outcomes.

A post hoc secondary analysis.

The multinational STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial.

Participants allocated to the standard strategy of the STARRT-AKI trial.

The exposure was time from randomization to RRT initiation, evaluated in quartiles and as a continuous variable.

The primary outcome was all-cause mortality at 90 days. Secondary outcomes were RRT dependence, RRT-free days, and hospital-free days, all at 90 days, as well length of ICU and hospital stay. Of the 1462 participants allocated to the standard strategy group, 903 (62%) received RRT. Median time (interquartile range) to RRT initiation was 12.1 hours (8.3-13.8 hr), 24.5 hours (21.8-26.5 hr), 46.8 hours (35.2-52.1 hr), and 96.1 hours (76.7-139.2 hr) in quartiles 1-4, respectively. Prolonged time to RRT initiation was associated with a lower risk of death at 90 days (quartile 4 vs. 1: adjusted odds ratio, 0.63 [95% CI, 0.42-0.94]); further analyses using cubic splines and inverse probability weighting to account for immortal time bias showed no association with the risk of death. There was no association between time to RRT initiation and RRT-free days, hospital-free days, or lengths of ICU or hospital stay. Longer delay to RRT initiation had a linear association with RRT dependence at 90 days.

Among patients with no urgent indications and who received RRT in the standard strategy of the STARRT-AKI trial, longer deferral of RRT initiation was not associated with a higher risk of mortality.

Acute kidney injury (AKI) is associated with a significant burden of mortality worldwide. Each episode of AKI increases the long-term risk of death, especially if there is no recovery or insufficient renal recovery (i.e. restoration of kidney function). This narrative review summarizes relevant studies on the definition and prediction of renal recovery. The following databases were searched for references: PubMed, Web of Science, Cochrane Library, Scopus. The period lasted from 1990 until 2024. The currently available criteria for renal recovery have been identified and discussed. Regarding restoration of kidney function prediction, seven studies on alternative or novel biomarkers have been reviewed. In the context of kidney replacement therapy and renal recovery, findings from four large, prospective randomized studies have been summarized. A standardized definition of renal recovery is presently not available. Specific biomarkers allow for an estimation of the likelihood of renal recovery under certain conditions. According to current knowledge, no dialysis method has been definitively shown to be advantageous for the recovery process.

This study aimed to assess the clinical impact of oXiris-continuous hemofiltration adsorption on patients with septic shock and their prognosis.

A retrospective study.

Septic shock patients.

The oXiris group underwent hemofiltration adsorption using oXiris hemofilters and septic shock standard treatment, while the control group received septic shock standard treatment.

The changes in inflammatory indicators and short-term mortality rate were evaluated. Propensity score matching (PSM) was conducted based on the 1:2 ratio between the oXiris and control groups to account for any baseline data differences.

Results showed that after 24 h, 48 h, and 72 h of treatment, PCT, IL-6, and hs-CRP levels in the oXiris group were significantly lower than those in the control group (P < 0.05). However, there were no significant differences in norepinephrine equivalents and organ function status (APACHE II score, SOFA score, Lac) between the two groups at the same time points. The 72-h mortality rate (21.88% vs. 34.04%) and the 7-day mortality rate (28.12% vs. 44.68%) were lower in the oXiris group compared to the control group, but not statistically significant. The 28-day mortality rate did not show a significant difference between the two groups (53.19% vs. 56.25%).

oXiris continuous hemofiltration adsorption technology may reduce the levels of inflammatory factors in patients with septic shock; however, it does not appear to enhance organ function or improve the 28-day mortality rate in these patients.

Acute kidney injury (AKI) is a syndrome characterized by a rise in creatinine or a decrease in urinary flow, according to the Kidney Disease Improving Global Outcomes (KDIGO) definition. It is diagnosed in 15% of inpatients and 50% of patients in the intensive care unit (ICU), and it is related to increased mortality. As part of a global effort aimed at the elimination of preventable deaths from AKI, there is a growing interest in identifying biomarkers that can be point-of-care and that are not influenced by the variability in patient characteristics in a relevant way. Neutrophil gelatinase-associated lipocalin (NGAL), particularly in its 25 kDa form, which is exclusively released by renal tubules, has emerged as a promising biomarker with potential use in the diagnosis of AKI in the critically ill, including its use in guiding the initiation and/or weaning of renal replacement therapy (RRT). The objective of this review is to summarize the current understanding of NGAL in acute settings, emphasizing biological and genomic insights.

Kidney injury and disease pose a significant global health burden. Despite existing diagnostic methods, early detection remains challenging due to the lack of specific molecular markers to identify and stage various kidney lesions. Urinary exosomes, extracellular vesicles secreted by kidney cells, offer a promising solution. These vesicles contain a variety of biomolecules, such as proteins, RNA, and DNA. These biomolecules can reflect the unique physiological and pathological states of the kidney. This review explores the potential of urinary exosomes as biomarkers for a range of kidney diseases, including renal failure, diabetic nephropathy, and renal tumors. By analyzing specific protein alterations within these exosomes, we aim to develop more precise and tailored diagnostic tools to detect kidney diseases at an early stage and improve patient outcomes. While challenges persist in isolating, characterizing, and extracting reliable information from urinary exosomes, overcoming these hurdles is crucial for advancing their clinical application. The successful implementation of urinary exosome-based diagnostics could revolutionize early kidney disease detection, enabling more targeted treatment and improved patient outcomes.

The 2012 Kidney Disease Improving Global Outcomes guidelines clearly define emergent indications for kidney replacement therapy; however, whether dialysis should be initiated in critically ill patients without these indications remains unclear. This review briefly summarizes the results of recent landmark trials and discusses their limitations originating from a criteria-based approach at a single time point. Moreover, a personalized approach based on each patient's demand-capacity balance and its future benefits as a platform for kidney support therapy in critically ill patients are discussed.

Ursodeoxycholic acid (UDCA), traditionally recognized for its hepatoprotective effects, has also shown potential in protecting kidney injury. This study aimed to evaluate the protective effects of UDCA against sepsis-induced acute kidney injury (AKI) and to elucidate the underlying mechanisms.

Sixty male C57BL/6 N mice were utilized to establish a sepsis-induced AKI model through intravenous injection of lipopolysaccharides (LPS, 10 mg/kg). UDCA (15, 30, and 60 mg/kg) was administered intraperitoneally once daily for 7 days before LPS injection. Kidney injury was evaluated by HE staining and biochemical markers, including serum creatinine (Cr), blood urea nitrogen (BUN), urinary protein, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), and retinol binding protein (RBP). Oxidative stress parameters and nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) pathway, pro-inflammatory cytokines and nuclear factor-kappa B (NF-κB) pathway were also evaluated. Additionally, HK-2 cells were treated with LPS in vitro, and cell viability and apoptosis were detected using CCK-8 kit and flow cytometer, respectively.

UDCA significantly attenuated LPS-induced renal histopathological damage and improved renal function, as evidenced by reduction in serum Cr, BUN, and urinary protein levels. UDCA also up-regulated the protein expression of zonula occludens-1 (ZO-1) and Ezrin in the kidney, and reduced the urinary levels of NGAL, KIM-1, NAG, and RBP. Moreover, UDCA inhibited NF-κB p65 phosphorylation and reduced pro-inflammatory cytokines levels (TNF-α, IL-1β, and IL-6) in both serum and kidney. UDCA alleviated oxidative stress by activating the Nrf2/HO-1 pathway in the kidney. In vitro, UDCA reduced LPS-induced cell injury and apoptosis in HK-2 cells, with these protective effects being blocked by the Nrf2 inhibitor ML385.

Our present study demonstrated that UDCA exerts protective effects against sepsis-induced AKI by attenuating oxidative stress and inflammation, primarily through the activation of the Nrf2/HO-1 pathway and inhibition of the NF-κB pathway. These findings highlight the therapeutic potential of UDCA in preventing sepsis-induced AKI.

Acute kidney injury (AKI) is common in critically ill patients and is associated with increased morbidity and mortality. Its complications often require renal replacement therapy (RRT). Invasive mechanical ventilation (IMV) and infections are considered risk factors for the occurrence of AKI. The use of IMV and non-invasive ventilation (NIV) has changed over the course of the pandemic. Concomitant with this change in treatment a reduction in the incidences of AKI and RRT was observed. We aimed to investigate the impact of IMV on RRT initiation by comparing critically ill patients with and without COVID-19. Furthermore, we wanted to investigate the rates and timing of RRT as well as the outcome of patients, who were treated with RRT.

A total of 8,678 patients were included, of which 555 (12.8%) in the COVID-19 and 554 (12.8%) in the control group were treated with RRT. In the first week of ICU stay the COVID-19 patients showed a significantly lower probability for RRT initiation (day 1: p < 0.0001, day 2: p = 0.021). However, after day 7 a reversed HR was found. In mechanically ventilated patients the risk was significantly higher for the initiation of RRT over the entire stay. While in non-COVID-19 patients this was a non-significant trend, in COVID-19 patients the risk for RRT was significantly increased. The median delay between initiation of IMV and requirement of RRT was observed to be longer in COVID-19 patients (5 days [IQR: 2-11] vs. 2 days [IQR: 1-5]). The analysis restricted to patients with RRT showed a significantly higher risk for ICU death in patients requiring IMV compared to patients without IMV.

The analysis demonstrated that IMV as well as COVID-19 are associated with an increased risk for initiation of RRT. The association between IMV and risk of RRT initiation was given for all investigated time intervals. Additionally, COVID-19 patients showed an increased risk for RRT initiation during the entire ICU stay within patients admitted to an ICU due to respiratory disease. In COVID-19 patients treated with RRT, the risk of death was significantly higher compared to non-COVID-19 patients.

Acute kidney injury (AKI) is a common, heterogeneous, multifactorial condition, which is part of the overarching syndrome of acute kidney diseases and disorders. This condition's incidence highest in low-income and middle-income countries. In the short term, AKI is associated with increased mortality, an increased risk of complications, extended stays in hospital, and high health-care costs. Long-term complications include chronic kidney disease, kidney failure, cardiovascular morbidity, and an increased risk of death. Several strategies are available to prevent and treat AKI in specific clinical contexts. Otherwise, AKI care is primarily supportive, focused on treatment of the underlying cause, prevention of further injury, management of complications, and short-term renal replacement therapy in case of refractory complications. Evidence confirming that AKI subphenotyping is necessary to identify precision-oriented interventions is growing. Long-term follow-up of individuals recovered from AKI is recommended but the most effective models of care remain unclear.

Acute Kidney Injury (AKI) is a common complication in patients with Acute Respiratory Distress Syndrome (ARDS) receiving VV-ECMO support, carrying a high risk of progression to Renal Replacement Therapy (RRT). Both AKI and RRT are linked to an increased risk of mortality. This study aims to evaluate the risk factors associated with the need for RRT in patients undergoing VV-ECMO. Methods: This is a retrospective case-control study involving patients on VV-ECMO therapy admitted to the intensive care unit (ICU) between 2019 and 2023. Patients on VV ECMO support, with or without RRT, were included and their severity scores and associated mortality were calculated. A multivariate logistic regression analysis was performed to assess the variable RRT using odds ratios (OR) with their corresponding confidence intervals (CI) for the outcome variables. Results: A total of 192 subjects were included, with a mortality rate of 39.6%. Of these, 68.7% were male, with an average ICU stay of 25.1 days and a need for RRT in 19.7% of cases. The multivariate analysis independently associated the use of vasopressors with RRT norepinephrine OR 5.61 (95% CI, 1.64-19.1) and vasopressin OR 4.64 (95% CI, 2.15-10.0)). An increase in creatinine levels before ECMO support is associated with an increased risk OR 2.21 (95% CI 1.54-3.18), and 24 h after ECMO support, the risk rises further adjusted odds ratio (AOR) 3.32 (95% IC 1.55-7.09). The accuracy of severity scores presented weak discrimination and similar behavior, except for DEOx for the primary outcome, with an AUC of 0.79 (95% CI, 0.72-0.87), and APACHE II with an AUC of 0.68 (95% CI, 0.59-0.78). Conclusions: The prediction of RRT in patients on VV-ECMO support was superior for DEOx, which is influenced by the use of vasopressors, creatinine levels, and platelet transfusion prior to cannulation. This could be useful for predicting early interventions in this patient population.

Acute Kidney Injury (AKI) is a significant medical condition characterized by the abrupt decline in kidney function.Low-intensity pulsed ultrasound (LIPUS), a non-invasive therapeutic technique employing low-intensity acoustic wave pulses, has shown promise in promoting tissue repair and regeneration. A novel LIPUS system was developed and evaluated in rat AKI models, focusing on its effects on glomerular filtration rate (GFR), blood urea nitrogen (BUN), serum creatinine (SCr), and the Notch1-Akt-eNOS signaling pathway. The results demonstrated that LIPUS treatment improved GFR, BUN, SCr levels, and renal pathology in AKI rats. In vitro experiments using HUVEC cells revealed that LIPUS stimulation promoted angiogenesis, cell migration mechanically-dependent calcium ion influx, which was partially attenuated by TRPV1 knockdown. RNA sequencing analysis indicated LIPUS-induced activation of the Notch pathway, phosphorylation of Akt and eNOS. Furthermore, inhibition or genetic silencing of Notch1 abolished the beneficial effects of LIPUS on angiogenesis, renal function, and Akt-eNOS phosphorylation in both cells and AKI rats. These findings suggest that LIPUS-induced calcium influx promotes Akt-eNOS phosphorylation, nitric oxide (NO) production, angiogenesis, and improved renal function in AKI via Notch1-Akt-eNOS signaling, positioning LIPUS as a promising therapeutic strategy for AKI by targeting vascular regeneration.

While renal replacement therapy (RRT) allows for precise fluid management as well as addressing electrolyte imbalances and the removal of other necessary compounds, its early initiation has not shown benefit in the general critically ill population. Moreover, the effects of early RRT initiation specifically in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) also remain unclear. This retrospective study investigated adult patients who underwent VA-ECMO between April 2018 and March 2022 and used the clone-censor-weight method to emulate a hypothetical target trial and compare two groups: patients who initiated RRT within 2 days of VA-ECMO initiation (Early) and those who did not (Late). The primary outcomes were 28-day and 90-day hospital mortality analyzed by Cox proportional hazards models and the secondary outcome was 90-day RRT dependence by pooled logistic regression models. Inverse probability censoring weights were applied to adjust the models. A total of 2,513 VA-ECMO patients were cloned into both groups. The 28-day and 90-day mortalities were lower in the Early group (HR 0.59 [95% CI 0.53-0.68] and 0.67 [0.61-0.75]). However, the early group experienced greater RRT dependence at 90 days than the late group (OR 2.58 [1.94-3.46]). In conclusion, early initiation of RRT (within 2 days of VA-ECMO) was associated with lower hospital mortality but with a higher likelihood of 90-day RRT dependence in adult patients on VA-ECMO.

Eligibility criteria for randomized clinical trials (RCTs) are designed to select clinically relevant patient populations. However, not all eligibility criteria are strongly justified, potentially excluding marginalized groups, and limiting the generalizability of trial findings.

To summarize and evaluate the justification of exclusion criteria in published RCTs in critical care medicine.

A systematic sampling review of parallel-group RCTs published in the top 5 general internal medicine journals by impact factor (The Lancet, New England Journal of Medicine, Journal of the American Medical Association, British Medical Journal, and Annals of Internal Medicine) between January 1, 2018, and February 23, 2023, was conducted. RCTs enrolling adults in intensive care units (ICUs) and RCTs enrolling critically ill patients who required life-sustaining interventions typically initiated in the ICU were included. All study exclusion criteria were categorized as either poorly justified, potentially justified, or strongly justified, adapting previously established criteria, independently and in duplicate.

In total, 225 studies were identified, 75 of which were included. The median (IQR) number of exclusion criteria per trial was 19 (14-24), with 1455 total exclusion criteria. Common exclusion criteria were related to the risk of adverse reaction to interventions (302 criteria [20.8%]), followed by inability to obtain consent (120 criteria [8.2%]), and treatment limitation decisions (97 criteria [6.7%]). Most exclusion criteria were either strongly justified (1080 criteria [74.2%]) or potentially justified (297 criteria [20.4%]), whereas 5.4% (78 criteria) were poorly justified. Of the 78 poorly justified exclusion criteria, the most common were pregnancy (19 criteria [24.4%]), communication barriers (11 criteria [14.1%]), lactation (10 criteria [12.8%]), and lack of health insurance (10 criteria [12.8%]). Overall, 45 of 75 studies (60.0%) had at least 1 poorly justified exclusion criteria.

Most exclusion criteria in critical care medicine RCTs were strongly justifiable. Across poorly justified criteria, the most common exclusions were pregnant or lactating persons, those with communication barriers, and individuals without health insurance. This highlights the need to carefully consider exclusion criteria when designing trials to minimize the inappropriate exclusion of participants and enhance generalizability.

The KDIGO recommendation in acute kidney injury (AKI) patients requiring kidney replacement therapy is to deliver a Urea Kt/V of 1.3 for intermittent thrice weekly hemodialysis, and an effluent volume of 20-25 ml/kg/hour when using continuous renal replacement therapy (CRRT). Considering that prior studies have suggested equivalent outcomes when using CRRT-prolonged intermittent renal replacement therapy (PIRRT) effluent doses below 20 mL/kg/h, our group investigated the possible benefits of low effluent volume CRRT-PIRRT (12.5 ml/Kg/hour).

Thirty-six AKI patients that had been treated in the previous 12 months by CRRT-PIRRT with low effluent volume were included in the present retrospective observational study. The total effluent volume, derived from the formula [25 (or 12.5 ml) × kg body weight × 24], was administered over 24 h in CRRT and over 10 h in daily PIRRT. The control group consisted of the last 36 AKI patients previously treated with standard effluent volume CRRT (25 ml/kg/hour). Mortality within 90 days, shift from low effluent volume to standard effluent volume due to dialysis inadequacy, and remission of AKI were the end points. The two groups were homogeneous for age, sex, and sequential organ failure assessment (SOFA) score. Patients with AKI caused by metformin-induced lactic acidosis were excluded because they were treated with standard effluent volume CRRT until the lactic acidosis was corrected by subsequently reducing the effluent volume to 12.5 ml/kg/hour.

The two groups were homogeneous as for baseline features. The UKt/V in the low effluent volume group was 0.51 ± 0.04 in CRRT and 0.50 ± 0.07 in PIRRT per session (Table 3). The UKt/V in the standard effluent volume group was 1.00 ± 0.02 in CRRT and 0.95 ± 0.05 in PIRRT per session. No differences were observed between the 2 groups regarding death from any cause at 90 days, and recovery of renal function. No patient was switched from low effluent volume to standard effluent volume due to inadequate control of uremic toxins. Serum creatinine at discharge from the hospital in patients with no KRT dependence was 2.1 ± 0.6 mg/dl in standard effluent volume and 1.9 ± 0.5 in low effluent volume (p = 0.37). All low effluent volume patients showed adequate metabolic, electrolyte, and acid-base profile control. In the low effluent volume group, the incidence of hypophosphatemia was lower than in the standard effluent volume group (5 vs 15, p = 0.003).

In this single-center retrospective study, low effluent volume CRRT-PIRRT was associated with similar outcomes to standard effluent volume CRRT-PIRRT, which is consistent with the results of prior observational studies. Randomized controlled studies comparing low effluent volume with standard effluent volume are needed.

Objective: The combination of catecholamine-resistant vasodilatory shock and acute kidney injury (AKI) is associated with high morbidity and mortality. The role of angiotensin II (ANGII) in this setting is unclear. Methods: We conducted a post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS) 3 trial which assessed the effect of Intravenous ANG II or placebo in patients with refractory vasodilatory shock in 75 intensive care units across nine countries in North America, Australasia, and Europe. We included patients with all stages AKI at initiation of ANG II or placebo and assessed 28-day mortality as primary outcome. We studied mean arterial pressure (MAP) response and days alive and free from renal replacement therapy (RRT) up to day 7 as secondary outcome. Results: Of 321 ATHOS-3 patients, 203 (63%) had AKI at randomization, with stage 3 AKI being dominant (67%). Median age was 63 years and median APACHE II score was 30. By day 28, overall, 118 (58%) of patients had died (53% with ANGII vs. 63% with placebo, hazard ratio = 0.75, 95% CI [0.52-1.08], P = 0.121). Among AKI stage 3 patients, however, ANGII was associated with significantly lower mortality (48% vs. 67%, hazard ratio = 0.57, 95% CI [0.36-0.91], P = 0.024). Additionally, in this subgroup, compared with placebo, patients receiving ANGII were more likely to achieve a MAP response (P < 0.001) and had more days alive and free from RRT (P < 0.001). Conclusions: Compared with placebo, in patients with catecholamine-resistant vasodilatory shock and stage 3 AKI, ANGII is associated with lower 28-day, greater likelihood of MAP response, and more days alive and free from RRT. These findings support the conduct of future ANGII trials in patients with stage 3 AKI.

Acute kidney injury (AKI) is prevalent in critically ill patients and is associated with an increased risk of in-hospital mortality. Nephrology consultation may be protective, but this has rarely been evaluated in South Korea.

This multicenter retrospective study was based on the electronic medical records (EMRs) of two third-affiliated hospitals. We extracted the records of patients admitted to intensive care units (ICUs) between 2011 and 2020, and retrospectively detected AKI using the modified serum creatinine criteria of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The AKI diagnosis date was defined as the first day of a significant change in serum creatinine level (≥0.3 mg/dL) within 48 hours. Nephrology consultation status was retrieved from the EMRs.

In total, 2,461 AKI patients were included; the median age was 65 years (interquartile range [IQR], 56-75 years), 1,459 (59.3%) were male, and 1,065 (43.3%) were of AKI stage 3. During a median of 5 days (IQR, 3-11 days) of ICU admission, nephrology consultations were provided to 512 patients (20.8%). Patients who received such consultations were older, had more comorbidities, and more commonly required dialysis. In a multivariable model, nephrology consultation reduced the risk of in-hospital mortality by 30% (hazard ratio, 0.71; 95% confidence interval, 0.57-0.88). Other factors significant for in-hospital mortality were older age, a higher sequential organ failure assessment (SOFA) score, sepsis, diabetes, hypertension, heart disease, and cancer.

For AKI patients in ICUs, nephrology consultation reduced the risk of in-hospital mortality, particularly among those with multiple comorbidities. Therefore, nephrology consultation should not be omitted during ICU care.

Accurate estimation of in-hospital outcomes for patients with acute kidney injury (AKI) is crucial for aiding physicians in making optimal clinical decisions. We aimed to review prediction models constructed by machine learning methods for predicting AKI prognosis using administrative databases.

A systematic review following PRISMA guidelines.

Adult patients diagnosed with AKI who are admitted to either hospitals or intensive care units.

We searched PubMed, Embase, Web of Science, Scopus, and Cumulative Index to Nursing and Allied Health for studies published between January 1, 2014 and February 29, 2024. Eligible studies employed machine learning models to predict in-hospital outcomes of AKI based on administrative databases.

Extracted data included prediction outcomes and population, prediction models with performance, feature selection methods, and predictive features.

The included studies were qualitatively synthesized with assessments of quality and bias. We calculated the pooled model discrimination of different AKI prognoses using random-effects models.

Of 3,029 studies, 27 studies were eligible for qualitative review. In-hospital outcomes for patients with AKI included acute kidney disease, chronic kidney disease, renal function recovery or kidney failure, and mortality. Compared with models predicting the mortality of patients with AKI during hospitalization, the prediction performance of models on kidney function recovery was less accurate. Meta-analysis showed that machine learning methods outperformed traditional approaches in mortality prediction (area under the receiver operating characteristic curve, 0.831; 95% CI, 0.799-0.859 vs 0.772; 95% CI, 0.744-0.797). The overlapping predictive features for in-hospital mortality identified from ≥6 studies were age, serum creatinine level, serum urea nitrogen level, anion gap, and white blood cell count. Similarly, age, serum creatinine level, AKI stage, estimated glomerular filtration rate, and comorbid conditions were the common predictive features for kidney function recovery.

Many studies developed prediction models within specific hospital settings without broad validation, restricting their generalizability and clinical application.

Machine learning models outperformed traditional approaches in predicting mortality for patients with AKI, although they are less accurate in predicting kidney function recovery. Overall, these models demonstrate significant potential to help physicians improve clinical decision making and patient outcomes.

CRD42024535965.

The timing of coronary angiography in patients with successfully resuscitated out-of-hospital cardiac arrest and missing ST-segment elevations on the electrocardiogram has been investigated in 2 large randomized controlled trials, TOMAHAWK (Angiography After Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation) and COACT (Coronary Angiography After Cardiac Arrest Trial). Both trials found neutral results for immediate vs delayed/selective coronary angiography on short-term all-cause mortality. The TOMAHAWK trial showed a tendency towards harm with immediate coronary angiography, though not statistically significant with traditional frequentist methods. Probabilistic analyses of both trials may enable greater clinical understanding of the trial findings.

The purpose of this study was to perform reanalyses of both trials within a Bayesian framework.

Post hoc analyses of both multicenter randomized controlled trials were performed in both cohorts separately and combined. The primary endpoint, 30-day all-cause mortality, was analyzed using Bayesian logistic regression. A spectrum of priors included "flat," "neutral," "optimistic," and "pessimistic" priors based on assumptions made when designing both trials.

In the TOMAHAWK trial, immediate coronary angiography showed a very high posterior probability of increased mortality between 90% and 97% across all priors. The ORs across all priors were directed towards harm. Similarly, COACT showed odds ratios ranging from 0.98 to 1.11 for the 30-day mortality endpoint. When combining both trials, immediate coronary angiography showed a high probability of increased mortality between 83% and 95%, again with ORs across all priors indicating a direction towards harm.

Bayesian reanalyses showed a very high probability of increased 30-day mortality risk with immediate compared with delayed/selective coronary angiography in the TOMAHAWK trial and combined trial cohort. These findings may shift the current understanding of both trials from a "neutral" towards a likely "harmful" effect of immediate coronary angiography after successfully resuscitated out-of-hospital cardiac arrest without ST-segment elevations. Therefore, adoption of a delayed strategy of coronary angiography might be preferred in clinical practice until the results of the DISCO (Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest) trial become available.

Acute kidney injury (AKI) is a prevalent complication in critically ill patients that affects the timing of renal replacement therapy (RRT) initiation. This study aimed to develop and validate the SACrA score for predicting non-emergent initiations (BUN ≥112 mg/dL or oliguria for >72 h) of RRT in critically ill patients.

We conducted a retrospective cohort study using data from two cohorts. The derivation cohort included patients admitted to the ICU between November 2021 and December 2023, whereas the validation cohort included patients admitted between September 2019 and October 2021. The primary outcome was non-emergent RRT initiation. The multivariate logistic regression with stepwise selection based on the Akaike information criterion finalized the model, including the variables, such as sex, albumin (Alb), creatinine (Cr), and APACHE II score (SACrA).

The derivation and validation cohorts comprised 470 and 476 patients, respectively. The SACrA score showed a strong predictive performance for non-emergent RRT initiation in both the cohorts. Cohort 1 had an ROC-AUC of 0.971, with a calibration slope of 0.982 and an intercept of 0.009, whereas cohort 2 had an ROC-AUC of 0.918, with a calibration slope of 0.988 and an intercept of 0.004.

The SACrA score is a robust tool for predicting non-emergent RRT initiation in critically ill patients using readily available clinical variables. Though additional data are needed to validate the SACrA score, our analysis suggests the tool may help clinicians make informed decisions, reduce unnecessary RRT, and thereby improve patient outcomes.

Net ultrafiltration (UFNET) during continuous renal replacement therapy (CRRT) can control fluid balance (FB), but is usually 0 ml·h-1 in patients with vasopressors due to the risk of hemodynamic instability associated with CRRT (HIRRT). We evaluated a UFNET strategy adjusted by functional hemodynamics to control the FB of patients with vasopressors, compared to the standard of care.

In this randomized, controlled, open-label, parallel-group, multicenter, proof-of-concept trial, adults receiving vasopressors, CRRT since ≤ 24 h and cardiac output monitoring were randomized (ratio 1:1) to receive during 72 h a UFNET ≥ 100 ml·h-1, adjusted using a functional hemodynamic protocol (intervention), or a UFNET ≤ 25 ml·h-1 (control). The primary outcome was the cumulative FB at 72 h and was analyzed in patients alive at 72 h and in whom monitoring and CRRT were continuously provided (modified intention-to-treat population [mITT]). Secondary outcomes were analyzed in the intention-to-treat (ITT) population.

Between June 2021 and April 2023, 55 patients (age 69 [interquartile range, IQR: 62; 74], 35% female, Sequential Organ Failure Assessment (SOFA) 13 [11; 15]) were randomized (25 interventions, 30 controls). In the mITT population, (21 interventions, 24 controls), the 72 h FB was -2650 [-4574; -309] ml in the intervention arm, and 1841 [821; 5327] ml in controls (difference: 4942 [95% confidence interval: 2736-6902] ml, P < 0.01). Hemodynamics, oxygenation and the number of HIRRT at 72 h, and day-90 mortality did not statistically differ between arms.

In patients with vasopressors, a UFNET fluid removal strategy secured by a hemodynamic protocol allowed active fluid balance control, compared to the standard of care.

Sepsis is defined as "being evoked as a life-threatening organ dysfunction caused by an inadequate host response to infection". The most recent German S3 guidelines were published in 2018 and the Surviving Sepsis Campaign (SSC) last published the current recommendations for the treatment of sepsis and septic shock in 2021.

This article explores and discusses which evidence in the treatment of sepsis and septic shock has been confirmed.

Discussion of the 2018 German S3 guidelines, supplementation of the content of the 2021 international guidelines and recent research results since 2021.

The primary objective for managing sepsis and septic shock still includes rapid identification, early initiation of anti-infective treatment, and focus cleansing when feasible. In addition, the focus is on hemodynamic stabilization, including the early use of vasopressors for prevention of hypervolemia and, if necessary, the use of organ support procedures. Supportive treatment, such as the administration of corticosteroids and the use of apheresis, can be advantageous in specific scenarios. The focus is increasingly shifting towards post-intensive care unit (ICU) follow-up care, improving the quality of life after surviving sepsis and the close involvement of relatives of the patient.

Despite the fact that considerable progress has been made in understanding the pathophysiology and treatment of sepsis, the early administration of anti-infective agents, focus control, nuanced volume therapy and the use of catecholamines continue to be fundamental to sepsis management. New recommendations emphasize the early use of vasopressors (primarily norepinephrine) and the administration of corticosteroids, especially in cases of septic shock and pneumonia.

The physiology of the kidney has long been understood, and its mechanisms are well described. The pathology of renal failure is also a deeply researched area. It seems logical, therefore, to create devices that can replace the lost normal function of the kidney. Using the physical processes that take place in the kidney, such as diffusion or convection across a membrane, various renal replacement therapies (RRT) have been created. There are those that are used intermittently and those that are used for longer periods. What they have in common is that all RRTs have the same purpose; to replace the excretory function of the kidney that has been lost. CRRT is an extracorporeal renal replacement therapy that effectively replicates the excretory function of the kidneys in cases of acute renal failure. However, it has become increasingly evident that this rapidly advancing treatment modality offers benefits beyond merely substituting kidney function, with its applications continuing to expand significantly with non-renal and other indications. The use of these devices has raised new questions, many of which are still not clearly answered. When should this start? Who should receive it? How long should it last? What indication should it be for? What modality should it be with? How does it change the pharmacokinetics of the medicines? To answer these questions, it is first worth understanding the mechanisms behind the processes and the factors that influence them. This should not only focus on the procedures used in RRT therapies, but also consider the patient's condition and the physicochemical properties of the drugs. In this review, we aim to provide a literature summary to highlight the factors that may influence the success of RRT therapies.

Renal replacement therapy (RRT) is an important treatment option for sepsis-associated acute kidney injury (AKI); however, the optimal timing for its initiation remains controversial. Herein, we investigated the clinical outcomes of early continuous kidney replacement therapy (CKRT), defined as CKRT initiation within 6 hours of sepsis-associated AKI onset, which was earlier than the initiation time defined in previous studies.

We used clinical data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. This study included patients aged ≥ 18 years who met the sepsis diagnostic criteria and received CKRT because of stage 2 or 3 AKI. Early and late CKRTs were defined as CKRT initiation within 6 hours and after 6 hours of the development of sepsis-associated AKI, respectively.

Of the 33,236 patients diagnosed with sepsis, 553 underwent CKRT for sepsis-associated AKI. After excluding cases of early mortality and patients with a dialysis history, 45 and 334 patients were included in the early and late CKRT groups, respectively. After propensity score matching, the 28-day mortality rate was significantly lower in the early CKRT group than in the late CKRT group (26.7% vs. 43.9%, P = 0.035). The early CKRT group also had a significantly greater number of days free of mechanical ventilation (median, 19; interquartile range [IQR], 3-25) and vasopressor administration (median, 21; IQR, 5-26) than the late CKRT group did (median, 10.5; IQR, 0-23; P = 0.037 and median, 13.5; IQR, 0-25; P = 0.028, respectively). The Kaplan-Meier curve also showed that early CKRT initiation was associated with an improved 28-day mortality rate (log-rank test, P = 0.040). In contrast, there was no significant difference in the 28-day mortality between patients who started CKRT within 12 hours and those who did not (log-rank test, P = 0.237).

Early CKRT initiation improved the survival of patients with sepsis-associated AKI. Initiation of CKRT should be considered as early as possible after sepsis-associated AKI onset, preferably within 6 hours.

Acute kidney injury (AKI) is a sudden onset of renal injury that occurs within a few hours or days. Ischemia-reperfusion (IR) is a major cause of AKI. There are multiple dysregulated mechanisms behind the pathogenesis of AKI and IR which urges the need for finding multi-targeting therapies. Natural products are multi-targeting agents with promising sources of anti-inflammation, antioxidant, and antiapoptosis. Among them, astaxanthin (AST) is a keto-carotenoid with a high antioxidant potential. Using solid lipid nanoparticles (SLNs) as a novel formulation of AST helps to increase its efficacy and reduce side effects against AKI. After SLN preparation and loading of AST, the physicochemical properties were evaluated, using scanning electron microscopy (SEM) and dynamic light scattering (DLS) tests. For the in vivo study, 28 rats were divided into four groups, including sham, ischemia/reperfusion (I/R), and groups receiving protective and daily doses of AST-SLN (5 and 10 mg/kg, i.p.) during all 5 days before ischemia. Exactly 24 h after ischemia, kidneys were isolated for histological studies, and also, serum levels of catalase (CAT), glutathione (GSH), nitrite, blood urea, and creatinine were measured. The results indicated that intraperitoneal administration of SLN-AST reduced oxidative stress by decreasing serum nitrite levels, while increasing CAT and GSH. SLN-AST also improved renal function by decreasing serum urea and creatinine and preventing tissue damage. Therefore, SLN-AST could be a hopeful adjuvant candidate to prevent AKI by modulating renal function, preventing tissue damage, and through antioxidant mechanisms.

Acute kidney injury (AKI) is a common syndrome in hospitalized patients and is associated with increased morbidity and mortality. The focus of AKI care requires a shift away from strictly supportive management of established injury to the early identification and timely prevention of worsening renal injury. Identifying patients at risk for developing or progression of severe AKI is crucial for improving patient outcomes, reducing the length of hospitalization and minimizing resource utilization. Implementation of dynamic risk scores and incorporation of novel biomarkers show promise for early detection and minimizing progression of AKI. Like any risk assessment tools, these require further external validation in a variety of clinical settings prior to widespread implementation. Additionally, alerts that may minimize exposure to a variety of nephrotoxic medications or prompt early nephrology consultation are shown to reduce the incidence and progression of AKI severity and enhance renal recovery. While dynamic risk scores and alerts are valuable, implementation requires thoughtfulness and should be used in conjunction with the overall clinical picture in certain situations, particularly when considering the initiation of fluid and diuretic administration or renal replacement therapy. Despite the contemporary challenges encountered with alert fatigue, implementing an alert-based bundle to improve AKI care is associated with improved outcomes, even when implementation is incomplete. Lastly, all alert-based interventions should be validated at an institutional level and assessed for their ability to improve institutionally relevant and clinically meaningful outcomes, reduce resource utilization and provide cost-effective interventions.

Fluid accumulation, presently defined as a pathologic state of overhydration/volume overload associated with clinical impact, is common and associated with worse outcomes. At times, deresuscitation, the active removal of fluid via diuretics or ultrafiltration, is necessary. There is no consensus regarding deresuscitation in children admitted to the pediatric intensive care unit. Little is known regarding perceptions and practices among pediatric intensivists and nephrologists regarding fluid provision and deresuscitation.

Cross-sectional electronic survey of pediatric nephrologists and intensivists from academic societies in the United States designed to better understand fluid management between disciplines. A clinical vignette was used to characterize the perceptions of optimal timing and method of deresuscitation initiation at four timepoints that correspond to different stages of shock.

In total, 179 respondents (140 intensivists, 39 nephrologists) completed the survey. Most 75.4% (135/179) providers believe discussing fluid balance and initiating fluid deresuscitation in pediatric intensive care unit (PICU) patients is "very important". The first clinical vignette time point (corresponding to resuscitation phase of early shock) had the most dissimilarity between intensivists and nephrologists (p = 0.01) with regards to initiation of deresuscitation. However, providers demonstrated increasing agreement in their responses to initiate deresuscitation as the clinical vignette progressed. Compared to intensivists, nephrologists were more likely to choose "dialysis or ultrafiltration" as a deresuscitation method during the optimization [10.3 vs. 2.9% (p = 0.07)], stabilization [18.0% vs. 3.6% (p < 0.01)], and evacuation [48.7% vs. 23.6% (p < 0.01)] phases of shock. Conversely, intensivists were more likely to utilize scheduled diuretics than nephrologists [47.1% vs. 28.2% (p = 0.04)] later on in the patient course.

Most physicians believe that discussing fluid balance and deresuscitation is important. Nevertheless, when to initiate deresuscitation and how to accomplish it differed between nephrologist and intensivists. Widely understood and operationalizable definitions, further research, and eventually evidence-based guidelines are needed to help guide care.

The objective of this study was to determine the impact of the timing of KRT, dichotomized by a temporal criterion or by creatinine level, in patients with COVID-19-related AKI. This was a retrospective study involving 512 adult patients admitted to the ICU. All participants had laboratory-confirmed COVID-19 and a confirmed diagnosis of AKI. The potential predictors were the determination of the timing of KRT based on a temporal criterion (days since hospital admission) and that based on a serum creatinine cutoff criterion. Covariates included age, sex, and the SOFA score, as well as the need for mechanical ventilation and vasopressors. The main outcome measure was in-hospital mortality. We evaluated 512 patients, of whom 69.1% were men. The median age was 64 years. Of the 512 patients, 76.6% required dialysis after admission. The overall in-hospital mortality rate was 72.5%. When the timing of KRT was determined by the temporal criterion, the risk of in-hospital mortality was significantly higher for later KRT than for earlier KRT-84% higher in the univariate analysis (OR = 1.84, 95%, [CI]: 1.10-3.09) and 140% higher after adjustment for age, sex, and SOFA score (OR = 2.40, 95% CI: 1.36-4.24). When it was determined by the creatinine cutoff criterion, there was no such difference between high and low creatinine at KRT initiation. In patients with COVID-19-related AKI, earlier KRT might be associated with lower in-hospital mortality.