Acute Failure Research Articles

Acute kidney injury and in-hospital outcomes after transcatheter aortic valve replacement in patients without chronic kidney disease: insights from the national inpatient sample

Abstract Background Acute kidney injury (AKI) complicates transcatheter aortic valve replacement (TAVR), leading to higher mortality. The incidence and effects of AKI on clinical outcomes in patients undergoing TAVR without chronic kidney disease (CKD) are unclear. We aimed to determine the association between AKI and in-hospital outcomes in patients with TAVR using propensity score matching (PSM). Methods Using International Classification of Diseases-10th Revision codes, we queried the National Inpatient Sample for TAVR performed between 2016 and 2021. Patients were divided into two groups according to perioperative AKI development. Patients with CKD or on permanent hemodialysis at baseline were excluded. We conducted 1:1 PSM to assemble a cohort of patients with similar baseline characteristics. Multivariate logistic regression was used to assess the association between AKI and in-hospital outcomes. Sensitivity analysis was conducted to evaluate the robustness of our inferences. Results Of 47,372 unweighted patient admissions for TAVR, 1617 (3.41%) had a concomitant diagnosis of AKI. The incidence of AKI decreased from 4.82 to 3.18% from 2016 to 2021 (P-trend < 0.01). Before PSM, patients with AKI had a significantly higher rate of in-hospital mortality compared with those without AKI (6.12% vs. 0.48%, respectively; odds ratio [OR] 8.59, 95% confidence interval [CI] 6.32–11.68). Using the PSM algorithm, 1579 well-matched patients were included in each group. After PSM, an association was observed between patients with TAVR and concomitant AKI and a higher risk of in-hospital mortality (6.21% vs. 1.08%, respectively; OR 5.96; 95% CI 3.54–10.04). In subgroup analyses stratified according to age (≤ 80 and > 80 years), sex (male/female), and hypertension status, consistent associations were observed between AKI and the risk of in-hospital mortality. AKI patients were at higher risk for acute myocardial infarction (OR 1.78, 95% CI 1.35–2.34), major bleeding (OR 1.62, 95% CI 1.13–2.33), blood transfusion (OR 1.65, 95% CI 1.28–2.11), and cardiogenic shock (OR 3.73, 95% CI 2.77–5.01). No significant betweengroup differences were observed in stroke (P = 0.12). Conclusion AKI was a strong predictor of in-hospital mortality in patients undergoing TAVR without CKD and was associated with higher post-procedure complication rates.

The effect of dexmedetomidine on acute kidney injury after elective major abdominal surgery : a retrospective single-center propensity score matched study

BackgroundMajor abdominal surgery is a kind of high-risk surgery type for postoperative acute kidney injury (AKI) among non-cardiac surgeries. Despite dexmedetomidine exerts significant renal protective effects in cardiac surgeries and animal studies, whether it is associated with a lower incidence of AKI in major abdominal surgeries remains unclear.MethodsFrom January 2019 to July 2021, patients undergoing elective major abdominal surgery in West China Hospital were enrolled. Participants were divided into two groups based on exposure to continuous intravenous dexmedetomidine: the Dex group (exposed) and the Control group (not exposed). The primary outcome was the incidence of AKI in the postoperative 7 days. Secondary outcomes included intraopertive average urine output, renal function on the first day after surgery, incidence of postoperative dialysis, postoperative intensive care unit (ICU) admission, in-hospital mortality, length of hospital stay, incidence of intraoperative hypotension and bradycardia, and intraoperative use of inotropes and vasopressors. Propensity score matching (PSM), based on participants’ baseline and intraoperative characteristics, was performed to minimize potential bias. Furthermore, a subgroup analysis was conducted based on the infusion rate and the use of a loading dose to explore the effects of different methods of dexmedetomidine administration on AKI. The subgroups included: loading dose, non-loading dose, low-infusion rate (infusion rate ≤ 0.4 µg/kg/h), and high-infusion rate (infusion rate > 0.4 µg/kg/h).ResultsAfter PSM with a ratio of 1:1, a total of 8836 patients were successfully matched. Dexmedetomidine administration had no association with the incidence of postoperative AKI, serum creatinine (Scr) level on the first postoperative day, incidence of postoperative dialysis, postoperative ICU admission, in-hospital mortality, length of hospital stay, intraoperative hypotension, or the use of inotropes and vasopressors, but had association with increased intraoperative average urine output (122.95 (76.80, 189.27) vs. 104.65 (67.04, 161.07) ml/h, P < 0.001), higher value of estimated glomerular filtration rate (eGFR) (97.33 ± 15.95 vs. 96.13 ± 16.35 ml/min/1.73m2, P < 0.001) on the first day after surgery and a higher incidence of intraoperative bradycardia (37.0% vs. 30.6%; P < 0.001). In the loading dose subgroup, dexmedetomidine use was significantly associated with a reduced incidence of postoperative AKI (odds ratio (OR): 0.44, 95% confidence interval (CI): 0.23–0.76, P = 0.006).The association between dexmedetomidine and postoperative AKI was absent in subgroups of high or low infusion rate and no loading dose use.ConclusionIn this single-center retrospective propensity-matched study, we did not detect a significant overall difference in post-operative AKI rates between patients treated with or without dexmedetomidine during major abdominal surgery. However, though additional prospective data are needed, our study found that administering dexmedetomidine with a loading dose may be associated with lower rates of AKI, potentially indicating a renoprotective effect of loading-dose dexmedetomidine in this setting.

Amino Acid Infusion for Kidney Protection in Cardiac Surgery Patients with Chronic Kidney Disease: A Secondary Analysis of the PROTECTION Trial

Background: In the PROTECTION trial, intravenous amino acids (AA) decreased the occurrence of acute kidney injury (AKI) in cardiac surgery patients with cardiopulmonary bypass (CPB). Recruitment of renal functional reserve may be responsible for such protection. However, patients with chronic kidney disease (CKD) have diminished renal functional reserve, and AA may be less protective in such patients. Thus, a separate investigation of such patients is warranted. Methods: We defined CKD as an estimated glomerular filtration rate (eGFR)&lt;60 mL·min-1·1.73 m-2 and patients with eGFR≥60 mL·min-1·1.73 m-2 served as controls. The primary outcome was the occurrence of AKI. Secondary outcomes included severity of AKI, need for and duration of renal replacement therapy, and all-cause mortality. Results: Among CKD patients (n=812), compared with placebo, AA significantly decreased the rate of AKI (43.1% vs 50.3%; RR, 0.86; 95%CI, 0.74 to 0.99; p=0.041; number needed to treat [NNT]=14) with a median percentage increase in eGFR from baseline to postoperative day three of 12.7% vs. 6.5% (p=0.002). In eGFR-based CKD subgroups (30 to 39, 40 to 49, and 50 to 59 mL·min-1·1.73 m-2) the AA effect was similar (interaction p=0.50). Finally, AA infusion decreased the occurrence of severe (stage 3) AKI (2.7% vs. 5.6%; RR 0.48; 95%CI, 0.24 to 0.98; p=0.038). Conclusions: AA infusion protected CKD patients undergoing CPB from developing AKI, with an absolute risk reduction of 7% and a NNT of 14 in a cohort with a &gt;45% rate of AKI. Moreover, it delivered a &gt;50% relative risk reduction in severe AKI.

A Machine Learning-Based Prediction Model for Acute Kidney Injury in Patients With Community-Acquired Pneumonia: Multicenter Validation Study.

Acute kidney injury (AKI) is common in patients with community-acquired pneumonia (CAP) and is associated with increased morbidity and mortality. This study aimed to establish and validate predictive models for AKI in hospitalized patients with CAP based on machine learning algorithms. We trained and externally validated 5 machine learning algorithms, including logistic regression, support vector machine, random forest, extreme gradient boosting, and deep forest (DF). Feature selection was conducted using the sliding window forward feature selection technique. Shapley additive explanations and local interpretable model-agnostic explanation techniques were applied to the optimal model for visual interpretation. A total of 6371 patients with CAP met the inclusion criteria. The development of CAP-associated AKI (CAP-AKI) was recognized in 1006 (15.8%) patients. The 11 selected indicators were sex, temperature, breathing rate, diastolic blood pressure, C-reactive protein, albumin, white blood cell, hemoglobin, platelet, blood urea nitrogen, and neutrophil count. The DF model achieved the best area under the receiver operating characteristic curve (AUC) and accuracy in the internal (AUC=0.89, accuracy=0.90) and external validation sets (AUC=0.87, accuracy=0.83). Furthermore, the DF model had the best calibration among all models. In addition, a web-based prediction platform was developed to predict CAP-AKI. The model described in this study is the first multicenter-validated AKI prediction model that accurately predicts CAP-AKI during hospitalization. The web-based prediction platform embedded with the DF model serves as a user-friendly tool for early identification of high-risk patients.

Comparison of outcomes of Impella-assisted high-risk percutaneous coronary intervention in patients with and without prior coronary artery bypass graft.

Limited data is available regarding in-hospital outcomes of patients undergoing high-risk percutaneous coronary intervention (HR-PCI) with Impella with and without a prior history of coronary artery bypass grafting (CABG). We performed a retrospective study from the Nationwide Inpatient Sample from year 2016 to 2020. We identified patients who underwent Impella and percutaneous coronary intervention on the same day and excluded those with cardiogenic shock. Subsequently, we stratified them into those with and without prior CABG. During the study period, 18 925 patients underwent HR-PCI. Among these, 2043 (10.8%) patients had prior CABG. Patients without prior CABG had a higher percentage of acute coronary syndrome at presentation (62.7 vs 56.1%, P = 0.008). The proportion of females was significantly higher in those without prior CABG (32.4 vs 21.7%, P < 0.001). On multivariate analysis, there was no statistically significant difference in the in-hospital mortality (5.8% in CABG vs 8.5% in non-CABG, P = 0.52). Patients without prior CABG had higher rates of acute kidney injury, major bleeding, and blood transfusions. There were no significant differences in rates of cardiac arrest, ventricular arrhythmias, acute stroke, coronary dissections, and coronary perforations. Those without prior CABG had a longer duration of hospitalization (6.8 vs 9.3 days, P < 0.001) and higher hospital charges ($292 267 vs $322 206, P < 0.035). Our study highlights that a history of previous CABG does not increase the risk of in-hospital mortality in patients undergoing Impella-assisted HR-PCI but is associated with reduced rates of complications.

10 tips on how to reduce iatrogenic AKI

Abstract Acute kidney injury (AKI) is a heterogeneous syndrome associated with worse clinical outcomes. Many treatments and procedures in the hospitalized patient can cause AKI. Hence, the incidence of iatrogenic AKI is expected to be high. In this review, we provide 10 practical tips on how to manage and avoid iatrogenic AKI. We cover identification of vulnerable patients by epidemiological data and recommend the usage of renal stress biomarkers for enhanced screening of high-risk patients. Further, we discuss the limitations of current diagnostic criteria of AKI. As a key takeaway, we suggest the implementation of novel damage biomarkers in clinical routine to identify subclinical AKI, which may guide novel clinical management pathways. To further reduce the incidence of procedure-associated AKI, we advocate for certain preventive measures. Foremost, this includes improvement of hemodynamics and avoidance of nephrotoxic drugs whenever possible. In cases of severe AKI, we provide tips for the implementation and management of renal replacement therapy and highlight the advantages of regional citrate anticoagulation. The furosemide stress test might be of help in recognizing patients who will require renal replacement therapy. Finally, we discuss the progression of AKI to acute and chronic kidney disease and management of this growing issue. Both can develop after episodes of AKI and have major implications for patient co-morbidity and long-term renal and non-renal outcomes. Hence, we recommend long-term monitoring of kidney parameters after AKI.

Collagen type III formation but not degradation is associated with risk of kidney disease progression and mortality after acute kidney injury

Abstract Background Acute kidney injury (AKI), a rapid decrease in kidney function, is associated with increased risk of adverse outcomes including development and progression of CKD. Kidney fibrosis is one of the pathological processes central to this AKI to CKD transition. Here we investigate the association of biomarkers of collagen type III turnover with adverse outcome following AKI. Methods We measured three biomarkers reflecting collagen type III formation (PRO-C3) and degradation (C3M and C3C) in plasma samples collected 1 year after an episode of AKI in 800 patients (392 patients with AKI and 408 non-AKI controls) from the prospective AKI Risk in Derby (ARID) study. Patients were followed until 3 years after the episode of AKI and the following outcomes were assessed: kidney disease progression, mortality, heart failure, CV events, and hospital readmission. Results PRO-C3 levels were elevated in the AKI group compared to the controls (P&amp;lt;0.001), whereas C3M and C3C levels were not different between groups. In multivariate models including common risk factors, PRO-C3 was prognostic for kidney disease progression and mortality in the AKI group and for heart failure in the control group. C3M and C3C were not prognostic for any of the investigated outcomes. Conclusions Circulating PRO-C3, a biomarker of fibroblast activity, was prognostic for kidney disease progression and mortality when measured one year after an episode of AKI. Biomarkers of fibroblast activity may help patient stratification after an episode of AKI by identifying patients at higher risk of kidney disease progression.

Slc25a21 in cisplatin-induced acute kidney injury: a new target for renal tubular epithelial protection by regulating mitochondrial metabolic homeostasis

Acute kidney injury (AKI) is a significant global health issue, which is often caused by cisplatin therapy and characterized by mitochondrial dysfunction. Restoring mitochondrial homeostasis in tubular cells could exert therapeutic effects. Here, we investigated Slc25a21, a mitochondrial carrier, as a potential target for AKI intervention. Renal Slc25a21 expression is negatively associated with kidney function in both AKI patients and cisplatin-induced murine models. Sustaining renal expression of Slc25a21 slowed down AKI progression by reducing cellular apoptosis, necroptosis, and the inflammatory response, likely through its regulation of 2-oxoadipate conversion. Slc25a21 is highly expressed in proximal tubular epithelial cells, and its down-regulation contributes to compromised mitochondrial biogenesis and integrity, as well as impaired oxidative phosphorylation. Mechanistically, reduced Slc25a21 in AKI disrupts mitochondrial 2-oxoadipate transport, affecting related metabolites influx and the tricarboxylic acid cycle. These findings demonstrate a previously unappreciated metabolic function of Slc25a21 in tubular cells, and suggest that targeting mitochondrial metabolic homeostasis by sustaining Slc25a21 expression could be a potential novel therapeutic strategy for AKI.

Acute kidney injury and its associated factors among patients with acute decompensated heart failure admitted to the university of Gondar Hospital, Northwest Ethiopia: a hospital-based cross-sectional study

BackgroundHeart failure often leads to hospitalization and can directly impact other organs, such as the kidneys. Acute kidney injury (AKI) is a common complication in patients hospitalized for acute decompensated heart failure (ADHF) and is associated with worse outcomes. However, there are limited data on the magnitude of AKI among hospitalized ADHF patients in resource-limited settings such as Ethiopia. This study sought to determine the prevalence of AKI and the factors associated with AKI in ADHF patients in Northwest Ethiopia.MethodA hospital-based cross-sectional study was conducted at the University of Gondar Hospital in Northwest Ethiopia from June 1 to September 30, 2022. A total of 239 participants were included using consecutive sampling. Demographic information was collected through patient interviews, and relevant clinical and laboratory data were obtained from the patients’ medical records. The data were analyzed using STATA version 15.0. Bivariate and multivariate logistic regression analyses were carried out to identify independently associated factors of AKI among patients with ADHF. A P value < 0.05 was considered to indicate statistical significance.ResultsThe overall prevalence of AKI in ADHF patients was 25.1% (CI = 19.98–31.03). Older age ≥ 60 years(AOR = 2.95, 95%CI:1.34–6.21), diabetes mellitus (AOR = 9.55,95%CI:2.68–33.99),Hypertension (AOR = 2.34,95% CI:1.08–5.07), sepsis (AOR = 2.13,95%CI:1.09–4.8), use of loop diuretics (AOR = 4.03,95%CI:1.86–8.69) and previous history of AKI (AOR = 11.56,95%CI:4.02–33.26) were independently associated with the occurrence of AKI among ADHF patients.ConclusionA quarter of the patients admitted with ADHF developed AKI. Older age; comorbid diabetes mellitus, hypertension, or sepsis; a previous history of AKI; and the use of loop diuretics were associated with the occurrence of AKI. Such clinical characteristics available at hospital admission can be used to identify patients at increased risk for developing AKI.

Association between EASIX and acute kidney injury in critically ill cancer patients

BackgroundTo analyze the relationship between endothelial activation and stress index (EASIX) and the occurrence of acute kidney injury (AKI) in critically ill cancer patients. MethodsCritically ill cancer patients were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Multivariate logistic regression was used to analyze the association between EASIX and the occurrence of AKI in critically ill cancer patients.ResultsOne thousand forty-one cancer patients were retrospectively included, including 607 men and 434 women with mean age of 64.86 ± 13.67 years. Univariate analysis showed that high EASIX levels were associated with an increased risk of AKI occurrence in intensive care unit (ICU) cancer patients (OR: 1.47,95% CI: 1.13–1.91, P < 0.05). After adjusting for other confounders, high EASIX levels remained an independent risk factor predicting the development of AKI (OR: 1.42,95% CI: 1.08–1.88, P < 0.05). Trends in effect sizes were generally consistent across all subgroups in the prespecified subgroup analyses.ConclusionEASIX is an independent risk factor for AKI in critically ill cancer patients. More prospective studies are needed to validate the effect of EASIX on the occurrence of AKI in critically ill cancer patients in the future.

Prophylactic trimethoprim-sulfamethoxazole is safe in adult patients with primary central nervous system lymphoma receiving high-dose methotrexate.

This retrospective study investigated the potential drug-drug interactions between trimethoprim-sulfamethoxazole (TMP-SMZ) and high-dose methotrexate (HD-MTX) in adult patients with primary central nervous system lymphoma (PCNSL). A total of 143 Chinese adult patients with PCNSL who received 498 cycles of MTX were included. Differences in the pharmacokinetics of MTX, including Cmax, clearance (CL) and AUC0-48h with and without co-administration of TMP-SMZ were assessed. The incidence of MTX-related acute kidney injury (AKI), hepatotoxicity, myelosuppression, and delayed MTX elimination at 48 and 72h were also compared. Patients were divided into two cohorts for analysis: 146 cycles with TMP-SMZ exposure and 352 cycles without TMP-SMZ exposure. Patients who received TMP-SMZ concurrently with HD-MTX exhibited a 1.13-fold increase in Cmax, a 1.12-fold increase in AUC0-48h and a reduction in CL by 0.87-fold for MTX. There was no significant difference in the incidence of MTX-related AKI, hepatotoxicity, myelosuppression, or delayed MTX elimination between the two cohorts. Prophylactic TMP-SMZ might lead to increased MTX exposure but has no impact on the incidence of myelosuppression, AKI, and hepatotoxicity. These results suggested that prophylactic TMP-SMZ is safe for adult patients with PCNSL receiving HD-MTX.

Acute kidney injury with hypernatremia and major adverse kidney events

Abstract Introduction Consequences of hypernatremia in AKI (AKI-HyperNa) is poorly understood. We analyzed the risk of major adverse kidney events (MAKE) in comparison with AKI and normal serum sodium (AKI-normalNa). Such data could help in understanding this complex interaction. Methods In this retrospective cohort we compared the AKI-hyperNa with the AKI-normalNa regarding the risk of MAKE, which include death, new dialysis requirement, and worsening kidney function (≥ 25% decrease in eGFR), at 10 (MAKE10) and at 30–90 days (MAKE30–90) using multivariate logistic regression and area under the curve (AUC) analysis. Also the association between serum sodium levels (per 1 mEq/L increase) and the number of days with hypernatremia. Results A total of 357 patients were included (78 with AKI-hyperNa and 279 with AKI-normalNa). Compared to the AKI-normalNa, AKI-hyperNa were predominantly male (73% vs. 59%), experienced hypernatremia for a longer duration (3 days vs. 0 days), and took 5 days to normalize serum sodium levels. After multivariate regression analysis AKI-hyperNa group had higher risk of MAKE10 (OR 5.7, CI 2.5–12.89, p &amp;lt; 0.001) with an AUC of 0.79. Also its components such as mortality and decreased eGFR (OR 2.13, CI 1.11–4.07, p = 0.021 and OR 20.14, CI 7.69–10.03, p = 0.001, respectively). A similar trend for MAKE30–90 (OR 4.17, CI 1.73–10.03, p ≤ 0.001).A gradual increase in serum sodium was associated with a higher risk of MAKE (OR 1.07, CI 1.04–1.11, p ≤ 0.001), as was the number of days spend with hypernatremia (OR 1.51, CI 1.22–1.87, p = 0.001). Conclusions In this cohort, AKI-hyperNa compared with AKI-normalNa, had a 5-fold risk of short- and long-term MAKE. This event was more frequently observed as serum sodium increased and it was closely related to the number of days that hypernatremia persisted.

Diazoxide-Associated Hyperglycemia: A Critical Case Precipitating Hyperosmolar Hyperglycemic State in a Child.

Diazoxide is the first-line treatment for children with hyperinsulinemic hypoglycemia (HI). In these cases, diazoxide raises blood glucose levels by suppressing insulin release, preventing hypoglycemia, and potentially devastating end-organ sequelae. Hyperosmolar hyperglycemic state (HHS) is an exceedingly rare side effect of diazoxide. This complication has been described in neonates and in adults, but few children. An 8-year-old female with genetic duplication of glucokinase, and consequent hyperinsulinemia, presented to the emergency department with evidence of hypovolemic shock secondary to severe dehydration with signs of encephalopathy. Point-of-care glucose was > 600mg/dL. Additional labs were consistent with HHS complicated by acute kidney injury, sodium 106 mEq/L, potassium 2.5 mEq/L, chloride < 60 mEq/L, carbon dioxide 20 mEq/L, glucose 2105mg/dL, BUN 107mg/dL, and creatinine 3.99mg/dL. The patient received aggressive fluid resuscitation and vasopressor support, and was admitted to the pediatric intensive care unit. A diazoxide level was obtained during admission revealing serum concentration previously shown to be associated with hyperglycemia. We posit the patient was predisposed to hyperglycemia based on elevated diazoxide serum concentration. We hypothesize severe dehydration led to renal impairment, which decreased diazoxide clearance, causing worsening hyperglycemia and ultimately, HHS. The differential diagnosis also included diabetic ketoacidosis, surreptitious administration of diazoxide, spontaneous resolution of genetic condition, and malabsorption or excretory crisis but none of these adequately explained the patient's presentation. Regardless, this case highlights the potentially lethal complication of HHS as a side effect of diazoxide therapy.

Robot-assisted partial nephrectomy in complex renal tumors using the Versius platform: An initial but promising experience

ABSTRACT Background and objectives The widespread utilization of robotic surgeries in urology encouraged several teams to explore the option of performing robot-assisted partial nephrectomy (RAPN), taking advantage of its magnified stereoscopic vision and the articulating instruments that facilitate tumor resection and the reconstructive steps of hemostasis and renorrhaphy. The implementation of the CMR Versius system in RAPN, especially in complex masses, has not been explored yet. Herein, we present our initial experience in performing RAPN in complex renal masses using this novel platform. Methods Between July 2022 and November 2023, thirty patients who had complex renal masses and were candidates for RAPN were enrolled in this study. Tumor complexity was assessed using the preoperative aspects of the dimension used for anatomic (PADUA) nephrometry scores. Perioperative data were prospectively collected and analyzed. ‘TRIFECTA’ was defined as free surgical margins, warm ischemia time (WIT)< 30 minutes, and no major complications (>Clavien-Dindo II). Results All cases were successfully completed with no conversion to radical, open, or laparoscopic surgery. The median PADUA score was 9.5 (8–11). The mean docking time, console time, and total operative time were 9.17 ± 0.91, 149 ± 14.27, and 177.17 ± 29.53 minutes, respectively. The mean WIT was 26.67 ± 3.66 minutes. Surgical margins were free in all cases. TRIFECTA was fulfilled in 25/30 patients (83.33%). Five patients (16.66%) did not fulfill TRIFECTA; two patients had prolonged WIT > 30 minutes, two had prolonged WIT with prolonged urine leakage necessitating DJ stent insertion, and the fifth patient had only prolonged urine leakage and DJ insertion. None of the patients developed tumor recurrence or acute kidney injury during follow-up. Conclusion Performing RAPN with the CMR Versius platform is a feasible option in complex renal masses with slightly increased but accepted WIT and total operative time. It should be wisely restricted to well-experienced teams.

CUL4B protects kidneys from acute injury by restraining p53/PAI-1 signaling

Acute kidney injury (AKI) caused by nephrotoxins, ischemia reperfusion (IR) or sepsis is associated with high morbidity and mortality. Unveiling new mechanisms underlying AKI can help develop new therapeutic strategy. Cullin 4B (CUL4B) is a scaffold protein in the CUL4B-RING E3 ubiquitin ligase (CRL4B) complex. Here, we demonstrate that CUL4B can protect kidneys from acute injury induced by cisplatin and IR. CUL4B is upregulated in mouse tubular epithelial cells (TECs) after cisplatin treatment or IR. Loss of CUL4B in kidneys exacerbates renal injury, inflammation, and apoptosis of TECs caused by cisplatin and IR. Transcriptome analysis reveals that Cul4b deficiency enhances injury-induced PAI-1 expression. CUL4B suppresses PAI-1 expression by promoting polyubiquitination and degradation of p53. Inhibition of either PAI-1 or p53 can prevent the aggravated renal injury and inflammation caused by loss of CUL4B. Our work has identified the kidney-protective role of CUL4B against acute injury.

Continuous renal replacement therapy with adsorbing filter oXiris in the treatment of sepsis associated acute kidney injury: a single-center retrospective observational study

Background and objectiveCritical bedside ultrasound is widely used in clinical practice, and it can monitor renal perfusion. The reduction of renal perfusion and inflammatory injury are two contributing factors to sepsis-associated acute kidney injury (SA-AKI).The aim of this study was to examine whether the oXiris filter was useful in the continuous renal replacement therapy(CRRT) treatment of SA-AKI patients.Design, setting, participants, and measurementsWe performed a retrospective single-center observational study and enrolled two hundred and forty-three SA-AKI patients from January 2022 to December 2023, who were divided into the oXiris group (n = 88) and the control group (n = 155). The primary endpoints were the 28-day recovery of renal function and 28-day all-cause mortality. The secondary endpoints included renal Doppler markers (RRI, RVSI, and PDU), SOFA, vasoactive-inotropic score (VIS), inflammatory markers (PCT, CRP, IL-10 and TNFα), lactate level, and length of stay in ICU and hospital.ResultsFor the primary endpoint, the rates of complete recovery, partial recovery, and dialysis dependence were observed to be 60.3%, 13.6%, and 26.1% in the oXiris group, respectively, compared to 63.9%, 15.5%, and 20.6% in the control group. The 28-day all-cause mortality was not different in the two groups (22.7% vs. 27.1%). For the secondary endpoint, the oXiris group exhibited greater reductions in VIS scores compared to the control group within the first 24 h (p = 0.001) and 48 h (p < 0.001) of CRRT. Following 48-h of CRRT, lactate levels in the oXiris group were significantly lower than those in the control group (p = 0.014). Prior to CRRT, levels of IL-6 were higher in the oXiris group (p = 0.036), but these differences were not significant after CRRT (p > 0.05). The levels of RRI at T1 (p = 0.002) and T2 (p = 0.001) were lower in the oXiris group than in the control group. Even after adjusting for AKI stage, multivariable Cox regression analysis showed that SOFA and inflammatory factors (TNFα, IL-10, and IL-6), oXiris were significantly associated with a lower 28-day mortality among SA-AKI patients when compared to M150 [HR = 0.466, 95%CI 0.233–0.934, p = 0.031].ConclusionOur findings suggest that the use of the oXiris filter in CRRT is associated with reduced inflammatory injury and improvement in renal perfusion. However, it is not associated with improved 28-day recovery of renal function and 28-day all-cause mortality.

Acute kidney injury in elderly patients receiving invasive mechanical ventilation: early versus late onset

BackgroundAcute kidney injury (AKI) is a severe complication in critical patients receiving invasive mechanical ventilation (MV). However, AKI which occurs in the first 48 h after MV (early AKI) and thus likely associated with the MV settings is probably different from AKI occurring following 48 h (late AKI). This study is aimed at exploring the incidence of early and late AKI in elderly patients receiving MV and identifying their different risk factors and outcomes.MethodsThis retrospective, observational, multicenter cohort study consecutively included 3271 elderly patients (≥ 75 years) receiving invasive MV at four medical centers of Chinese PLA General Hospital from 2008 to 2020. The diagnosis of AKI was made following the 2012 KDIGO criteria and categorized into early (≤ 48 h) or late (> 48 h-7 days) according to the time from MV.ResultsThere were totally 1292 cases enrolled for the final analysis. Among them, 376 patients (29.1%) developed early AKI versus 132 (10.2%) developed late AKI. The 28-day mortality rates of the non-AKI, early AKI, and late AKI patients were 14.4, 46.8, and 61.4%, respectively. After 90 days, mortality rates of three groups were 33.2, 60.6, and 72.7%, respectively. Risk factors for early AKI included PaO2/FIO2, serum creatinine, hemoglobin, and positive end-expiratory pressure at the beginning of MV, while those for late AKI were PaO2/FIO2, serum creatinine, and hemoglobin. In the multivariable adjusted analysis, both early AKI (HR = 4.035; 95% CI = 3.166–5.142; P < 0.001) and late AKI (HR = 6.272; 95% CI = 4.654–8.453; P < 0.001) were related to the increased 28-day mortality relative to non-AKI. AKI was significantly related to 90-day mortality: early AKI (HR = 2.569; 95% CI = 2.142–3.082; P < 0.001) and late AKI (HR = 3.692; 95% CI = 2.890–4.716; P < 0.001).ConclusionsAKI mostly develops in the initial 48 h following MV, which is related to the health and MV settings; while AKI occurring following 48 h is not associated with MV settings. Therefore, a strategy for kidney protection in patients with MV should take these differences into consideration.

A genotype-guided prediction model for the incidence of persistent acute kidney injury following lung transplantation

BackgroundThis study aimed to develop a nomogram for predicting persistent renal dysfunction in acute kidney injury (AKI) following lung transplantation (LTx).MethodA total of 229 LTx patients were enrolled, and genotyping for 153 single nucleotide polymorphisms (SNPs) was performed. The cohort was randomly divided into training (n = 183) and validation (n = 46) sets in an 8:2 ratio. Statistically significant SNPs identified through pharmacogenomic analysis were combined with clinical factors to construct a comprehensive prediction model for persistent AKI using multivariate logistic regression analysis. Discrimination and calibration analyses were conducted to evaluate the performance of the model. Decision curve analysis was used to assess its clinical utility. Due to the small sample size, bootstrap internal sampling with 500 iterations was adopted for validation to prevent overfitting of the model.ResultsThe final nomogram comprised nine predictors, including body mass index, thrombin time, tacrolimus initial concentration, rs757210, rs1799884, rs6887695, rs1494558, rs2069762 and rs2275913. In the training set, the area under the receiver operating characteristic curve of the nomogram was 0.781 (95%CI: 0.715–0.846), while in the validation set it was 0.698 (95%CI: 0.542–0.855), indicating good model fit. As demonstrated by 500 Bootstrap internal sampling validations, the model has high discrimination and calibration. Additionally, decision curve analysis confirmed its clinical applicability.ConclusionThis study presents a genotype-guided nomogram that can be used to assess the risk of persistent AKI following LTx and may assist in guiding personalized prevention strategies in clinical practice.

Preparing for stormy weather: building VA health system resilience for dialysis emergency preparedness in the era of climate change.

Climate change has been implicated as the driver for the increasing number, intensity, duration, and consequences of catastrophic weather events. As a result of extreme weather events, climate change has also been implicated as an important mediator of adverse kidney health outcomes, not only increasing the risk for the development of acute and chronic kidney diseases, but also disrupting the delivery of critical kidney health services. In particular, the delivery of dialysis services during major emergencies remains an ongoing and increasing problem, with a recognized need for improved emergency preparedness and disaster management (EP-DM) strategies to mitigate the increased risk of morbidity and mortality associated with missed dialysis treatment. There are increasing reports detailing the challenges of kidney dialysis care in times of crisis, to include those resulting from both man-made and natural disasters. Optimized management of the high-risk vulnerable dialysis patient population must include both facility-facing comprehensive continuity of operations and emergency response plans, and ongoing patient-facing emergency preparedness education. This review discusses the adverse impact of climate change-related natural disasters on the delivery of dialysis services, and the evolving EP-DM strategies developed and implemented by the Veterans Health Administration (VA) to optimize the care and well being of the vulnerable end stage kidney disease (ESKD) patient population.

Defining normal serum creatinine in pregnancy -results from the AKID UK prospective cohort study

Abstract Background Abnormal kidney function in pregnancy may represent chronic kidney disease or pregnancy-associated acute kidney injury - both associated with adverse outcomes during and after pregnancy. Serum creatinine remains the standard biomarker for kidney function in pregnancy but normal levels change dynamically through pregnancy and at term. Existing gestation-specific reference ranges for serum creatinine, and recommendations to investigate for abnormal kidney function in pregnancy are based on limited data. Data describing trajectories of serum creatinine through pregnancy and the normal, physiological increase in serum creatinine at term are also lacking. Methods We recruited 476 healthy pregnant individuals aged 16 years or over, 2019-21, measuring serum creatinine in the first, second and third trimesters of pregnancy, , at birth and postpartum. Clinical data were abstracted. Gestation-specific reference ranges for serum creatinine were defined as mean±1.96 x SD, after excluding those with adverse pregnancy outcomes. Trajectories of serum creatinine through pregnancy, and the change in serum creatinine at delivery were described. Results 1875 creatinine measurements were recorded. Reference ranges for serum creatinine in the first, second and third trimesters of healthy pregnancy were 37-67μmol/L (0.42-0.75mg/dl), 34-63μmol/L (0.38-0.71mg/dl), and 34-66μmol/L (0.39-0.75mg/dl). Increasing serum creatinine in early pregnancy was more common in those with hypertensive disorders of pregnancy, prior to disease onset. In healthy participants, median serum creatinine increase from 36 weeks to birth was 6.8% (95% CI 4.5%, 9.1%). Conclusions Investigation for abnormal kidney function in pregnancy should be considered at a lower creatinine threshold than currently recommended. Detecting abnormal creatinine trajectories may help early identification of high-risk pregnancies.