Diagnostic Efficacy and Safety of Low-Contrast-Dose Dual-Energy CT in Patients With Renal Impairment Undergoing Transcatheter Aortic Valve Replacement.

OBJECTIVE: This study aimed to evaluate the diagnostic efficacy and safety of low-contrast-dose, dual-source dual-energy CT before transcatheter aortic valve replacement (TAVR) in patients with compromised renal function. MATERIALS AND METHODS: A total of 54 consecutive patients (female:male, 26:38; 81.9 ± 7.3 years) with reduced renal function underwent pre-TAVR dual-energy CT with a 30-mL contrast agent between June 2022 and March 2023. Monochromatic (40- and 50-keV) and conventional (120-kVp) images were reconstructed and analyzed. The subjective quality score, vascular attenuation, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were compared among the imaging techniques using the Friedman test and post-hoc analysis. Interobserver reliability for aortic annular measurement was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. The procedural outcomes and incidence of post-contrast acute kidney injury (AKI) were assessed. RESULTS: Monochromatic images achieved diagnostic quality in all patients. The 50-keV images achieved superior vascular attenuation and CNR (P < 0.001 in all) while maintaining a similar SNR compared to conventional CT. For aortic annular measurement, the 50-keV images showed higher interobserver reliability compared to conventional CT: ICC, 0.98 vs. 0.90 for area and 0.97 vs. 0.95 for perimeter; 95% limits of agreement width, 0.63 cm² vs. 0.92 cm² for area and 5.78 mm vs. 8.50 mm for perimeter. The size of the implanted device matched CT-measured values in all patients, achieving a procedural success rate of 92.6%. No patient experienced a serum creatinine increase of ≥ 1.5 times baseline in the 48-72 hours following CT. However, one patient had a procedural delay due to gradual renal function deterioration. CONCLUSION: Low-contrast-dose imaging with 50-keV reconstruction enables precise pre-TAVR evaluation with improved image quality and minimal risk of post-contrast AKI. This approach may be an effective and safe option for pre-TAVR evaluation in patients with compromised renal function.

Diagnostic value of multi-parameter ultrasound evaluation in sepsis complicated by acute kidney injury.

BACKGROUND: This study aimed to discuss the diagnostic value of multi-parameter ultrasound evaluation in sepsis complicated with acute kidney injury (AKI). METHODS: Patients were divided into an AKI group (n = 50) and a non-injury group (n = 50) based on the presence of AKI. The clinical characteristics were collected, and renal function parameters between the two groups were compared, including 24-h urine volume, serum creatinine, urea, serum cystatin C (CysC), renal parenchymal thickness (RPT), renal artery resistance index (RI), and multi-parameter ultrasound scoring (MPUS). Additionally, logistic regression analysis was conducted to determine the influencing factors of sepsis complicated with AKI. The prediction value was evaluated using a receiver operating characteristic (ROC) curve. RESULTS: In the AKI group, creatinine, CysC, urea, MPUS score, RPT, and RI values were significantly higher, while the 24-h urine volume was lower than those in the non-injury group (p < 0.01). Moreover, multivariate logistic analysis indicated that high CysC and RI values were independent risk factors, whereas high 24-h urine volume and low MPUS were independent protective factors for sepsis-induced AKI. The ROC curve demonstrated that RI (AUC = 0.906) was more effective than 24-h urine volume (AUC = 0.797), CysC (AUC = 0.730), and MPUS (AUC = 0.794) in identifying sepsis-induced AKI. CONCLUSION: High RI values increase the risk of sepsis-induced AKI, whereas low MPUS may reduce it. RI showed high diagnosis values for sepsis complicated with AKI.

Acute kidney injury in children undergoing cardiac surgery: predictive value of kidney arterial Doppler-based variables.

BACKGROUND: Acute kidney injury (AKI) is a common condition in critically ill children and is associated with increased morbidity and mortality. This study aimed to assess the performance of point-of-care ultrasonography to predict AKI in children undergoing cardiac surgery. METHODS: In this prospective study, consecutive children underwent kidney Doppler ultrasound examination within 24 h following cardiac surgery, and an experienced operator obtained both renal resistive index (RRI) and renal pulsatility index (RPI). AKI was defined by the Kidney Disease Improving Global Outcome (KDIGO) criteria. The primary outcome was the diagnosis of severe AKI (KDIGO stage 2 or 3) on day 3. RESULTS: A total of 58 patients were included. Median age and weight were 12.9 months (IQR 6.0-37.9) and 7.36 kg (IQR 5.19-11.40), respectively. On day 3, 13 patients were classified as having AKI, of which 11 were severe. RRI could effectively predict AKI (area under the ROC curve [AUC] 0.83, 95% CI 0.71-0.92; p < 0.001) as well as RPI (AUC 0.81, 95% CI 0.69-0.90; p < 0.001). The optimal cutoff value for RRI was 0.85 (sensitivity, 73%; specificity, 83%; positive predictive value [PPV], 50%; and negative predictive value [NPV], 93%), while for RPI was 1.95 (sensitivity, 73%; specificity, 78%; PPV, 44%; and NPV, 92%). Similar results were found in the analysis for prediction on day 5. Significant correlations were found between Doppler-based variables and estimated GFR and furosemide dose on day 3. CONCLUSIONS: Kidney Doppler ultrasound may be a promising tool for predicting AKI in children undergoing cardiac surgery.

Discovering a New Drug Against Acute Kidney Injury by Using a Tailored Photoacoustic Imaging Probe.

Acute kidney injury (AKI) has become an increasing concern for patients due to the widespread clinical use of nephrotoxic drugs. Currently, the early diagnosis of AKI is still challenging and the available therapeutic drugs cannot meet the clinical demand. Herein, this work has investigated the key redox couple involved in AKI and develops a tailored photoacoustic (PA) imaging probe (AB-DiOH) which can reversibly respond to hypochlorite (ClO-)/glutathione (GSH) with high specificity and sensitivity. This probe enables the real-time monitoring of AKI by noninvasive PA imaging, with better detection sensitivity than the blood test. Furthermore, this probe is utilized for screening nephroprotective drugs among natural products. For the first time, astragalin is discovered to be a potential new drug for the treatment of AKI. After oral administration, astragalin can be efficiently absorbed by the animal body, alleviate kidney injury, and meanwhile induce no damage to other normal tissues. The treatment mechanism of astragalin has also been revealed to be the simultaneous inhibition of oxidative stress, ferroptosis, and cuproposis. The developed PA imaging probe and the discovered drug candidate provide a promising new tool and strategy for the early diagnosis and effective treatment of AKI.

Objectified kidney ultrasound echogenicity and size metrics as potential predictors for kidney function in children.

BACKGROUND: Kidney echogenicity is typically determined subjectively but may have a quantifiable relationship to kidney function. Similarly, kidney length has been shown to correlate with kidney function. This study sought to quantify echogenicity using readily available software. Secondarily, we aimed to evaluate the correlation between quantified echogenicity and kidney length to the estimated glomerular filtration rate (eGFR) in children with acute kidney injury (AKI) and chronic kidney disease (CKD). METHODS: In a single-center retrospective observational study, echogenicity index (EI) was determined using a ratio of right kidney to liver mean pixel density. The kidney length ratio (KLR) was determined by the actual to predicted lengths of both kidneys. Both variables were correlated to eGFR using correlation analyses and predictive capacity was determined with receiver operating characteristic curve (ROC) analysis. RESULTS: Of 94 subjects, 46% (43/94) had AKI, 28% (26/95) had CKD and 26% (25/95) were controls. The higher the EI the lower the eGFR (r = - 0.46, p < 0.0001). EI between 1.0 and 1.1 predicted an eGFR < 90 ml/min/1.73m2 with an AUC of 0.71-0.78 while an EI between 1.1 and 1.2 predicted an eGFR < 60 ml/min/1.73m2 with AUC of 0.75-0.80. Overall, the larger the KLR the lower the eGFR (r = - 0.25, p 0.018). CONCLUSION: We have developed an accessible methodology to quantify kidney echogenicity. Overall, there was an inverse correlation between EI and eGFR in pediatric CKD and AKI. However, these correlations did not persist within subgroups which could be due to small sample size and heterogeneity of etiologies. Overall, KLR had a weaker correlation to eGFR, compared to EI. Despite these correlations, both EI and KLR had "fair" to "good" performance as a biomarker for an eGFR < 60 ml/min/1.73m2.

A Lipid Droplet-Specific NIR Fluorescent Probe with a Large Stokes Shift for In Vivo Visualization of Polarity in Contrast-Induced Acute Kidney Injury.

The research on lipid droplets (LDs) has attracted great attention in the field of biomedical science in recent years. LD malfunction is found to be associated with the development of acute kidney injury (AKI). To monitor this biological process and explain related pathological behavior, the development of excellent LD fluorescent probes with a polarity-sensitive character would provide a desirable strategy. Herein, we designed a new polarity-susceptible fluorescent probe named LD-B with LD targetability, which exhibits very weak fluorescence in highly polar solvents based on the twisted intramolecular charge transfer effect but enhanced fluorescence in low polar environments, enabling us to visualize polarity alteration. The probe LD-B also possesses the merits of intense near-infrared (NIR) emission, good photostability, large Stokes shift, low toxicity, faster metabolic rate, and wash-free ability; thereby, it would contribute to efficient LD fluorescence visualization application. Using LD-B via confocal laser scanning fluorescence imaging and a small-animal imaging system in vivo, we first manifested a prominent rise of LD polarity in contrast-induced AKI (CI-AKI), not only at the cellular level but also in animals in vivo. Furthermore, the in vivo studies suggest that LD-B could accumulate in the kidney. In addition, the normal cell lines (including kidney cells) exhibiting a greater polarity of LDs than the cancer cells have been demonstrated systemically. Altogether, our work presents an effective approach for the medical diagnosis of LDs related to CI-AKI and identification of potential therapeutic markers.

Development and Validation of a Risk Model for Predicting Contrast-Associated Acute Kidney Injury in Patients With Cancer: Evaluation in Over 46,000 CT Examinations.

BACKGROUND. Patients with cancer undergo frequent CT examinations with iodinated contrast media and may be uniquely predisposed to contrast-associated acute kidney injury (CA-AKI). OBJECTIVE. The purpose of this study was to develop and validate a model for predicting the risk of CA-AKI after contrast-enhanced CT in patients with cancer. METHODS. This retrospective study included 25,184 adult patients (12,153 men, 13,031 women; mean age, 62.3 ± 13.7 [SD] years) with cancer who underwent 46,593 contrast-enhanced CT examinations between January 1, 2016, and June 20, 2020, at one of three academic medical centers. Information was recorded regarding demographics, malignancy type, medication use, baseline laboratory values, and comorbid conditions. CA-AKI was defined as a 0.3-mg/dL or greater increase in serum creatinine level from baseline within 48 hours after CT or a 1.5-fold or greater increase in the peak measurement within 14 days after CT. Multivariable models accounting for correlated data were used to identify risk factors for CA-AKI. A risk score for predicting CA-AKI was generated in a development set (n = 30,926) and tested in a validation set (n = 15,667). RESULTS. CA-AKI occurred after 5.8% (2682/46,593) of CT examinations. The final multivariable model for predicting CA-AKI included hematologic malignancy, diuretic use, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, chronic kidney disease (CKD) stage 3a, CKD stage 3b, CKD stage 4 or 5, serum albumin level less than 3.0 g/dL, platelet count less than 150 × 103/µL, 1+ or greater proteinuria on baseline urinalysis, diabetes mellitus, heart failure, and contrast medium volume 100 mL or greater. A risk score (range, 0-53 points) was generated with these variables. The most points (13) were for CKD stage 4 or 5 and for albumin level less than 3 g/dL. The frequency of CA-AKI progressively increased in higher risk categories. For example, in the validation set, CA-AKI occurred after 2.2% of CT examinations in the lowest risk category (score ≤ 4) and after 32.7% of CT examinations in the highest risk category (score ≥ 30). The Hosmer-Lemeshow test result indicated that the risk score was a good fit (p = .40). CONCLUSION. A risk model in which readily available clinical data are used to predict the likelihood of CA-AKI after contrast-enhanced CT in patients with cancer was developed and validated. CLINICAL IMPACT. The model may help facilitate appropriate implementation of preventive measures in the care of patients at high risk of CA-AKI.

Effect of angiography timing on acute kidney injury after cardiac surgery in patients with preoperative renal dysfunction.

BACKGROUND: Cardiac surgery-associated acute kidney injury (AKI) is one of the common complications of cardiac surgery. Preoperative angiography helps assess heart disease but may increase the risk of AKI. Although more and more patients with preoperative renal dysfunction can undergo cardiac surgery with the advances in surgical techniques, there is little research on the effect of angiography on postoperative AKI in these patients. This study investigates whether angiography increases the risk of AKI after cardiac surgery in patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m2). METHODS: Patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m2) who underwent angiography and cardiac surgery successively from January 2015 to December 2020 were retrospectively enrolled in this study. The primary outcome was postoperative AKI, defined as the Kidney Disease: Improving Global Outcomes Definition and Staging (KDIGO) criteria. Univariate analysis and multivariate regression were performed to identify the association between angiography timing and AKI. RESULTS: A total of 888 consecutive eligible patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m2) were enrolled in this study. The incidence of AKI was 48.31%. Male (OR = 1.903), the interval between angiography and surgery (0-2d OR = 2.161; 3-6d OR = 3.291), cross-clamp duration (OR = 1.009), were identified as predictors for AKI. The interval between angiography and surgery was also associated with AKI in the patients with 15 ≤ eGFR < 30ml/min/1.73m2 (0-2d OR = 4.826; 3-6d OR = 5.252), 30 ≤ eGFR < 45 ml/min/1.73m2 (0-2d OR = 2.952; 3-6d OR = 3.677), but not associated with AKI in patients with 45 ≤ eGFR < 60 ml/min/1.73m2. CONCLUSIONS: In patients with preoperative renal dysfunction, the interval between angiography and cardiac surgery (0-2d and 3-6d) was associated with AKI. For patients with poorer preoperative renal function, the interval between angiography and cardiac surgery is of great concern.

A Comparative Study of 18F-FAPI-42 and 18F-FDG PET/CT for Evaluating Acute Kidney Injury in Cancer Patients.

PURPOSE: Compare the value of imaging using positron 18F-labeled fibroblast activation protein inhibitor-42 (18F-FAPI-42) and 18F-labeled deoxyglucose (18F-FDG) for assessment of AKI. PROCEDURES: This study analyzed cancer patients who received 18F-FAPI-42 and 18F-FDG PET/CT imaging. Eight patients had AKI with bilateral ureteral obstruction (BUO), eight had BUO (CKD1-2) with no acute kidney disease (AKD), and eight had no ureteral obstruction (UO) with normal renal function. The average standardized uptake value (SUVave) of the renal parenchyma (RP-SUVave), the blood pool SUVave (B- SUVave), SUVave in the highest region of the renal collective system (RCS-SUVave), and the highest serum creatinine level (top SCr) were recorded. RESULTS: The 18F-FAPI-42 and 18F-FDG results showed that radiotracer of renal parenchyma was more concentrated in the AKI group than in the other two groups, whereas the RP-SUVave from 18F-FAPI-42 was higher than that from 18F-FDG in the AKI group (all P < 0.05). 18F-FAPI-42 imaging in the AKI group showed uptake by the renal parenchyma with a diffuse increase, but very little radiotracer in the renal collecting system, similar to a "super kidney scan." The renal parenchyma also had an increase of SUVave, with accumulation of radiotracer in the renal collecting system. AKI was more severe when a patient had a "super kidney scan" in both kidneys (P < 0.05). The B-SUVave level was higher in the AKI group than in the other two groups in 18F-FAPI-42 (both P < 0.05). CONCLUSIONS: 18F-FAPI-42 imaging had higher RP-SUVave than 18F-FDG imaging in cancer patients who had BUO with AKI. An increased renal parenchyma uptake in both kidneys and low radiotracer distribution in the collecting system suggest more severe AKI.

Evaluating renal microcirculation in patients with acute kidney injury by contrast-enhanced ultrasonography: a protocol for an observational cohort study.

BACKGROUND: Acute kidney injury (AKI) in critically ill patients has poor renal outcome with high mortality. Changes in intra-renal microcirculation and tissue oxygenation are currently considered essential pathophysiological mechanisms to the development and progression of AKI. This study aims to investigate the characteristics of contrast-enhanced ultrasonography (CEUS) derived parameters in biopsy-proven AKI patients, and examine the predictive value of these markers for renal outcome. METHODS AND DESIGN: This prospective observational study will enroll AKI patients who are diagnosed and staging following KDIGO (Kidney Disease: Improving Global Outcomes) criteria. All patients undergo a kidney biopsy and pathological tubulointerstitial nephropathy is confirmed. The CEUS examination will be performed at 0, 4 and 12 weeks after biopsy to monitor renal microcirculation. The percentage decrease of serum creatinine, 4-week and 12-week eGFR (estimated glomerular filtration rate) will also be reviewed as renal prognosis. The relationship of CEUS parameters with clinical and pathological markers will be analyzed. We perform a lassologit procedure to select potential affecting variables, including clinical, laboratory indexes and CEUS markers, to be included in the logistic regression model, and examine their predictive performance to AKI outcomes. DISCUSSION: If we are able to show that CEUS derived parameters contribute to diagnosis and prognosis of AKI, the quality of life of patients will be improved while healthcare costs will be reduced. TRIAL REGISTRATION: This study is retrospectively registered on the Chinese Medical Research Registration information System( https://61.49.19.26/login ) on December 31, 2021: MR-11-22-003,503. This study has been approved by the Ethics and Scientific Research Department of Peking University First Hospital.

Parametric MRI Detects Aristolochic Acid Induced Acute Kidney Injury.

Exposure to aristolochic acid (AA) is of increased concern due to carcinogenic and nephrotoxic effects, and incidence of aristolochic acid nephropathy (AAN) is increasing. This study characterizes renal alterations during the acute phase of AAN using parametric magnetic resonance imaging (MRI). An AAN and a control group of male Wistar rats received administration of aristolochic acid I (AAI) and polyethylene glycol (PEG), respectively, for six days. Both groups underwent MRI before and 2, 4 and 6 days after AAI or PEG administration. T2 relaxation times and apparent diffusion coefficients (ADCs) were determined for four renal layers. Serum creatinine levels (sCr) and blood urea nitrogen (BUN) were measured. Tubular injury scores (TIS) were evaluated based on histologic findings. Increased T2 values were detected since day 2 in the AAN group, but decreased ADCs and increased sCr levels and BUN were not detected until day 4. Significant linear correlations were observed between T2 of the cortex and the outer stripe of outer medulla and TIS. Our results demonstrate that parametric MRI facilitates early detection of renal injury induced by AAI in a rat model. T2 mapping may be a valuable tool for assessing kidney injury during the acute phase of AAN.

Small-Molecule Photoacoustic Imaging Probe with Aggregation-Enhanced Amplitude for Real-Time Visualization of Acute Kidney Injury.

Acute kidney injury (AKI) has become a growing issue for patients with the extensive use of all kinds of drugs in clinic. Photoacoustic (PA) imaging provides a noninvasive and real-time imaging method for studying kidney injury, but it has inherent shortages in terms of high background signal and low detection sensitivity for exogenous imaging agents. Intriguingly, J-aggregation offers to tune the optical properties of the dyes, thus providing a platform for developing new PA probes with desired performance. In this study, a small-molecule PA probe (BDP-3) was designed and synthesized. We serendipitously discovered that BDP-3 can transform into renal clearable nanoaggregates under physiological conditions. The hydrodynamic diameter of the BDP-3 increased from 0.64 ± 0.11 to 3.74 ± 0.39 nm when the content of H2O increased from 40 to 90%. In addition, it was surprising that such a transforming process can significantly enhance its PA amplitude (2.06-fold). On this basis, PA imaging with BDP-3 was applied as a new method for the noninvasive detection of AKI induced by anticancer drugs, traditional Chinese medicine, and clinical contrast agents in animal models and exhibited higher sensitivity than the conventional serum index test, demonstrating great potential for further clinical diagnostic applications.

A Novel Radiomics-Based Machine Learning Framework for Prediction of Acute Kidney Injury-Related Delirium in Patients Who Underwent Cardiovascular Surgery.

Acute kidney injury (AKI) can be caused by multiple etiologies and is characterized by a sudden and severe decrease in kidney function. Understanding the independent risk factors associated with the development of AKI and its early detection can refine the risk management and clinical decision-making of high-risk patients after cardiovascular surgery. A retrospective analysis was performed in a single teaching hospital between December 1, 2019, and December 31, 2020. The diagnostic performance of novel biomarkers was assessed using random forest, support vector machine, and multivariate logistic regression. The nomogram from multivariate analysis of risk factors associated with AKI indicated that only LVEF, red blood cell input, and ICUmvat contribute to AKI differentiation and that the difference is statistically significant (P < 0.05). Seven radiomics biomarkers were found among 65 patients to be highly correlated with AKI-associated delirium. The importance of the variables was determined using the multilayer perceptron model; fivefold cross-validation was applied to determine the most important delirium risk factors in radiomics of the hippocampus. Finally, we established a radiomics-based machine learning framework to predict AKI-induced delirium in patients who underwent cardiovascular surgery.

Diffusion kurtosis imaging and arterial spin labeling for the noninvasive evaluation of persistent post-contrast acute kidney injury.

OBJECTIVE: We investigated whether diffusion kurtosis imaging (DKI) and arterial spin labeling (ASL) facilitated the assessment of serial alterations in persistent post-contrast acute kidney injury (PC-AKI). MATERIALS AND METHODS: We randomly divided 24 rats into four PC-AKI groups (days 1, 3, 7, and 13, n = 6/group), with an additional six control animals. We conducted functional magnetic resonance imaging (MRI), diffusion kurtosis imaging (DKI), and arterial spin-labeling (ASL) analyses. Mean kurtosis (MK), axial kurtosis (Ka), mean diffusivity (MD), fractional anisotropy (FA), radial kurtosis (Kr), and renal blood flow (RBF) maps were normalized to baseline (prior to contrast injection) to calculate adjusted △RBF, △MK, △Ka, △MD, △FA, and △Kr values. We also investigated urinary neutrophil gelatinase associated lipocalin (NGAL), serum cystatin C (CysC), aquaporin-2 (AQP2), hypoxia-inducible factor-1 (HIF-1α), and histological indices. RESULTS: In the inner stripe of the outer medulla, when compared with controls, decreased △FA and △MD levels were observed on days 1, 3, and 7, and a distinct elevation in △MK and △Kr on days 1-13, and a persistent decrease in △RBF on days 1-13, and a prominent increase in △Ka on days 7 and 13 in PC-AKI animals (all p < 0.05). △Ka and △MK were positively correlated with AQP-2 (r = 0.8086, p < 0.0001 and r = 0.7314, p < 0.0001, respectively), and △RBF was highly correlated with HIF-1α (r = -0.7592, p < 0.0001). Moreover, both CysC and NGAL were significantly elevated in PC-AKI animals when compared with controls from days 1-13 (all p < 0.05). Renal histological data indicated severe tubular and glomerular injury at days 1-13 in all PC-AKI groups. CONCLUSION: ASL and DKI may be noninvasively and longitudinally used to detect PC-AKI and predict further outcomes.

Contrast-Associated Acute Kidney Injury in Patients with and without Diabetes Mellitus Undergoing Computed Tomography Angiography and Local Thrombolysis for Acute Lower Limb Ischemia.

PurposeRepetitive iodinated contrast media exposure may be harmful for the kidneys. The aim of the present study was to evaluate if patients with diabetes mellitus (DM) undergoing CT angiography (CTA) and local continuous thrombolysis for acute lower limb ischemia (ALI) had an increased risk of developing contrast-associated acute kidney injury (CA-AKI) compared to patients without DM. Methods: This is a retrospective study of patients undergoing CTA and local continuous thrombolysis due to ALI between 2001 and 2018. CA-AKI was defined as a 25% increase in serum creatinine within 72 hours after latest contrast administration. Results: There was no difference (P = .30) in the frequency of CA-AKI between patients with (27.9%; n = 43) and without DM (20.6%; n = 170). Among patients with CA-AKI, patients with DM had a lower (P < .001) estimated glomerular filtration rate (eGFR) at discharge (55 ml/min/1.73 m2) than at admission (70 ml/min/1.73 m2), while no such difference was found in the group without DM (P = .20). The gram-iodine dose/eGFR ratio was higher (P < .001) in patients with CA-AKI (median 1.49, [IQR 1.34-1.81]) than in those who did not develop CA-AKI (median 1.05 [IQR 1.00-1.13]). There was a trend that gram-iodine dose/eGFR ratio (OR 1.42/standard deviation increment, 95% CI 1.00-2.02; P = .050) was associated with an increased risk of CA-AKI, after adjusting for DM, age, and gender. Conclusions: The frequency of CA-AKI was high after CTA and local continuous thrombolysis for ALI without shown increased frequency for the DM group. Among patients with CA-AKI, however, patients with DM had worse renal function at discharge than those without DM. The gram-iodine dose/eGFR ratio in these patients needs to be lower to improve renal outcomes, particularly in patients with DM.

Ultrasound Hepatic Vein Ratios Are Associated With the Development of Acute Kidney Injury After Cardiac Surgery.

OBJECTIVE: The authors investigated the use of hepatic venous and right-heart ultrasound parameters in predicting cardiac surgery-associated acute kidney injury (AKI). DESIGN: This was a prospective, contextual, descriptive two-center study. Blood tests,clinical and ultrasound data were obtained preoperatively, and postoperative day one, and day four. The hepatic vein, inferior vena cava, and right-heart Doppler ultrasound parameters were obtained and analyzed. SETTING: The sites of the study were Johannesburg, South Africa, and Aarhus, Denmark. PARTICIPANTS: Adult patients who satisfied inclusion criteria, between August 2019 and January 2020, were included, with a total of 152 participants. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median (interquartile range) age of patients was 68 (55-73) years, predominantly male, and the majority were hypertensive. Of 152 patients analyzed, 54 (35%) patients developed AKI. Among these, 37 (69%) were classified as Kidney Disease: Improving Global Outcomes (KDIGO) stage I, 11 (20%) as stage II, while six (11%) were stage III. Age (adjusted odds ratio [AOR] 1.05, 95% confidence interval [CI] 1.00-1.10 p = 0.031), The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II (AOR 1.43, 95% CI 1.14-1.80, p = 0.005], and preoperative serum creatinine (AOR 1.04, 95% CI 1.01-1.08, p = 0.013) were predictive of AKI. Those who developed AKI had experienced longer cardiopulmonary bypass (CPB) times (p < 0.001). Preoperatively, hepatic vein S-wave measurements were significantly higher in patients with AKI (p < 0.05). On postoperative day one (D1), the hepatic vein flow ratios of patients with AKI were significantly decreased, driven by low S waves and high D waves, and accompanied by significantly elevated central venous pressure (CVP) levels. CVP levels on D1 postoperatively were predictive of AKI (AOR 1.31, 95% CI 1.11-1.55, p = 0.001). Measurements of right ventricular (RV) base, tricuspid annular plane excursion (TAPSE), and inferior vena cava were not associated with the development of AKI (p > 0.05). CONCLUSION: There was an association between the development of AKI and a decrease in hepatic flow ratios on D1, driven by low S-wave and high D-wave velocities. The presence of venous congestion was reflected by significantly elevated CVP values, which were independently associated with AKI on D1. RV base and TAPSE measurements were, however, not associated with AKI. These parameters may reflect perioperative circumstances, including prolonged CPB times and potential fluid management, which can be modified in this period.

Perfusion Analysis of Kidney Injury in Rats With Cirrhosis Induced by Common Bile Duct Ligation Using Arterial Spin Labeling MRI.

BACKGROUND: Arterial spin labeling (ASL) has been proven to be effective in ischemia-induced acute kidney injury (AKI); however, validation of ASL magnetic resonance imaging (MRI) is limited in AKI in the presence of cirrhosis. PURPOSE: To investigate the feasibility of ASL in revealing renal blood flow (RBF) changes in kidney injury in the presence of cirrhosis and to assess its value in the early diagnosis of disease. STUDY TYPE: Longitudinal. ANIMAL MODEL: Rats were randomized into baseline group (N = 3), sham surgery group (N = 18), and common bile duct ligation (BDL) group (N = 48). All groups were divided into six subgroups based on different sacrificed time points. FIELD STRENGTH/SEQUENCE: 3 T scanner, prototypic pulsed ASL sequence using flow-sensitive alternating inversion recovery preparation, half-Fourier acquisition single-shot turbo spin echo sequence. ASSESSMENT: RBF measurement was performed by ASL. Hematoxylin-eosin (HE) score, Hypoxia-inducible factor-1alpha (HIF-1α) score, peritubular capillar (PTC) density, alanine aminotransferase, aspartate aminotransferase, serum total bilirubin, total bile acids, serum creatinine (Scr), and blood urea nitrogen (BUN) were harvested. STATISTICAL TESTS: Analysis of variance, Pearson's correlation coefficient, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. RESULTS: RBF, HE score, HIF-1α score, and PTC density after BDL were significantly different from baseline. RBF was highly correlated with HE score, HIF-1α score, and PTC density (r = -0.7598, r = -0.7434, r = 0.6406, respectively). RBF and Scr began to differ significantly from baseline at day 3 and 7 after intervention, respectively. The areas under the curves of RBF, Scr, and BUN for distinguishing non-AKI from AKI in cirrhosis were 1.00, 0.888, and 0.911, while those for distinguishing mild from severe kidney injury were 0.961, 0.830, and 0.857, respectively. DATA CONCLUSION: ASL allows the longitudinal assessment of the degree of AKI induced by cholestatic cirrhosis in rats and can serve as a noninvasive marker for the early and accurate diagnosis of AKI. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Coassembly of hypoxia-sensitive macrocyclic amphiphiles and extracellular vesicles for targeted kidney injury imaging and therapy.

BACKGROUND: Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs). RESULTS: In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α4ß1 and αLß2, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects. CONCLUSION: This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs.

Utility of bedside ultrasound derived hepatic and renal parenchymal flow patterns to guide management of acute kidney injury.

PURPOSE OF REVIEW: Ideal fluid management of critically ill patients is maintaining an adequate perfusion pressure but avoiding venous congestion. Venous excess ultrasound score (VExUS) quantifies venous congestion to guide the management of fluid balance. RECENT FINDINGS: VExUS of abdominal veins measures fluid tolerance and helps clinicians avoid congestion. VExUS scoring predicts the development of acute kidney injury (AKI) that is a common hospital problem resulting in higher mortality and morbidity. VExUS can predict patients at risk of developing AKI post cardiac surgery. VExUS has been associated with an increase in adverse outcomes in a general intensive care population. Hepatic vein ultrasound can manifest as a sequela of right heart failure and pulmonary hypertension. Intrarenal congestion suggests poorer prognosis in heart failure patients. VExUS score has been used in decision-making to remove fluid in patients with cardiorenal syndrome. VExUS scoring may help curtail overly aggressive fluid resuscitation for patients with septic shock and help avoid iatrogenic 'salt water drowning'. SUMMARY: We summarize the technique and clinical practice of VExUS to help guide fluid balance across different populations of critically ill patients.

An Activatable Near-Infrared Fluorescence Probe for in Vivo Imaging of Acute Kidney Injury by Targeting Phosphatidylserine and Caspase-3.

Renal-clearable and target-responsive near-infrared (NIR) fluorescent imaging probes have been promising for in vivo diagnosis of acute kidney injury (AKI). However, designing an imaging probe that is renal-clearable and concurrently responsive toward multiple molecular targets to facilitate early detection of AKI with improved sensitivity and specificity is challenging. Herein, by leveraging the receptor-mediated binding and retention effect along with enzyme-triggered fluorescence activation, we design and synthesize an activatable small-molecule NIR fluorescent probe (1-DPA2) using a "one-pot sequential click reaction" approach. 1-DPA2 can target both the externalized phosphatidylserine (PS) and active caspase-3 (Casp-3), two essential biomarkers of apoptosis, producing enhanced 808 nm NIR fluorescence and a high signal-to-background ratio (SBR) amenable to detecting the onset of cisplatin-induced AKI in mice as early as 24 h post-treatment with cisplatin. We not only monitor the gradual activation of Casp-3 in the kidney of mice upon AKI progression but also can report on the progressive recovery of kidney functions in AKI mice following N-acetyl-l-cysteine (NAC) therapy via real-time fluorescence imaging by 1-DPA2. This study demonstrates the ability of 1-DPA2 for longitudinal monitoring of renal cell apoptosis by concurrently targeting PS externalization and Casp-3 activation, which is efficient for early diagnosis of AKI and useful for prediction of potential drug nephrotoxicity as well as in vivo screening of anti-AKI drugs' efficacy.