Kidney Doppler ultrasonography in critical care nephrology.

Color pulsed-wave Doppler ultrasound (CPWD-US) emerges as a pivotal tool in intensive care units (ICUs) for diagnosing acute kidney injury (AKI) swiftly and non-invasively. Its bedside accessibility allows for rapid assessments, making it a primary imaging modality for AKI characterization. Furthermore, CPWD-US serves as a guiding instrument for key diagnostic-interventional procedures such as renal needle biopsy and percutaneous nephrostomy, while also facilitating therapy response monitoring and AKI progression tracking. This review shifts focus towards the integration of renal ultrasound into ICU workflows, offering contemporary insights into its utilization through a diagnostic standard-oriented approach. By presenting a flow chart, this review aims to provide practical guidance on the appropriate use of point-of-care ultrasound in critical care scenarios, enhancing diagnostic precision, patient management and safety, albeit amidst a backdrop of limited evidence regarding long-term outcomes.

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.

Inferior vena cava-aortic ratio measurement as a promising modality in assessing intravascular volume in children with sepsis.

BACKGROUND: Hemodynamic monitoring is crucial for the comprehensive management of children with sepsis, particularly those involving the kidneys. Sepsis-associated acute kidney injury (S-AKI) is closely linked to poor outcomes. Recently, ultrasonography modalities have been widely accepted as a non-invasive, rapid, and reliable tool for assessing volume status. We conducted research to determine intravascular volume based on ultrasound examination in S-AKI patients. METHODS: A prospective cohort study was conducted between December 2023 and March 2024 in the Pediatric Intensive Care Unit (PICU) at Hasan Sadikin General Hospital. We divided the patients into two groups: those with sepsis without AKI and those with S-AKI. The intravascular volume was measured by the IVC/Ao (inferior vena cava/abdominal aorta) ratio using two-dimensional ultrasonography and USCOM before and 24 h after fluid treatment. The results were analyzed using SPSS 25, with a significance level of p < 0.05. RESULTS: A total of 36 pediatric patients (aged 1 month-18 years) with sepsis were included. The IVC/Ao ratio before and after the fluid intervention demonstrated significant differences between the two groups (p < 0.001). USCOM Cardiac Index (CI) before and after the intervention also showed significant differences between the two groups (p < 0.001). Patients with S-AKI exhibited a poor hemodynamic response in the IVC/Ao ratio two-dimensional ultrasonography and USCOM examination. CONCLUSIONS: IVC/Ao ratio measurement is as accurate as USCOM and can be used as a simple and cost-effective alternative for hemodynamic monitoring.

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.

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.

Kidney-Targeted Near-Infrared Fluorescence Probe Reveals That SO2 Is a Biomarker for Cisplatin-Induced Acute Kidney Injury.

With the widespread use of drugs, drug-induced acute kidney injury (AKI) has become an increasingly serious health concern worldwide. Currently, early diagnosis of drug-induced AKI remains challenging because of the lack of effective biomarkers and noninvasive imaging tools. SO2 plays important physiological roles in living systems and is an important antioxidant for maintaining redox homeostasis. However, the relationship between SO2 (in water as SO32-/HSO3-) and drug-induced AKI remains largely unknown. Herein, we report the highly sensitive near-infrared fluorescence probe DSMN, which for the first time reveals the relationship between SO2 and drug-induced AKI. The probe responds to SO32-/HSO3- selectively and rapidly (within seconds) and shows a significant turn-on fluorescence at 710 nm with a large Stokes shift (125 nm). With these properties, the probe was successfully applied to detect SO2 in living cells and mice. Importantly, the probe can selectively target the kidneys, allowing for the detection of changes in the SO2 concentration in the kidneys. Based on this, DSMN was successfully used to detect cisplatin-induced AKI and revealed an increase in the SO2 levels. The results indicate that SO2 is a new biomarker for AKI and that DSMN is a powerful tool for studying and diagnosing drug-induced AKI.

Vanin-1-Activated Chemiluminescent Probe: Help to Early Diagnosis of Acute Kidney Injury with High Signal-to-Noise Ratio through Urinalysis.

Acute kidney injury (AKI) is a common medical condition with high morbidity and mortality. Although urinalysis provides a noninvasive and convenient diagnostic method for AKI at the molecular level, the low sensitivity of current chemical probes used in urinalysis hinders the time diagnosis of AKI. Herein, we achieved the sensitive and early diagnosis of AKI by the development of a chemiluminescent probe CL-Pa suitable for detection of urinary Vanin-1. Vanin-1 is considered as an early and sensitive biomarker for AKI, while few chemical probes have been applied to for its efficient detection. By virtue of the low autofluorescence interference during urine imaging in the chemiluminescence model, CL-Pa could realize the monitoring of the up-regulated urinary Vanin-1 with a high signal-to-noise ratio (∼588). Importantly, under the help of CL-Pa, the up-regulation of urinary Vanin-1 of cisplatin-induced AKI mice at 12 h post cisplatin injection was detected, which was much earlier than clinical biomarkers (sCr and BUN) and change of kidney histology (48 h post cisplatin injection). Furthermore, using this probe, the fluctuation of urinary Vanin-1 of mice with different degrees of AKI was monitored. This study demonstrated the ability of CL-Pa in sensitively detecting drug-induced AKI through urinalysis and suggested the great potential of CL-Pa for early diagnosis of AKI and evaluate the efficiency of anti-AKI drugs clinically.

Contrast-enhanced CT and Acute Kidney Injury: Risk Stratification by Diabetic Status and Kidney Function.

Background Diabetes mellitus may be associated with an increased likelihood of CT contrast material-induced acute kidney injury (CI-AKI), but this has not been studied in a large sample with and without kidney dysfunction. Purpose To investigate whether diabetic status and estimated glomerular filtration rate (eGFR) are associated with the likelihood of acute kidney injury (AKI) following CT contrast material administration. Materials and Methods This retrospective multicenter study included patients from two academic medical centers and three regional hospitals who underwent contrast-enhanced CT (CECT) or noncontrast CT between January 2012 and December 2019. Patients were stratified according to eGFR and diabetic status, and subgroup-specific propensity score analyses were performed. The association between contrast material exposure and CI-AKI was estimated with use of overlap propensity score-weighted generalized regression models. Results Among the 75 328 patients (mean age, 66 years ± 17 [SD]; 44 389 men; 41 277 CECT scans; 34 051 noncontrast CT scans), CI-AKI was more likely in patients with an eGFR of 30-44 mL/min/1.73 m2 (odds ratio [OR], 1.34; P < .001) or less than 30 mL/min/1.73 m2 (OR, 1.78; P < .001). Subgroup analyses revealed higher odds of CI-AKI among patients with an eGFR less than 30 mL/min/1.73 m2, with or without diabetes (OR, 2.12 and 1.62; P = .001 and .003, respectively), when they underwent CECT compared with noncontrast CT. Among patients with an eGFR of 30-44 mL/min/1.73 m2, the odds of CI-AKI were higher only in those with diabetes (OR, 1.83; P = .003). Patients with an eGFR less than 30 mL/min/1.73 m2 and diabetes had higher odds of 30-day dialysis (OR, 1.92; P = .005). Conclusion Compared with noncontrast CT, CECT was associated with higher odds of AKI in patients with an eGFR of less than 30 mL/min/1.73 m2 and in patients with diabetes with an eGFR of 30-44 mL/min/1.73 m2; higher odds of 30-day dialysis were observed only in patients with diabetes with an eGFR less than 30 mL/min/1.73 m2. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Davenport in this issue.

Risk of Acute Kidney Injury Following Contrast-enhanced CT in a Cohort of 10 407 Children and Adolescents.

Background Previous studies have challenged the concept of contrast material-induced acute kidney injury (AKI) in adults; however, limited data exist for children and adolescents. Purpose To calculate the incidence and determine the risks of AKI in patients who received intravenous iodinated contrast media for CT. Materials and Methods This retrospective study was performed at a children's hospital from January 2008 to January 2018 and included patients aged 0-17 years in whom serum creatinine levels were measured within 48 hours before and after CT with or without contrast media. The incidence of AKI was measured according to the AKI Network guidelines. A subgroup analysis with propensity score matching of cases with control patients was performed. Differences before and after stratification based on estimated glomerular filtration rate (eGFR) were explored. Adjusted risk models were developed using log-binomial generalized estimating equations to estimate relative risk (RR). Results From a total of 54 000 CT scans, 19 377 scans from 10 407 patients (median age, 8.5 years; IQR, 3-14; 5869 boys, 4538 girls) were included in the analysis. Incidence rate of AKI for the entire sample was 1.5%; it was 1.4% (123 of 8844) in the group that underwent contrast-enhanced CT and 1.6% (171 of 10 533) in the group that did not (P = .18). In the contrast-enhanced CT group, AKI incidence was higher in the group with eGFR of at least 60 mL/min/1.73 m2 and in the group with eGFR lower than 60 mL/min/1.73 m2 (1.3% and 8.5%, respectively; P < .001) compared with the noncontrast group (0.1% and 2.7%, respectively; P < .001). Age was found to be a protective factor against AKI, with an RR of 0.96 (95% CI: 0.94, 0.99; P = .01), and contrast media increased risk in the subgroup analysis, with an RR of 2.19 (95% CI: 1.11, 4.35; P = .02). Conclusion The overall incidence of acute kidney injury after contrast-enhanced CT in children and adolescents was very low, and exposure to contrast media did not increase the risk consistently for acute kidney injury among different groups and analyses. © RSNA, 2022 See also the editorial by McDonald in this issue.

Perfusion and T2 Relaxation Time as Predictors of Severity and Outcome in Sepsis-Associated Acute Kidney Injury: A Preclinical MRI Study.

BACKGROUND: Preventing sepsis-associated acute kidney injury (S-AKI) can be challenging because it develops rapidly and is often asymptomatic. Probability assessment of disease progression for therapeutic follow-up and outcome are important to intervene and prevent further damage. PURPOSE: To establish a noninvasive multiparametric MRI (mpMRI) tool, including T1 , T2 , and perfusion mapping, for probability assessment of the outcome of S-AKI. STUDY TYPE: Preclinical randomized prospective study. ANIMAL MODEL: One hundred and forty adult female SD rats (65 control and 75 sepsis). FIELD STRENGTH/SEQUENCE: 9.4T; T1 and perfusion map (FAIR-EPI) and T2 map (multiecho RARE). ASSESSMENT: Experiment 1: To identify renal injury in relation to sepsis severity, serum creatinine levels were determined (31 control and 35 sepsis). Experiment 2: Animals underwent mpMRI (T1 , T2 , perfusion) 18 hours postsepsis. A subgroup of animals was immediately sacrificed for histology examination (nine control and seven sepsis). Result of mpMRI in follow-up subgroup (25 control and 33 sepsis) was used to predict survival outcomes at 96 hours. STATISTICAL TESTS: Mann-Whitney U test, Spearman/Pearson correlation (r), P < 0.05 was considered statistically significant. RESULTS: Severely ill septic animals exhibited significantly increased serum creatinine levels compared to controls (70 ± 30 vs. 34 ± 9 µmol/L, P < 0.0001). Cortical perfusion (480 ± 80 vs. 330 ± 140 mL/100 g tissue/min, P < 0.005), and cortical and medullary T2 relaxation time constants were significantly reduced compared to controls (41 ± 4 vs. 37 ± 5 msec in cortex, P < 0.05, 52 ± 7 vs. 45 ± 6 msec in medulla, P < 0.05). The combination of cortical T2 relaxation time constants and perfusion results at 18 hours could predict survival outcomes at 96 hours with high sensitivity (80%) and specificity (73%) (area under curve of ROC = 0.8, Jmax = 0.52). DATA CONCLUSION: This preclinical study suggests combined T2 relaxation time and perfusion mapping as first line diagnostic tool for treatment planning. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Acute kidney injury in critically ill children: predictive value of renal arterial Doppler assessment.

BACKGROUND: Renal resistive index (RRI) and renal pulsatility index (RPI) are Doppler-based variables proposed to assess renal perfusion at the bedside in critically ill patients. This study aimed to assess the accuracy of such variables to predict acute kidney injury (AKI) in mechanically ventilated children. METHODS: Consecutive children aged <14 years underwent kidney Doppler ultrasound examination within 24 h of invasive mechanical ventilation. Renal resistive index (RRI) and renal pulsatility index (RPI) were measured. The primary outcome was severe AKI (KDIGO stage 2 or 3) on day 3. RESULTS: On day 3, 22 patients were classified as having AKI, of which 12 were severe. RRI could effectively predict severe AKI (area under the ROC curve [AUC] = 0.94) as well as RPI (AUC = 0.86). The optimal cut-off for RRI was 0.85 (sensitivity, 91.7%; specificity, 84.7%; PPV, 50.0%; and NPV, 98.4%). Similar results were obtained when the accuracy to predict AKI on day 5 was assessed. Significant correlations were observed between RRI and estimated glomerular filtration rate at enrollment (ρ = -0.495) and on day 3 (ρ = -0.467). CONCLUSIONS: Renal Doppler ultrasound may be a promising tool to predict AKI in critically ill children under invasive mechanical ventilation. IMPACT: Early recognition of acute kidney injury (AKI) is essential to promptly initiate supportive care aimed at restoring renal perfusion, which may prevent or attenuate acute tubular necrosis. Renal arterial Doppler-based parameters are rapid, noninvasive, and repeatable variables that may be promising for the prediction of AKI in children. To the best of our knowledge, this is the first study to evaluate the use of renal Doppler-based variables to predict AKI in critically ill children. The present study found that Doppler-based variables could accurately predict the occurrence of severe AKI and were correlated with urinary output and diuretic use.

Early assessment of acute kidney injury in severe acute pancreatitis with multimodal DWI: an animal model.

OBJECTIVES: To evaluate the feasibility of multimodal diffusion-weighted imaging (DWI) for detecting the occurrence and severity of acute kidney injury (AKI) caused by severe acute pancreatitis (SAP) in rats. METHODS: SAP was induced in thirty rats by the retrograde injection of 5.0% sodium taurocholate through the biliopancreatic duct. Six rats underwent MRI of the kidneys 24 h before and 2, 4, 6, and 8 h after this AKI model was generated. Conventional and functional MRI sequences were used, including intravoxel incoherent motion imaging (IVIM), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DTI). The main DWI parameters and histological results were analyzed. RESULTS: The fast apparent diffusion coefficient (ADC) of the renal cortex was significantly reduced at 2 h, as was the fractional anisotropy (FA) value of the renal cortex on DTI. The mean kurtosis (MK) values for the renal cortex and medulla gradually increased after model generation. The renal histopathological score was negatively correlated with the medullary slow ADC, fast ADC, and perfusion scores for both the renal cortex and medulla, as were the ADC and FA values of the renal medulla in DTI, whereas the MK values of the cortex and medulla were positively correlated (r = 0.733, 0.812). Thus, the cortical fast ADC, medullary MK, FADTI, and slow ADC were optimal parameters for diagnosing AKI. Of these parameters, cortical fast ADC had the highest diagnostic efficacy (AUC = 0.950). CONCLUSIONS: The fast ADC of the renal cortex is the core indicator of early AKI, and the medullary MK value might serve as a sensitive biomarker for grading renal injury in SAP rats. CLINICAL RELEVANCE STATEMENT: The multimodal parameters of renal IVIM, DTI, and DKI are potential beneficial for the early diagnosis and severity grading of renal injury in SAP patients. KEY POINTS: • The multimodal parameters of renal DWI, including IVIM, DTI, and DKI, may be valuable for the noninvasive detection of early AKI and the severity grading of renal injury in SAP rats. • Cortical fast ADC, medullary MK, FA, and slow ADC are optimal parameters for early diagnosis of AKI, and cortical fast ADC has the highest diagnostic efficacy. • Medullary fast ADC, MK, and FA as well as cortical MK are useful for predicting the severity grade of AKI, and the renal medullary MK value exhibits the strongest correlation with pathological scores.

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.

Association between intrarenal venous flow from Doppler ultrasonography and acute kidney injury in patients with sepsis in critical care: a prospective, exploratory observational study.

BACKGROUND: Intrarenal venous flow (IRVF) patterns assessed using Doppler renal ultrasonography are real-time bedside visualizations of renal vein hemodynamics. Although this technique has the potential to detect renal congestion during sepsis resuscitation, there have been few studies on this method. We aimed to examine the relationship between IRVF patterns, clinical parameters, and outcomes in critically ill adult patients with sepsis. We hypothesized that discontinuous IRVF was associated with elevated central venous pressure (CVP) and subsequent acute kidney injury (AKI) or death. METHODS: We conducted a prospective observational study in two tertiary-care hospitals, enrolling adult patients with sepsis who stayed in the intensive care unit for at least 24 h, had central venous catheters placed, and received invasive mechanical ventilation. Renal ultrasonography was performed at a single time point at the bedside after sepsis resuscitation, and IRVF patterns (discontinuous vs. continuous) were confirmed by a blinded assessor. The primary outcome was CVP obtained at the time of renal ultrasonography. We also repeatedly assessed a composite of Kidney Disease Improving Global Outcomes of Stage 3 AKI or death over the course of a week as a secondary outcome. The association of IRVF patterns with CVP was examined using Student's t-test (primary analysis) and that with composite outcomes was assessed using a generalized estimating equation analysis, to account for intra-individual correlations. A sample size of 32 was set in order to detect a 5-mmHg difference in CVP between IRVF patterns. RESULTS: Of the 38 patients who met the eligibility criteria, 22 (57.9%) showed discontinuous IRVF patterns that suggested blunted renal venous flow. IRVF patterns were not associated with CVP (discontinuous flow group: mean 9.24 cm H2O [standard deviation: 3.19], continuous flow group: 10.65 cm H2O [standard deviation: 2.53], p = 0.154). By contrast, the composite outcome incidence was significantly higher in the discontinuous IRVF pattern group (odds ratio: 9.67; 95% confidence interval: 2.13-44.03, p = 0.003). CONCLUSIONS: IRVF patterns were not associated with CVP but were associated with subsequent AKI in critically ill adult patients with sepsis. IRVF may be useful for capturing renal congestion at the bedside that is related to clinical patient outcomes.

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.

Predictive performance of renal resistive index, semiquantitative power Doppler ultrasound score and renal venous Doppler waveform pattern for acute kidney injury in critically ill patients and prediction model establishment: a prospective observational study.

BACKGROUND: This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score and renal venous Doppler waveform (RVDW) pattern in predicting acute kidney injury (AKI) in critically ill patients and establish prediction models. METHODS: This prospective observational study included 234 critically ill patients. Renal ultrasound was measured within 24 h after intensive care unit admission. The main outcome was the highest AKI stage within 5 days after admission according to the Kidney Disease Improving Global Outcomes criteria. RESULTS: Patients in the AKI stage 3 group had significantly higher RRI, RVDW pattern and lower PDU score (p < 0.05). Only lactate, urine volume, serum creatinine (SCr) on admission, PDU score and RVDW pattern were statistically significant predictors (p < 0.05). Model 1 based on these five variables (area under the curve [AUC] = 0.938, 95% confidence interval [CI] 0.899-0.965, p < 0.05) showed the best performance in predicting AKI stage 3, and difference in AUC between it and the clinical model including lactate, urine volume and SCr (AUC = 0.901, 95% CI 0.855-0.936, p < 0.05) was statistically significant (z statistic = 2.224, p = 0.0261). The optimal cut-off point for a nomogram based on Model 1 was ≤127.67 (sensitivity: 95.8%, specificity: 82.3%, Youden's index: 0.781). CONCLUSIONS: The nomogram model including SCr, urine volume, lactate, PDU score and RVDW pattern upon admission exhibited a significantly stronger capability for AKI stage 3 than each single indicator and clinical model including SCr, urine volume and lactate.

Renal hemodynamic evaluation protocol based on the pathophysiological mechanism of acute kidney injury: Critical Care UltraSound Guided-A(KI)BCDE.

The multiple etiological characteristics of acute kidney injury (AKI) have brought great challenges to its clinical diagnosis and treatment. Renal injury in critically ill patients always indicates hemodynamic injury. The Critical Care UltraSound Guided (CCUSG)-A(KI)BCDE protocol developed by the Chinese Critical Ultrasound Study Group (CCUSG), respectively, includes A(KI) diagnosis and risk assessment and uses B-mode ultrasound, Color doppler ultrasound, spectral Doppler ultrasound, and contrast Enhanced ultrasound to obtain the hemodynamic characteristics of the kidney so that the pathophysiological mechanism of the occurrence and progression of AKI can be captured and the prognosis of AKI can be predicted combined with other clinical information; therefore, the corresponding intervention and treatment strategies can be formulated to achieve targeted, protocolized, and individualized therapy.

NIR-II Photoacoustic-Active DNA Origami Nanoantenna for Early Diagnosis and Smart Therapy of Acute Kidney Injury.

Herein, we designed and synthesized a novel microRNA (miR)-responsive nanoantenna capable of early diagnosis and smart treatment of acute kidney injury (AKI). The nanoantenna was made of two miniature gold nanorods (AuNRs) (e.g., length: ∼48 nm; width: ∼9 nm) linked together by a rectangular DNA origami nanostructure (rDONs) scaffold (e.g., length: ∼90 nm; width: ∼60 nm) (rDONs@AuNR dimer). The surface plasmon resonance peak of the constructed nanoantenna is located within the NIR-II window (e.g., ∼1060 nm), thus guaranteeing photoacoustic (PA) imaging of the nanoantenna in deep tissues. Intriguingly, the nanoantenna displayed exclusive kidney retention in both healthy mice and ischemia reperfusion-induced AKI mice by leveraging the kidney-targeting ability of rDONs. Distinguished from the stable signals in the healthy mice, the PA signals of the nanoantenna would turn down in the AKI mice due to the AuNR detached from rDONs upon interaction with miR-21, which were up-expressed in AKI mice. The limit of detection toward miR-21 was down to 2.8 nM, enabling diagnosis of AKI as early as 10 min post-treatment with ischemia reperfusion, around 2 orders of magnitude earlier than most established probes. Moreover, the naked rDON scaffold generated by AKI could capture more reactive oxygen species (e.g., 1.5-fold more than rDONs@AuNR dimer), alleviating ischemic AKI. This strategy provided a new avenue for early diagnosis and smart treatment of AKI.

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.

Multifunction-Harnessed Afterglow Nanosensor for Molecular Imaging of Acute Kidney Injury In Vivo.

Afterglow is superior to other optical modalities for biomedical applications in that it can exclude the autofluorescence background. Nevertheless, afterglow has rarely been applied to the high-contrast "off-to-on" activatable sensing scheme because the complicated afterglow systems hamper the additional inclusion of sensory functions while preserving the afterglow luminescence. Herein, a simple formulation of a multifunctional components-incorporated afterglow nanosensor (MANS) is developed for the superoxide-responsive activatable afterglow imaging of cisplatin-induced kidney injury. A multifunctional iridium complex (Ir-OTf) is designed to recover its photoactivities (phosphorescence and the ability of singlet oxygen-generating afterglow initiator) upon exposure to superoxide. To construct the nanoscopic afterglow detection system (MANS), Ir-OTf is incorporated with another multifunctional molecule (rubrene) in the polymeric micellar nanoparticle, where rubrene also plays dual roles as an afterglow substrate and a luminophore. The multiple functions covered by Ir-OTf and rubrene renders the composition of MANS quite simple, which exhibits superoxide-responsive "off-to-on" activatable afterglow luminescence for periods longer than 11 min after the termination of pre-excitation. Finally, MANS is successfully applied to the molecular imaging of cisplatin-induced kidney injury with activatable afterglow signals responsive to pathologically overproduced superoxide in a mouse model without autofluorescence background.