PET image-guided kidney injury theranostics enabled by a bipyramidal DNA framework.

Understanding the pharmacokinetic profiles of nanomaterials in living organisms is essential for their application in disease treatment. Bipyramidal DNA frameworks (BDFs) are a type of DNA nanomaterial that have shown prospects in the fields of molecular imaging and therapy. To serve as a reference for disease-related studies involving the BDF, we constructed a 68Ga-BDF and employed positron emission tomography (PET) imaging to establish its pharmacokinetic model in healthy mice. Our investigation revealed that the BDF was primarily eliminated from the body via the urinary system. Ureteral obstruction could significantly alter the metabolism of the urinary system. By utilizing the established pharmacokinetic model, we sensitively observed distinct imaging indicators in unilateral ureteral obstruction and acute kidney injury (a complication of ureteral obstruction) mouse models. Furthermore, we observed that the BDF showed therapeutic effects in an AKI model. We believe that the established pharmacokinetic model and unique renal excretion characteristics of the BDF will provide researchers with more information for studying kidney diseases.

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.

Bioinspired BSA@polydopamine@Fe Nanoprobe with Self-Purification Capacity for Targeted Magnetic Resonance Imaging of Acute Kidney Injury.

Contrast-enhanced magnetic resonance imaging (CE-MRI) of acute kidney injury (AKI) is severely hindered by the poor targeting capacity and potential toxicity of current contrast agents. Herein, we propose one-step fabrication of a bovine serum albumin@polydopamine@Fe (BSA@PDA@Fe, BPFe) nanoprobe with self-purification capacity for targeted CE-MRI of AKI. BSA endows the BPFe nanoprobe with renal tubule-targeting ability, and PDA is capable of completely inhibiting the intrinsic metal-induced reactive oxygen species (ROS), which are always involved in Fe/Mn-based agents. The as-prepared nanoprobe owns a tiny size of 2.7 nm, excellent solubility, good T1 MRI ability, superior biocompatibility, and powerful antioxidant capacity. In vivo CE-MRI shows that the BPFe nanoprobe can accumulate in the renal cortex due to the reabsorption effect toward the serum albumin. In the AKI model, impaired renal reabsorption function can be effortlessly detected via the diminishment of renal cortical signal enhancement. More importantly, the administration of the BPFe nanoprobe would not aggravate renal damage of AKI due to the outstanding self-purification capacity. Besides, the BPFe nanoprobe is employed for CE-MR angiography to visualize fine vessel structures. This work provides an MRI contrast agent with good biosafety and targeting ability for CE-MRI of kidney diseases.

A Comparison Between Two Different Definitions of Contrast-Associated Acute Kidney Injury for Long-Term Mortality in Patients with Chronic Kidney Disease Undergoing Coronary Angiography.

Background: Contrast-associated acute kidney injury (CA-AKI) is a prevalent complication following coronary angiography (CAG). However, there is ongoing controversy surrounding its precise definition. Although previous studies have demonstrated the successful application of appropriate definitions in managing high-risk CA-AKI patients, there remains limited research on the association between different definitions and prognosis specifically in patients with chronic kidney disease (CKD). Methods: A total of 4197 CKD patients undergoing coronary angiography (CAG) were included in this study. Two definitions of contrast-associated acute kidney injury (CA-AKI) were used: CA-AKIA, which was defined as an increase of ≥0.5 mg/dL or >25% in serum creatinine (SCr) from baseline within 72 hours after CAG, and CA-AKIB, which was defined as an increase of ≥0.3 mg/dL or >50% in SCr from baseline within 48 hours after CAG. Cox regression analysis was employed to assess the association between these two definitions and long-term mortality. Additionally, population attributable risks (PARs) were calculated to evaluate the impact of CA-AKI definitions on long-term prognosis. Results: During the median follow-up period of 4.70 (2.50-7.78) years, the overall long-term mortality was 23.6%, and the long-term mortality in patients with CA-AKI according to both CA-AKIA and CA-AKIB criteria were 33.5% and 33.8%, respectively. We found that CA-AKIA (HR: 1.45, 95% CI: 1.23-1.70, p<0.001) and CA-AKIB (HR: 1.44, 95% CI: 1.23-1.69, p<0.001) were associated with long-term mortality. The PARs were the highest for CA-AKIA (5.87%), followed by CA-AKIB (5.70%). Conclusion: Contrast-associated acute kidney injury (CA-AKI) is a frequently observed complication in CKD patients undergoing coronary angiography (CAG), and both definitions of CA-AKI are significantly correlated with a poor long-term prognosis. Consequently, in the clinical management of CKD patients, it is crucial to prioritize CA-AKI, irrespective of the specific CA-AKI definition used.

Shear wave elastography: A noninvasive approach for assessing acute kidney injury in critically ill patients.

Traditional markers, such as serum creatinine and blood urea nitrogen, frequently show delayed elevations following acute kidney injury (AKI), limiting their utility for prompt detection and timely intervention in AKI management. Shear wave elastography (SWE) exhibits potential for AKI diagnosis by measuring tissue stiffness. Our study aimed to evaluate the diagnostic performance of SWE in detecting AKI by measuring the stiffness of kidney tissue. Between July 2022 and December 2022, a total of 103 consecutive participants who met the eligibility criteria were prospectively enrolled, underwent SWE measurements, and were classified into AKI or non-AKI groups based on the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A receiver operating characteristic (ROC) curve was drawn to examine the feasibility of differentiating between AKI and non-AKI patients and assessing diagnostic performance. The effects of tissue anisotropy on SWE measurements were also examined. Our results revealed that patients in the AKI group exhibited significantly increased stiffness values in specific kidney regions compared with those in the non-AKI group. For the diagnosis of AKI, the optimal cut-off values were identified as 9.9 kPa, 2.9 kPa, and 4.4 kPa for the upper pole medulla, middle cortex, and middle medulla, respectively, in the longitudinal plane. Correspondingly, the areas under the ROC curves for these regions were 0.737 (95% confidence interval [CI]: 0.637, 0.822), 0.736 (95% CI: 0.637, 0.821), and 0.784 (95% CI: 0.688, 0.861). Additionally, we observed a significant variability in stiffness values due to tissue anisotropy, specifically in the segments of the upper pole cortex, and medulla across both longitudinal and transverse planes. SWE serves as a noninvasive approach for the quantification of tissue stiffness and shows promise as an adjunctive tool for the assessment of AKI.

Resistive index as predictor of acute kidney injury in patients with non-ST-segment elevation myocardial infarction.

BACKGROUND: Acute kidney injury (AKI) is common in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Early detection of AKI is likely to speed diagnosis and implementation of measures to preserve renal function. To evaluate if renal Doppler resistive index (RI) would predict AKI in patients with NSTEMI on presentation in the emergency department. METHODS: Patients with NSTEMI at the emergency department were included. The renal Doppler RI was measured. Baseline demographic data and clinical characteristics of patients at admittance were recorded. Based on discharge diagnosis, the patients were divided into AKI group and no-AKI group. Multiple logistic regression analysis was performed to determine predictor variables significantly associated with AKI. RESULTS: A total of 293 patients were included in the analysis; 44 (15.0%) developed AKI without need for dialysis. There were statistical differences in the age, incidence of diabetes mellitus and cerebrovascular disease, beta-receptor blockers, serum creatinine and renal index between the two groups. Using multivariate logistic regression analysis, age [OR 1.87; 95% confidence interval (CI) 1.595-2.585; p = 0.027], diabetes mellitus (OR 2.007, 95% CI: 1.489-2.793; p = 0.014), serum creatinine (OR 1.817, 95% CI: 1.568-2.319; p = 0.013), and RI (OR 2.168, 95% CI: 1.994-4.019; p = 0.003) predicted AKI in patients with NSTEMI. According to receiver operating characteristic (ROC) analysis, RI showed a significantly increased area under the curve (AUC) compared to serum creatitine (AUC: 0.891 vs 0.679; p < 0.001). CONCLUSIONS: Renal Doppler RI may be a useful predictor of AKI in patients with NSTEMI in the emergency department.

Microglia dysfunction drives disrupted hippocampal amplitude of low frequency after acute kidney injury.

AIMS: Acute kidney injury (AKI) has been associated with a variety of neurological problems, while the neurobiological mechanism remains unclear. In the present study, we utilized resting-state functional magnetic resonance imaging (rs-fMRI) to detect brain injury at an early stage and investigated the impact of microglia on the neuropathological mechanism of AKI. METHODS: Rs-fMRI data were collected from AKI rats and the control group with a 9.4-Tesla scanner at 24, 48, and 72 h post administration of contrast medium or saline. The amplitude of low-frequency fluctuations (ALFF) was then compared across the groups at each time course. Additionally, flow cytometry and SMART-seq2 were employed to evaluate microglia. Furthermore, pathological staining and Western blot were used to analyze the samples. RESULTS: MRI results revealed that AKI led to a decreased ALFF in the hippocampus, particularly in the 48 h and 72 h groups. Additionally, western blot suggested that AKI-induced the neuronal apoptosis at 48 h and 72 h. Flow cytometry and confocal microscopy images demonstrated that AKI activated the aggregation of microglia into neurons at 24 h, with a strong upregulation of M1 polarization at 48 h and peaking at 72 h, accompanying with the release of proinflammatory cytokines. The ALFF value was strongly correlated with the proportion of microglia (|r| > 0.80, p < 0.001). CONCLUSIONS: Our study demonstrated that microglia aggregation and inflammatory factor upregulation are significant mechanisms of AKI-induced neuronal apoptosis. We used fMRI to detect the alterations in hippocampal function, which may provide a noninvasive method for the early detection of brain injury after AKI.

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.

Contrast Agent-Free 3D Renal Ultrafast Doppler Imaging Reveals Vascular Dysfunction in Acute and Diabetic Kidney Diseases.

To combat the irreversible decline in renal function associated with kidney disease, it is essential to establish non-invasive biomarkers for assessing renal microcirculation. However, the limited resolution and/or vascular sensitivity of existing diagnostic imaging techniques hinders the visualization of complex cortical vessels. Here, a 3D renal ultrafast Doppler (UFD) imaging system that uses a high ultrasound frequency (18 MHz) and ultrahigh frame rate (1 KHz per slice) to scan the entire volume of a rat's kidney in vivo is demonstrated. The system, which can visualize the full 3D renal vascular branching pyramid at a resolution of 167 µm without any contrast agent, is used to chronically and noninvasively monitor kidneys with acute kidney injury (AKI, 3 days) and diabetic kidney disease (DKD, 8 weeks). Multiparametric UFD analyses (e.g., vessel volume occupancy (VVO), fractional moving blood volume (FMBV), vessel number density (VND), and vessel tortuosity (VT)) describe rapid vascular rarefaction from AKI and long-term vascular degeneration from DKD, while the renal pathogeneses are validated by in vitro blood serum testing and stained histopathology. This work demonstrates the potential of 3D renal UFD to offer valuable insights into assessing kidney perfusion levels for future research in diabetes and kidney transplantation.

Diagnostic utility of two-dimensional shear wave elastography in nephropathic dogs and its correlation with renal contrast-enhanced ultrasound in course of acute kidney injury.

Aims of our study were to evaluate the feasibility and diagnostic value of two-dimensional shear wave elastography in dogs with acute kidney injury, chronic kidney disease, and acute on chronic kidney disease, its correlation with renal functional (creatinine, urea), and prognostic parameters (serum calcium-phosphorus product, urinary output), and with contrast-enhanced ultrasound (qualitative and quantitative evaluation). The study was prospective. A group of healthy (Group A) and a group of nephropathic dogs (Group B) were included. Shear wave elastography was performed on the left kidney of the subjects of both groups; contrast-enhanced ultrasound was performed only in dogs with acute kidney injury and acute on chronic kidney disease. Sixty-four dogs were included (Group A, n=24; Group B, n=40). The renal stiffness values were significantly higher in Group B than Group A; optimal cut-off stiffness values for detection of renal pathology were: ≥1.51 m/sec (area under the curve, 0.84; 95% confidence interval 0.74-0.94) and ≥6.75 kPa (area under the curve, 0.84; 95% confidence interval 0.73-0.94). For contrast-enhanced ultrasound, a significant positive correlation was found between renal stiffness, area under the curve, and wash-out area under the curve values of cortex quantitative analysis. No correlations were found between renal stiffness and renal functional and prognostic parameters. Shear wave elastography showed diagnostic utility to detect renal abnormalities in dogs with acute kidney injury, chronic kidney disease and acute on chronic kidney disease, however, it could not differentiate between these different nephropathies.

Contrast-enhanced ultrasound in evaluating the severity of acute kidney injury: An animal experimental study.

PURPOSE: Early assessment of the severity of acute kidney injury (AKI) is critical to the prognosis of patients. Renal microcirculation hemodynamic changes and inflammatory response are the essential links of AKI induced by ischemia-reperfusion injury (IRI). This study aims to explore the value of contrast-enhanced ultrasound (CEUS) based on vascular cell adhesion molecule-1 (VCAM-1) targeted microbubbles (TM) in evaluating the renal microcirculation hemodynamics and inflammatory response of different severity of AKI. METHODS: Eighteen male C57BL/6J mice were randomly divided into three groups (n = 6): sham operation (sham) group, mild IRI-AKI (m-AKI) group, and severe IRI-AKI (s-AKI) group. CEUS based on VCAM-1 TM was used to evaluate renal microcirculation perfusion and inflammatory response. Pearson's correlation was used to analyze the correlation between ultrasonic variables and pro-inflammatory factors. RESULTS: Compared with the sham group, AUC in m-AKI and s-AKI groups was significantly decreased, and s-AKI group was lower than m-AKI group (P < 0.05). NID of m-AKI and s-AKI groups was significantly higher than that of the sham group, and s-AKI group was higher than that of m-AKI group (P < 0.05). There was a linear positive correlation between NID and VCAM-1 protein expression (r = 0.7384, P < 0.05). NID and AUC were correlated with TNF-α and IL-6 levels (P < 0.05). Compared with early AKI biomarkers, CEUS based on VCAM-1 TM has higher sensitivity in evaluating the severity of AKI. CONCLUSIONS: CEUS based on VCAM-1 TM can evaluate renal microcirculation perfusion and inflammatory response in mild and severe AKI, which may provide helpful information for assessing the severity of 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.

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.

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.

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.

Direct mapping of kidney function by DCE-MRI urography using a tetrazinanone organic radical contrast agent.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are ongoing global health burdens. Glomerular filtration rate (GFR) is the gold standard measure of kidney function, with clinical estimates providing a global assessment of kidney health without spatial information of kidney- or region-specific dysfunction. The addition of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to the anatomical imaging already performed would yield a 'one-stop-shop' for renal assessment in cases of suspected AKI and CKD. Towards urography by DCE-MRI, we evaluated a class of nitrogen-centered organic radicals known as verdazyls, which are extremely stable even in highly reducing environments. A glucose-modified verdazyl, glucoverdazyl, provided contrast limited to kidney and bladder, affording functional kidney evaluation in mouse models of unilateral ureteral obstruction (UUO) and folic acid-induced nephropathy (FAN). Imaging outcomes correlated with histology and hematology assessing kidney dysfunction, and glucoverdazyl clearance rates were found to be a reliable surrogate measure of GFR.