Isoflurane preconditioning protects against renal ischemia/reperfusion injury in diabetes via activation of the Brg1/Nrf2/HO-1 signaling pathway.

PURPOSE: To examine whether isoflurane preconditioning (IsoP) has a protective effect against renal ischemia/reperfusion injury (I/RI) in diabetic conditions and to further clarify the underlying mechanisms. METHODS: Control and streptozotocin-induced diabetic rats were randomly assigned to five groups, as follows: normal sham, normal I/R, diabetic sham, diabetic I/R, and diabetic I/R + isoflurane. Renal I/RI was induced by clamping renal pedicle for 45 min followed by reperfusion for 24 h. IsoP was achieved by exposing the rats to 2% isoflurane for 30 min before vascular occlusion. Kidneys and blood were collected after reperfusion for further analysis. Renal histology, blood urea nitrogen, serum creatinine, oxidative stress, inflammatory cytokines, and renal cell apoptosis were assessed. Furthermore, the expression of brahma related gene 1 (Brg1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and nuclear factor-κB (NF-κB) were determined. RESULTS: Compared with control, diabetic rats undergoing I/R presented more severe renal injury, oxidative stress, inflammatory reaction, and apoptosis with the impairment of Brg1/Nrf2/HO-1 signaling. All these alterations were significantly attenuated by pretreatment with isoflurane. CONCLUSIONS: These findings suggest that isoflurane could alleviate renal I/RI in diabetes, possibly through improving Brg1/Nrf2/HO-1 signaling.

The value of tissue quantitative diffusion analysis of ultrasound elastography in the diagnosis of early-stage chronic kidney disease.

PURPOSE: To explore the value of tissue quantitative diffusion analysis of ultrasound elastography in the diagnosis of early-stage chronic kidney disease (CKD). METHODS: The observation group comprised 54 patients with early-stage CKD treated at Fuzhou No 7 Hospital, and the control group consisted of 40 healthy individuals who underwent physical examinations at the same hospital. The renal parenchyma of the participants were examined using ultrasonography, color Doppler ultrasonography, and tissue quantitative diffusion analysis of ultrasound elastography. Renal dimensions (diameter, thickness, and renal parenchyma thickness), interlobar artery blood flow parameters, and 11 elastic characteristic values were analyzed and compared between the two groups. The area under the receiver-operating characteristic (ROC) curve, cut-off values, sensitivity, and specificity were calculated using the ROC curve analysis. RESULTS: There were no significant differences in the blood flow parameters of the interlobar artery and the dimensions of renal meridians between the two groups. In the observation group, the mean (MEAN) decreased, while the blue area ratio and skewness, increased, compared to the control group (p < 0.05). In addition, the ROC curve revealed that the blue area ratio, MEAN, and skewness had significant diagnostic value (the area under the curve > 0.7). Notably, the best cut-off value of the MEAN was found to be 106, indicating that a MEAN value less than 106 represented early-stage CKD. Also, this cutoff value had a sensitivity of 80% and a specificity of 81%. CONCLUSION: Tissue quantitative diffusion analysis of ultrasound elastography can quantitatively evaluate renal parenchymal damage in early-stage CKD using quantitative diffusion parameters, with the MEAN parameter, having a cutoff of 106, being particularly effective. This parameter and cutoff value offer a valuable tool for the early detection and diagnosis of CKD, potentially improving patient outcomes through earlier intervention. CLINICAL TRIAL NUMBER: Not applicable.

Super-selective renal artery embolization (SRAE) for iatrogenic and traumatic renal hemorrhage.

PURPOSE: To present the radiological and clinical outcomes of super-selective transcatheter renal artery embolization in patients with renal injury hemorrhage, and share our experience. METHODS: 43 patients with renal injury hemorrhage who underwent 46 SRAEs were enrolled in this retrospective review study. Records, images, and outcomes were reviewed. The individual embolic method and its observed effects were investigated. RESULTS: Angiography showed free extravasation in 25 angiograms, pseudoaneurysm in 15 angiograms, and arteriovenous fistulas in 1 angiogram. Most patients achieved initial clinical success (38/43, 88.4%), and 41 patients achieved final clinical success (41/43, 95.3%). 9/11 patients who adopted empirical embolization achieved initial clinical success (81.8%). In our study, the combination of PVA particles and micro-coils has emerged as the most commonly utilized material combination (24/46, 52.2%). Significant differences in hemoglobin levels were observed before and after the embolization procedure (p = 0.026, 95%CI: 1.03-15.54). Post-embolization clinical follow-up showed no evidence of recurrent hematuria, progression of hematoma, hypertension, and no reflux of the embolic agent. CONCLUSION: Though SRAE showed satisfactory results across a broad range of renal injury hemorrhage, there are still some aspects that need attention: (1) Surgical procedure should be understood, including the surgical site, access routes, and placement of implants, such as double-J stents. (2) In cases where identifying the bleeding point proves challenging, consider the possibility of an accessory renal artery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2400085050, Registration Date: 30 May 2024, retrospectively, non-randomized.

The Dual-specificity Phosphatase 3 (DUSP3): A Potential Target Against Renal Ischemia/Reperfusion Injury.

Renal ischemia/reperfusion (I/R) injury is a common clinical challenge faced by clinicians in kidney transplantation. I/R is the leading cause of acute kidney injury, and it occurs when blood flow to the kidney is interrupted and subsequently restored. I/R impairs renal function in both short and long terms. Renal ischemic preconditioning refers to all maneuvers intended to prevent or attenuate ischemic damage. In this context, the present review focuses on the dual-specificity phosphatase 3 (DUSP3), also known as vaccinia H1-related phosphatase, an uncommon regulator of mitogen-activated protein kinase (MAPK) phosphorylation. DUSP3 has different biological functions: (1) it acts as a tumor modulator and (2) it is involved in the regulation of immune response, thrombosis, hemostasis, angiogenesis, and genomic stability. These functions occur either through MAPK-dependent or MAPK-independent mechanisms. DUSP3 genetic deletion dampens kidney damage and inflammation caused by I/R in mice, suggesting DUSP3 as a potential target for preventing renal I/R injury. Here, we discuss the putative role of DUSP3 in ischemic preconditioning and the potential mechanisms of such an attenuated inflammatory response via improved kidney perfusion and adequate innate immune response.

Gross morphological and ultrasonographic dimensions of normal feline kidney with reference to resistive index.

Ultrasonography with color Doppler is the most quantitative analysis method for intra-renal parameters. There is a wide variation between authors in the measurement site and referencing the inter-lobar resistivity index (RI) in felines. Our objective is to morphometrically and ultrasonographically investigate the normal renal dimensions and vasculatures and draw up a normal reference value for the renal inter-lobar artery resistivity index (RI) using a Pulsed wave-Doppler ultrasonography. A total of twelve adult domestic cats were sedated and treated according to IACUC regulation guidelines to be examined using Doppler ultrasound. The same cats were used for morphometric investigation and divided into three groups regarding the used technique. The size difference between the right and left kidneys is slight, measuring 17 g (weight), 3.65 ± 0.06 cm (length), 2.54 ± 0.08 cm (width), and 2.21 ± 0.03 cm (thickness) for the right kidney, and about 15 g, 3.42 ± 0.06 cm, 2.32 ± 0.05 cm, and 2.13 ± 0.03 cm for the left one, respectively. There are three patterns of renal arteries' point of origin. The mean RI values of both kidneys were 0.57 ± 0.08 (0.50-0.67) in the right kidney and 0.60 ± 0.08 (0.51-0.69) in the left kidney. The gross examination and ultrasonography measurements did not have a statistically different effect on the actual renal dimensions. Moreover, 0.69 is considered the standard resistivity index (RI) threshold of the feline inter-lobar artery with no correlation to the animal's body weight.

Multifocal Renal Infarction and Diabetic Ketoacidosis: Diagnostic Challenges and Anticoagulation Management in a Complex Case.

BACKGROUND Incidental findings of renal infarct secondary to thrombosis in acutely ill patients present a unique challenge in diagnosis. We present a case of idiopathic renal infarct to highlight its workup and management and encourage further investigation of renal infarctions. CASE REPORT A 68-year-old woman with a past medical history of diet-controlled diabetes, hypertension, and hyperlipidemia presented to the Emergency Department (ED) for abdominal pain. She was found to be in diabetic ketoacidosis with pyelonephritis, so she was admitted to the Intensive Care Unit (ICU) for insulin and dextrose drip. Due to her abdominal pain, she underwent computed tomography (CT) of her abdomen and pelvis with contrast. This revealed multifocal infarcts of her right kidney with noncalcified thrombus at the proximal right renal artery. Subsequent CT angiography confirmed a right renal artery thrombus. She was started on subcutaneous enoxaparin and downgraded to basic level of care. Her history was negative for prior thrombosis, hypercoagulable state, and abdominal trauma. Echocardiogram and limited hypercoagulable workup were largely unremarkable. A multidisciplinary team evaluated the patient and recommended no surgical intervention. Following downgrade from the ICU, the patient was transitioned from enoxaparin to apixaban. She was discharged with plans for anticoagulation for 6 months, aspirin daily, and repeat CT angiogram abdomen/pelvis in 1 month. CONCLUSIONS This case illustrates the difficulties in elucidating the cause of incidental renal thrombosis in an acutely ill patient. Diagnostic workup is limited in the inpatient setting, but therapeutic anticoagulation remains the standard of treatment regardless of etiology.

Exploring the relationship between ventricular fibrillation recurrence after defibrillation in myocardial infarction and the effectiveness of renal sympathetic denervation therapy.

OBJECTIVE: This study aimed to explore the association between electrophysiological markers of early recurrence after defibrillation in post-myocardial infarction ventricular fibrillation and the therapeutic effects of sympathetic renal denervation, as well as to investigate the potential underlying mechanisms. METHODS: Experimental research was conducted using an animal model. Myocardial infarction was induced, followed by defibrillation treatment for ventricular fibrillation cases, and the electrophysiological markers of early recurrence were recorded. Subsequently, a subset of animals underwent sympathetic renal denervation intervention, and the therapeutic effects were compared between the sympathetic renal denervation group and the control group. Electrocardiogram monitoring, histological analysis of myocardial tissue, and neurotransmitter measurements were also performed. RESULTS: Following defibrillation treatment, early recurrence was observed in ventricular fibrillation cases. The electrophysiological markers revealed significantly higher ST segment elevation and T wave changes in the early recurrence group. However, in the sympathetic renal denervation intervention group, the early recurrence rate was significantly reduced, and the electrocardiogram showed improved stability and regularity. Additionally, histological analysis of myocardial tissue demonstrated less cellular damage and lower levels of myocardial fibrosis in the sympathetic renal denervation group. Neurotransmitter measurements revealed a significant decrease in sympathetic nerve activity in the sympathetic renal denervation intervention group. CONCLUSION: The results of this study indicate an association between electrophysiological markers of early recurrence after defibrillation in post-myocardial infarction ventricular fibrillation and the therapeutic effects of sympathetic renal denervation. Sympathetic renal denervation intervention can significantly reduce the early recurrence rate, improve electrocardiogram characteristics, and alleviate myocardial damage and fibrosis. Furthermore, the reduction in sympathetic nerve activity may be one of the potential underlying mechanisms of sympathetic renal denervation intervention.

A gradient model of renal ischemia reperfusion injury to investigate renal interstitial fibrosis.

Background: The progression from acute kidney injury to chronic kidney disease poses a significant health challenge. Nonetheless, a constraint in existing animal models of renal ischemia/reperfusion (I/R) injury is the necessity for a severe injury, almost reaching a life-threatening level, to trigger the subsequent onset of renal fibrosis. Hence, we explored an adapted gradient approach to induce I/R injury, aiming to promote the progression of renal fibrosis while preserving the overall normal functioning of the kidney. Methods: In each group, 6-8 male C57BL/6 mice were used for model construction, with all undergoing sodium pentobarbital anesthesia and left kidney removal. Subsequently, a silk thread was passed beneath the lower renal branch, elevating the right kidney under a 20-g weight's tension via a pulley system for durations of 30, 40, or 60 min. Afterwards, we lowered the kidney, sutured the wound, and administered intraperitoneal saline. Mice in different groups were euthanized following reperfusion for 1, 3, 7, or 28 days. Results: We observed a complete cessation of blood flow in the lower pole, while an incomplete cessation in the upper pole in the elevated kidney. Significant renal impairment was evident on day 1 with a 60min ischemic period (187.0 ± 65.3 vs 17.9 ± 4.8 µmol/L serum creatinine in normal; p < .001), but not with 30 or 40min. On day 1, tubular necrosis and hyaline cast formation was evident in both lower and upper poles. On day 3, renal function returned to normal and remained normal through day 28. Histologic damage resolved in the upper pole over days 3 to 7, resulting in normal histology on day 28. By contrast, there was sustained tubular damage tubular in the lower pole on days 3 and 7, which failed to resolve and led to significant renal fibrosis by day 28. Conclusion: We created a model demonstrating clinically "silent" renal fibrosis.

Significance of intrarenal vascular lesions in Ig A nephropathy prognosis.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the predominant primary glomerulonephritis globally and remains a subject of active research with a focus on understanding its course and prognosis. Although vascular lesions are associated with IgAN, the current histopathological grading systems do not consider intrarenal vascular lesions when predicting patient prognosis. Therefore, this retrospective study conducted at Kyungpook National University Hospital between October 2016 and December 2021, aimed to elucidate the significance of intrarenal vascular lesions in IgAN by comparing the clinical data of patients with and without such lesions. METHODS: Data of patients with biopsy-confirmed primary IgAN between October 2016 and June 2021 at Kyungpook National University Hospital (Daegu, South Korea) were collected, and their medical records were reviewed. All slides from these 138 cases were independently pathologically reviewed by two nephropathologists (Y. J. K. and M. S. K.) using light microscope. The vascular lesions included in this study were fibrous intimal thickening, arteriolar wall thickening, and arteriolar hyalinosis. All cases were reviewed according to the Oxford Classification of IgA Nephropathy (2016) and Haas classification. RESULTS: Of the 138 patients, 88 exhibited at least one intrarenal vascular lesion. Patients with arteriolar wall thickening demonstrated a reduced estimated glomerular filtration rate (eGFR), elevated serum creatinine level and urine protein-to-creatinine ratio, an increased proportion of global glomerulosclerosis, and a higher histologic grade of interstitial fibrosis and tubular atrophy at the time of biopsy. CONCLUSION: Arteriolar wall thickening in IgAN are associated with reduced eGFR and global glomerulosclerosis. Moreover, reduced eGFR and global glomerulosclerosis are correlated with the progression to end-stage renal disease. Although the direct correlation between vascular lesions and end-stage renal disease is not entirely clear, a marginally significant association (log-rank test, p = 0.06) was observed with arterial wall thickening. This study suggests the potential importance of vascular lesions in the prognosis of IgAN, encouraging further investigation using larger cohort studies to establish a clearer association.

Duplex Color Doppler Evaluation of Intrarenal Resistive Index in Type 2 Diabetic Patients Having Diabetic Nephropathy.

Diabetic nephropathy (DN) is considered the most frequent cause of end-stage renal disease (ESRD). For early diagnosis and follow up of renal function in patient with established DN, Duplex Doppler Sonography can be used as noninvasive tool. The aim and objective of the study was to determine whether resistive index could remain higher in type 2 diabetic patients having nephropathy in comparison with that of non-diabetic controls. This case-control study was done in the department of Radiology and Imaging, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) from 1st Octy 2014 to 30th June 2015. Total 65 diabetic nephropathy patients were taken as study group and 65 healthy subjects were included as healthy control subjects. Duplex Color Doppler sonography of interlobar artery was carried out in both groups for the measurement of Peak systolic velocity, end diastolic velocity and arterial Resistive Index (RI). The RI of interlobar artery of left kidney in control group was 0.58±0.08 (mean±SD) and the mean RI of interlobar artery of left kidney in diabetic nephropathy patients was 0.74±0.53 (mean±SD). The difference of RI of interlobar artery of left kidney in the two groups was statistically significant and the RI of right kidney of control and that of case groups were 0.60±0.09 and 0.76±0.031 (mean±SD) respectively. In between control and case groups the RI of right kidney was statistically significant (p = <0.5). So, resistive index of interlobar artery was increased in type 2 diabetic nephropathy patients in comparison to control group. Study findings reveal that resistive index remains significantly higher in patients with diabetic nephropathy than control group. For this reason, RI can be used for early diagnosis of diabetic nephropathy by Duplex Doppler ultrasonography.

From ex ovo to in vitro: xenotransplantation and vascularization of mouse embryonic kidneys in a microfluidic chip.

Organoids are emerging as a powerful tool to investigate complex biological structures in vitro. Vascularization of organoids is crucial to recapitulate the morphology and function of the represented human organ, especially in the case of the kidney, whose primary function of blood filtration is closely associated with blood circulation. Current in vitro microfluidic approaches have only provided initial vascularization of kidney organoids, whereas in vivo transplantation to animal models is problematic due to ethical problems, with the exception of xenotransplantation onto a chicken chorioallantoic membrane (CAM). Although CAM can serve as a good environment for vascularization, it can only be used for a fixed length of time, limited by development of the embryo. Here, we propose a novel lab on a chip design that allows organoids of different origin to be cultured and vascularized on a CAM, as well as to be transferred to in vitro conditions when required. Mouse embryonic kidneys cultured on the CAM showed enhanced vascularization by intrinsic endothelial cells, and made connections with the chicken vasculature, as evidenced by blood flowing through them. After the chips were transferred to in vitro conditions, the vasculature inside the organoids was successfully maintained. To our knowledge, this is the first demonstration of the combination of in vivo and in vitro approaches applied to microfluidic chip design.

Catheter-based renal denervation in the treatment of arterial hypertension: An expert consensus statement on behalf of the French Society of Hypertension (SFHTA), French Society of Radiology (SFR), French Society of Interventional Cardiology (GACI), French Society of Cardiology (SFC), French Association of Private Cardiologists (CNCF), French Association of Hospital Cardiologists (CNCH), French Society of Thoracic and Cardiovascular Surgery (SFCTCV) and French Society of Vascular and Endovascular Surgery (SCVE).

Several high-quality, randomized, sham-controlled trials have provided evidence supporting the efficacy and safety of radiofrequency, ultrasound and alcohol catheter-based renal denervation (RDN) for reducing blood pressure (BP). A French clinical consensus document has therefore been developed to propose guidance for the appropriate use of RDN in the management of hypertension along with a dedicated care pathway and management strategy. The French experts group concluded that RDN can serve as an adjunct therapy for patients with confirmed uncontrolled, resistant essential hypertension despite treatment with≥3 antihypertensive drugs, including a long-acting calcium channel blocker, a renin-angiotensin system blocker and a thiazide/thiazide-like diuretic at maximally tolerated doses. Patients should have (1) an estimated glomerular filtration rate of≥40mL/min/1.73m2; (2) an eligible renal artery anatomy on pre-RDN scans and (3) exclusion of secondary forms of hypertension. Additional indications might be considered for patients with difficult-to-control hypertension. Any indication of RDN should be validated by multidisciplinary hypertension teams consisting of both hypertension specialists and endovascular interventionalists in European Society of Hypertension (ESH) Excellence Centres or ESH-BP clinics. Patients should be informed about the benefit/risk ratio of RDN. Expertise in renal artery interventions and training in RDN techniques are needed for endovascular interventionalists conducting RDN procedures while centres offering RDN should have the necessary resources to manage potential complications effectively. Lastly, all patients undergoing RDN should have their data collected in a nationwide French registry to facilitate monitoring and evaluation of RDN outcomes, contributing to ongoing research and quality improvement efforts.

miR-199a-5p aggravates renal ischemia-reperfusion and transplant injury by targeting AKAP1 to disrupt mitochondrial dynamics.

Renal ischemia-reperfusion injury (IRI) is a complex pathophysiological process and a major cause of delayed graft function (DGF) after transplantation. MicroRNA (miRNA) has important roles in the pathogenesis of IRI and may represent promising therapeutic targets for mitigating renal IRI. miRNA sequencing was performed to profile microRNA expression in mouse kidneys after cold storage and transplantation (CST). Lentivirus incorporating a miR-199a-5p modulator was injected into mouse kidney in situ before syngenetic transplantation and unilateral IRI to determine the effect of miR-199a-5p in vivo. miR-199a-5p mimic or inhibitor was transfected cultured tubular cells before ATP depletion recovery treatment to examine the role of miR-199a-5p in vitro. Sequencing data and microarray showed upregulation of miR-199a-5p in mice CST and human DGF samples. Lentivirus incorporating a miR-199a-5p mimic aggravated renal IRI, and protective effects were obtained with a miR-199a-5p inhibitor. Treatment with the miR-199a-5p inhibitor ameliorated graft function loss, tubular injury, and immune response after CST. In vitro experiments revealed exacerbation of mitochondria dysfunction upon ATP depletion and repletion model in the presence of the miR-199a-5p mimic, whereas dysfunction was attenuated when the miR-199a-5p inhibitor was applied. miR-199a-5p was shown to target A-kinase anchoring protein 1 (AKAP1) by double luciferase assay and miR-199a-5p activation reduced dynamin-related protein 1 (Drp1)-s637 phosphorylation and mitochondrial length. Overexpression of AKAP1 preserved Drp1-s637 phosphorylation and reduced mitochondrial fission. miR-199a-5p activation reduced AKAP1 expression, promoted Drp1-s637 dephosphorylation, aggravated the disruption of mitochondrial dynamics, and contributed to renal IRI.NEW & NOTEWORTHY This study identifies miR-199a-5p as a key regulator in renal ischemia-reperfusion injury through microRNA sequencing in mouse models and human delayed graft function. miR-199a-5p worsens renal IRI by aggravating graft dysfunction, tubular injury, and immune response, while its inhibition shows protective effects. miR-199a-5p downregulates A-kinase anchoring protein 1 (AKAP1), reducing dynamin-related protein 1 (Drp1)-s637 phosphorylation, increasing mitochondrial fission, and causing dysfunction. Targeting the miR-199a-5p/AKAP1/Drp1 axis offers therapeutic potential for renal IRI, as AKAP1 overexpression preserves mitochondrial integrity by maintaining Drp1-s637 phosphorylation.

Anatomic and functional evidence for renal autonomic innervation in normotensive and hypertensive rats.

Renal denervation (RDN) has been used for treating resistant hypertension. A few recent studies have shown vagal innervation of kidneys causing confusion. This study aimed to provide anatomical and functional evidence for renal autonomic innervation. Experiments were performed in male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Pseudorabies virus (PRV) in the paraventricular nucleus and rostral ventrolateral medulla was prevented by bilateral RDN, but not subdiaphragmatic vagotomy. PRV did not appear in the dorsal motor nucleus of the vagus and nucleus tractus solitarii 72 h after renal injection of PRV. Adrenergic fibers were approximately seven times more than cholinergic fibers in the main renal artery (MRA) and its first (1RA) and second grade (2RA) branches. Adrenergic fibers in 1RA were more than those in MRA and 2RA. Tyrosine hydroxylase immunoreactivity in these arteries was higher in SHR than in WKY. Norepinephrine (NE) increased and α-receptor antagonist reduced vascular ring tension of renal arteries. The effect of NE was greater in 1RA and 2RA than in MRA, which was prevented by α-receptor antagonist. Acetylcholine (ACh) or blockage of ß-receptors, M receptors, or N receptors had no significant effects on vascular ring tension and the effect of NE. Renal blood flow was reduced by electrical stimulation of renal nerves but not affected by stimulation of the subdiaphragmatic vagus. These results provide anatomical and functional evidence that kidneys are innervated and renal blood flow is regulated by renal sympathetic nerves rather than the vagus. Renal vasoconstriction is regulated by NE and adrenergic fibers rather than ACh or cholinergic fibers in WKY and SHR.NEW & NOTEWORTHY Kidneys are innervated by renal nerves rather than the vagus. Adrenergic fibers in renal arteries are about seven times more than cholinergic fibers. Renal vasoconstriction is regulated by norepinephrine and adrenergic fibers rather than acetylcholine or cholinergic fibers. Renal blood flow is regulated by renal sympathetic nerves and is not affected by the vagus. These findings provide anatomical and functional evidence for renal autonomic innervation in normotensive and hypertensive rats.

Renal resistive index in patients supported with a durable continuous flow left ventricular assist device.

BACKGROUND: The impact of continuous flow resulting from contemporary left ventricular assist devices (LVAD) on renal vascular physiology is unknown. Renal resistive index (RRI) reflects arterial compliance, as well as renal vascular resistance, contributed by afferent and efferent arteriolar tone, the renal interstitium as well as renal venous pressures. METHODS: Prospective, single center study with renal Doppler evaluation at baseline (pre-implant) and at 3-months support. Outcomes assessed include need for post-operative renal replacement therapy (RRT), worsening renal function (WRF) defined as persistent increase from pre-implant KDIGO chronic kidney disease stage, right ventricular (RV) failure, and survival to transplantation. RESULTS: Pre-implant RRI did not predict cardiorenal outcomes including right heart failure, need for renal replacement therapy or worsening renal function. Post-implant RRI was significantly lower than pre-implant RRI, with a distinct Doppler waveform characteristic of continuous flow. Post-implant renal end-diastolic velocity, but not RRI, correlated strongly with LVAD flow (Spearman rho -0.99, p < 0.001), with trend toward correlation with mean arterial pressure (Spearman's rho 0.63, p = 0.129). There was a negative correlation between post-implant RRI and mean pulmonary artery pressure (Spearman's rho -0.81, p = 0.049), likely driven by elevated pulmonary capillary wedge pressure (Spearman's rho -0.83, p = 0.058). CONCLUSION: The hemodynamic contributors to RRI in LVAD supported patients are complex. Higher mean pulmonary artery and pulmonary capillary wedge pressures seen in lower RRI may reflect a smaller difference in systolic and diastolic flow. Future simultaneous Doppler assessment of the LVAD outflow graft and RRI may help understand the hemodynamic interactions contributing to this index.

Anatomical and Developmental Abnormalities of Ureters and Renal Pelvis Existing with Accessory Renal Arteries: Cadaveric Study.

BACKGROUND: Anatomical and developmental variations of ureters and renal pelvis have been observed frequently during routine human cadaveric dissection and surgical practice; however, their coexistence with accessory or aberrant renal arteries is exceptionally rare. Accordingly, this study was designed to evaluate the prevalence of anatomical and developmental abnormalities of ureters and renal pelvis existing with accessory renal arteries in human cadavers. MATERIALS AND METHODS: This study was carried out on 50 human cadavers including dissected specimens (25 males and 25 females) the kidneys, renal pelvis, and ureters along with their arteries were exposed and the anomalous abnormalities of the renal pelvis and ureters existing with accessory renal arteries were observed. Photographs of the anomalous and developmental variations were taken for proper documentation. RESULTS: Among the 50 cadavers studied, unilateral double ureters were found in 5 cadavers (10%), rare bilateral "S-"shaped loop of ureter with quadruple uretic constrictors in the abdominal segment of the ureter was observed in one female cadaver (2%), accessory or aberrant renal arteries were found in 15 cadavers (30%), hydronephrosis involving the renal pelvis and ureters was observed in 9 cadavers (18%). Interestingly, this prevalence was higher among males (28%) compared to females (8%). Moreover, the occurrence of bilateral hydronephrosis of the kidneys, renal pelvis, and ureters was identified in a single male cadaver, representing 2% of the sample. Notably, the prevalence of double ureter, hydronephrosis accompanied by congenital double and triple accessory renal arteries was documented in nine cadavers, accounting for 18% of the cohort. CONCLUSION: Anatomical and developmental variations of the ureters, renal pelvis, and renal vasculature, as well as their relationships to surrounding structures, hold clinical significance due to their impact on various surgical procedures, including kidney transplantation, abdominal aorta reconstruction, interventional radiology, and urologic operations. Therefore, identifying these potential developmental variations is essential for effective surgical management to preserve renal function and ensure optimal patient outcomes.

Résumé Contexte:Des variations anatomiques et développementales des uretères et du bassinet du rein ont été fréquemment observées au cours de routines d'examens cadavériques humains. dissection et pratique chirurgicale; cependant, leur coexistence avec des artères rénales accessoires ou aberrantes est exceptionnellement rare. En conséquence, cette étude a été conçu pour évaluer la prévalence des anomalies anatomiques et du développement des uretères et du bassinet du rein existant avec des anomalies rénales accessoires. artères dans les cadavres humains.Matériels et méthodes:Cette étude a été réalisée sur 50 cadavres humains dont des spécimens disséqués (25 mâles et 25 femmes), les reins, le bassinet et les uretères ainsi que leurs artères ont été exposés et les anomalies anormales du système rénal un bassin et des uretères existant avec des artères rénales accessoires ont été observés. Des photographies des variations anormales et développementales ont été prises pour une documentation appropriée.Résultats:Parmi les 50 cadavres étudiés, des doubles uretères unilatéraux ont été retrouvés dans 5 cadavres (10 %), de rares cas bilatéraux. Une anse de l'uretère en forme de « S ¼ avec des quadruples constricteurs urétiques dans le segment abdominal de l'uretère a été observée chez un cadavre féminin (2 %). des artères rénales accessoires ou aberrantes ont été retrouvées chez 15 cadavres (30 %), une hydronéphrose impliquant le bassinet et les uretères rénaux a été observée chez 9 cadavres (18 %). Il est intéressant de noter que cette prévalence était plus élevée chez les hommes (28 %) que chez les femmes (8 %). De plus, la survenue de conflits bilatéraux une hydronéphrose des reins, du bassinet du rein et des uretères a été identifiée sur un seul cadavre masculin, représentant 2 % de l'échantillon. Notamment, le La prévalence du double uretère et de l'hydronéphrose accompagnée d'artères rénales accessoires doubles et triples congénitales a été documentée dans neuf cas. cadavres, représentant 18% de la cohorte.Conclusion:Variations anatomiques et développementales des uretères, du bassinet et du rein le système vasculaire, ainsi que leurs relations avec les structures environnantes, revêtent une importance clinique en raison de leur impact sur diverses procédures chirurgicales, y compris la transplantation rénale, la reconstruction de l'aorte abdominale, la radiologie interventionnelle et les opérations urologiques. Par conséquent, identifier ces les variations potentielles du développement sont essentielles à une prise en charge chirurgicale efficace afin de préserver la fonction rénale et de garantir des résultats optimaux pour les patients.

Cerebral, Splanchnic, and Renal Transit Time Measurement and Blood Volume Estimation Using Contrast-Enhanced Ultrasonography.

ABSTRACT: We aimed to measure cerebral, splanchnic, and renal transit times and the associated blood volumes using contrast ultrasound. In healthy individuals, regional transit times were calculated from time-intensity curves generated as ultrasound contrast passed through the associated inflow and outflow vessels. These included the internal carotid artery and internal jugular vein (brain), the superior mesenteric artery and portal vein (intestines), and the renal artery and renal vein (kidney). An organ's blood volume relative to the stroke volume delivered to that organ with each cardiac cycle was calculated from the product of heart rate and transit time of contrast passage through the associated vascular bed. The fraction of systemic stroke volume received by each organ was calculated from the respective velocity-time integral and inflow vessel cross-sectional area and used to estimate absolute organ blood volume. The cohort consisted of 16 participants (age: 42 ± 13 years; 5 female) without known cerebrovascular, gastrointestinal, or renal disease. Cerebral, splanchnic, and renal transit times were obtained for 15, 14, and 8 individuals, respectively. Anatomic variability of the renal vessels confounded the acquisition of renal transit times. For all organs, transit times were reproducible and the associated blood volumes were generally comparable to reference values. Cerebral, gastrointestinal, and renal transit times/blood volumes can be reasonably acquired from contrast ultrasound, although the latter is less reliably available. Assessment of the impact on regional blood volumes of pharmacologic or other interventions is a next step toward clinical application of this technique.

ANKRD1 aggravates renal ischaemia‒reperfusion injury via promoting TRIM25-mediated ubiquitination of ACSL3.

BACKGROUND: Renal ischaemia‒reperfusion injury (IRI) is the primary cause of acute kidney injury (AKI). To date, effective therapies for delaying renal IRI and postponing patient survival remain absent. Ankyrin repeat domain 1 (ANKRD1) has been implicated in some pathophysiologic processes, but its role in renal IRI has not been explored. METHODS: The mouse model of IRI-AKI and in vitro model were utilised to investigate the role of ANKRD1. Immunoprecipitation-mass spectrometry was performed to identify potential ANKRD1-interacting proteins. Protein‒protein interactions and protein ubiquitination were examined using immunoprecipitation and proximity ligation assay and immunoblotting, respectively. Cell viability, damage and lipid peroxidation were evaluated using biochemical and cellular techniques. RESULTS: First, we unveiled that ANKRD1 were significantly elevated in renal IRI models. Global knockdown of ANKRD1 in all cell types of mouse kidney by recombinant adeno-associated virus (rAAV9)-mitigated ischaemia/reperfusion-induced renal damage and failure. Silencing ANKRD1 enhanced cell viability and alleviated cell damage in human renal proximal tubule cells exposed to hypoxia reoxygenation or hydrogen peroxide, while ANKRD1 overexpression had the opposite effect. Second, we discovered that ANKRD1's detrimental function during renal IRI involves promoting lipid peroxidation and ferroptosis by directly binding to and decreasing levels of acyl-coenzyme A synthetase long-chain family member 3 (ACSL3), a key protein in lipid metabolism. Furthermore, attenuating ACSL3 in vivo through pharmaceutical approach and in vitro via RNA interference mitigated the anti-ferroptotic effect of ANKRD1 knockdown. Finally, we showed ANKRD1 facilitated post-translational degradation of ACSL3 by modulating E3 ligase tripartite motif containing 25 (TRIM25) to catalyse K63-linked ubiquitination of ACSL3, thereby amplifying lipid peroxidation and ferroptosis, exacerbating renal injury. CONCLUSIONS: Our study revealed a previously unknown function of ANKRD1 in renal IRI. By driving ACSL3 ubiquitination and degradation, ANKRD1 aggravates ferroptosis and ultimately exacerbates IRI-AKI, underlining ANKRD1's potential as a therapeutic target for kidney IRI. KEY POINTS/HIGHLIGHTS: Ankyrin repeat domain 1 (ANKRD1) is rapidly activated in renal ischaemia‒reperfusion injury (IRI) models in vivo and in vitro. ANKRD1 knockdown mitigates kidney damage and preserves renal function. Ferroptosis contributes to the deteriorating function of ANKRD1 in renal IRI. ANKRD1 promotes acyl-coenzyme A synthetase long-chain family member 3 (ACSL3) degradation via the ubiquitin‒proteasome pathway. The E3 ligase tripartite motif containing 25 (TRIM25) is responsible for ANKRD1-mediated ubiquitination of ACSL3.

Inhibition of complement factor C5a or C5aR for cholesterol crystal embolism-related vascular thrombosis with microvascular injury and its consequences.

Cholesterol crystal embolism (CCE) implies immunothrombosis, tissue necrosis, and organ failure but no specific treatments are available. As CCE involves complement activation, we speculated that inhibitors of the C5a/C5aR axis would be sufficient to attenuate the consequences of CCE like that with systemic vasculitis. Cholesterol microcrystal injection into the kidney artery of wild-type mice initiated intra-kidney immunothrombosis within a few hours followed by a sudden drop of glomerular filtration rate and ischemic kidney necrosis after 24 hours. Genetic deficiency of either C3 or C5aR prevented immunothrombosis, glomerular filtration rate drop, and ischemic necrosis at 24 hours as did preemptive treatment with inhibitors of either C5a or C5aR. Delayed C5a blockade after crystal injection still resolved crystal clots and prevented all consequences. Thus, selective blockade of C5a or C5aR is sufficient to attenuate the consequences of established CCE and prospective inhibition in high-risk patients may be clinically feasible and safe.

An adaptive spatiotemporal filter for ultrasound localization microscopy based on density canopy clustering.

Ultrasound Localization Microscopy (ULM) facilitates structural and hemodynamic imaging of microvessels with a resolution of tens of micrometers. In ULM, the extraction of effective microbubble signals is crucial for image quality. Singular Value Decomposition (SVD) is currently the most prevalent method for microbubble signal extraction in ULM. Most existing ULM studies employ a fixed SVD filter threshold using empirical values which will lead to imaging quality degradation due to the insufficient separation of blood signals. In this study, we propose an adaptive and non-threshold SVD filter based on canopy-density clustering, termed DCC-SVD. This filter automatically classifies the components of the SVD based on the density of their spatiotemporal features, eliminating the need for parameter selection. In in vitro tube phantom, DCC-SVD demonstrated its ability to adaptive separation of blood and bubble signal at varying microbubble concentrations and flow rates. We compared the proposed DCC-SVD method with the Block-match 3D (BM3D) filter and a classical adaptive method called spatial similarity matrix (SSM), using concentration-variable in vivo rat brain data, as well as open-source rat kidney and mouse tumor datasets. The proposed DCC-SVD improved the global spatial resolution by approximately 4 µm from 30.39 µm to 26.02 µm. It also captured vessel structure absent in images obtained by other methods and yielded a smoother vessel intensity profile, making it a promising spatiotemporal filter for ULM imaging.