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Ultrasonography (Seoul, Korea) Oct 2023The aim of this study was to quantify renal microcirculatory perfusion in braindead donors using contrast-enhanced ultrasonography (CEUS), and to establish an accurate,...
PURPOSE
The aim of this study was to quantify renal microcirculatory perfusion in braindead donors using contrast-enhanced ultrasonography (CEUS), and to establish an accurate, noninvasive, and convenient index for predicting delayed graft function (DGF) post-transplantation.
METHODS
In total, 90 brain-dead donor kidneys (training group, n=60; validation group, n=30) examined between August 2020 and November 2022 were recruited in this prospective study. CEUS was performed on the kidneys of brain-dead donors 24 hours before organ procurement and time-intensity curves were constructed. The main measures were arrival time, time to peak, and peak intensity of the kidney segmental arteries, cortex, and medulla. Recipients were divided into DGF and non-DGF groups according to early post-transplant graft function. The area under the receiver operating characteristic curve (AUC) was used to assess diagnostic performance.
RESULTS
The arrival time of the kidney segmental artery and cortex and the time interval between the time to peak of the segmental artery and cortex were identified as independent factors associated with DGF by multivariate stepwise regression analysis. A new index for the joint prediction model of three variables, the contrast-enhanced ultrasonography/Kidney Donor Profile index (CEUS-KDPI), was developed. CEUS-KDPI showed high accuracy for predicting DGF (training group: AUC, 0.91; sensitivity, 90.5%; specificity, 92.3%; validation group: AUC, 0.84; sensitivity, 75.0%; specificity, 92.3%).
CONCLUSION
CEUS-KDPI accurately predicted DGF after kidney transplantation. CEUS may be a potential noninvasive tool for bedside examinations before organ procurement and may be used to predict early renal function after kidney transplants kidneys from donors after brain death.
PubMed: 37722724
DOI: 10.14366/usg.23006 -
Quantitative Imaging in Medicine and... Sep 2023Acute kidney injury (AKI) is frequently found in deceased donors; however, few studies have reported the use of imaging to detect and identify this phenomenon. The...
BACKGROUND
Acute kidney injury (AKI) is frequently found in deceased donors; however, few studies have reported the use of imaging to detect and identify this phenomenon. The purpose of this study was to detect renal microcirculatory perfusion in brain-dead donors using contrast-enhanced ultrasonography (CEUS), investigate the value of CEUS in identifying AKI, and analyze the correlation between CEUS and preimplantation biopsy results and early post-transplant renal function of grafts.
METHODS
This prospective study recruited 94 kidneys from brain-dead donors (AKI =44, non-AKI =50) from August 2020 to November 2022. The inclusion criteria were age ≥18 years and brain death. The exclusion criteria encompassed donors maintained with extracorporeal membrane oxygenation (ECMO) and the presence of irregular kidney anatomy. The mean age of the donors was 45.1±10.4 [standard deviation (SD)] years, and the majority were male (86.2%). CEUS was performed prior to organ procurement, and time-intensity curves (TICs) were constructed. The time to peak (TTP) and peak intensity (PI) of kidney segmental artery (KA), kidney cortex (KC), and kidney medulla (KM) were calculated using TIC analysis.
RESULTS
Arrival time (AT) of KA (P<0.001) and TTP of kidney cortex (TTPKC) (P<0.001) of the non-AKI group were significantly shorter than those of the AKI group. The PI of the KA (P=0.003), KM (P=0.005), and kidney cortex (PIKC; P<0.001) of the non-AKI group were significantly higher than those of the AKI group. Multivariable logistic regression analysis showed that serum creatinine [odds ratio (OR) =1.06; 95% CI: 1.03-1.1; P<0.001], TTPKC (OR =1.38; 95% CI: 1.03-1.84; P=0.03), and PIKC (OR =0.95; 95% CI: 0.91-1; P=0.046) were the independent factors of AKI. The area under the receiver operating characteristic curve (AUC) for identifying AKI for TTPKC and PIKC was 0.73 and 0.71, respectively. TTPKC showed a weak correlation with interstitial fibrosis (r=0.23; P=0.03), PIKC showed a weak correlation with arterial intimal fibrosis ((r=-0.29; P=0.004) and arteriolar hyalinosis (r=-0.27; P=0.008), and PIKC showed the strongest correlation with eGFR on postoperative day 7 (r=-0.46; P=0.046) in the donor kidneys with AKI.
CONCLUSIONS
CEUS can be used to identify AKI in brain-dead donors. Furthermore, there is a correlation between CEUS-derived parameters and pretransplant biopsy results and early preimplantation renal function of grafts.
PubMed: 37711792
DOI: 10.21037/qims-23-207 -
BMC Nephrology Sep 2023Delayed cerebral ischemia is a clinical entity commonly encountered in patients presenting with acute neurological injury and is often complicated by dysnatremias, such...
BACKGROUND
Delayed cerebral ischemia is a clinical entity commonly encountered in patients presenting with acute neurological injury and is often complicated by dysnatremias, such as the cerebral salt wasting syndrome. In this case report, we described an exceptional case of polyuria attributed to an initial cerebral salt wasting phenomenon and iatrogenic-induced medullary washout.
CASE PRESENTATION
A 53-year-old woman was admitted to our hospital for the management of a Modified Fisher scale grade 4 subarachnoid hemorrhage due to a ruptured posterior communicating aneurysm. She was initially managed with coil embolization and external ventricular drain due to secondary hydrocephalus. Throughout the course of her hospitalization, she developed severe polyuria reaching up to 40L per day. To keep up with the excessive urinary losses and maintain appropriate cerebral perfusion, fluid replacement therapy was adjusted every hour, reaching up to 1.3 L of crystalloid per hour in addition to aminergic support. An initial diagnosis of partial diabetes insipidus, followed by a cerebral salt wasting syndrome was suspected. While the urine output continued to increase, her serum urea concentration progressively decreased to a point of almost being undetectable on day 9. At that time, the presence of an interstitial medulla washout was hypothesized. Various pharmacological and non-pharmacological interventions were progressively introduced to regain normal renal homeostasis, including non-steroidal anti-inflammatory drugs, fludrocortisone, oral urea and high-protein intake. Medications were progressively weaned, and the patient was successfully discharged from the ICU.
CONCLUSIONS
Cerebral salt wasting should be considered in the initial differential diagnosis of a patient presenting with polyuria in the context of acute neurological injury. Early recognition of this entity is critical to quickly implement proper management. However, as shown in this case report, the concomitance of delayed cerebral ischemia may complexify that management.
Topics: Humans; Female; Middle Aged; Polyuria; Cerebral Infarction; Kidney; Anti-Inflammatory Agents, Non-Steroidal; Blood Urea Nitrogen
PubMed: 37658303
DOI: 10.1186/s12882-023-03281-4 -
Biology Open Sep 2023This study focuses on ischaemia-reperfusion injury (IRI) in kidneys, a cause of acute kidney injury (AKI) and end-stage kidney disease (ESKD). Traditional kidney damage...
This study focuses on ischaemia-reperfusion injury (IRI) in kidneys, a cause of acute kidney injury (AKI) and end-stage kidney disease (ESKD). Traditional kidney damage assessment methods are semi-quantitative and subjective. This study aims to use a convolutional neural network (CNN) to segment murine kidney structures after IRI, quantify damage via CNN-generated pathological measurements, and compare this to conventional scoring. The CNN was able to accurately segment the different pathological classes, such as Intratubular casts and Tubular necrosis, with an F1 score of over 0.75. Some classes, such as Glomeruli and Proximal tubules, had even higher statistical values with F1 scores over 0.90. The scoring generated based on the segmentation approach statistically correlated with the semiquantitative assessment (Spearman's rank correlation coefficient=0.94). The heatmap approach localised the intratubular necrosis mainly in the outer stripe of the outer medulla, while the tubular casts were also present in more superficial or deeper portions of the cortex and medullary areas. This study presents a CNN model capable of segmenting multiple classes of interest, including acute IRI-specific pathological changes, in a whole mouse kidney section and can provide insights into the distribution of pathological classes within the whole mouse kidney section.
Topics: Animals; Mice; Deep Learning; Semantics; Acute Kidney Injury; Disease Models, Animal; Necrosis; Reperfusion Injury
PubMed: 37642317
DOI: 10.1242/bio.059988 -
Oak Acorn Poisoning in Cattle during Autumn 2022: A Case Series and Review of the Current Knowledge.Animals : An Open Access Journal From... Aug 2023Oak poisoning is a known intoxication in grazing animals, but is slightly described in the literature. This case report describes 7 cattle from 3 different farms...
Oak poisoning is a known intoxication in grazing animals, but is slightly described in the literature. This case report describes 7 cattle from 3 different farms admitted to the clinic for ruminants of the University of Liège for suspected acorn poisoning in the autumn of 2022. The clinical signs were, anorexia, apathy with polyuria with low density. Further investigations led to the diagnosis of renal failure (blood urea 162 ± 88 mg/dL; blood creatinine 12 ± 4 mg/L). Supportive treatment, based on infusions (NaCl 0.9%) and electrolyte rebalancing, was administered and renal values were assessed every 24-48 h. Of these animals, 5/7 were euthanized. At necropsy, digestive erosions and ulcerations, oedema and renal hemorrhages, between the pyloric/caliceal cavity and the medulla were observed. Histopathological examination revealed necrosis of the renal tubules. The renal values of the two remaining animals were reduced, their general condition improved, and they were discharged. Acorn poisoning is a serious disease with no specific antidote or characteristic symptoms. Animals are identified as sick too late, when renal failure is already established. Farmers should be made more aware in order to prevent exposure, especially in years when acorns are abundant. Furthermore, there is no antidote for this intoxication.
PubMed: 37627469
DOI: 10.3390/ani13162678 -
Function (Oxford, England) 2023Non-enzymatic activation of renin via its interaction with prorenin receptor (PRR) has been proposed as a key mechanism of local renin-angiotensin system (RAS)...
Non-enzymatic activation of renin via its interaction with prorenin receptor (PRR) has been proposed as a key mechanism of local renin-angiotensin system (RAS) activation. The presence of renin and angiotensinogen has been reported in the rostral ventrolateral medulla (RVLM). Overactivation of bulbospinal neurons in the RVLM is linked to hypertension (HTN). Previous studies have shown that the brain RAS plays a role in the pathogenesis of the deoxycorticosterone (DOCA)-salt HTN model. Thus, we hypothesized that PRR in the RVLM is involved in the local activation of the RAS, facilitating the development of DOCA-salt HTN. Selective PRR ablation targeting the RVLM (PRR mice) resulted in an unexpected sex-dependent and biphasic phenotype in DOCA-salt HTN. That is, PRR females (but not males) exhibited a significant delay in achieving maximal pressor responses during the initial stage of DOCA-salt HTN. Female PRR subsequently showed exacerbated DOCA-salt-induced pressor responses during the "maintenance" phase with a maximal peak at 13 d on DOCA-salt. This exacerbated response was associated with an increased sympathetic drive to the resistance arterioles and the kidney, exacerbated fluid and sodium intake and output in response to DOCA-salt, and induced mobilization of fluids from the intracellular to extracellular space concomitant with elevated vasopressin. Ablation of PRR suppressed genes involved in RAS activation and catecholamine synthesis in the RVLM but also induced expression of genes involved in inflammatory responses. This study illustrates complex and sex-dependent roles of PRR in the neural control of BP and hydromineral balance through autonomic and neuroendocrine systems. Graphical abstract.
Topics: Animals; Female; Mice; Blood Pressure; Desoxycorticosterone Acetate; Hypertension; Prorenin Receptor; Receptors, Cell Surface; Renin; Sodium Chloride; Vasoconstrictor Agents
PubMed: 37609445
DOI: 10.1093/function/zqad043 -
Function (Oxford, England) 2023Integrated computational modeling provides a mechanistic and quantitative framework to characterize alterations in mitochondrial respiration and bioenergetics in...
Integrated computational modeling provides a mechanistic and quantitative framework to characterize alterations in mitochondrial respiration and bioenergetics in response to different metabolic substrates . These alterations play critical roles in the pathogenesis of diseases affecting metabolically active organs such as heart and kidney. Therefore, the present study aimed to develop and validate thermodynamically constrained integrated computational models of mitochondrial respiration and bioenergetics in the heart and kidney cortex and outer medulla (OM). The models incorporated the kinetics of major biochemical reactions and transport processes as well as regulatory mechanisms in the mitochondria of these tissues. Intrinsic model parameters such as Michaelis-Menten constants were fixed at previously estimated values, while extrinsic model parameters such as maximal reaction and transport velocities were estimated separately for each tissue. This was achieved by fitting the model solutions to our recently published respirometry data measured in isolated rat heart and kidney cortex and OM mitochondria utilizing various NADH- and FADH-linked metabolic substrates. The models were validated by predicting additional respirometry and bioenergetics data, which were not used for estimating the extrinsic model parameters. The models were able to predict tissue-specific and substrate-dependent mitochondrial emergent metabolic system properties such as redox states, enzyme and transporter fluxes, metabolite concentrations, membrane potential, and respiratory control index under diverse physiological and pathological conditions. The models were also able to quantitatively characterize differential regulations of NADH- and FADH-linked metabolic pathways, which contribute differently toward regulations of oxidative phosphorylation and ATP synthesis in the heart and kidney cortex and OM mitochondria.
Topics: Rats; Animals; NAD; Oxygen Consumption; Energy Metabolism; Mitochondria; Respiration; Kidney Cortex; Kidney; Computer Simulation
PubMed: 37575476
DOI: 10.1093/function/zqad038 -
Study on the therapeutic effect of glucocorticoids on acute kidney injury in rats exposed to diquat.Biomedicine & Pharmacotherapy =... Oct 2023To preliminarily explore, whether glucocorticoids have a therapeutic effect on diquat-induced acute kidney injury in rats.
AIMS
To preliminarily explore, whether glucocorticoids have a therapeutic effect on diquat-induced acute kidney injury in rats.
METHOD
150 Wistar rats were randomly divided into six groups: exposure model group (DQ group), dexamethasone control group (GC group), blank control group (Ctrl group), dexamethasone 2.1 mg/kg dose group (DQ+L-GC group), dexamethasone 4.2 mg/kg dose group (DQ+M-GC group), and dexamethasone 8.4 mg/kg dose group (DQ+H-GC group), with 25 rats in each group. Each group was further divided into five subgroups, 24 h, 3 d, 7 d, 14 d, and 21 d after exposure, according to the feeding time and the course of treatment, with five animals in each subgroup. The rats in DQ, DQ+L-GC, DQ+M-GC, and DQ+H-GC groups were administered 115.5 mg/kg diquat by gavage, respectively. Moreover, 30 min after gavage, rats in DQ+L-GC group, DQ+M-GC group, DQ+H-GC group and GC group were intragastric administered dexamethasone 2.1 mg/kg, 4.2 mg/kg, 8.4 mg/kg and 8.4 mg/kg, respectively. After 7 days, the intraperitoneal injection of dexamethasone was changed to 6.3 mg/kg prednisone by intragastric administration. Subsequently, 7 days later, it was changed to 3.15 mg/kg prednisone by intragastric administration until the end of the experiment on 21 days. After the start of the experiment, changes in the conditions of the rats in each group were observed at a fixed time every day, changes in the body weight of the rats were monitored at the same time, and the death of the rats was recorded at 24 h, 3 d, 7 d, 14 d, and 21 d after exposure. The rats were sacrificed by an intraperitoneal injection of 100 mg/kg sodium pentobarbital overdose. Blood was collected by puncture of the inferior vena cava, used to determine Cr and BUN. The upper segment of the left kidney was collected for histopathological examination. Elisa was used to detect neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in the lower segment of left kidney. TLR4, Myd88, and NF-κB were detected in the right kidney.
RESULTS
(1) After exposure, most rats in DQ group, DQ+L-GC group, DQ+M-GC group and DQ+H-GC group showed shortness of breath, oliguria, diarrhea, yellow hair and other symptoms. No symptoms and related signs were observed in Ctrl group and GC group. (2) The weight of rats in the Ctrl group and the GC group increased slowly during the test. the body weight of the rats in the DQ, DQ+L-GC, DQ+M-GC, and DQ+H-GC groups continued to decrease after self-infection. Body weight dropped to the lowest point at approximately 7 d, and gradually increased from 7 d to 21 d. (3) A small amount of capillary congestion in the medulla was observed after 7 days in the GC group. The DQ group showed tubular atrophy, edema of the epithelial cells, and over time, the tubules were seen dilated and became irregular in shape; large amount of capillary congestion was also observed in the renal cortex and medulla. The renal injury in the DQ+L-GC group was less than that in the DQ group. DQ+H-GC group had no obvious injury before 7 d, but more renal tubules were seen in the DQ+H-GC group from 7 d to 14 d. (4) Compared with the DQ group, there was no difference before 14 d, and at 14 d-21 d, DQ+L-GC group, DQ+M-GC group, DQ+H-GC group all had different degrees of decline. NGAL content: Compared with the DQ group, the content of NGAL and KIM-1 in kidney tissue of the DQ+L-GC, DQ+M-GC, and DQ+H-GC groups decreased compared with the DQ group at each time node. (5) Compared with the Ctrl group, the expression of TNF-α, TLR4, MyD88, NF-κB in the DQ, DQ+L-GC, DQ+M-GC, and DQ+H-GC groups at each time node increased in the renal tissue. The content of TNF-α, TLR4, MyD88, NF-κB in kidney tissue of the DQ+L-GC, DQ+M-GC, and DQ+H-GC groups at each time node was lower than that in the DQ group.
CONCLUSION
(1) Diquat can cause kidney damage in rats, mainly manifested as renal tubular atrophy, epithelial cell edema, capillary congestion and dilation, and the renal function damage indicators have been improved to varying degrees. (2) Glucocorticoids have therapeutic effects on acute kidney injury in rats exposed to diquat. During the treatment, the efficacy of glucocorticoids did not increase with increasing doses after reaching a dose of 4.2 mg/kg. (3) TLR4 receptor-mediated TLR4/Myd88/NF-κB signaling pathway is involved in the inflammatory response of acute kidney injury in diquat poisoning rats. Glucocorticoids can inhibit the inflammatory response, thereby affecting the expression of TLR4/Myd88/NF-κB signaling pathway-related proteins.
Topics: Rats; Animals; Rats, Wistar; NF-kappa B; Glucocorticoids; Diquat; Lipocalin-2; Prednisone; Myeloid Differentiation Factor 88; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Acute Kidney Injury; Kidney; Dexamethasone; Body Weight; Atrophy
PubMed: 37573654
DOI: 10.1016/j.biopha.2023.115310 -
Fujita Medical Journal Aug 2023Sepsis is a life-threatening condition characterized by multi-organ dysfunction due to host immune system dysregulation in response to an infection. During sepsis,...
OBJECTIVES
Sepsis is a life-threatening condition characterized by multi-organ dysfunction due to host immune system dysregulation in response to an infection. During sepsis, neutrophils release neutrophil extracellular traps (NETs) as part of the innate immune response. However, excessive NETs play a critical role in the development of organ failure during sepsis. Although recombinant human soluble thrombomodulin (rTM) can inhibit NET formation in the lungs and liver of a mouse model of endotoxin shock, its effects on the kidneys are unclear.
METHODS
The specific effects of NETs and rTM on the renal cortex and renal medulla were examined in a mouse model of endotoxin shock generated by intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), followed by i.p. injection of rTM or an identical volume of saline 1 h later.
RESULTS
LPS injection increased serum creatinine, blood urea nitrogen, and histone H3 levels. However, rTM administration significantly decreased histone H3 and citrullinated histone H3 (citH3) levels. Immunohistochemical analysis revealed no significant changes in citH3 quantity in the renal cortex of any group. However, in the renal medulla, the increase in citH3 induced by LPS was abolished in the LPS+rTM group.
CONCLUSIONS
Our findings demonstrate that rTM can suppress NETs in the renal medulla of mice with endotoxin-induced acute kidney injury.
PubMed: 37554943
DOI: 10.20407/fmj.2022-026 -
Acta Physiologica (Oxford, England) Sep 2023Renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI) in ovine sepsis. Oxidative/nitrosative stress, inflammation, and impaired nitric oxide...
AIM
Renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI) in ovine sepsis. Oxidative/nitrosative stress, inflammation, and impaired nitric oxide generation may contribute to such pathophysiology. We tested whether the antioxidant and anti-inflammatory drug, tempol, may modify these responses.
METHODS
Following unilateral nephrectomy, we inserted renal arterial catheters and laser-Doppler/oxygen-sensing probes in the renal cortex and medulla. Noanesthetized sheep were administered intravenous (IV) Escherichia coli and, at sepsis onset, IV tempol (IVT; 30 mg kg h ), renal arterial tempol (RAT; 3 mg kg h ), or vehicle.
RESULTS
Septic sheep receiving vehicle developed renal medullary hypoperfusion (76 ± 16% decrease in perfusion), hypoxia (70 ± 13% decrease in oxygenation), and AKI (87 ± 8% decrease in creatinine clearance) with similar changes during IVT. However, RAT preserved medullary perfusion (1072 ± 307 to 1005 ± 271 units), oxygenation (46 ± 8 to 43 ± 6 mmHg), and creatinine clearance (61 ± 10 to 66 ± 20 mL min ). Plasma, renal medullary, and cortical tissue malonaldehyde and medullary 3-nitrotyrosine decreased significantly with sepsis but were unaffected by IVT or RAT. Consistent with decreased oxidative/nitrosative stress markers, cortical and medullary nuclear factor-erythroid-related factor-2 increased significantly and were unaffected by IVT or RAT. However, RAT prevented sepsis-induced overexpression of cortical tissue tumor necrosis factor alpha (TNF-α; 51 ± 16% decrease; p = 0.003) and medullary Thr-495 phosphorylation of endothelial nitric oxide synthase (eNOS; 63 ± 18% decrease; p = 0.015).
CONCLUSIONS
In ovine Gram-negative sepsis, renal arterial infusion of tempol prevented renal medullary hypoperfusion and hypoxia and AKI and decreased TNF-α expression and uncoupling of eNOS. However, it did not affect markers of oxidative/nitrosative stress, which were significantly decreased by Gram-negative sepsis.
Topics: Animals; Sheep; Tumor Necrosis Factor-alpha; Creatinine; Renal Circulation; Kidney; Acute Kidney Injury; Hypoxia; Sepsis; Escherichia coli
PubMed: 37548350
DOI: 10.1111/apha.14025