3D autofluorescence imaging of hydronephrosis and renal anatomical structure using cryo-micro-optical sectioning tomography.

Rationale: Mesoscopic visualization of the main anatomical structures of the whole kidney in vivo plays an important role in the pathological diagnosis and exploration of the etiology of hydronephrosis. However, traditional imaging methods cannot achieve whole-kidney imaging with micron resolution under conditions representing in vivo perfusion. Methods: We used in vivo cryofixation (IVCF) to fix acute obstructive hydronephrosis (unilateral ureteral obstruction, UUO), chronic spontaneous hydronephrosis (db/db mice), and their control mouse kidneys for cryo-micro-optical sectioning tomography (cryo-MOST) autofluorescence imaging. We quantitatively assessed the kidney-wide pathological changes in the main anatomical structures, including hydronephrosis, renal subregions, arteries, veins, glomeruli, renal tubules, and peritubular functional capillaries. Results: By comparison with microcomputed tomography imaging, we confirmed that IVCF can maintain the status of the kidney in vivo. Cryo-MOST autofluorescence imaging can display the main renal anatomical structures with a cellular resolution without contrast agents. The hydronephrosis volume reached 26.11 ± 6.00 mm3 and 13.01 ± 3.74 mm3 in 3 days after UUO and in 15-week-old db/db mouse kidneys, respectively. The volume of the cortex and inner stripe of the outer medulla (ISOM) increased while that of the inner medulla (IM) decreased in UUO mouse kidneys. Db/db mice also showed an increase in the volume of the cortex and ISOM volume but no atrophy in the IM. The diameter of the proximal convoluted tubule and proximal straight tubule increased in both UUO and db/db mouse kidneys, indicating that proximal tubules were damaged. However, some renal tubules showed abnormal central bulge highlighting in the UUO mice, but the morphology of renal tubules was normal in the db/db mice, suggesting differences in the pathology and severity of hydronephrosis between the two models. UUO mouse kidneys also showed vascular damage, including segmental artery and vein atrophy and arcuate vein dilation, and the density of peritubular functional capillaries in the cortex and IM was reduced by 37.2% and 49.5%, respectively, suggesting renal hypoxia. In contrast, db/db mouse kidneys showed a normal vascular morphology and peritubular functional capillary density. Finally, we found that the db/db mice displayed vesicoureteral reflux and bladder overactivity, which may be the cause of hydronephrosis formation. Conclusions: We observed and compared main renal structural changes in hydronephrosis under conditions representing in vivo perfusion in UUO, db/db, and control mice through cryo-MOST autofluorescence imaging. The results indicate that cryo-MOST with IVCF can serve as a simple and powerful tool to quantitatively evaluate the in vivo pathological changes in three dimensions, especially the distribution of body fluids in the whole kidney. This method is potentially applicable to the three-dimensional visualization of other tissues, organs, and even the whole body, which may provide new insights into pathological changes in diseases.

Effects of Norepinephrine on Renal Cortical and Medullary Blood Flow in Atherosclerotic Rabbits.

OBJECTIVE: The aim of this study was to explore the effect of norepinephrine (NE) on renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis. METHODS: Atherosclerosis was induced in 21 New Zealand white rabbits by feeding them a cholesterol-rich diet for 16 weeks. Thirteen healthy New Zealand white rabbits were randomly selected as controls. After atherosclerosis induction, standard ultrasonography was performed to confirm that there was no plaque or accelerated flow at the origin of the renal artery. Contrast-enhanced ultrasound (CEUS) was performed at baseline and during intravenous injection of NE. The degree of contrast enhancement of renal cortex and medulla after the injection of contrast agents was quantified by calculating the enhanced intensity. RESULTS: The serum nitric oxide (NO) level in atherosclerotic rabbits was higher than that in healthy rabbits (299.6±152 vs. 136.5±49.5, P<0.001). The infusion of NE induced a significant increase in the systolic blood pressure (112±14 mmHg vs. 84±9 mmHg, P=0.016) and a significant decrease in the enhanced intensity in renal cortex (17.78±2.07 dB vs. 21.19±2.03 dB, P<0.001) and renal medulla (14.87±1.82 dB vs. 17.14±1.89 dB, P<0.001) during CEUS. However, the enhanced intensity in the cortex and medulla of healthy rabbits after NE infusion showed no significant difference from that at baseline. CONCLUSION: NE may reduce renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis, partly by reducing the serum NO level.

Detection of impaired renal allograft function in paediatric and young adult patients using arterial spin labelling MRI (ASL-MRI).

The study aimed to discriminate renal allografts with impaired function by measuring cortical renal blood flow (cRBF) using magnetic resonance imaging arterial spin labelling (ASL-MRI) in paediatric and young adult patients. We included 18 subjects and performed ASL-MRI on 1.5 T MRI to calculate cRBF on parameter maps. cRBF was correlated to calculated glomerular filtration rate (GFR) and compared between patient groups with good (GFR ≥ 60 mL/min/1.73 m2) and impaired allograft function (GFR < 60 mL/min/1.73 m2). Mean cRBF in patients with good allograft function was significantly higher than in patients with impaired allograft function (219.89 ± 57.24 mL/min/100 g vs. 146.22 ± 41.84 mL/min/100 g, p < 0.008), showing a highly significant correlation with GFR in all subjects (r = 0.75, p < 0.0001). Also, the diffusion-weighted imaging (DWI-MRI) apparent diffusion coefficient (ADC) and Doppler measurements of peak-systolic and end-diastolic velocities and the resistive index (PS, ED, RI) were performed and both methods showed no significant difference between groups. ADC implied no correlation with GFR (r = 0.198, p = 0.464), while PS indicated moderate correlation to GFR (r = 0.48, p < 0.05), and PS and ED moderate correlation to cRBF (r = 0.58, p < 0.05, r = 0.56, p < 0.05, respectively). Cortical perfusion as non-invasively measured by ASL-MRI differs between patients with good and impaired allograft function and correlates significantly with its function.

Early critical cortical infarction by anti-angiotensin II type 1 receptor antibody: A case report and literature review.

RATIONALE: Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been demonstrated to increase the risk of antibody-mediated rejection. We report a case of AT1R-Ab mediated rejection which caused early critical cortical infarction. PATIENT CONCERNS: A 52-year-old man with end-stage kidney disease underwent preemptive kidney transplantation (KT) from his wife. He had no immunologic risk except ABO incompatibility. Proper desensitization treatment were applied prior to KT. On postoperative day 1, he showed stable clinical course with adequate urine output, but there was no decrease in serum creatinine level and imaging studies showed hypoperfusion in the transplanted kidney. DIAGNOSES: Allograft biopsy revealed total cortical infarction with severe necrotizing vasculitis, but the medullary area was preserved. Serum AT1R-Ab concentration was elevated from 10.9 U/mL before KT to 19.1 U/mL on 7 days after KT. INTERVENTIONS: He was treated with plasmapheresis, intravenous immunoglobulin, rituximab, high-dose methylprednisolone, and bortezomib. OUTCOMES: The treatment showed a partial response, and he was discharged with 7.3 mg/dL creatinine level. At 4 months, his creatinine plateaued at 5.5 mg/dL and AT1R-Ab decreased to 3.6 U/mL. LESSONS: This case highlights the risk of early active antibody-mediated rejection by preformed AT1R-Ab, suggesting its ability to exhibit atypical histopathologic findings, such as total cortical infarction.

Diabetes Affects the A1 Adenosine Receptor-Dependent Action of Diadenosine Tetraphosphate (Ap4A) on Cortical and Medullary Renal Blood Flow.

Diabetes through adenosine A1 receptor (A1R) and P2 receptors (P2Rs) may lead to disturbances in renal microvasculature. We investigated the renal microvascular response to Ap4A, an agonist of P2Rs, in streptozotocin-induced diabetic rats. Using laser Doppler flowmetry, renal blood perfusion (RBP) was measured during infusion of Ap4A alone or in the presence of A1R antagonist, either DPCPX (8-cyclopentyl-1,3-dipropylxanthine) or 8-cyclopentyltheophylline (CPT). Ap4A induced a biphasic response in RBP: a phase of rapid decrease was followed by a rapid increase, which was transient in diabetic rats but extended for 30 min in nondiabetic rats. Phase of decreased RBP was not affected by DPCPX or CPT in either group. Early and extended increases in RBP were prevented by DPCPX and CPT in nondiabetic rats, while in diabetic rats, the early increase in RBP was not affected by these antagonists. A1R mRNA and protein levels were increased in isolated glomeruli of diabetic rats, but no changes were detected in P2Y1R and P2Y2R mRNA. Presence of unblocked A1R is a prerequisite for the P2R-mediated relaxing effect of Ap4A in nondiabetic conditions, but influence of A1R on P2R-mediated renal vasorelaxation is abolished under diabetic conditions.

Diffusion tensor imaging in renal artery stenosis: a preliminary report.

OBJECTIVE: To investigate the diffusion properties in the kidneys affected by renal artery stenosis (RAS) using diffusion tensor imaging (DTI). METHODS: In this prospective study, 35 patients with RAS and 15 patients without renal abnormalities were enrolled and examined using DTI. Cortical and medullary regions of interest (ROIs) were located to obtain the corresponding values of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA). The cortical and medullary ADC and FA were compared in the kidney affected by variable degrees of stenosis (RAS 50-75% and >75%) vs controls, using the one-way ANOVA and Student's t-test. The Spearman correlation test was used to correlate the mean ADC and FA values in the cortex and medulla with the estimate glomerular filtration rate (eGFR). RESULTS: For the controls, the ADC value was significantly (p = 0.03) higher in the cortex than in the medulla; the FA value was significantly (p = 0.001) higher in the medulla than in the cortex. Compared with the controls, a significant reduction in the cortical ADC was present with a RAS of 50-75% and >75% (p = 0.001 and 0.041, respectively); a significant reduction in the medullary FA was verified only for RAS >75% (p = 0.023). The Spearman correlation test did not show a statistically significant correlation between the cortical and medullary ADC and FA, and the eGFR. CONCLUSION: The alterations of the diffusional parameters caused by RAS can be detected by DTI and could be useful in the diagnostic evaluation of these patients. ADVANCES IN KNOWLEDGE: 1. Magnetic resonance DTI could provide useful information about renal involvement in RAS.2. Magnetic resonance DTI allows non-invasive repeatable evaluation of the renal parenchyma, without contrast media.

Mitochondrial Metabolism in Acute Kidney Injury.

The kidney is a highly metabolic organ that requires substantial adenosine triphosphate for the active transport required to maintain water and solute reabsorption. Aberrations in energy availability and energy utilization can lead to cellular dysfunction and death. Mitochondria are essential for efficient energy production. The pathogenesis of acute kidney injury is complex and varies with different types of injury. However, multiple distinct acute kidney injury syndromes share a common dysregulation of energy metabolism. Pathways of energy metabolism and mitochondrial dysfunction are emerging as critical drivers of acute kidney injury and represent new potential targets for treatment. This review shows the basic metabolic pathways that all cells depend on for life; describes how the kidney optimizes those pathways to meet its anatomic, physiologic, and metabolic needs; summarizes the importance of metabolic and mitochondrial dysfunction in acute kidney injury; and analyzes the mitochondrial processes that become dysregulated in acute kidney injury including mitochondrial dynamics, mitophagy, mitochondrial biogenesis, and changes in mitochondrial energy metabolism.

Resuscitation with PEGylated carboxyhemoglobin preserves renal cortical oxygenation and improves skeletal muscle microcirculatory flow during endotoxemia.

PEGylated carboxyhemoglobin (PEGHbCO), which has carbon monoxide-releasing properties and plasma expansion and oxygen-carrying properties, may improve both skeletal microcirculatory flow and renal cortical microcirculatory Po2 (CµPo2) and, subsequently, limit endotoxemia-induced acute kidney injury. Anesthetized, ventilated Wistar albino rats (n = 44) underwent endotoxemic shock. CµPo2 was measured in exposed kidneys using a phosphorescence-quenching method. Rats were randomly assigned to the following five groups: 1) unresuscitated lipopolysaccharide (LPS), 2) LPS + Ringer's acetate (RA), 3) LPS + RA + 0.5 µg·kg·-1min-1 norepinephrine (NE), 4) LPS + RA + 320 mg/kg PEGHbCO, and 5) LPS + RA + PEGHbCO + NE. The total volume was 30 mL/kg in each group. A time control animal group was used. Skeletal muscle microcirculation was assessed by handheld intravital microscopy. Kidney immunohistochemistry and myeloperoxidase-stained leukocytes in glomerular and peritubular areas were analyzed. Endotoxemia-induced histological damage was assessed. Plasma levels of IL-6, heme oxygenase-1, malondialdehyde, and syndecan-1 were assessed by ELISA. CµPo2 was higher in the LPS + RA + PEGHbCO-resuscitated group, at 35 ± 6mmHg compared with 21 ± 12 mmHg for the LPS+RA group [mean difference: -13.53, 95% confidence interval: (-26.35; -0.7156), P = 0.035]. The number of nonflowing, intermittent, or sluggish capillaries was smaller in groups infused with PEGHbCO compared with RA alone (P < 0.05), while the number of normally perfused vessels was greater (P < 0.05). The addition of NE did not further improve CµPo2 or microcirculatory parameters. Endotoxemia-induced kidney immunohistochemistry and histological alterations were not mitigated by PEGHbCO 1 h after resuscitation. Renal leukocyte infiltration and plasma levels of biomarkers were similar across groups. PEGHbCO enhanced CµPo2 while restoring skeletal muscle microcirculatory flow in previously nonflowing capillaries. PEGHbCO should be further evaluated as a resuscitation fluid in mid- to long-term models of sepsis-induced acute kidney injury.

Losartan protects against intermittent hypoxia-induced peritubular capillary loss by modulating the renal renin-angiotensin system and angiogenesis factors.

Obstructive sleep apnea is characterized by chronic intermittent hypoxia (CIH), which is a risk factor for renal peritubular capillary (PTC) loss, and angiotensin II receptor blockers can alleviate PTC loss. However, the mechanism by which losartan (an angiotensin II receptor blocker) reduces CIH-induced PTC loss and attenuates kidney damage is still unknown. Thus, in this study, we examined the protective effects of losartan against CIH-induced PTC loss and explored the underlying mechanisms in rat CIH model. The immunohistochemical staining of CD34 and morphological examination showed that CIH reduced PTC density and damaged tubular epithelial cells. Immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), real-time quantitative PCR, and western blot analysis results revealed that CIH increased the expression of hypoxia inducible factor-1α (HIF-1α), angiotensin II (Ang II), angiotensin II type 1 receptor (AT1R), pro-angiogenesis factor vascular endothelial growth factor (VEGF), and anti-angiogenesis factor thrombospondin-1 (TSP-1) in the renal cortex of rats. CIH may up-regulate VEGF expression and simultaneously increase TSP-1 production. By histopathological, immunohistochemistry, ELISA, RT-qPCR, and western blot analysis, we found that the expressions of renal renin-angiotensin system (RAS), HIF-1α, VEGF, and TSP-1 were decreased, and PTC loss and tubular epithelial cell injury were attenuated with losartan treatment. Losartan ameliorated CIH-induced PTC loss by modulating renal RAS to improve the crosstalk between endothelial cells and tubular epithelial cells and subsequently regulate the balance of angiogenesis factors. Our study provided novel insights into the mechanisms of CIH-induced kidney damage and indicated that losartan could be a potential therapeutic agent for renal protection by alleviating CIH-induced PTC loss.

Ischemic Renal Injury: Can Renal Anatomy and Associated Vascular Congestion Explain Why the Medulla and Not the Cortex Is Where the Trouble Starts?

The kidneys receive approximately 20% of cardiac output and have a low fractional oxygen extraction. Quite paradoxically, however, the kidneys are highly susceptible to ischemic injury (injury associated with inadequate blood supply), which is most evident in the renal medulla. The predominant proposal to explain this susceptibility has been a mismatch between oxygen supply and metabolic demand. It has been proposed that unlike the well-perfused renal cortex, the renal medulla normally operates just above the threshold for hypoxia and that further reductions in renal perfusion cause hypoxic injury in this metabolically active region. An alternative proposal is that the true cause of ischemic injury is not a simple mismatch between medullary metabolic demand and oxygen supply, but rather the susceptibility of the outer medulla to vascular congestion. The capillary plexus of the renal outer medullary region is especially prone to vascular congestion during periods of ischemia. It is the failure to restore the circulation to the outer medulla that mediates complete and prolonged ischemia to much of this region, leading to injury and tubular cell death. We suggest that greater emphasis on developing clinically useful methods to help prevent or reverse the congestion of the renal medullary vasculature may provide a means to reduce the incidence and cost of acute kidney injury.

Renal hemodynamics and fatty acid uptake: effects of obesity and weight loss.

Human studies of renal hemodynamics and metabolism in obesity are insufficient. We hypothesized that renal perfusion and renal free fatty acid (FFA) uptake are higher in subjects with morbid obesity compared with lean subjects and that they both decrease after bariatric surgery. Cortical and medullary hemodynamics and metabolism were measured in 23 morbidly obese women and 15 age- and sex-matched nonobese controls by PET scanning of [15O]-H2O (perfusion) and 14(R,S)-[18F]fluoro-6-thia-heptadecanoate (FFA uptake). Kidney volume and radiodensity were measured by computed tomography, cardiac output by MRI. Obese subjects were re-studied 6 mo after bariatric surgery. Obese subjects had higher renal volume but lower radiodensity, suggesting accumulation of water and/or lipid. Both cardiac output and estimated glomerular filtration rate (eGFR) were increased by ~25% in the obese. Total renal blood flow was higher in the obese [885 (317) (expressed as median and interquartile range) vs. 749 (300) (expressed as means and SD) ml/min of controls, P = 0.049]. In both groups, regional blood perfusion was higher in the cortex than medulla; in either region, FFA uptake was ~50% higher in the obese as a consequence of higher circulating FFA levels. Following weight loss (26 ± 8 kg), total renal blood flow was reduced (P = 0.006). Renal volume, eGFR, cortical and medullary FFA uptake were decreased but not fully normalized. Obesity is associated with renal structural, hemodynamic, and metabolic changes. Six months after bariatric surgery, the hemodynamic changes are reversed and the structural changes are improved. On the contrary, renal FFA uptake remains increased, driven by high substrate availability.

Increased renal cortical stiffness is associated with coronary artery disease severity in patients with acute coronary syndrome.

Atherosclerosis is the primary etiological factor associated with acute coronary syndrome (ACS). Kidneys have a highly arterial vascular structure and are therefore commonly affected by atherosclerosis, including those affecting the coronary arteries. Renal shear wave elastography (SWE) is an ultrasonographic method, which provides reliable information regarding the condition of the renal parenchyma.We investigated the relationship between SWE findings and the severity of coronary atherosclerosis.We calculated the following: the renal cortical stiffness (rCS) evaluated via SWE, the renal resistive index, the renal pulsatility index, the acceleration time, and the mean Syntax score (SS). Patients with a mean SS <12 were categorized into a low-risk (LR) and those with a mean SS ≥12 were categorized into the high-risk (HR) group.Our study included 132 patients-76 in the LR and 56 in the HR group. Creatinine, high-sensitivity C-reactive protein (hs-CRP), and rCS were significantly higher, but the glomerular filtration rate (GFR) was significantly lower in the HR group. The Hs-CRP (odds ratio [OR] 1.220), GFR (OR 0.967), and rCS (OR 1.316) were observed to be independent predictors for the HR group. The cutoff value of rCS using receiver-operating characteristic curve analysis was 4.43 for the prediction of HR patients and showed 60.7% sensitivity and 57.9% specificity (area under the curve 0.642).SWE which shows renal parenchymal injury and atherosclerosis in renal vessels may give an idea about the severity of coronary atherosclerosis.

Mesenchymal Stromal Cells Are Retained in the Porcine Renal Cortex Independently of Their Metabolic State After Renal Intra-Arterial Infusion.

The regenerative capacities of mesenchymal stromal cells (MSCs) make them suitable for renal regenerative therapy. The most common delivery route of MSC is through intravenous infusion, which is associated with off-target distribution. Renal intra-arterial delivery offers a targeted therapy, but limited knowledge is available regarding the fate of MSCs delivered through this route. Therefore, we studied the efficiency and tissue distribution of MSCs after renal intra-arterial delivery to a porcine renal ischemia-reperfusion model. MSCs were isolated from adipose tissue of healthy male pigs, fluorescently labeled and infused into the renal artery of female pigs. Flow cytometry allowed MSC detection and quantification in tissue and blood. In addition, quantitative polymerase chain reaction was used to trace MSCs by their Y-chromosome. During infusion, a minor number of MSCs left the kidney through the renal vein, and no MSCs were identified in arterial blood. Ischemic and healthy renal tissues were analyzed 30 min and 8 h after infusion, and 1-4 × 104 MSCs per gram of tissue were detected, predominantly, in the renal cortex, with a viability >70%. Confocal microscopy demonstrated mainly glomerular localization of MSCs, but they were also observed in the capillary network around tubuli. The infusion of heat-inactivated (HI) MSCs, which are metabolically inactive, through the renal artery showed that HI-MSCs were distributed in the kidney in a similar manner to regular MSCs, suggesting a passive retention mechanism. Long-term MSC survival was analyzed by Y-chromosome tracing, and demonstrated that a low percentage of the infused MSCs were present in the kidney 14 days after administration, while HI-MSCs were completely undetectable. In conclusion, renal intra-arterial MSC infusion limited off-target engraftment, leading to efficient MSC delivery to the kidney, most of them being cleared within 14 days. MSC retention was independent of the metabolic state of MSC, indicating a passive mechanism.

Cortical Perfusion and Tubular Function as Evaluated by Magnetic Resonance Imaging Correlates with Annual Loss in Renal Function in Moderate Chronic Kidney Disease.

BACKGROUND: Chronic hypoxia is a well-recognized factor in the pathogenesis of chronic kidney disease (CKD). Loss of microcirculation is thought to lead to enhanced renal hypoxia, which in turn results in the development of fibrosis, a hallmark of progressive CKD. To evaluate the role of functional magnetic resonance imaging (MRI), we performed perfusion, oxygenation, and diffusion MRI measurements in individuals with diabetes and stage 3 CKD. METHODS: Fifty-four subjects (41 individuals with diabetes and stage 3 CKD and 13 healthy controls) participated in this study. Data with blood oxygenation level dependent (BOLD), arterial spin labeling perfusion and diffusion MRI were acquired using a 3T scanner. RESULTS: Renal cortical perfusion was reduced in CKD compared to the controls (109.54 ± 25.38 vs. 203.17 ± 27.47 mL/min/100 g; p < 0.001). Cortical apparent diffusion coefficient showed no significant reduction in CKD compared to controls (1,596.10 ± 196.64 vs. 1,668.72 ± 77.29 × 10-6 mm2/s; p = 0.45) but was significantly associated with perfusion. Cortical R2* values were modestly increased in CKD (20.76 ± 4.08 vs. 18.74 ± 2.37 s-1; p = 0.12). Within the CKD group, R2*_Medulla and R2*_Kidney were moderately and negatively associated with estimated glomerular filtration rate. There was a significant association between cortical perfusion and medullary response to furosemide with annual loss of renal function, used as an estimate of CKD progression. CONCLUSIONS: Subjects with a moderate degree of CKD had significantly lower renal perfusion. Diffusion and BOLD MRI showed more modest differences between the groups. Individuals with progressive CKD had lower perfusion and response to furosemide.

Clopidogrel Partially Counteracts Adenosine-5'-Diphosphate Effects on Blood Pressure and Renal Hemodynamics and Excretion in Rats.

BACKGROUND: Adenosine-5'-diphosphate (ADP) can influence intrarenal vascular tone and tubular transport, partly through activation of purine P2Y12 receptors (P2Y12-R), but their actual in vivo role in regulation of renal circulation and excretion remains unclear. METHODS: The effects of intravenous ADP infusions of 2-8mg/kg/hour were examined in anesthetized Wistar rats that were untreated or chronically pretreated with clopidogrel, 20mg/kg/24hours, a selective P2Y12-R antagonist. Renal blood flow (transonic probe) and perfusion of the superficial cortex and medulla (laser-Doppler fluxes) were measured, together with urine osmolality (Uosm), diuresis (V), total solute (UosmV), sodium (UNaV) and potassium (UKV) excretion. RESULTS: ADP induced a gradual, dose-dependent 15% decrease of mean arterial pressure, a sustained increase of renal blood flow and a 25% decrease in renal vascular resistance. Clopidogrel pretreatment attenuated the mean arterial pressure decrease, and did not significantly alter renal blood flow or renal vascular resistance. Renal medullary perfusion was not affected by ADP whereas Uosm decreased from 1,080 ± 125 to 685 ± 75 mosmol/kg H20. There were also substantial significant decreases in UosmV, UNaV and UKV; all these changes were attenuated or abolished by clopidogrel pretreatment. Two-weeks' clopidogrel treatment decreased V while UosmUosmV and UNaV increased, most distinctly after 7 days. Acute clopidogrel infusion modestly decreased mean arterial pressure and significantly increased outer- and decreased inner-medullary perfusion. CONCLUSIONS: Our functional studies show that ADP can cause systemic and renal vasodilation and a decrease in mean arterial pressure, an action at least partly mediated by P2Y12 receptors. We confirmed that these receptors exert tonic action to reduce tubular water reabsorption and urine concentration.

Assessment of Perfusion and Oxygenation of the Human Renal Cortex and Medulla by Quantitative MRI during Handgrip Exercise.

BACKGROUND: Renal flow abnormalities are believed to play a central role in the pathogenesis of nephropathy and in primary and secondary hypertension, but are difficult to measure in humans. Handgrip exercise is known to reduce renal arterial flow (RAF) by means of increased renal sympathetic nerve activity. METHODS: To monitor medullary and cortical oxygenation under handgrip exercise-reduced perfusion, we used contrast- and radiation-free magnetic resonance imaging (MRI) to measure regional changes in renal perfusion and blood oxygenation in ten healthy normotensive individuals during handgrip exercise. We used phase-contrast MRI to measure RAF, arterial spin labeling to measure perfusion, and both changes in transverse relaxation time (T2*) and dynamic blood oxygenation level-dependent imaging to measure blood oxygenation. RESULTS: Handgrip exercise induced a significant decrease in RAF. In the renal medulla, this was accompanied by an increase of oxygenation (reflected by an increase in T2*) despite a significant drop in medullary perfusion; the renal cortex showed a significant decrease in both perfusion and oxygenation. We also found a significant correlation (R2=0.8) between resting systolic BP and the decrease in RAF during handgrip exercise. CONCLUSIONS: Renal MRI measurements in response to handgrip exercise were consistent with a sympathetically mediated decrease in RAF. In the renal medulla, oxygenation increased despite a reduction in perfusion, which we interpreted as the result of decreased GFR and a subsequently reduced reabsorptive workload. Our results further indicate that the renal flow response's sensitivity to sympathetic activation is correlated with resting BP, even within a normotensive range.

Ultrasound Localization Microscopy and Super-Resolution: A State of the Art.

Because it drives the compromise between resolution and penetration, the diffraction limit has long represented an unreachable summit to conquer in ultrasound imaging. Within a few years after the introduction of optical localization microscopy, we proposed its acoustic alter ego that exploits the micrometric localization of microbubble contrast agents to reconstruct the finest vessels in the body in-depth. Various groups now working on the subject are optimizing the localization precision, microbubble separation, acquisition time, tracking, and velocimetry to improve the capacity of ultrasound localization microscopy (ULM) to detect and distinguish vessels much smaller than the wavelength. It has since been used in vivo in the brain, the kidney, and tumors. In the clinic, ULM is bound to improve drastically our vision of the microvasculature, which could revolutionize the diagnosis of cancer, arteriosclerosis, stroke, and diabetes.

Dynamic tissue perfusion assessment reflects associations between antihypertensive treatment and renal cortical perfusion in patients with chronic kidney disease and hypertension.

PURPOSE: Renal cortical perfusion measured in noninvasive, dynamic ultrasonic method is connected with the hemodynamic cardiac properties and renal function. Antihypertensive drugs affect the functioning of the heart and kidneys. The aim of the study was to evaluate the effect of a chronic use of antihypertensive drugs on ultrasound parameters of renal cortical perfusion. METHODS: The study included 56 consecutive patients (49 M + 7 F, age 54.0 ± 13.3) with stable chronic kidney disease and hypertension. Color Doppler dynamic tissue perfusion measurement was used to assess renal cortical perfusion. RESULTS: Patients were treated with a mean of 2.7 ± 1.4 antihypertensive drugs, of which diuretics accounted for 25%, angiotensin-converting enzyme inhibitors (ACE-I) together with angiotensin receptor blockers (ARB) 24%, beta-blockers (BB) 23%, calcium channel blockers 16%, alpha-1 blockers (α1B) 9% and centrally acting drugs 3%. All investigated groups of drugs correlated significantly with parameters of renal perfusion. In multivariable regression analyses adjusted to age, diuretics were connected with the decrease (r = - 0.473) and ACE-I + ARB (r = 0.390) with the improvement of proximal and whole renal cortex perfusion (R2 = 0.28; p < 0.001), whereas BB (r = - 0.372) and α1B (r = - 0.280) independently correlated with worsened perfusion of renal distal cortex (R2 = 0.21, p < 0.01). CONCLUSIONS: The type of antihypertensive therapy had a significant influence on the ultrasound parameters of renal cortical perfusion. Noninvasive, ultrasonic dynamic tissue perfusion measurement method appears to be an adequate tool to assess the impact of drugs on renal cortical perfusion.