Renal sympathetic denervation improves pressure-natriuresis relationship in cardiorenal syndrome: insight from studies with Ren-2 transgenic hypertensive rats with volume overload induced using aorto-caval fistula.

The aim was to evaluate the effects of renal denervation (RDN) on autoregulation of renal hemodynamics and the pressure-natriuresis relationship in Ren-2 transgenic rats (TGR) with aorto-caval fistula (ACF)-induced heart failure (HF). RDN was performed one week after creation of ACF or sham-operation. Animals were prepared for evaluation of autoregulatory capacity of renal blood flow (RBF) and glomerular filtration rate (GFR), and of the pressure-natriuresis characteristics after stepwise changes in renal arterial pressure (RAP) induced by aortic clamping. Their basal values of blood pressure and renal function were significantly lower than with innervated sham-operated TGR (p < 0.05 in all cases): mean arterial pressure (MAP) (115 ± 2 vs. 160 ± 3 mmHg), RBF (6.91 ± 0.33 vs. 10.87 ± 0.38 ml.min-1.g-1), urine flow (UF) (11.3 ± 1.79 vs. 43.17 ± 3.24 µl.min-1.g-1) and absolute sodium excretion (UNaV) (1.08 ± 0.27 vs, 6.38 ± 0.76 µmol.min-1.g-1). After denervation ACF TGR showed improved autoregulation of RBF: at lowest RAP level (80 mmHg) the value was higher than in innervated ACF TGR (6.92 ± 0.26 vs. 4.54 ± 0.22 ml.min-1.g-1, p < 0.05). Also, the pressure-natriuresis relationship was markedly improved after RDN: at the RAP of 80 mmHg UF equaled 4.31 ± 0.99 vs. 0.26 ± 0.09 µl.min-1.g-1 recorded in innervated ACF TGR, UNaV was 0.31 ± 0.05 vs. 0.04 ± 0.01 µmol min-1.g-1 (p < 0.05 in all cases). In conclusion, in our model of hypertensive rat with ACF-induced HF, RDN improved autoregulatory capacity of RBF and the pressure-natriuresis relationship when measured at the stage of HF decompensation.

Urinary oxygen tension and its role in predicting acute kidney injury: A narrative review.

Acute kidney injury occurs frequently in the perioperative setting. The renal medulla often endures hypoxia or hypoperfusion and is susceptible to the imbalance between oxygen supply and demand due to the nature of renal blood flow distribution and metabolic rate in the kidney. The current available evidence demonstrated that the urine oxygen pressure is proportional to the variations of renal medullary tissue oxygen pressure. Thus, urine oxygenation can be a candidate for reflecting the change of oxygen in the renal medulla. In this review, we discuss the basic physiology of acute kidney injury, as well as techniques for monitoring urine oxygen tension, confounding factors affecting the reliable measurement of urine oxygen tension, and its clinical use, highlighting its potential role in early detection and prevention of acute kidney injury.

Molecular Mechanisms Associated with Aging Kidneys and Future Perspectives.

The rapid growth of the elderly population is making the need for extensive and advanced information about age-related organ dysfunction a crucial research area. The kidney is one of the organs most affected by aging. Aged kidneys undergo functional decline, characterized by a reduction in kidney size, decreased glomerular filtration rate, alterations in renal blood flow, and increased inflammation and fibrosis. This review offers a foundation for understanding the functional and molecular mechanisms of aging kidneys and for selecting identifying appropriate targets for future treatments of age-related kidney issues.

In vivo mapping of hemodynamic responses mediated by tubuloglomerular feedback in hypertensive kidneys.

The kidney has a sophisticated vascular structure that performs the unique function of filtering blood and managing blood pressure. Tubuloglomerular feedback is an intra-nephron negative feedback mechanism stabilizing single-nephron blood flow, glomerular filtration rate, and tubular flow rate, which is exhibited as self-sustained oscillations in single-nephron blood flow. We report the application of multi-scale laser speckle imaging to monitor global blood flow changes across the kidney surface (low zoom) and local changes in individual microvessels (high zoom) in normotensive and spontaneously hypertensive rats in vivo. We reveal significant differences in the parameters of TGF-mediated hemodynamics and patterns of synchronization. Furthermore, systemic infusion of a glucagon-like-peptide-1 receptor agonist, a potential renoprotective agent, induces vasodilation in both groups but only alters the magnitude of the TGF in Sprague Dawleys, although the underlying mechanisms remain unclear.

Change in renal blood flow in response to intrarenal pressure alterations induced by ureteroscopy in an in-vivo porcine model.

INTRODUCTION: High irrigation rates are commonly used during ureteroscopy and can increase intrarenal pressure (IRP) substantially. Concerns have been raised that elevated IRP may diminish renal blood flow (RBF) and perfusion of the kidney. Our objective was to investigate the real-time changes in RBF while increasing IRP during Ureteroscopy (URS) in an in-vivo porcine model. METHODS: Four renal units in two porcine subjects were used in this study, three experimental units and one control. For the experimental units, RBF was measured by placing an ultrasonic flow cuff around the renal artery, while performing ureteroscopy in the same kidney using a prototype ureteroscope with a pressure sensor at its tip. Irrigation was cycled between two rates to achieve targeted IRPs of 30 mmHg and 100 mmHg. A control data set was obtained by placing the ultrasonic flow cuff on the contralateral renal artery while performing ipsilateral URS. RESULTS: At high IRP, RBF was reduced in all three experimental trials by 10-20% but not in the control trial. The percentage change in RBF due to alteration in IRP was internally consistent in each porcine renal unit and independent of slower systemic variation in RBF encountered in both the experimental and control units. CONCLUSION: RBF decreased 10-20% when IRP was increased from 30 to 100 mmHg during ureteroscopy in an in-vivo porcine model. While this reduction in RBF is unlikely to have an appreciable effect on tissue oxygenation, it may impact heat-sink capacity in vulnerable regions of the kidney.

Impaired renal autoregulation and pressure-natriuresis: any role in the development of heart failure in normotensive and angiotensin II-dependent hypertensive rats?

The aim of the present study was to assess the autoregulatory capacity of renal blood flow (RBF) and of the pressure-natriuresis characteristics in the early phase of heart failure (HF) in rats, normotensive and with angiotensin II (ANG II)-dependent hypertension. Ren-2 transgenic rats (TGR) were employed as a model of ANG II-dependent hypertension. HF was induced by creating the aorto-caval fistula (ACF). One week after ACF creation or sham-operation, the animals were prepared for studies evaluating in vivo RBF autoregulatory capacity and the pressure-natriuresis characteristics after stepwise changes in renal arterial pressure (RAP) induced by aortic clamping. In ACF TGR the basal mean arterial pressure, RBF, urine flow (UF), and absolute sodium excretion (UNaV) were all significantly lower tha n in sham-operated TGR. In the latter, reductions in renal arterial pressure (RAP) significantly decreased RBF whereas in ACF TGR they did not change. Stepwise reductions in RAP resulted in marked decreases in UF and UNaV in sham-operated as well as in ACF TGR, however, these decreases were significantly greater in the former. Our data show that compared with sham-operated TGR, ACF TGR displayed well-maintained RBF autoregulatory capacity and improved slope of the pressure-natriuresis relationship. Thus, even though in the very early HF stage renal dysfunction was demonstrable, in the HF model of ANG II-dependent hypertensive rat such dysfunction and the subsequent HF decompensation cannot be simply ascribed to impaired renal autoregulation and pressure-natriuresis relationship.

Renal arterial infusion of tempol prevents medullary hypoperfusion, hypoxia, and acute kidney injury in ovine Gram-negative sepsis.

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-1 h-1 ), renal arterial tempol (RAT; 3 mg kg-1 h-1 ), 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-1 ). 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.

The differences in renal hemodynamic response following high-intensity exercise between younger and older males.

BACKGROUND: Renal blood flow (RBF) decreases with exercise, but this change is only temporary, and habitual exercise may be an effective method to improve renal function. The kidney shows structural and functional changes with aging, but it is unclear how aging affects the hemodynamic response of the kidneys to exercise. Therefore, we evaluated the differences in the hemodynamic response of the kidneys to high-intensity exercise between younger and older men. METHODS: Sixteen men (8 young and 8 older) underwent an incremental exercise test using a cycle ergometer with a 1-min warm up followed by exercise at 10-20 W/min until the discontinuation criteria were met. Renal hemodynamics were assessed before exercise, immediately after exercise, and at 60-min after exercise using ultrasound echo. RESULTS: High-intensity exercise significantly reduced RBF in both groups (younger: ∆ - 53 ± 16%, p = 0.0005; older: ∆ - 53 ± 19%, p = 0.0004). In the younger group, RBF returned to the pre-exercise level 60-min after exercise (∆ - 0.4 ± 5.7%, p > 0.9999). In contrast, RBF 60-min after exercise was significantly lower than that before exercise in the older group (∆ - 24 ± 19%, p = 0.0006). The older group had significantly lower RBF than younger adults 60-min after exercise (423 ± 32 vs. 301 ± 98 mL/min, p = 0.0283). CONCLUSIONS: Our findings demonstrate that RBF following high-intensity exercise recovered 60-min after exercise in younger group, whereas RBF recovery was delayed in the older group.

Impaired microvascular circulation in distant organs following renal ischemia.

Mortality in acute kidney injury (AKI) patients remains very high, although very important advances in understanding the pathophysiology and in diagnosis and supportive care have been made. Most commonly, adverse outcomes are related to extra-renal organ dysfunction and failure. We and others have documented inflammation in remote organs as well as microvascular dysfunction in the kidney after renal ischemia. We hypothesized that abnormal microvascular flow in AKI extends to distant organs. To test this hypothesis, we employed intravital multiphoton fluorescence imaging in a well-characterized rat model of renal ischemia/reperfusion. Marked abnormalities in microvascular flow were seen in every organ evaluated, with decreases up to 46% observed 48 hours postischemia (as compared to sham surgery, p = 0.002). Decreased microvascular plasma flow was found in areas of erythrocyte aggregation and leukocyte adherence to endothelia. Intravital microscopy allowed the characterization of the erythrocyte formations as rouleaux that flowed as one-dimensional aggregates. Observed microvascular abnormalities were associated with significantly elevated fibrinogen levels. Plasma flow within capillaries as well as microthrombi, but not adherent leukocytes, were significantly improved by treatment with the platelet aggregation inhibitor dipyridamole. These microvascular defects may, in part, explain known distant organ dysfunction associated with renal ischemia. The results of these studies are relevant to human acute kidney injury.

Complex dynamics in a fractional order nephron pressure and flow regulation model.

Cardiovascular diseases can be attributed to irregular blood pressure, which may be caused by malfunctioning kidneys that regulate blood pressure. Research has identified complex oscillations in the mechanisms used by the kidney to regulate blood pressure. This study uses established physiological knowledge and earlier autoregulation models to derive a fractional order nephron autoregulation model. The dynamical behaviour of the model is analyzed using bifurcation plots, revealing periodic oscillations, chaotic regions, and multistability. A lattice array of the model is used to study collective behaviour and demonstrates the presence of chimeras in the network. A ring network of the fractional order model is also considered, and a diffusion coupling strength is adopted. A basin of synchronization is derived, considering coupling strength, fractional order or number of neighbours as parameters, and measuring the strength of incoherence. Overall, the study provides valuable insights into the complex dynamics of the nephron autoregulation model and its potential implications for cardiovascular diseases.

Magnetic Resonance Imaging to Evaluate Kidney Structure, Function, and Pathology: Moving Toward Clinical Application.

Recent advances in multiparametric magnetic resonance imaging (MRI) allow multiple quantitative measures to assess kidney morphology, tissue microstructure, oxygenation, kidney blood flow, and perfusion to be collected in a single scan session. Animal and clinical studies have investigated the relationship between the different MRI measures and biological processes, although their interpretation can be complex due to variations in study design and generally small participant numbers. However, emerging themes include the apparent diffusion coefficient derived from diffusion-weighted imaging, T1 and T2 mapping parameters, and cortical perfusion being consistently associated with kidney damage and predicting kidney function decline. Blood oxygen level-dependent (BOLD) MRI has shown inconsistent associations with kidney damage markers but has been predictive of kidney function decline in several studies. Therefore, multiparametric MRI of the kidneys has the potential to address the limitations of existing diagnostic methods to provide a noninvasive, noncontrast, and radiation-free method to assess whole kidney structure and function. Barriers to be overcome to facilitate widespread clinical application include improved understanding of biological factors that impact MRI measures, development of a larger evidence base for clinical utility, standardization of MRI protocols, automation of data analysis, determining optimal combination of MRI measures, and health economic evaluation.

Sex and strain differences in renal hemodynamics in mice.

The present study was to examine sex and strain differences in glomerular filtration rate (GFR) and renal blood flow (RBF) in C57BL6, 129/Sv, and C57BLKS/J mice, three commonly used mouse strains in renal research. GFR was measured by transdermal measurement of FITC-sinitrin clearance in conscious mice. RBF was measured by a flow probe placed in the renal artery under an anesthetic state. In C57BL6 mice, there were no sex differences in both GFR and RBF. In 129/Sv mice, females had significantly greater GFR than males at age of 24 weeks, but not at 8 weeks. However, males had higher RBF and lower renal vascular resistance (RVR). Similar to 129/Sv, female C57BLKS/J had significantly greater GFR at both 8 and 24 weeks, lower RBF, and higher RVR than males. Across strains, male 129/Sv had lower GFR and higher RBF than male C57BL6, but no significant difference in GFR and greater RBF than male C57BLKS/J. No significant difference in GFR or RBF was observed between C57BL6 and C57BLKS/J mice. Deletion of eNOS in C57BLKS/J mice reduced GFR in both sexes, but decreased RBF in males. Furthermore, there were no sex differences in the severity of renal injury in eNOS-/- dbdb mice. Taken together, our study suggests that sex differences in renal hemodynamics in mice are strain and age dependent. eNOS was not involved in the sex differences in GFR, but in RBF. Furthermore, the sexual dimorphism did not impact the severity of renal injury in diabetic nephropathy.

Novel Concepts in Nephron Sodium Transport: A Physiological and Clinical Perspective.

The kidneys play a critical role in maintaining total body sodium (Na+) balance across a wide range of dietary intake, accomplished by a concerted effort involving multiple Na+ transporters along the nephron. Furthermore, nephron Na+ reabsorption and urinary Na+ excretion are closely linked to renal blood flow and glomerular filtration such that perturbations in either of them can modify Na+ transport along the nephron, ultimately resulting in hypertension and other Na+-retentive states. In this article, we provide a brief physiological overview of nephron Na+ transport and illustrate clinical syndromes and therapeutic agents that affect Na+ transporter function. We highlight recent advances in kidney Na+ transport, particularly the role of immune cells, lymphatics, and interstitial Na+ in regulating Na+ reabsorption, the emergence of potassium (K+) as a regulator of Na+ transport, and the evolution of the nephron to modulate Na+ transport.

Renal blood flow during exercise: understanding its measurement with Doppler ultrasound.

The sympathetic nervous system (SNS) has a critical role in continuously coordinating responses to stimuli internal and external to the human body by appropriately modulating the activity of the organs it innervates. The SNS is activated in response to various physiological stressors, including exercise, which can involve a significant increase in SNS activity. An increase in SNS activity directed toward the kidneys causes vasoconstriction of afferent arterioles within the kidneys. This sympathetically mediated renal vasoconstriction decreases renal blood flow (RBF), causing significant blood flow redistribution toward active skeletal muscles during exercise. In research studies, different modes, intensities, and durations of exercise have been used to investigate the sympathetically mediated RBF response to exercise, and several methodological approaches have been used to quantify RBF. Doppler ultrasound provides noninvasive, continuous, real-time measurements of RBF and has emerged as a valid and reliable technique to quantify RBF during exercise. This innovative methodology has been applied in studies in which the RBF response to exercise has been examined in healthy young and older adults and patient populations such as those with heart failure and peripheral arterial disease. This valuable tool has enabled researchers to produce clinically relevant findings that have furthered our understanding of the effect of SNS activation on RBF in populations of health and disease. Therefore, the focus of this narrative review is to highlight the use of Doppler ultrasound in research studies that have provided important findings furthering our knowledge of the impact of SNS activation on RBF regulation in humans.

GLP-1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading.

Background GLP-1 (glucagon-like peptide-1) receptor agonists exert beneficial long-term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP-1 depends on GLP-1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in renal plasma flow. In rodents, angiotensin II constricts vasa recta and lowers medullary perfusion. The current randomized, controlled, crossover study was designed to test the hypothesis that GLP-1 increases renal medullary perfusion in healthy humans. Methods and Results Healthy male participants (n=10, aged 27±4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1-hour infusion of either GLP-1 (1.5 pmol/kg per minute) or placebo together with infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal arterial blood flow, oxygenation (R2*), and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. GLP-1 infusion increased medullary perfusion (32±7%, P<0.001) and cortical perfusion (13±4%, P<0.001) compared with placebo. Here, NaCl infusion decreased medullary perfusion (-5±2%, P=0.007), whereas cortical perfusion remained unchanged. R2* values increased by 3±2% (P=0.025) in the medulla and 4±1% (P=0.008) in the cortex during placebo, indicative of decreased oxygenation, but remained unchanged during GLP-1. Blood flow in the renal artery was not altered significantly by either intervention. Conclusions GLP-1 increases predominantly medullary but also cortical perfusion in the healthy human kidney and maintains renal oxygenation during NaCl loading. In perspective, suppression of angiotensin II by GLP-1 may account for the increase in regional perfusion. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04337268.

Remember Diabetes Mellitus When Assessing Renal Blood Flow in Hypertensive Patients: A Renal Frame Count Study.

BACKGROUND: Diabetes mellitus (DM) progresses with dynamic changes in renal blood flow and glomerular filtration. Renal frame count (RFC) is a cineangiographical parameter that is capable of presenting microvascular and macrovascular changes in the renal blood flow. We aimed to show the changes, which may be caused by DM in the perfusion, by using RFC. METHODS: Totally 110 hypertensive subjects consisting of 55 DM patients and 55 non-DM patients as a control group who underwent renal angiography were retrospectively enrolled in the study. The RFC values of all subjects were calculated and compared to each other. RESULTS: There were no significant differences between the two groups in terms of basal demographic characteristics and antihypertensive medications. The RFC value measured from the left renal artery was significantly lower in the DM group compared to the control group. (11.33±2.55, 13.49±3.24, respectively; p<0.001). The RFC value measured the right renal artery was detected to be significantly lower in the DM group than the control group (11.07±2.43, 13.33±3.07, respectively; p<0.001). The mean RFC value was also significantly lower in the DM group compared to the control group (11.20±2.18, 13.41±2.84, respectively;p<0.001). In the multivariable linear regression analysis conducted to determine the variables which may affect mean RFC, it was determined that only the HbA1C level had a relation with the mean RFC value. CONCLUSION: To the best of our knowledge, this is the first study to show the influence of DM on RFC. RFC seems to decrease in DM subjects.

The effects of recruitment of renal functional reserve on renal cortical and medullary oxygenation in non-anesthetized sheep.

AIM: Recruitment of renal functional reserve (RFR) with amino acid loading increases renal blood flow and glomerular filtration rate. However, its effects on renal cortical and medullary oxygenation have not been determined. Accordingly, we tested the effects of recruitment of RFR on renal cortical and medullary oxygenation in non-anesthetized sheep. METHODS: Under general anesthesia, we instrumented 10 sheep to enable subsequent continuous measurements of systemic and renal hemodynamics, renal oxygen delivery and consumption, and cortical and medullary tissue oxygen tension (PO2 ). We then measured the effects of recruitment of RFR with an intravenous infusion of 500 ml of a clinically used amino acid solution (10% Synthamin® 17) in the non-anesthetized state. RESULTS: Compared with baseline, Synthamin® 17 infusion significantly increased renal oxygen delivery mean ± SD maximum increase: (from 0.79 ± 0.17 to 1.06 ± 0.16 ml/kg/min, p < 0.001), renal oxygen consumption (from 0.08 ± 0.01 to 0.15 ± 0.02 ml/kg/min, p < 0.001), and glomerular filtration rate (+45.2 ± 2.7%, p < 0.001). Renal cortical tissue PO2 increased by a maximum of 26.4 ± 1.1% (p = 0.001) and medullary tissue PO2 increased by a maximum of 23.9 ± 2.8% (p = 0. 001). CONCLUSIONS: In non-anesthetized healthy sheep, recruitment of RFR improved renal cortical and medullary oxygenation. These observations might have implications for the use of recruitment of RFR for diagnostic and therapeutic purposes.

Arterial spin labeling and diffusion-weighted MR imaging: quantitative assessment of renal pathological injury in chronic kidney disease.

PURPOSE: The aim of the study was to investigate the performance of arterial spin labeling (ASL), diffusion-weighted imaging (DWI), and clinical biomarkers in assessing renal pathological injury in CKD. MATERIALS AND METHODS: Forty-five biopsy-proven CKD patients and 17 healthy volunteers underwent DWI and ASL examinations. Renal cortical blood flow (RBF) and apparent diffusion coefficient (ADC) values were acquired. Correlations between RBF, ADC, serum creatinine (SCr), estimated glomerular filtration rate (eGFR), and pathological scores were assessed. The diagnostic efficacy of SCr, eGFR, RBF, and ADC in assessing renal pathological injury was assessed by ROC curve analysis. RESULTS: The cortical RBF, ADC, SCr, and eGFR were significantly correlated with the renal histology score (all p < 0.01). The AUC values of SCr, eGFR, RBF, and ADC were 0.705 (95% confidence interval (CI): 0.536-0.827), 0.718 (0.552-0.839), 0.823 (0.658-0.916), and 0.624 (0.451-0.786), respectively, in discriminating the minimal-mild renal pathological injury group (N = 30) from the control group (N = 17). The diagnostic ability of ASL was significantly higher than that of DWI (p = 0.049) and slightly but not significantly higher than that of eGFR and SCr (p = 0.151 and p = 0.129, respectively). When compared with that of eGFR, the sensitivity of ASL in detecting early renal injury increased from 50 to 70% (p = 0.014). However, in differentiating between the minimal-mild and moderate-severe renal injury groups (N = 15), there was no significant difference in diagnostic ability among the four parameters (all p > 0.05). CONCLUSION: ASL is practicable for noninvasive evaluation of renal pathology, especially for predicting early renal pathological injury in CKD patients.

Multiparametric renal magnetic resonance imaging: A reproducibility study in renal allografts with stable function.

Monitoring renal allograft function after transplantation is key for the early detection of allograft impairment, which in turn can contribute to preventing the loss of the allograft. Multiparametric renal MRI (mpMRI) is a promising noninvasive technique to assess and characterize renal physiopathology; however, few studies have employed mpMRI in renal allografts with stable function (maintained function over a long time period). The purposes of the current study were to evaluate the reproducibility of mpMRI in transplant patients and to characterize normal values of the measured parameters, and to estimate the labeling efficiency of Pseudo-Continuous Arterial Spin Labeling (PCASL) in the infrarenal aorta using numerical simulations considering experimental measurements of aortic blood flow profiles. The subjects were 20 transplant patients with stable kidney function, maintained over 1 year. The MRI protocol consisted of PCASL, intravoxel incoherent motion, and T1 inversion recovery. Phase contrast was used to measure aortic blood flow. Renal blood flow (RBF), diffusion coefficient (D), pseudo-diffusion coefficient (D*), flowing fraction ( f ), and T1 maps were calculated and mean values were measured in the cortex and medulla. The labeling efficiency of PCASL was estimated from simulation of Bloch equations. Reproducibility was assessed with the within-subject coefficient of variation, intraclass correlation coefficient, and Bland-Altman analysis. Correlations were evaluated using the Pearson correlation coefficient. The significance level was p less than 0.05. Cortical reproducibility was very good for T1, D, and RBF, moderate for f , and low for D*, while medullary reproducibility was good for T1 and D. Significant correlations in the cortex between RBF and f (r = 0.66), RBF and eGFR (r = 0.64), and D* and eGFR (r = -0.57) were found. Normal values of the measured parameters employing the mpMRI protocol in kidney transplant patients with stable function were characterized and the results showed good reproducibility of the techniques.

A Novel Role of Semaphorin 3C in Modulating Systemic and Renal Hemodynamics.

BACKGROUND: Alterations of renal hemodynamics play an essential role in renal homeostasis and kidney diseases. Recent data indicated that semaphorin 3C (SEMA3C), a secreted glycoprotein involved in vessel development, can modulate renal vascular permeability in acute kidney injury, but whether and how it might impact systemic and renal hemodynamics is unknown. OBJECTIVES: The objective of the study was to explore the effect of SEMA3C on systemic and renal hemodynamics. METHODS: SEMA3C recombinant protein was administered intravenously in two-month-old wild-type mice, and the variations of mean arterial pressure, heart rate, renal blood flow, and renal vascular resistance were measured and analyzed. RESULTS: Acute administration of SEMA3C induced (i) systemic hemodynamic changes, including mean arterial pressure decrease and heart rate augmentation; (ii) renal hemodynamic changes, including reduced vascular resistance and elevated renal blood flow. Continuous perfusion of SEMA3C had no significant effect on systemic or renal hemodynamics. CONCLUSION: SEMA3C is a potent vasodilator affecting both systemic and renal hemodynamics in mice.