Renal Cortical Blood Flow Research Articles

Effect of intrarenal pelvic pressure on pyelo-tubular backflow and renal cortical blood perfusion during mini-percutaneous nephrolithotomy.

To investigate the effects of intrarenal pelvic pressure (IPP) on pyelo-tubular backflow and renal cortical blood perfusion during mini-percutaneous nephrolithotomy (MPCNL). Dynamic changes in pyelo-tubular backflow and renal cortical blood perfusion were studied in six patients undergoing MPCNL using dynamic contrast-enhanced ultrasonography (CEUS) and IPP monitoring. CEUS of intrarenal pelvic perfusion revealed that renal tubules began to exhibit contrast agent reflux when IPP exceeded 34 mmHg during the MPCNL procedure. There was a positive correlation between renal tubule contrast agent reflux and IPP (P < 0.05). Intravenous CEUS of renal cortical blood flow demonstrated that both intrarenal pelvic perfusion time and IPP during MPCNL significantly affected renal cortical blood perfusion. Intrarenal pelvic perfusion time and pressure were negatively correlated with contrast agent peak intensity (PI) and area under the curve (AUC) (P < 0.05). Longer intrarenal pelvic perfusion times and higher pressures resulted in decreased renal cortical blood perfusion. This study directly confirmed through dynamic CEUS and real-time IPP monitoring that an increase in IPP above the threshold of approximately 34 mmHg during MPCNL in patients leads to reflux through the renal tubules and a significant decrease in renal cortical blood perfusion. The safe upper limit for intrarenal pelvic perfusion pressure during MPCNL is approximately 34 mmHg.

Evaluation of Early Renal Changes in Type 2 Diabetes Mellitus Using Multiparametric MR Imaging.

To evaluate the clinical value of early renal changes in type 2 diabetes mellitus (T2DM) using multiparameter MRI. The study included 41 diabetics (normoalbuminuria: n = 23; microalbuminuria: n = 18) and 30 healthy controls. All subjects underwent intravoxel incoherent motion diffusion-weighted imaging (IVIM), blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) examinations. One-way analysis of variance was used to compare MRI parameters among the three groups. Pearson correlation analysis was used to evaluate the relationship between MRI parameters and estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR). Receiver operating characteristic analysis was performed to assess the diagnostic performance. There were statistical differences in cortical D, D*, f, renal blood flow (RBF) and medulla D, D*, f, R2* among the three groups (P < 0.05). The cortical or medullary D, cortical f, and RBF were significantly positively correlated with eGFR (all P < 0.01). The cortical or medullary D, D*, f, cortical RBF were negatively correlated with ACR (all P < 0.05).To evaluate early kidney changes and degree of diabetes, cortical combined D and RBF (AUC [area under the curve] = 0.796 and 0.947, respectively) was better than single D or RBF (all P > 0.05); medullary combined D and R2* (AUC = 0.899 and 0.923, respectively) was better than single D or R2* (all P > 0.05), except single D (P = 0.005) in differentiating normoalbuminuria group from control group. The early changes of renal diffusion and perfusion, oxygenation level, and blood flow in T2DM could be evaluated noninvasively and quantitatively using IVIM, BOLD and ASL. Renal medullary combined IVIM-derived D and BOLD-derived R2* and cortical combined IVIM-derived D and ASL-derived RBF were better for evaluating early renal changes in T2DM.

Standardized evaluation methodology for renal cortical blood perfusion in elderly patients using contrast‐enhanced ultrasound: A Chinese expert consensus (2024 edition)

AbstractAs a sensitive and non‐invasive method for assessing changes in renal cortical blood perfusion in the elderly, contrast‐enhanced ultrasound (CEUS) can indirectly reflect changes in kidney filtration and reabsorption function, thus providing feasibility for early evaluation of renal function changes. However, significant differences exist among researchers in terms of operational methods, contrast agent selection, post‐data analysis, and many other aspects, leading to substantial heterogeneity in results. This hinders horizontal comparisons and greatly limits the clinical application of contrast‐enhanced ultrasound for evaluating renal cortical blood flow perfusion. Based on the latest domestic and overseas literature and discussions with clinical experts, this consensus provides recommended guidelines for the evaluation of renal cortical blood flow perfusion using contrast‐enhanced ultrasound. It is hoped that this consensus will promote a better understanding of CEUS among medical practitioners at all levels and standardize the examination of renal cortical blood flow perfusion with CEUS.

Unraveling a Novel Mechanism of Altered Glomerular Hemodynamics in Pre-diabetic Obesity

Background: In pre-diabetic obesity, disrupted glomerular autoregulation leads to increased glomerular capillary pressure and renal blood flow, causing potential barotrauma-induced glomerular damage. A decrease in Afferent arteriole ( Af-Art) resistance causes higher glomerular capillary pressure but the underlying mechanism behind this, specifically in pre-diabetic obesity, remains unclear. Hyperinsulinemia is common in pre-diabetic obesity, but its role in reducing Af-Art resistance in the kidneys is unknown. Kidney blood flow is auto-regulated by vasoconstriction via tubuloglomerular feedback (TGF) and vasodilation through the Distal convoluted tubule-2/connecting tubule (DCT-2/CNT) mechanism. Our earlier studies indicate increased Af-Art dilation in pre-diabetic obese rats through the DCT-2/CNT mechanism without affecting TGF. This DCT-2/CNT induced Af-Art dilation requires initiation from epithelial sodium channels (ENaC) present at this tubular segment and interestingly insulin is a known ENaC activator. Hypothesis: We hypothesize that in the context of pre-diabetic obesity, hyperinsulinemia contributes to an increase in renal cortical blood flow (CBF) by increasing DCT-2/CNT-induced Af-Art dilation, subsequently leading to glomerular injury. Methods: We assessed the effects of insulin on Af-Art dilation by perfusing juxtaposed DCT-2/CNT segments with insulin in normal rabbits. Contribution of DCT-2/CNT induced Af-Art dilation was measured by co-administration of the ENaC blocker benzamil. To study hyperinsulinemia's role in an in-vivo setting without altering blood glucose levels, we used a hyperinsulinemic-euglycemic (HI-EUG) clamp in obese rats with intravenous (IV) glucose and insulin infusions. Renal CBF and blood pressure were monitored using a laser Doppler probe and femoral artery catheter, respectively, both with and without benzamil administration (400 μg/kg, IV). To evaluate insulin's potential role in causation of renal damage, we infused insulin directly into one kidney of lean rats for 6 weeks via a renal sub-capsular catheter, with the contralateral kidney serving as control. Glomerular basement membrane (GBM) thickness, a marker of renal damage, was measured via electron microscopy. Untargeted lipidomic analysis of the renal cortex was performed to identify potential renal damage pathways in insulin infused kidneys. Results: Insulin perfusion in rabbits' DCT-2/CNT potentiated the dilation of adherent Af-Art compared to control infusions with artificial tubular fluid. ENaC inhibition reversed the insulin-induced Af-Art dilation, confirming that insulin increases Af-Art dilation through the ENaC-initiated DCT-2/CNT mechanism. In obese rats, insulin delivery using a HI-EUG clamp resulted in a significant 20.8±4.9% increase in CBF, which was negated by the administration of the ENaC blocker benzamil, indicating the potential involvement of DCT-2/CNT-mediated vasodilation. Neither the HI-EUG clamp nor benzamil infusion affected blood pressure. Additionally, continuous direct insulin infusion into the kidneys of lean rats led to an increase in glomerular basement membrane (GBM) thickness and ceramide accumulation in the renal cortex, both indicative of renal damage. Conclusion: Our study demonstrates that insulin directly augments DCT-2/CNT-mediated Af-Art dilation and increases renal cortical blood flow in obese rats. Chronic renal insulin infusion led to structural changes and damage markers in the kidney, independent of blood glucose and blood pressure levels. Henry Ford Health System Internal Funding. Pilot and Feasibility grant from southeast center for integrated metabolomics. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Arterial spin labeling in assessment of interstitial fibrosis in renal allografts

Objective: To explore the feasibility and application value of arterial spin labeling (ASL) in evaluating the degree of renal fibrosis after kidney transplantation. Methods: This is a cross-sectional study. Renal transplant recipients who received treatment at the First Affiliated Hospital of Soochow University from December 2021 to December 2022 were enrolled. All participants underwent ASL scan, and the values of renal cortical renal blood flow (RBF) were measured through post-processing software. The participants were divided into different groups according to the Banff interstitial fibrosis score (ci score) of the transplanted kidneys, and then relevant indicators were compared. One-way analysis of variance was conducted to compare the differences in renal cortical RBF among the groups. Spearman correlation analysis was employed to investigate the association between renal cortical RBF and ci score of the transplanted kidney. Receiver operating characteristic curve was used to analyze the diagnostic effectiveness of renal cortical RBF and laboratory indicators for distinguishing varying degrees of fibrosis in transplanted kidneys. The Delong test was utilized to compare the area under the curve (AUC). Results: A total of 60 patients (42 males and 18 females) were included in the study, with a mean age of (44.6±10.8) years. All patients were divided into 4 groups: ci0 group (ci score=0, 11 cases), ci1 group (ci score=1, 21 cases), ci2 group (ci score=2, 20 cases), and ci3 group (ci score=3, 8 cases). With an increase in the degree of fibrosis in the transplanted kidney, there was a corresponding decrease in the renal cortical RBF value. The differences in renal cortical RBF values among the 4 groups were statistically significant[ci0 group: (214.9±28.5) ml·(100 g)-1·min-1; ci1 group: (181.7±29.3) ml·(100 g)-1·min-1; ci2 group: (158.8±39.2) ml·(100 g)-1·min-1; ci3 group: (123.1±27.2) ml·(100 g)-1·min-1; F=14.02, P<0.001]. The renal cortical RBF was moderately negatively correlated with the ci score (r=-0.644, P<0.001). The AUC for discriminating between ci0 and ci1-3 of renal cortical RBF and 24-hour urine protein was 0.881 (95%CI: 0.772-0.950) and 0.680 (95%CI: 0.547-0.795), respectively. The AUC for renal cortical RBF was significantly higher than that for 24-hour urine protein (P=0.047). The renal cortical RBF can distinguish between ci0-1 and ci2-3, as well as ci0-2 and ci3, with the corresponding AUC value of 0.796 (95%CI: 0.673-0.889) and 0.900 (95%CI: 0.795-0.963), respectively. Conclusion: ASL can quantitatively assess renal blood perfusion in transplanted kidneys and demonstrates high operational efficacy in distinguishing varying degrees of fibrosis in the transplanted kidneys.

Diagnostic and Prognostic Potential of Multiparametric Renal MRI in Kidney Transplant Patients.

Multiparametric MRI provides assessment of functional and structural parameters in kidney allografts. It offers a non-invasive alternative to the current reference standard of kidney biopsy. To evaluate the diagnostic and prognostic utility of MRI parameters in the assessment of allograft function in the first 3-months post-transplantation. Prospective. 32 transplant recipients (54 ± 17 years, 20 females), divided into two groups according to estimated glomerular filtration rate (eGFR) at 3-months post-transplantation: inferior graft function (IGF; eGFR<45 mL/min/1.73 m2 , n = 10) and superior graft function (SGF; eGFR ≥ 45 mL/min/1.73 m2 , n = 22). Further categorization was based on the need for hemodialysis (C1) and decrease in s-creatinine (C2) at 1-week post-transplantation: delayed-graft-function (DGF: n = 4 C1, n = 10 C2) and early graft-function (EGF: n = 28 C1, n = 22 C2). 3-T, pseudo-continuous arterial spin labeling, T1-mapping, and diffusion-weighted imaging. Multiparametric MRI was evaluated at 1-week in all patients and 3-months after transplantation in 28 patients. Renal blood flow (RBF), diffusion coefficients (ADC, ΔADC, D, D, D*, flowing fraction f), T1 and T1 were calculated in cortex and medulla. The diagnostic and prognostic value of these parameters, obtained at 3-months and 1-week post-transplantation, respectively, was evaluated in the cortex to discriminate between DGF and EGF, and between SGF and IGF. Logistic regression, receiver-operating-characteristics, area-under-the-curve (AUC), confidence intervals (CIs), analysis-of-variance, t-test, Wilcoxon-Mann-Whitney test, Fisher's exact test, Pearson's correlation. P-value<0.05 was considered significant. DGF patients exhibited significantly lower cortical RBF and f and higher D*. The diagnostic value of MRI for detecting DGF was excellent (AUC = 100%). Significant differences between patients with IGF and SGF were found in RBF, ∆T1 , and ∆D. Multiparametric MRI showed higher diagnostic (AUC = 95.32%; CI: 88%-100%) and prognostic (AUC = 97.47%, CI: 92%-100%) values for detecting IGF than eGFR (AUC = 89.50%, CI: 79%-100%). Multiparametric MRI may show high diagnostic and prognostic value in transplanted patients, yielding better results compared to eGFR measurements. 2 TECHNICAL EFFICACY: Stage 1.

T1 mapping combined with arterial spin labeling MRI to identify renal injury in patients with liver cirrhosis.

We investigated the capability and imaging criteria of T1 mapping and arterial spin labeling (ASL) MRI to identify renal injury in patients with liver cirrhosis. We recruited 27 patients with cirrhosis and normal renal function (cirrhosis-NR), 10 with cirrhosis and renal dysfunction (cirrhosis-RD) and 23 normal controls (NCs). All participants were examined via renal T1 mapping and ASL imaging. Renal blood flow (RBF) derived from ASL was measured from the renal cortex, and T1 values were measured from the renal parenchyma (cortex and medulla). MRI parameters were compared between groups. Diagnostic performances for detecting renal impairment were statistically analyzed. Cortical T1 (cT1) and medullary T1 (mT1) were significantly lower in the NCs than in the cirrhosis-NR group. The cortical RBF showed no significant changes between the NCs and cirrhosis-NR group but was markedly decreased in the cirrhosis-RD group. The areas under the curve (AUCs) for discriminating cirrhosis-NR from NCs were 0.883 and 0.826 by cT1 and mT1, respectively. Cortical RBF identified cirrhosis-RD with AUC of 0.978, and correlated with serum creatinine (r = -0.334) and the estimated glomerular filtration rate (r = 0.483). A classification and regression tree based on cortical RBF and cT1 achieved 85% accuracy in detecting renal impairment in the cirrhosis. Renal T1 values might be sensitive predictors of early renal impairment in patients with cirrhosis-NR. RBF enabled quantifying renal perfusion impairment in patients with cirrhosis-RD. The diagnostic algorithm based on cortical RBF and T1 values allowed detecting renal injury during cirrhosis.

Thrombomodulin Protects Against Cell-Free Hemoglobin Mediated Acute Kidney Injury in Sickle Cell Anemia

Thrombomodulin (TM) is a transmembrane protein that plays a pivotal role in maintaining microvascular health. Functions of TM include 1) binding thrombin and inhibiting its interaction with fibrinogen, 2) augmenting protein C function, and 3) down-regulating complement activation. Reduced TM function has been implicated in several thrombotic microangiopathies, including atypical hemolytic uremic syndrome and disseminated intravascular coagulation (DIC) (PMID 29866818). Previous in vitro studies have demonstrated that cell-free hemoglobin (Hb) mediates loss of TM from the endothelial surface which, in turn, is associated with a higher risk of kidney injury in patients with sickle cell disease (PMID 34929051). Infusion of intact, soluble TM may restore TM's function in the microvasculature, as observed in critically ill patients with DIC (PMID 17059423). In transgenic sickle mice (Townes model, Jackson Laboratory; Bar Harbor, Maine), we investigated whether 1) cell-free Hb reduces TM function leading to glomerular endothelial and kidney injury and 2) if infusion of intact, soluble TM (Asahi Kasei Pharma ©; Tokyo, Japan) can restore TM function and reduce the toxic effects of cell-free Hb in the kidney. Sickle mice (4 male, 4 females per condition) were challenged with cell-free Hb (0.24g/kg intravenous [iv]) or normal saline followed 2 hours later by either infusion of TM (5mg/kg subcutaneous, 1mg/kg iv) or normal saline. Blood and urine samples were collected 24 hours after the challenge and the mice were sacrificed for histopathologic evaluation. In a separate set of similar experiments, sickle mice (3 males, 3 females per condition) received iv microbubbles (Vevo MicroMarker TM Contrast) 24 hours after the challenge to assess renal cortical blood flow by contrast-enhanced ultrasound (Vevo2100 system). Mean ± standard error of mean values are provided. Comparisons between Hb-only and Hb+TM conditions were made using the Mann-Whitney test. Vasculopathy: Infusion of cell-free Hb resulted in decreased TM antithrombotic function within the glomerulus; infusion of TM 2 hours after the challenge restored these functions (fibrinogen relative fluorescent intensity [RFI]: control, 24.2 ± 0.9; Hb-only, 40.6 ± 1.7; Hb+TM: 26.8 ± 1.6) and anti-complement function (C3 RFI: control, 12.9 ± 0.4; Hb-only, 19.3 ± 1.4; Hb+TM, 14.1 ± 0.5) (P≤0.007). Circulating vascular injury biomarkers rose in the cell-free Hb challenged sickle mice and this was abated with TM rescue for p-selectin (control, 271 ± 25 ng/mL; Hb-only, 533 ± 47 ng/mL; Hb+TM, 356 ± 34 ng/mL), VEGF (control, 59 ± 4 pg/mL; Hb-only, 93 ± 7 pg/mL; Hb+TM 69 ± 3 pg/mL), and vWF (control: 91 ± 9 ng/mL, Hb-only: 299 ± 31 ng/mL, Hb+TM: 183 ± 22 ng/mL) (P≤0.01). Kidney Damage: Urine biomarkers of tubular injury increased after the cell-free Hb challenge and improved with TM (KIM-1: control, 317 ± 66 pg/day; Hb-only, 1201 ± 142 pg/day; Hb+TM, 638 ± 78 pg/day; P=0.003) (NGAL: control, 234 ± 34 ng/day; Hb-only, 1624 ± 145 ng/day; Hb+TM, 767 ± 118 ng/day; P=0.003). An elevation in serum creatinine concentration is used to define acute kidney injury. The cell-free Hb challenge led to an acute rise in serum creatinine while the TM rescued mice had serum creatinine concentrations that were significantly lower than the Hb-only challenged mice (P=0.03) and similar to the control conditions (Figure 1A). Preliminary testing of TM administered 24 hours after the cell-free Hb challenge has also led to kidney protective effects as assessed by serum creatinine, p-selectin, and vWF (P &amp;lt; 0.05). Cortical Blood Flow: Peak enhancement, a measure of relative blood volume, was reduced in the cell-free Hb challenged mice compared to control conditions by contrast-enhanced ultrasound. The TM-rescued mice had improved peak enhancement compared to the Hb-only treated mice (P=0.03) and similar to control conditions (Figure 1B). In conclusion, cell-free Hb reduces TM function resulting in increased vascular and kidney injury and decreased cortical blood flow. Infusion of soluble TM 2 hours after the cell-free Hb challenge restores TM function, protects against vascular and kidney injury, and preserves cortical blood flow. Our data highlights TM as a potential candidate therapy to preserve vascular function and abate kidney injury in patients with sickle cell disease during severe vaso-occlusive or hyperhemolytic episodes, when concentrations of cell-free Hb increase several fold.

Organ blood flow assessment with the ModulHeart cardiorenal support device.

ModulHeart (Puzzle Medical Devices Inc) is a novel percutaneous flow entrainment pump anchored in the descending aorta. The current study evaluates the hemodynamic effect of ModulHeart support and its impact on cerebral, myocardial, and renal blood flow. ModulHeart was implanted in the descending aorta of four healthy calves. A ramp protocol (2000 RPM increments) was performed with the pump operating at five different speeds from 14 000 to 22 000 RPM. For each speed, pressures proximal and distal to the pump, and right heart catheterization measurements were recorded. Stable-isotope labeled microspheres were injected in the left ventricle to evaluate organ perfusion. Thermodilution cardiac output increased by 23% at 22 000 RPM. Greater pump speeds resulted in greater pump gradients, up to 10 mm Hg in mean arterial pressure at 22 000 RPM, without significant reduction of proximal perfusion pressures. Arterial pulse pressure remained stable at all speeds. ModulHeart was not associated with a reduction in cerebral or myocardial blood flow at any speed. Renal cortical and medullary blood flow increased by up to 50% and 40%, respectively. The ModulHeart device implanted in the descending aorta of healthy calves resulted in significant arterial pressure gradients and preserved pulse pressure. Greater pump speeds translated into greater increases in renal blood flow, with no decrease in cerebral or myocardial perfusion.

Adenosine reuptake inhibition reduces diabetes-induced glomerular hyperfiltration via the adenosine A2a receptor.

Diabetes-induced glomerular hyperfiltration is an early alteration in kidney function in diabetes. Previous studies have shown that reduced adenosine A2a receptor signaling contributes to diabetes-induced glomerular hyperfiltration. The present study investigated the effects of enhanced interstitial adenosine concentration by inhibition of cellular adenosine reuptake, thereby promoting endogenous adenosine signaling. Insulinopenic diabetes was induced by streptozotocin in adult male Sprague-Dawley rats. Two weeks after diabetes induction, kidney function in terms of glomerular filtration rate, and total, cortical, and medullary renal blood flows were evaluated under thiobutabarbital anesthesia during baseline and after renal artery infusion of two doses of the adenosine reuptake inhibitor dilazep. Dilazep did not affect mean arterial pressure indicating that the effects of the interventions were intrarenal. Diabetics had increased glomerular filtration rate compared with controls and dilazep dose-dependently decreased glomerular filtration rate in diabetics, whereas it had no significant effect in controls. Dilazep increased cortical renal blood flows in controls, whereas medullary blood flow was not significantly changed. Dilazep did not affect total renal blood flow in any of the groups but decreased cortical blood flow in diabetics, resulting in decreased filtration fraction by dilazep in diabetics. Pretreatment with the adenosine A2a antagonist ZM241385 prevented intrarenal dilazep-mediated effects on glomerular filtration rate and filtration fraction in diabetics. In conclusion, enhancing intrarenal adenosine signaling by dilazep normalizes diabetes-induced glomerular hyperfiltration at least in part by activation of adenosine A2a receptors.

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

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. 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. 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). ASL is practicable for noninvasive evaluation of renal pathology, especially for predicting early renal pathological injury in CKD patients.

Evaluation of interstitial fibrosis in chronic kidney disease by multiparametric functional MRI and histopathologic analysis.

To investigate the diagnostic value of functional MRI to assess renal interstitial fibrosis in patients with chronic kidney disease (CKD). We prospectively recruited 80 CKD patients who underwent renal biopsies and 16 healthy volunteers to undergo multiparametric functional MRI examinations. The Oxford MEST-C classification was used to score the interstitial fibrosis. The diagnostic performance of functional MRI to discriminate interstitial fibrosis was evaluated by calculating the area under the receiver operating characteristic (ROC) curves. IgA nephropathy (60%) accounted for the majority of pathologic type in the CKD patients. Apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) was correlated with interstitial fibrosis (rho = -0.73). Decreased renal blood flow (RBF) derived from arterial spin labeling (rho = -0.78) and decreased perfusion fraction (f) derived from DWI (rho = -0.70) were accompanied by increased interstitial fibrosis. The T1 value from T1 mapping correlated with interstitial fibrosis (rho = 0.67) (all p < 0.01). The areas under the ROC curve for the discrimination of ≤ 25% vs. > 25% and ≤ 50% vs. > 50% interstitial fibrosis were 0.87 (95% confidence interval, 0.78 to 0.94) and 0.93 (0.86 to 0.98) by ADC, 0.84 (0.74 to 0.91) and 0.94 (0.86 to 0.98) by f, 0.93 (0.85 to 0.98) and 0.90 (0.82 to 0.96) by RBF, and 0.91 (0.83 to 0.96) and 0.77 (0.66 to 0.85) by T1, respectively. Functional MRI parameters were strongly correlated with the interstitial fibrosis of CKD. Therefore, it might a powerful tool to assess interstitial fibrosis of CKD noninvasively. • In CKD patients, the renal cortical ADC value decreased and T1 value increased significantly compared with healthy volunteers. • Functional MRI revealed significantly decreased renal perfusion in CKD patients compared with healthy volunteers. • The renal cortical ADC, f, RBF, and T1 values were strongly correlated with the interstitial fibrosis of CKD.

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

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. 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. 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. NE may reduce renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis, partly by reducing the serum NO level.

The diagnostic efficacy of diffusion tensor imaging generated by gadolinium-based magnetic resonance imaging for patients with chronic kidney disease.

Background:Chronic kidney disease (CKD) can lead to systemic inflammatory responses and other cardiovascular disease. Diffusion tensor imaging findings generated by gadolinium-based MRI (DTI-GBMRI) is regarded as a standard method for assessing the pathology of CKD. To evaluate the diagnostic value of DTI-GBMRI for renal histopathology and renal efficiency, renal fibrosis and damage, noninvasive quantification of renal blood flow (RBF) were investigated in patients with CKD.Methods:CKD patients (n = 186) were recruited and underwent diagnosis of renal diffusion tensor imaging findings generated by MRI (DTI-MRI) or DTI-GBMRI to identify the pathological characteristics and depict renal efficiency. The cortical RBFs and estimated glomerular filtration rate were compared in CKD patients undergone DTI-GBMRI (n = 92) or DTI-MRI (n = 94).Results:Gadolinium enhanced the diagnosis generated by DTI-MRI in renal fibrosis, renal damage, and estimated glomerular filtration rate. The superiority in sensitivity and accuracy of the DTI-GBMRI method in assessing renal function and evaluating renal impairment was observed in CKD patients compared with DTI-MRI. Outcomes demonstrated that DTI-GBMRI had higher accuracy, sensitivity, and specificity than DTI-MRI in diagnosing patients with CKD.Conclusion:In conclusion, DTI-GBMRI is a potential noninvasive method for measuring renal function, which can provide valuable information for clinical CKD diagnosis.

MP36-19 PROSTACYCLIN (TREPROSTINIL) THERAPY IMPROVES RENAL HEMODYNAMICS DURING RAT RENAL ISCHEMIA-REPERFUSION INJURY

You have accessJournal of UrologyCME1 May 2022MP36-19 PROSTACYCLIN (TREPROSTINIL) THERAPY IMPROVES RENAL HEMODYNAMICS DURING RAT RENAL ISCHEMIA-REPERFUSION INJURY Frances Kazal, Meiwen Ding, Dicken Ko, Reginald Gohh, and Nisanne Ghonem Frances KazalFrances Kazal More articles by this author , Meiwen DingMeiwen Ding More articles by this author , Dicken KoDicken Ko More articles by this author , Reginald GohhReginald Gohh More articles by this author , and Nisanne GhonemNisanne Ghonem More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002590.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Renal ischemia-reperfusion injury (IRI) is a crucial factor causing acute kidney injury (AKI). To date, no pharmacological treatments are available for the prevention of I/R-induced renal injury. Here, we investigate the renal hemodynamics and reno-protective effects of the prostacyclin analog, treprostinil, against renal IRI in vivo. METHODS: Male Sprague Dawley rats were subjected to bilateral renal ischemia (45 minutes) followed by reperfusion (1–48 hour). Treprostinil (100 ng/kg/min) was administered subcutaneously either (A) at the time of ischemia (IRI-immT) or (B) approximately 18-24 hours before renal IRI (IRI-preT). RESULTS: Serum and urine creatinine were elevated at 24 hours post-reperfusion in the IRI group vs. sham (P <0.001), which both the IRI-immT and IRI-preT reduced the peak of serum creatinine at 24 hours after renal IRI (P <0.001). Also, medullary and cortical renal blood flow (RBF) were significantly reduced in the IRI group vs. sham (P <0.001), whereas the IRI-immT (P <0.01) and IRI-preT (P <0.05) groups improved RBF at 90 minutes post-reperfusion and maintained throughout 120 minutes. In parallel, animals in the IRI injury group experienced a decreased eGFR, increased urinary sodium (UNa 2+) excretion and proteinuria during the first 24 hours post-reperfusion vs. sham (P <0.01). Meanwhile, treprostinil reduced the UNa 2+ and proteinuria and completely restored the eGRF to baseline by 48 hours post-reperfusion and, compared to the IRI group (P <0.01). CONCLUSIONS: This study demonstrates the efficacy of treprostinil in improving renal hemodynamics and kidney function early post-IRI in a clinically relevant rat model of AKI. Specifically, our data show that treprostinil remarkably increased renal blood flow and GFR, and reduced sodium excretion and proteinuria post-reperfusion. Importantly, these data suggest that treprostinil has the potential to serve as a therapeutic agent to protect the kidney against renal IRI. Source of Funding: Funding support for this project was provided in part by the Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the University of Rhode Island Core Lab (P20GM103430). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e605 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Frances Kazal More articles by this author Meiwen Ding More articles by this author Dicken Ko More articles by this author Reginald Gohh More articles by this author Nisanne Ghonem More articles by this author Expand All Advertisement PDF DownloadLoading ...

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.

Abstract 12867: Neuromodulation Of The Renal Nerves In Spontaneously Hypertensive Rats

Introduction: Hypertension is a global burden. Renal denervation has been touted as a possible therapeutic strategy for the treatment of hypertension. However, neuromodulation of the renal nerves’ traffic in hypertension has yet to receive a similar attention. Aim: This study investigated cardio-respiratory responses to renal nerve stimulation in a genetic model of hypertension, the spontaneously hypertensive rat (SHR). Methods: In pentobarbital-anesthetized male SHRs (n = 9), the left renal nerve was stimulated 5 times (5-6 minutes apart) at 5 Hz, 0.5 ms, 0.5 mA for 30s. Mean arterial pressure (MAP), heart rate (HR), left renal cortical blood flow (CBF) and cortical vascular resistance (CVR), hindquarter aortic blood flow (ABF) and vascular resistance (AVR), upper (UAP) and lower (LAP) airway pressure, airway flow (AF), airway resistance (AR), respiration rate (RR) and diaphragmatic EMG (dEMG) were measured and averaged. Results: Cardiovascular responses to renal nerve stimulation were characterized by reductions in MAP, HR, CBF and AVR, which were associated with increases in ABF and CVR. Respiratory responses to renal nerve stimulation, on the other hand, demonstrated increases in AF, RR and dEMG, decreases in AR and no change in UAP and LAP. Conclusions: Under hypertensive conditions, the renal nerves not only modulate cardiovascular function but also improve respiratory function. These studies suggest that neuromodulation of the renal nerves may offer a therapeutic alternative for hypertensive patients.

Workflow for automatic renal perfusion quantification using ASL-MRI and machine learning.

PurposeClinical applicability of renal arterial spin labeling (ASL) MRI is hampered because of time consuming and observer dependent post‐processing, including manual segmentation of the cortex to obtain cortical renal blood flow (RBF). Machine learning has proven its value in medical image segmentation, including the kidneys. This study presents a fully automatic workflow for renal cortex perfusion quantification by including machine learning‐based segmentation.MethodsFully automatic workflow was achieved by construction of a cascade of 3 U‐nets to replace manual segmentation in ASL quantification. All 1.5T ASL‐MRI data, including M0, T1, and ASL label‐control images, from 10 healthy volunteers was used for training (dataset 1). Trained cascade performance was validated on 4 additional volunteers (dataset 2). Manual segmentations were generated by 2 observers, yielding reference and second observer segmentations. To validate the intended use of the automatic segmentations, manual and automatic RBF values in mL/min/100 g were compared.ResultsGood agreement was found between automatic and manual segmentations on dataset 1 (dice score = 0.78 ± 0.04), which was in line with inter‐observer variability (dice score = 0.77 ± 0.02). Good agreement was confirmed on dataset 2 (dice score = 0.75 ± 0.03). Moreover, similar cortical RBF was obtained with automatic or manual segmentations, on average and at subject level; with 211 ± 31 mL/min/100 g and 208 ± 31 mL/min/100 g (P < .05), respectively, with narrow limits of agreement at −11 and 4.6 mL/min/100 g. RBF accuracy with automated segmentations was confirmed on dataset 2.ConclusionOur proposed method automates ASL quantification without compromising RBF accuracy. With quick processing and without observer dependence, renal ASL‐MRI is more attractive for clinical application as well as for longitudinal and multi‐center studies.

Nimbidiol ameliorates adverse renal remodeling and dysfunction in diabetic nephropathy

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) globally. DN is characterized by excess accumulation of extracellular matrix (ECM) proteins in the glomeruli and tubulointerstitium leading to progressive fibrosis and loss of renal function. Matrix metalloproteinases (MMPs) are a group of zinc-dependent endopeptidases that regulate synthesis and degradation of the ECM. Previously, we have shown that elevated MMP-9 and -13 cause adverse ECM remodeling in type-1 diabetic kidney. Nimbidiol is a diterpenoid derived from the root/stem-bark of the medicinal plant ‘Neem’ (Azadirachta indica) and is known to possess anti-diabetic properties. In in vivo cancer studies, neem extract has been reported to regulate ECM proteins and suppress metastasis by modulating MMP-9 and -2 expressions. The purpose of the present study was to investigate the potential role of Nimbidiol to modulate MMP-9 level thus regulate ECM protein accumulation and renal fibrosis during type-1 DN. In order to accomplish this, C57BL6/-Ins2Akita/J, (Akita) mice representing type-1 diabetes and C57BL6/J (WT) mice aged 12-14 weeks were treated without or with Nimbidiol (0.4 mg kg-1day-1) using micro-osmotic pump for eight consecutive weeks. Compared to the WT group, Akita mice showed distinct renovascular remodeling as evidenced by increased MMP-9 expression, ECM protein accumulation and elevated pro-fibrotic markers. The changes were associated with functional impairment that includes elevated renovascular resistive index (RI), reduced renal cortical blood flow and glomerular filtration rate (GFR). Nimbidiol treatment alleviated the adverse pathophysiological changes by decreasing collagen and fibronectin and increasing elastin expression. Our results suggest that Nimbidiol ameliorates renal fibrosis by reducing MMP-9 and ECM protein accumulation and improves renal function.

Exploring label dynamics of velocity-selective arterial spin labeling in the kidney.

PurposeVelocity‐selective arterial spin labeling (VSASL) has been proposed for renal perfusion imaging to mitigate planning challenges and effects of arterial transit time (ATT) uncertainties. In VSASL, label generation may shift in the vascular tree as a function of cutoff velocity. Here, we investigate label dynamics and especially the ATT of renal VSASL and compared it with a spatially selective pulsed arterial spin labeling technique, flow alternating inversion recovery (FAIR).MethodsArterial spin labeling data were acquired in 7 subjects, using free‐breathing dual VSASL and FAIR with five postlabeling delays: 400, 800, 1200, 2000, and 2600 ms. The VSASL measurements were acquired with cutoff velocities of 5, 10, and 15 cm/s, with anterior–posterior velocity‐encoding direction. Cortical perfusion‐weighted signal, temporal SNR, quantified renal blood flow, and arterial transit time were reported.ResultsIn contrast to FAIR, renal VSASL already showed fairly high signal at the earliest postlabeling delays, for all cutoff velocities. The highest VSASL signal and temporal SNR was obtained with a cutoff velocity of 10 cm/s at postlabeling delay = 800 ms, which was earlier than for FAIR at 1200 ms. Fitted ATT on VSASL was ≤ 0 ms, indicating ATT insensitivity, which was shorter than for FAIR (189 ± 79 ms, P < .05). Finally, the average cortical renal blood flow measured with cutoff velocities of 5 cm/s (398 ± 84 mL/min/100 g) and 10 cm/s (472 ± 160 mL/min/100 g) were similar to renal blood flow measured with FAIR (441 ± 84 mL/min/100 g) (P > .05) with good correlations on subject level.ConclusionVelocity‐selective arterial spin labeling in the kidney reduces ATT sensitivity compared with the recommended pulsed arterial spin labeling method, as well as if cutoff velocity is increased to reduce spurious labeling due to motion. Thus, VSASL has potential as a method for time‐efficient, single‐time‐point, free‐breathing renal perfusion measurements, despite lower tSNR than FAIR.