Renal Blood Flow Research Articles

Non-contrast preoperative MRI for determining renal perfusion and visualizing renal arteries in potential living kidney donors at 1.5 Tesla.

The aim of this work was to create and evaluate a preoperative non-contrast-enhanced (CE) magnetic resonance imaging (MRI)/angiography (MRA) protocol to assess renal function and visualize renal arteries and any abnormalities in potential living kidney donors. In total, 28 subjects were examined using scintigraphy to determine renal function. In addition, 3D-pseudocontinuous arterial spin labeling (pCASL), a 2D-non-CE electrocardiogram-triggered radial quiescent interval slice-selective (QISS-MRA), and 4D-CE time-resolved angiography with interleaved stochastic trajectories (CE-MRA) were performed to assess renal perfusion, visualize renal arteries and detect any abnormalities. Two glomerular filtration rates [described by Gates (GFRG) and according to the Chronic Kidney Disease Epidemiology Collaboration formula (GFRCKD-EPI)]. The renal volumes were determined using both MRA techniques. The mean value of regional renal blood flow (rRBF) on the right side was significantly higher than that on the left. The agreements between QISS-MRA and CE-MRA concerning the assessment of absence or presence of an aberrant artery and renal arterial stenosis were perfect. The mean renal volumes measured in the right kidney with QISS-MRA were lower than the corresponding values of CE-MRA. In contrast, the mean renal volumes measured in the left kidney with both MRA techniques were similar. The correlation between the GFRG and rRBF was compared in the same manner as that between GFRCKD-EPI and rRBF. The combination of pCASL and QISS-MRA constitute a reliable preoperative protocol with a total measurement time of <10min without the potential side effects of gadolinium-based contrast agents or radiation exposure.

Quantifying the integrated physiological effects of endothelin-1 on cardiovascular and renal function in healthy subjects: a mathematical modeling analysis.

Endothelin-1 (ET-1) is a potent vasoconstrictor with strong anti-natriuretic and anti-diuretic effects. While many experimental studies have elucidated the mechanisms of ET-1 through its two receptors, ETA and ETB, the complexity of responses and sometimes conflicting data make it challenging to understand the effects of ET-1, as well as potential therapeutic antagonism of ET-1 receptors, on human physiology. In this study, we aimed to develop an integrated and quantitative description of ET-1 effects on cardiovascular and renal function in healthy humans by coupling existing experimental data with a mathematical model of ET-1 kinetics and an existing mathematical model of cardiorenal function. Using a novel agnostic and iterative approach to incorporating and testing potential mechanisms, we identified a minimal set of physiological actions of endothelin-1 through ETA and ETB receptors by fitting the physiological responses (changes in blood pressure, renal blood flow, glomerular filtration rate (GFR), and sodium/water excretion) to ET-1 infusion, with and without ETA/ETB antagonism. The identified mechanisms align with previous experimental studies on ET-1 and offer novel insights into the relative magnitude and significance of endothelin's effects. This model serves as a foundation for further investigating the mechanisms of ET-1 and its antagonists.

544 Interleukin-6 protects renal dysfunction in mouse models of hypertension and salt-sensitive hypertension

OBJECTIVES/GOALS: We are investigating the role of IL-6 in regulating renal function by measuring mean arterial pressure (MAP), renal plasma flow (RPF) and glomerular filtration rate (GFR) in wild type (WT) and IL-6-knockout (KO) mice in established mouse models of angiotensin II (AII)-dependent- hypertension and -salt-sensitive hypertension. METHODS/STUDY POPULATION: Twelve-week-old male WT and KO mice on the C57BL6 background strain were infused with vehicle (V; saline) or angiotensin II (AII; 200 ng/kg/min) for 12-14 days. Half of the AII-treatment groups were maintained on a high salt (HS; 6% NaCl) diet for the duration of the experiment, while the other half of the AII treatment groups and both vehicle groups were fed normal rat chow. MAP was continuously measured by a fluid filled catheter in conscious mice for the duration of the experiment. RPF and GFR were measured on days 12-14 in anesthetized mice by the para-aminohippurate, and fluorescein isothiocynate-Inulin techniques, respectively. All data were analyzed by 2-way ANOVA; *p&lt;0.05 vs. WT, same treatment; #p&lt;0.05 vs.V, same genotype; ^p&lt;0.05, AII vs. AII+HS, same genotype. RESULTS/ANTICIPATED RESULTS: MAP was 31% lower in KO vs WT mice. AII increased MAP (1.2-fold) in WT but not KO mice. HS diet magnified AII-induced increases in MAP in WT and moderately increased MAP in AII-KO mice: [MAP (mmHg): WT+V, 130±7.0; KO+V, 91.0+4.0*; WT+AII, 153±5.0#; KO+AII, 83.0±4.0*; WT+AII+HS, 150±11#; KO+AII+HS, 93.0±4.0#]. AII infusion reduced RPF in the KO but not WT mice. Addition of HS reduced RPF in WT and exacerbated AII-induced reductions in RPF in KO mice [RPF (ml/min/g): WT+V, 1.82±0.23; KO+V, 1.91+0.40; WT+AII, 3.16±0.75#; KO+AII, 1.65±0.42*; WT+AII+HS, 1.10±0.31#^; KO+AII+HS, 1.13±0.XX#^]. The HS diet reduced GFR in AII-infused KO but not WT mice [GFR (µl/min/g): WT+V, 756±XX; KO+V, 788±XX; WT+AII, 1010±63*#; KO+AII, 756±23*; WT+AII+HS, 1100±150#; KO+AII+HS: 540±210*#^]. DISCUSSION/SIGNIFICANCE: The absence of IL-6 in male mice attenuated AII- and/or AII+HS-induced increases in MAP; however, it exacerbated HS-induced reductions in RPF and GFR. These findings suggest inhibiting IL-6 has therapeutic potential as an antihypertensive but not as a renal protective agent in hypertension and salt-sensitive hypertension disease states.

548 Metformin normalizes impaired renal and cardiac function in a rat model of transient undernutrition

OBJECTIVES/GOALS: In the U.S., over 4 million people including children experience transient periods of undernutrition annually. Cardio-metabolic and renal diseases are more prevalent in this population. We are investigating therapeutic strategies to reverse the long-term risk of these diseases in a rat model of transient undernutrition followed by refeeding. METHODS/STUDY POPULATION: Thirty six female Fischer rats (3-months of age) were initially divided into 2 groups. Half were fed regular chow (CT) while the other half were severely food restricted (sFR) by 60% from 0-2 weeks (wks) followed by refeeding from 2-14 wks (sFR-Refed). These 2 groups were then subdivided and treated ± metformin (Met) from wk 7 to wk 12 (n=9/group). High precision ultrasound was conducted on live rats to assess heart and kidney function immediately after the sFR period ended (wk 2) and at the end of the study (wk 14). At the conclusion of the experiment, the rats were sacrificed and the histology of the kidney and heart tissues were analyzed in hematoxylin and eosin-stained sections. The protein to DNA ratio was also calculated in homogenates from these tissues. RESULTS/ANTICIPATED RESULTS: In sFR-Refed rats, cardiac output (CO), heart rate (HR) and renal artery blood flow (RBF) were decreased by 11 ± 1.5%#, 7.0 ± 6.0% and 22 ± 0.6%#, respectively, compared to control (CT) rats; #p&lt;0.05. Mean glomerular diameter was reduced in the kidneys of sFR-refed rats compared to CT and this effect was attenuated by metformin treatment [(µm): CT, 406 ± 31; sFR-Refed, 383 ± 11, p&lt;0.06; CT+Met, 393 ± 18; sFR-Refed+Met, 407 ± 18*]. Furthermore, the mean cardiomyocyte thickness was reduced in sFR-Refed rats compared to controls while metformin treatment prevented this effect [(µm): CT, 16.4 ± 3.6; sFR-Refed, 11.5 ± 2.3#; CT+Met, 16.4 ± 3.6; sFR-Refed+Met, 15.9 ± 3.2*]. #p&lt;0.05 vs. CT, same treatment; *p&lt;0.05 vs. Met, same diet; two-way ANOVA. DISCUSSION/SIGNIFICANCE: These findings have promising implications for metformin use to mitigate long-term impairments in heart and kidney structure and function in individuals who have experienced bouts of undernutrition earlier in life for either voluntarily (e.g., very low calorie dieting) or involuntary (e.g., very low food security) reasons.

Episode of renal dysfunction in a child with eating disorder: a case report

Among the various organ dysfunctions seriously affected by eating disorders (EDs) is kidney damage. The kidneys are vital organs responsible for several essential functions, including the balance of the body's acid-base and mineral metabolism, the removal and excretion of substances, and the regulation of blood volume and pressure. Eating disorders are a widespread and clinically relevant class of multiorgan disorders that occur mainly in adolescence. EDs often have serious clinical manifestations, which are determined by electrolyte imbalance, endocrine and mental disorders, renal failure, and other disorders. Common eating disorders discussed in the literature and frequently encountered in clinical practice are anorexia nervosa and bulimia nervosa. Anorexia nervosa is a type of abnormal eating behaviour that involves the consumption of very little food and may include intentional vomiting or the misuse of laxatives or diuretics. Kidneys perform a number of vital functions to maintain homeostasis in our body. One of the main functions of the kidneys is blood filtration and the removal of metabolic products. This allows you to maintain the optimal level of fluid and electrolytes and remove toxins. Restriction of fluid intake and abuse of diuretics can cause a decrease in blood flow to the kidneys and further renal failure. The result of the latter is the development of serious violations of vital functions. Low dietary protein intake in people following a restricted diet (restrictive anorexia) leads to a decrease in glomerular filtration rate (GFR) and renal plasma flow. Treatment of acute kidney injury on the background of volume deficit due to fluid loss involves its termination and hydration orally or with the help of intravenous infusions of physiological solution depending on the severity of volume deficit and kidney damage, which was observed and described in this clinical case. Aim. To analyze the peculiarities of kidney injury in a child with an eating disorder. Materials and Methods. A detailed analysis of the case history of a pediatric patient diagnosed with eating disorder complicated with an acute episode of renal dysfunction was done. Basic anamnestic, clinical, laboratory, and instrumental data were analyzed and given in the paper. A graphic presentation is done with PowerPoint. Results. We describe a 14-year-old female patient diagnosed with ED and acute kidney injury (AKI) leading to intensive care unit interventions. Conclusions. AKIs can result from a number of conditions that are common among anorexics and include dehydration, high blood pressure, toxins, inadequate nutrition and possibly altered electrolytes. Serum creatinine, blood urea nitrogen (BUN), glomerular filtration rate (GFR), and electrolytes are among the kidney function markers that need to be monitored in the early stages of AKI linked to anorexia. The right medical care, which includes normalizing blood pressure and adequate hydration, leads to the patient's recovery. Further follow-ups on kidney function in such patients are of high importance

Effects of Beraprost with or without NOS Inhibition on Plasma Aldosterone and Hemodynamics in Healthy Cats.

The aim of the study was to evaluate the hemodynamic and RA system effects of the oral administration of the clinical dose of beraprost for feline CKD in healthy cats, and also to examine whether NOS inhibition reversed them. A placebo-controlled pharmacological sequential design study was carried out to assess the plasma aldosterone and renin concentrations (PAC and PRC), blood pressure, heart rate, and exploratorily to estimate renal plasma flow (RPF) and renal vascular resistance (RVR) with simplified methods. Beraprost reduced PAC when compared to the placebo (p < 0.05); this was reversed when NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was added to the beraprost treatment (p < 0.01). No differences in the PRC or hemodynamic parameters were detected between beraprost and the placebo. The correlation ratios (η2) showed opposite relationships between beraprost and the added L-NAME effects on PAC, mean blood pressure (MBP), heart rate, estimated RPF (p < 0.001), estimated RVR (p < 0.01), and PRC (p < 0.05). In healthy cats, the clinical dose of beraprost suppresses PAC, which can be reversed by the inhibition of NOS.

Salt-Sensitive Hypertension and the Kidney.

Salt-sensitive hypertension (SS-HT) is characterized by blood pressure elevation in response to high dietary salt intake and is considered to increase the risk of cardiovascular and renal morbidity. Although the mechanisms responsible for SS-HT are complex, the kidneys are known to play a central role in the development of SS-HT and the salt sensitivity of blood pressure (SSBP). Moreover, several factors influence renal function and SSBP, including the renin-angiotensin-aldosterone system, sympathetic nervous system, obesity, and aging. A phenotypic characteristic of SSBP is aberrant activation of the renin-angiotensin system and sympathetic nervous system in response to excessive salt intake. SSBP is also accompanied by a blunted increase in renal blood flow after salt loading, resulting in sodium retention and SS-HT. Obesity is associated with inappropriate activation of the aldosterone mineralocorticoid receptor pathway and renal sympathetic nervous system in response to excessive salt, and mineralocorticoid receptor antagonists and renal denervation attenuate sodium retention and inhibit salt-induced blood pressure elevation in obese dogs and humans. SSBP increases with age, which has been attributed to impaired renal sodium handling and a decline in renal function, even in the absence of kidney disease. Aging-associated changes in renal hemodynamics are accompanied by significant alterations in renal hormone levels and renal sodium handling, resulting in SS-HT. In this review, we focus mainly on the contribution of renal function to the development of SS-HT.

Abdominal Compartment Syndrome: Definitions, Epidemiology, and Management

Abdominal compartment syndrome (ACS) is a multifaceted and potentially life-threatening medical condition characterized by elevated intra-abdominal pressure. While ACS was initially associated with trauma, it has become evident that this syndrome can manifest in various clinical scenarios.&#x0D; The prevalence of ACS varies across diverse patient populations and clinical settings. Risk factors such as obesity, intra-abdominal tumors, ascites, and major surgery heighten the vulnerability to developing ACS. The pathophysiology of ACS involves a cascade of events compromising organ perfusion. This includes the compression of the inferior vena cava and renal veins, leading to reduced venous return and impaired renal blood flow, which can result in renal failure.&#x0D; Accurate diagnosis of ACS relies on the measurement of intra-abdominal pressure, often performed through bladder pressure measurement. Management encompasses a range of supportive measures, careful patient positioning, ventilatory support, and strategies to reduce intra-abdominal volume. Surgical decompression becomes necessary when conservative approaches fail, although this decision must consider individual patient factors.&#x0D; This review underscores the evolving landscape of ACS and emphasizes the imperative for continued research to address uncertainties in pathophysiology, diagnostic criteria, and management strategies. Enhanced understanding and refined approaches hold the potential to significantly improve outcomes for at-risk or affected patients.

A Study Assessing the Role of Renal Grayscale Ultrasonography and Flowmetry in Correlation With Renal Function Tests Across Various Renal Diseases.

Background Renal insufficiency, a critical concern in native and transplant kidneys, necessitates effective screening modalities for evaluation and management. Grayscale sonography has been a cornerstone in renal diagnostics, providing basic anatomical insights such as renal length, cortical thickness, and collecting system dilatation. Despite technological advancements, its impact on the differential diagnosis or management of renal disease remains limited, often showing normal findings in the presence of severe renal dysfunction. On the other hand, Doppler sonography, particularly the Doppler resistive index (RI), has shown potential in enhancing the assessment of renal dysfunction by quantifying alterations in renal blood flow and correlating with various renal pathologies and prognoses. Thus, this study aims to assess and compare the sensitivity of transabdominal and Doppler sonography as a diagnostic modality to evaluate medical renal diseases with altered renal function tests (RFTs). Methodology Participants included patients visiting the ultrasonography (USG)room at our hospital for USG of the kidneys, ureters, and bladder (USG KUB) and USG of the whole abdomen(USG W/A) with altered RFTs. Each underwent renal grayscale USG and RImeasurement, alongside standard RFTs, aiming to investigate the relationship between USG and RI findings and RFT outcomes to assess their predictive accuracy for renal function. Renal grayscale USG assessed parameters including renal dimensions, echogenicity, corticomedullary differentiation, and RI. Data management and charting were conducted with Microsoft Excel 2021 and Microsoft Word 2021. IBM SPSS Statistics for Windows, Version 24 (IBM Corp.,Armonk, NY) was utilized for data analysis. The analysis of variance (ANOVA) test examined relationships between renal parameters and RI across diagnostic groups. Furthermore, the chi-square test evaluated associations of renal ultrasound findings with RFTs and their significance. Results The study analyzed 93 patients with altered RFTs. Chronic kidney disease (CKD) affected 68 patients, primarily males in their fifth and sixth decades, showing reduced renal dimensions, increased cortical echogenicity, and elevated Doppler RI mean (RIm) with 83% sensitivity. Acute kidney injury (AKI) was found in 12 patients, mainly in their fourth decade, displaying increased renal parameters and elevated RIm with 75% sensitivity. Glomerular diseases, including nephrotic syndrome (NS) and nephritic syndrome (NeS), occurred in 9 patients, predominantly males in their fourth decade, with heightened renal cortical echogenicity and elevated RIm with 55.5% sensitivity. Lupus nephritis (LN) was detected in 4 female patients, despite normal renal parameters, showing elevated serum creatinine levels. Conclusions Doppler assessment of renal vascular waveforms effectively identifies chronic renal changes, aiding in the diagnosis of altered RFTs and guiding prognosis. While it detects typical changes like decreased size and parenchymal atrophy, it may not be as indicative of diabetic nephropathy. Key ultrasound indicators such as changes in echotexture and size, along with associated findings like ascites and effusions, help recognize altered renal function and minimize unnecessary interventions.

Effect of Dapagliflozin on Renal and Hepatic Glucose Kinetics in T2D and NGT Subjects.

Acute and chronic SGLT-2 inhibition increase endogenous glucose production (EGP). However, the organ - liver versus kidney - responsible for the increase in EGP has not been identified. 20 T2DM and 12 NGT subjects received [3-3H]-glucose infusion (to measure total EGP) in combination with arterial and renal vein catheterization and PAH infusion for determination of renal blood flow. Total EGP, net renal arteriovenous balance, and renal glucose production were measured before and 4 hours after dapagliflozin and placebo administration. Following DAPA, EGP increased in both T2D and NGT from baseline to 240 minutes, while there was a significant time-related decrease after placebo in T2D. Renal glucose production at baseline was <5% of basal EGP in both groups and did not change significantly following DAPA in either NGT and T2D. Renal glucose uptake (sum of tissue glucose uptake plus glucosuria) increased in both T2D and NGT following DAPA (P<0.05 vs placebo). The increase in RGU was entirely explained by the increase in glucosuria. Single dose of dapagliflozin significantly increased EGP, which primarily is explained by an increase in hepatic glucose production, establishing the existence of a novel renal-hepatic axis.

Characterization of kidneys in patients with systemic sclerosis by multi-parametric magnetic resonance quantitative imaging

PurposeTo determine the usefulness of multiparametric magnetic resonance (MR) quantitative imaging in characterizing the kidneys in systemic sclerosis (SSc) patients. Material and methodsForty-six SSc patients (47.9 ± 12.8 years, 40 females) and 22 age- and sex- matched healthy volunteers (46.1 ± 13.8 years, 20 females) were recruited and underwent renal MR imaging by acquiring blood oxygen level dependent and saturated multi-delay renal arterial spin labeling (SAMURAI) sequences. The T2* value, T1 value, renal blood flow (RBF), arterial bolus arrival time (aBAT), and tissue bolus arrival time (tBAT) of renal cortex were measured and compared among diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) groups and healthy controls using One-way ANOVA and analyzed by logistic regression. ResultsCompared to healthy volunteers, SSc patients with normal estimated glomerular filtration rate (n = 40) had significantly lower T2* value (P = 0.026) in the left renal cortex, longer T1 value (right: P = 0.015; left: P = 0.023), lower RBF (right: P < 0.001; left: P < 0.001), and shorter tBAT (right: P < 0.001; left: P = 0.005) in both right and left renal cortex after adjusting for demographics. The dcSSc patients (n = 23) had significantly lower RBF in both right (226.7 ± 65.2 mL/100 g/min vs. 278.2 ± 73.5 mL/100 g/min, P = 0.022) and left (194.5 ± 71.5 mL/100 g/min vs. 252.7 ± 84.4 mL/100 g/min, P = 0.020) renal cortex compared to the lcSSc patients (n = 23) after adjusting for demographics, but the significance of the difference was attenuated after further adjusting for modified Rodnan skin score and digital ulcers. ConclusionMulti-parametric MR quantitative imaging, particularly multi-delay ASL perfusion imaging, is a useful technique for characterizing the kidneys and classification of SSc patients.

Association of left ventricular diastolic dysfunction with inflammatory activity, renal dysfunction, and liver-related mortality in patients with cirrhosis and ascites.

Left ventricular diastolic dysfunction (LVDD) is the predominant cardiac abnormality in cirrhosis. We investigated the association of LVDD with systemic inflammation and its impact on renal function, occurrence of hepatorenal syndrome (HRS) and survival in patients with cirrhosis and ascites. We prospectively enrolled 215 patients with cirrhosis and ascites. We evaluated the diagnosis and grading of LVDD by Doppler echocardiography, inflammatory markers, systemic hemodynamics, vasoactive factors, radioisotope-assessed renal function and blood flow, HRS development and liver-related mortality. LVDD was diagnosed in 142 (66%) patients [grade 2/3: n = 61 (43%)]. Serum lipopolysaccharide-binding protein (LBP), plasma renin activity (PRA) and glomerular filtration rate (GFR) were independently associated with the presence of grade 2/3 LVDD and the severity of diastolic dysfunction. Serum tumor necrosis factor-α, cardiac output and plasma noradrenaline were also independently associated with the presence of grade 2/3 LVDD. The diastolic function marker E/e' was strongly correlated with serum LBP (r = 0.731; P < 0.001), PRA (r = 0.714; P < 0.001) and GFR (r = -0.609; P < 0.001) among patients with LVDD. The 5-year risk of HRS development and death was significantly higher in patients with grade 2/3 LVDD compared to those with grade 1 (35.5 vs. 14.4%; P = 0.01 and 53.3 vs. 28.2%; P = 0.03, respectively). The occurrence and severity of LVDD in patients with cirrhosis and ascites is closely related to inflammatory activity. Advanced LVDD is associated with baseline circulatory and renal dysfunction, favoring HRS development, and increased mortality.

Evaluation of renal tubular function by multiparametric functional MRI in early diabetes

PurposeTo evaluate the tubular function in an alloxan-induced type 1 diabetes mellitus (DM) rabbit model measured by renal oxygenation (R2*), oxygen extraction fraction (OEF), and renal blood flow (RBF) using blood oxygenation level dependent, asymmetric spin echo, and arterial spin labeling MRI.MethodsTwenty-six rabbits were randomized into the 3-day DM group (n = 13) and the 7-day DM group (n = 13). We performed pairs of multiparametric MRIs (before and after furosemide injection) at baseline and 3/7 days post-DM, and scored pathological kidney injury. We performed statistical analyses using non-parametric, chi-square, and Spearman correlation tests.ResultsAt baseline, medullary R2* significantly decreased by 24.97% and 16.74% in the outer and inner stripes of the outer medulla (OS and IS, p = 0.006 and 0.003, respectively) after furosemide administration. While the corresponding OEF decreased by 15.91% for OS and 16.67% for IS (both p = 0.003), and no significant change in medullary RBF was observed (p > 0.05). In the 3-day DM group, the decrease of medullary R2* and OEF post-furosemide became unremarkable, suggesting tubular dysfunction. We noticed similar changes in the 7-day DM group. Correlation analysis showed pathological tubular injury score significantly correlated with medullary ∆R2* (post-furosemide – pre-furosemide difference, r = 0.82 for OS and 0.82 for IS) and ∆OEF (r = 0.82 for OS and 0.82 for IS) (p < 0.001, respectively).Conclusion: The combination of medullary OEF and R2* in response to furosemide could detect renal tubular dysfunction in early DM.

Renal dysfunction in adults following cardiopulmonary bypass is linked to declines in S-nitroso hemoglobin: a case series.

Impaired kidney function is frequently observed in patients following cardiopulmonary bypass (CPB). Our group has previously linked blood transfusion to acute declines in S-nitroso haemoglobin (SNO-Hb; the main regulator of tissue oxygen delivery), reductions in intraoperative renal blood flow, and postoperative kidney dysfunction. While not all CPB patients receive blood, kidney injury is still common. We hypothesized that the CPB procedure itself may negatively impact SNO-Hb levels leading to renal dysfunction. After obtaining written informed consent, blood samples were procured immediately before and after CPB, and on postoperative day (POD) 1. SNO-Hb levels, renal function (estimated glomerular filtration rate; eGFR), and plasma erythropoietin (EPO) concentrations were quantified. Additional outcome data were extracted from the patients' medical records. Twenty-seven patients were enroled, three withdrew consent, and one was excluded after developing bacteremia. SNO-Hb levels declined after surgery and were directly correlated with declines in eGFR (R=0.48). Conversely, plasma EPO concentrations were elevated and inversely correlated with SNO-Hb (R=-0.53) and eGFR (R=-0.55). Finally, ICU stay negatively correlated with SNO-Hb concentration (R=-0.32). SNO-Hb levels are reduced following CPB in the absence of allogenic blood transfusion and are predictive of decreased renal function and prolonged ICU stay. Thus, therapies directed at maintaining or increasing SNO-Hb levels may improve outcomes in adult patients undergoing cardiac surgery.

Renal ultrasonography predicts worsening renal function in patients with heart failure under tolvaptan administration.

Renal dysfunction in patients with chronic heart failure predicts a poor prognosis. Tolvaptan has a diuretic effect in patients with chronic kidney disease and heart failure without adverse effects on renal function. We aimed to determine the effects of tolvaptan and predictors of worsening renal function in patients with heart failure. This post hoc analysis was a sub-analysis of a single-centre prospectively randomized trial on the early and short-term tolvaptan administration. We enrolled 201 participants with decompensated heart failure between January 2014 and March 2019 (early group, n=104; age: 79.0±12.8years; late group, n=97; age: 80.3±10.8years). Renal ultrasonography was performed before and after the administration of tolvaptan. Urine output and oral water intake significantly increased during tolvaptan administration. The difference between water intake and urine volume increased during tolvaptan administration. Changes in body weight, blood pressure, heart rate, and estimated glomerular filtration rate (eGFR) in both groups were comparable. The changes in peak-systolic velocity (PSV), acceleration time (AT) of the renal arteries, and resistance index were comparable. The changes in PSV and end-diastolic velocity (EDV) of the interlobar arteries increased following tolvaptan administration (Δmax PSV: 0.0±14.8cm/s before tolvaptan vs. 5.6±15.7cm/s after tolvaptan, P=0.002; Δmean PSV: 0.4±12.3 vs. 4.9±12.7cm/s, P=0.002; Δmax EDV: -0.2±3.5 vs. 1.4±4.0cm/s, P=0.001; Δmean EDV: -0.0±3.1 vs. 1.1±3.4cm/s, P=0.003). The renal artery AT was negatively correlated with the eGFR (Δmax AT: beta=-0.2354, P=0.044; Δmean AT: beta=-0.2477, P=0.035). Tolvaptan increased the PSV and EDV of the interlobar artery, which may mean tolvaptan increased renal blood flow. The renal artery AT may be a surrogate for worsening renal function.

The renal vasodilatation from β-adrenergic activation in vivo in rats is not driven by KV7 and BKCa channels.

The mechanisms behind renal vasodilatation elicited by stimulation of β-adrenergic receptors are not clarified. As several classes of K channels are potentially activated, we tested the hypothesis that KV7 and BKCa channels contribute to the decreased renal vascular tone in vivo and in vitro. Changes in renal blood flow (RBF) during β-adrenergic stimulation were measured in anaesthetized rats using an ultrasonic flow probe. The isometric tension of segmental arteries from normo- and hypertensive rats and segmental arteries from wild-type mice and mice lacking functional KV7.1 channels was examined in a wire-myograph. The β-adrenergic agonist isoprenaline increased RBF significantly in vivo. Neither activation nor inhibition of KV7 and BKCa channels affected the β-adrenergic RBF response. In segmental arteries from normo- and hypertensive rats, inhibition of KV7 channels significantly decreased the β-adrenergic vasorelaxation. However, inhibiting BKCa channels was equally effective in reducing the β-adrenergic vasorelaxation. The β-adrenergic vasorelaxation was not different between segmental arteries from wild-type mice and mice lacking KV7.1 channels. As opposed to rats, inhibition of KV7 channels did not affect the murine β-adrenergic vasorelaxation. Although inhibition and activation of KV7 channels or BKCa channels significantly changed baseline RBF in vivo, none of the treatments affected β-adrenergic vasodilatation. In isolated segmental arteries, however, inhibition of KV7 and BKCa channels significantly reduced the β-adrenergic vasorelaxation, indicating that the regulation of RBF in vivo is driven by several actors in order to maintain an adequate RBF. Our data illustrates the challenge in extrapolating results from in vitro to in vivo conditions.

R2R01: A long-acting single-chain peptide agonist of RXFP1 for renal and cardiovascular diseases.

The therapeutic potential of relaxin for heart failure and renal disease in clinical trials is hampered by the short half-life of serelaxin. Optimization of fatty acid-acetylated single-chain peptide analogues of relaxin culminated in the design and synthesis of R2R01, a potent and selective RXFP1 agonist with subcutaneous bioavailability and extended half-life. Cellular assays and pharmacological models of RXFP1 activation were used to validate the potency and selectivity of R2R01. Increased renal blood flow was used as a translational marker of R2R01 activity. Human mastocytes (LAD2 cells) were used to study potential pseudo-allergic reactions and CD4+ T-cells to study immunogenicity. The pharmacokinetics of R2R01 were characterized in rats and minipigs. In vitro, R2R01 had comparable potency and efficacy to relaxin as an agonist for human RXFP1. In vivo, subcutaneous administration of R2R01 increased heart rate and renal blood flow in normotensive and hypertensive rat and did not show evidence of tachyphylaxis. R2R01 also increased nipple length in rats, used as a chronic model of RXFP1 engagement. Pharmacokinetic studies showed that R2R01 has a significantly extended terminal half-life. The in vitro assays with LAD2 cells and CD4+ T-cells showed that R2R01 had low potential for pseudo-allergic and immunogenic reactions, respectively. R2R01 is a potent RXFP1 agonist with an extended half-life that increases renal blood flow in various settings including normotensive and hypertensive conditions. The preclinical efficacy and safety data supported clinical development of R2R01 as a potential new therapy for renal and cardiovascular diseases.

Maximal detrusor pressure can be predicted using technetium-99m-mertcaptoacetyltriglycine renal scintigraphy in the early stages of spinal cord injury.

Retrospective cohort study. To investigate the potential of technetium-99m-mercaptoacetyltriglycine (99mTc-MAG-3) renal scintigraphy for predicting maximal detrusor pressure in the early stages of spinal cord injury (SCI). Tertiary rehabilitation facility. Medical records of individuals with SCI admitted between January 2020 and April 2023 who underwent both 99mTc-MAG-3 renal scintigraphy and urodynamic study within 90 days of SCI onset were retrospectively reviewed. Pearson's coefficient analysis was performed to determine the relationship between 99mTc-MAG-3 renal scintigraphy findings and urodynamic study findings. A multivariate linear regression analysis was performed to determine the best predictors of maximal detrusor pressure. A multivariate logistic regression analysis was performed to determine risk factors for high detrusor pressure. Ninety-four participants were enrolled in this study. Pearson's correlation analysis showed that effective renal plasma flow (ERPF) and ERPF (% predicted) were significantly correlated with maximal detrusor pressure. The multivariate linear regression analysis demonstrated that ERPF (% predicted) was a significant predictor of maximal detrusor pressure. The multivariate logistic regression analysis showed that ERPF (% predicted) was significantly associated with high detrusor pressure. The receiver operating characteristic curve demonstrated that the predictive model had an area under the curve of 0.725, with an ERPF (% predicted) cut-off of 64.05%, sensitivity 1.000, and specificity 0.429. These results suggest that 99mTc-MAG-3 renal scintigraphy may be useful for predicting high detrusor pressure in early SCI and may guide the timing of urodynamic studies in individuals with early SCI for appropriate management of neurogenic lower urinary tract dysfunction.

Arterial spin labeling combined with T1 mapping for assessment of kidney function and histopathology in patients with long-term renal transplant survival after kidney transplantation.

The long-term survival of kidney transplants is often influenced by various factors, among which renal allograft rejection is the most notable factor. A noninvasive and reliable imaging biomarker correlating with kidney function and histopathology would facilitate longitudinal long-term follow-up of renal allografts. The aim of the study is to investigate the value of arterial spin labeling (ASL) combined with T1 mapping for assessing kidney function in patients with long-term renal transplant survival, and to establish radiological and histopathologic correlations between the magnetic resonance imaging (MRI) measurements and kidney allograft biopsy findings. Kidney transplant recipients who were admitted to the Department of Urology in First Affiliated Hospital of Soochow University between January and December 2022 were prospectively consecutively recruited [group A, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2; group B, 30≤ eGFR <60 mL/min/1.73 m2; group C, eGFR <30 mL/min/1.73 m2], and part of them underwent biopsies. All patients underwent ASL and T1 mapping. MRI parameters were calculated and analyzed. A total of 63 patients (Group A, 30 cases; Group B, 20 cases; and Group C, 13 cases) were included in this cross-sectional study. Cortical T1 increased, whereas renal blood flow (RBF) and ΔT1 [100% × (cortical T1 - medullary T1)/cortical T1] decreased with the decrease of eGFR. The RBF, cortical T1, and ΔT1 values were moderately correlated with eGFR (r=0.569, -0.573, and 0.672, respectively). The MRI parameters were moderately correlated with Banff scores, which determined renal allograft rejection and chronicity. The area under the curve (AUC) for the discrimination of groups A versus B and groups A versus C were 0.740 [95% confidence interval (CI): 0.597-0.854, P=0.004] and 0.923 (95% CI: 0.800-0.982, P<0.001), respectively, using ASL; 0.873 (95% CI: 0.749-0.950, P<0.001) and 0.926 (95% CI: 0.803-0.983, P<0.001), respectively, using T1 mapping; and 0.892 (95% CI: 0.771-0.962, P<0.001) and 0.956 (95% CI: 0.846-0.995, P<0.001), respectively, using multi-parameter MRI. The AUC for discrimination between groups B and C was 0.729 (95% CI: 0.546-0.868, P=0.02) using ASL. The RBF, cortical T1, and ΔT1 can serve as new imaging biomarkers of kidney function and histopathological microstructure.

Role of Cerebro Placental Ratio and Renal Artery Doppler Blood Flow in Pregnant Women with Idiopathic oligohydramnios

Role of Cerebro Placental Ratio and Renal Artery Doppler Blood Flow in Pregnant Women with Idiopathic oligohydramnios