Renal Blood Flow Research Articles

Characterization of a novel ovine model of hypertensive heart failure with preserved ejection fraction.

The lack of animal models which accurately represent heart failure with preserved ejection fraction (HFpEF) has been a major barrier to the mechanistic understanding and development of effective therapies for this prevalent and debilitating syndrome characterized by multisystem impairments. Herein, we describe the development and characterization of a novel large animal model of HFpEF in older, female sheep with chronic 2-kidney, 1-clip hypertension. At six weeks post-unilateral renal artery clipping, hypertensive HFpEF sheep had higher mean arterial pressure compared to similarly aged ewes without unilateral renal artery clipping (mean arterial pressure = 112.7±15.9 vs 76.0±10.1 mmHg, P < 0.0001). The hypertensive HFpEF sheep were characterized by (i) echocardiographic evidence of diastolic dysfunction (lateral e' = 0.11±0.02 vs 0.14±0.04 m/s, P = 0.011; lateral E/e' = 4.25±0.77 vs 3.63±0.54, P = 0.028) and concentric left ventricular hypertrophy without overt systolic impairment, (ii) elevated directly measured left ventricular end-diastolic pressure (13±5 vs 0.5±1 mmHg, P = 2.1x10-6), and (iii) normal directly measured cardiac output. Crucially, these hypertensive HFpEF sheep had impaired exercise capacity as demonstrated by their (i) attenuated cardiac output (P = 0.001), (ii) augmented pulmonary capillary wedge pressure (P = 0.026), and (iii) attenuated hindlimb blood flow (P = 3.4x10-4) responses, during graded treadmill exercise testing. In addition, exercise renal blood flow responses were also altered. Collectively, our data indicates that this novel ovine model of HFpEF may be a useful translational research tool since it exhibits similar and clinically relevant impairments as that of HFpEF patients.

Abstract 4135289: Renal Blood Perfusion is Closely Related to Right Ventricular Volume Overload in Congestive Heart Failure

Background: Cardiorenal syndrome (CRS) involves a bidirectional relationship where dysfunction in one organ exacerbates the other. A key factor in this interaction is the impact of right ventricular (RV) volume overload on renal blood flow, which is vital for the progression and management of heart failure (HF). Objective: This study aims to explore and quantify the relationship between right ventricular volume overload, i.e, echocardiographic assessments of right ventricular diameter (RVD), and the time-to-peak (TTP) of renal blood flow in patients with HF measured by 99mTc-DTPA renal scintigraphy. Methods: This single-center study included 304 stable, ambulatory HF patients admitted between October 2017 and August 2022. HF was diagnosed based on the 2016 ESC guidelines. Echocardiographic parameters, including RVD, and TTP of renal blood flow measured by 99mTc-DTPA renal scintigraphy, were collected. Statistical analysis was conducted using SPSS and R software, with Spearman correlation analysis used to assess the relationship between echocardiographic parameters and TTP. Results: The study showed there was a significant correlation between RVD and TTP (rs=0.535, P &lt;0.001), indicating that RV volume overload is closely related to impaired renal perfusion. The median TTP among the study population was 27.25 seconds (IQR: 21-39 seconds). Corrected for body surface area (BSA), RVD was found to be significantly higher in patients with heart failure with reduced ejection fraction (HFrEF) compared to heart failure with preserved ejection fraction (HFpEF) and heart failure with mid-range ejection fraction (HFmrEF) (HFrEF: 20.62 mm/m 2 , HFmrEF: 18.72 mm/m 2 , HFpEF: 18.09 mm/m 2 ; p &lt; 0.001). Furthermore, right atrial diameter (RAD) corrected for BSA (RAD/BSA) demonstrated the strongest correlation with TTP in the HFrEF subgroup (rs=0.602, p&lt;0.001). Conclusions: Our findings highlight the significant impact of right ventricular volume overload on renal perfusion, providing valuable insights into the pathophysiology of CRS. These results suggest that therapeutic strategies aimed at reducing RV overload could enhance renal perfusion and improve overall outcomes in HF patients.

Evaluation of Severe ultrasound and gene diagnosis in cardiac index and shock patient index of shock patients.

The kidney is the most vulnerable organ in severe patients. In severe cases, the fatality rate of acute kidney damage is as high as 30% ∼ 60%. Severe ultrasound is a non-invasive method to evaluate renal blood flow. It can give a semi-quantitative score of renal blood flow and measure the Resistance Index (RI), which can reflect renal artery blood flow to a certain extent. There is little literature on hemodynamic regulation in septic shock patients, but almost no research report on the relationship between hemodynamics and RI exists. Therefore, this paper proposed the analysis of severe ultrasound and gene diagnosis in cardiac index and peripheral vascular RI of shock patients. This paper mainly expounded on detecting renal function parameters and RI in patients with viral shock to understand further the correlation between them and renal flow and RI. It could be seen from the experimental results that the P values before and after resuscitation in the two groups with and without elevated Cardiac Output (CO) were 0.41 and 0.12, respectively, which were more significant than 0.05. RI had no apparent relationship with CO, and RI could not be used as an evaluation index for patients with early septic shock.

Study Of Calcium Magnesium And Phosphorus In Hypothyroidism - A Case Control Study

Background: Thyroid disorders are the most common endocrine abnormality in the world secondary to diabetes mellitus. Thyroid hormones are essential for growth, neuronal development, reproduction and regulation of energy metabolism. It influences the metabolism of all substrates including minerals. Many studies have shown that mineral metabolism is frequently disturbed in thyroid disorders. Materials and Methods: The study was conducted on sixty newly confirmed hypothyroid cases based on the thyroid profile and sixty euthyroid cases were recruited as controls. Blood samples were collected from all the patients for the estimation of serum T3, T4, FT3, FT4, TSH, calcium, phosphorus and magnesium by auto analyzer method. Modified spectrophotometric micro-method was used to measure Serum copper using Bathocuprine Disulphonate Disodium Salt (BCDS) and Guanidine hydrochloride salt. The Statistical software namely SPSS 18.0, and R environment ver.3.2.2 were used for the analysis of the data. Results: It was found that the levels of serum sodium, potassium and calcium were significantly decreased in cases than the controls. Serum magnesium and phosphorus were significantly elevated in cases than controls. Conclusion: Serum calcium, magnesium and phosphorous levels are significantly altered in patients having hypothyroidism. Thyroid diseases have wide spread systemic manifestations including their effects on bone and mineral metabolism. Also thyroid hormone affects the glomerular filtration rate, renal blood flow, tubular reabsorption and excretion of minerals which have direct effect on Calcium, Magnesium and phosphorous level. Thus monitoring of these minerals in hypothyroid patient will be of great benefit in improving clinical manifestation and can be treated appropriately

Study of renal blood flow in children with obstructive uropathies

Aim. To evaluate hemodynamic indicators of the kidneys in children with obstructive uropathies.Materials and Methods. The study was conducted at the Republican Scientific and Clinical Center of Pediatrics and Pediatric Surgery, involving 32 children aged 1 to 14 years, comprising 18 girls (56.3%) and 14 boys (43.7%). The children were divided into 3 groups: Group I with unilateral hydronephrosis - 14 (43.7%) children, Group II with bilateral hydronephrosis - 10 (31.3%) children, and Group III with ureterohydronephrosis - 8 (25%) children.Results and Discussion. Obstructive uropathy resulting from congenital kidney malformations, such as organic obstruction (hydronephrosis), causes dilation of the renal collecting system, increased ureteral pressure, reduced intrarenal blood flow, renal parenchyma atrophy, and progressive chronic renal failure.Conclusion. The above findings demonstrate that ultrasound using pulsed-wave Doppler and color Doppler mapping is an optimal non-invasive method for assessing renal hemodynamics.

The Influence of Anthropometric Factors on Renal mpMRI: Insights From Regional Analysis.

Multiparametric MRI (mpMRI) provides detailed insights into renal function, but the impact of anthropometric factors on renal imaging is not fully understood. To investigate regional correlations between mpMRI parameters and age, body mass index (BMI), and body surface area (BSA). Prospective, cross-sectional observational study. Twenty-nine healthy volunteers (44.5 ± 18.3 years, 18 females) without a history of renal disease. 3-T, pseudo-continuous arterial spin labeling, multi-echo gradient-recalled echo, diffusion-weighted imaging, T1 and T2 mapping. Bilateral kidneys were segmented into nine concentric layers (outer cortex to inner regions) and nine equiangular sections (lower to upper pole). Key parameters (renal blood flow [RBF], , apparent diffusion coefficient [ADC], T1 and T2 maps) were correlated with age, BMI, and BSA. Differences in parameters between age and BMI groups were also evaluated. Spearman correlation, Mann-Whitney U test, and rank-biserial correlation coefficient for effect size. A P-value <0.05 was considered statistically significant. RBF correlated negatively with age in all regions and BMI in inner layers and lower pole. ADC negatively correlated with BMI (significance was not reached in layers 2, 7, 8; P-value = 0.06-0.12) and BSA in layers 1-7. T1 negatively correlated with age in inner regions and lower medial pole. Significant positive correlations were found between age and (outermost layer, upper pole), age and T2 (inner and cranial-caudal regions), as well as BMI and T2 (except upper pole; P-value = 0.06). Significant differences between age groups were observed for RBF (all regions), (outermost and second innermost layers, central lateral region), T1 (innermost layer), and T2 (upper medial pole). Between BMI groups, ADC (middle layers, upper medial pole) and T2 (outermost and inner layers, lower pole to lateral region) differed significantly. Intrarenal variance of mpMRI parameters correlated with age, BMI, and BSA. 4 TECHNICAL EFFICACY: Stage 1.

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.

The Paradise Renal Denervation System: An FDA-approved catheter-based treatment option for resistant hypertension

Resistant hypertension is defined as office blood pressure &gt;140/90 mm Hg with a mean 24-hour ambulatory blood pressure of &gt;130/80 mm Hg in patients who are compliant with 3 or more antihypertensive medications. Those who persistently fail pharmaceutical therapy may benefit from interventional treatment, such as renal denervation. Sympathetic nervous activity in the kidney is a known contributor to increased blood pressure because it results in efferent and afferent arteriole vasoconstriction, reduced renal blood flow, increased sodium and water reabsorption, and the release of renin. The Recor Paradise Renal Denervation System is designed to target renal sympathetic nerves via ultrasound ablation. The RADIANCE trials have demonstrated that patients who underwent renal denervation had a significant decrease in systolic blood pressure as compared with those who underwent a sham procedure. Furthermore, the device was found to have a favorable safety profile, with minimal major adverse events. The Food and Drug Administration granted approval to Recor, and the Paradise system is expected to serve as an adjunctive therapy for patients with true-resistant hypertension.

Concentric-object and equiangular-object methods to perform standardized regional analysis in renal mpMRI.

Renal multiparametric magnetic resonance imaging (mpMRI) sequences, including T1-T2 mapping, Blood oxygenation level-dependent (BOLD), Renal blood flow (RBF), and Apparent Diffusion Coefficient (ADC) from diffusion-weighted imaging (DWI), provide insights into kidney function. However, consensus on selecting regions of interest (ROIs) is lacking. This study aims to describe and compare the Concentric Objects (CO) and Equiangular Objects (EO) methods for standardized ROI selection and assess their efficacy in capturing regional variations in renal MRI parameters. Twelve healthy volunteers underwent mpMRI renal scans. ROIs were selected manually and by applying the CO and EO algorithms to each mpMRI sequence. The methods were tested across various subregion configurations. Regional differences in renal MRI parameters were evaluated. CO and EO methods demonstrated statistically significant differences in mpMRI parameters across renal regions. ASL-RBF, BOLD-MRI, and T2-map results indicated substantial variations from the lower to upper kidney areas. This study implemented CO and EO algorithms in renal mpMRI, showing their potential for evaluating cortico-medullary and cranio-caudal profiles. The findings validate the CO method for BOLD and ADC measurements and presented ASL-RBF and T1-T2 map profiles. The EO method's utility needs further validation with renal patients.

Cardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study

Chronic kidney disease (CKD) affects ~10% of the population and cardiovascular disease is its commonest complication. Despite treatment, patient outcomes remain poor and newer therapies are urgently needed. Here, we investigated the systemic and renal effects of apelin in CKD. In a randomized, double-blind, placebo-controlled, crossover study, 24 subjects (12 patients with CKD and 12 matched healthy subjects) received pyroglutamated apelin-13 ([Pyr1]apelin-13, 1 nmol/min and 30 nmol/min) or matched placebo on two separate visits. Systemic and renal hemodynamics were monitored throughout. The co-primary endpoints were change in systemic vascular resistance index and renal blood flow. Secondary endpoints were change in blood pressure, cardiac output, pulse wave velocity, glomerular filtration rate, natriuresis, free water clearance and urinary protein excretion. In both health and CKD, 30 nmol/min [Pyr1]apelin-13 reduced mean arterial pressure by ~4%, systemic vascular resistance by ~12%, and increased cardiac index by ~10%, compared to placebo (p < 0.05 for all). Both doses of [Pyr1]apelin-13 increased renal blood flow by ~15%, natriuresis by ~20% and free water clearance by ~10%, compared to placebo (p < 0.05 for all). In patients with chronic kidney disease only, glomerular filtration rate fell by ~10%, effective filtration fraction by ~5% and proteinuria by ~25% (p < 0.01 for all). Apelin has short-term cardiovascular and renal benefits in CKD. If maintained longer-term, these should improve patient outcomes. Clinical trials of long-acting oral apelin agonists are justified in CKD and other conditions with impaired salt and water balance. Registration number at www.clinicalTrials.gov: NCT03956576. Funded by Kidney Research UK.

12518 Development Of A Four-compartment, Dynamic (In Vivo) Model For Insulin Disposition In Healthy Humans: Use Of Fick’s Law To Model Plasma-interstitial Insulin Flux

Abstract Disclosure: R.I. Dorin: None. C.R. Qualls: None. Introduction: Metabolic elimination of insulin (I) in vivo includes pathways mediated by high-affinity and potentially saturable insulin receptor binding; endogenous insulin secreted into the portal vein is subject to first pass elimination. The rate of insulin flux between vascular (Vp) and interstitial (Vi) compartments is often modeled by first order rate constants; here we analyzed an alternative approach using Fick’s law. Methods: The four-compartment, insulin (I) model is expressed by four differential equations that represent I flow (mass/time) in 4 volumes (V) (or compartments) having 3 corresponding elimination rate functions (α): (i) vascular plasma (Vp), (ii) interstitial (Vi, αi), (iii) hepatic (Vh, αh), and (iv) kidney (Vk, αk). Fick’s law was used to model diffusion of insulin between Vp and Vi; Michaelis-Menten like functions were used for saturable elimination functions (αh and αi); rates of hepatic (HPF) and renal (KPF) plasma flow were from literature. Realistic bounds for solved parameters (insulin permeability constant [k, L/min] and αi [min-[1]]) were developed by test bed analysis of published plasma (Ip) and interstitial (Ii) insulin concentration data. The inverse problem (estimating parameters) used Ip data from insulin-modified, frequently sampled iv glucose tolerance (IM-FSIVGT) studies performed in 40 healthy, non-diabetic women (1). Parameter solutions for individual subjects were obtained by iterative least squares method minimizing differences between model-predicted and measured Ip. Results: For infusion of exogenous I (ZI) at a constant rate (e.g., insulin clamp), reported steady state Ii/Ip data suggest that interstitial insulin elimination (αi) is conditionally saturable. Together with non-steady state data for Ip and Ii, initial estimates of k and αi were obtained. Steady state solutions give rise to four algebraic equations: (1) Ii/Ip = a, where a &amp;lt; 1 is consistent with experimental data, (2) Ih is a reduced version of a linear combination of Ip and endogenous insulin secretion (Zβ), where the factor of reduction (b) is &amp;lt;1, (3) Ik/Ip = d, where d&amp;lt;1, and (4) Ip is a linear combination of (i) ZI and (ii) the reduced (by factor b) Zβ. For Ip, this linear combination of ZI and reduced Zβ is also normalized by factor c (weighted sum of k, HPF, and KPF). Conclusions: (i) The proposed insulin flow model using Fick’s law was advantageous in providing realistic parameters and solutions that are tractable to physiologic interpretation, (ii) a simplified version of this model is generalizable to C-peptide, and (iii) since measurement of Ii is impractical in the clinical setting, the proposed prediction model may provide useful modeling adjunct to personalize pharmacokinetic and pharmacodynamic strategies for insulin administered by subcutaneous, iv, and hybrid closed-loop insulin pump routes. 1. Gower et al. Nutrition &amp; Metabolism (2016) 13:2 Presentation: 6/1/2024

8483 Changes in kidney hemodynamics during gender-affirming hormone therapy in transgender individuals - findings from the KNIGHT pilot study

Abstract Disclosure: S.A. van Eeghen: None. C. Wiepjes: None. L.L. Pyle: None. M. den Heijer: Research Investigator; Self; Kyowa Kirin. Other; Self; Novartis Pharmaceuticals. P. Bjornstad: Advisory Board Member; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Novo Nordisk, XORTX. Consulting Fee; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly &amp; Company, LG Chemistry, Horizon Pharma, Novo Nordisk, Sanofi. Research Investigator; Self; AstraZeneca, Merck, Horizon Pharma. Other; Self; Bayer, Inc. D. van Raalte: Consulting Fee; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Eli Lilly &amp; Company, Merck, Sanofi, MSD. Research Investigator; Self; AstraZeneca, Boehringer Ingelheim, Eli Lilly &amp; Company, Merck, Sanofi, MSD. N.J. Nokoff: Consulting Fee; Self; Neurocrine Biosciences, Inc, Ionis Pharmaceuticals Inc.. Research Investigator; Self; Neurocrine Biosciences, Inc. Other; Self; World Athletics. Background: Studies in transgender individuals have shown that gender-affirming hormone therapy (GAHT) impacts estimated glomerular filtration rate (eGFR). Masculinizing hormone therapy decreases, while feminizing hormone therapy increases eGFR, based on changes in serum creatinine and cystatin C. These substantial changes suggest an effect of sex hormones on kidney hemodynamics. To investigate this, we studied kidney hemodynamic changes before and after 3 months of gender-affirming hormone therapy (GAHT) in transgender individuals. Methods: This prospective observational pilot study assessed kidney hemodynamics in 23 transgender individuals assigned male at birth receiving feminizing hormone therapy and 21 transgender individuals assigned female at birth receiving masculinizing hormone therapy. Feminizing therapy included transdermal (n=16), sublingual (n=5), or oral estradiol (n=2), in combination with an anti-androgen (n=22); intramuscular triptorelin (n=16), spironolactone (n=5) or finasteride (n=1). Masculinizing therapy involved transdermal (n=17) or injected testosterone (n=4). Measures included glomerular filtration rate (GFR; Iohexol clearance), effective renal plasma flow (ERPF; p-aminohippurate clearance), and renal vascular resistance (RVR; mean arterial pressure/renal blood flow). Glomerular hydraulic pressure (PGLO), and afferent/efferent vascular resistance (RA/RE) were estimated by Gomez equations. Linear mixed models compared baseline and three-month measurements. Results: Individuals undergoing feminizing hormone therapy [median age 21 (IQR 19-29) years, BMI median 22.9 (IQR 18.9-30.7) kg/m²] had increased GFR by 2.8 mL/min per 1.73m² (95% CI, 0.01 to 5.6) and a nonsignificant increase in ERPF (+42 mL/min per 1.73m²; 95% CI, -5 to 90). RVR and RA significantly decreased [RVR: -0.007 mmHg/L/min (95% CI, -0.015 to -0.0003), RA: -294 dyn/s per cm5 (5% CI, -568 to -21)], indicating afferent vasodilation. In contrast, individuals receiving masculinizing therapy (median age median 20 (IQR 18-23) years, BMI median 24.2 (IQR 21.1-27.3) kg/m²) showed a slight, nonsignificant decrease in GFR (-2.1 mL/min per 1.73m²; 95% CI, -4.9 to 0.8), with no changes in other kidney hemodynamic parameters. Conclusions: In this cohort of transgender individuals, GFR increased during feminizing hormone therapy, likely due to afferent vasodilatation, while during masculinizing hormone therapy GFR tended to decrease. These findings suggest an influence of sex hormones on kidney hemodynamics, especially during feminizing hormone therapy. Presentation: 6/3/2024

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.

Randomized, placebo-controlled trial on the renal and systemic hemodynamic effects of empagliflozin

IntroductionSodium-glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcomes in type 2 diabetes (DM2) and chronic kidney disease (CKD). A decrease in renal blood flow (RBF) with attenuation of glomerular hyperfiltration may contribute. We examined renal and systemic hemodynamic effects of SGLT2i in relevant patient categories. MethodsUsing a double-blind placebo controlled cross-over design we randomized patients with DM2 and estimated glomerular filtration rate (eGFR) >60 ml/min/1.73m2 (n=16), patients with DM2 and eGFR 20-60 ml/min/1.73m2 (n=17) and patients with non-diabetic CKD and eGFR 20-60 ml/min/1.73m2 (n=16) to empagliflozin 10 mg daily or placebo for four weeks and crossed over to the opposite treatment after two-week washout. RBF was measured with 82Rubidium-positron emission-tomography/computed-tomography, GFR with 99mTechnetium-diethylene-triamine-pentaacetate-clearance. 24-hour blood pressure (BP) and total vascular resistance (TVR) were recorded using a Mobil-O-graph. ResultsCompared to placebo empagliflozin reduced RBF by 6% in the DM2-CKD group (p<0.001) with non-significant decreases of 4% in the DM2 group and 1% in the CKD group (p=0.29 and 0.72). Empagliflozin reduced GFR, BP and TVR in all groups, while renal vascular resistance (RVR) remained unchanged ConclusionEmpagliflozin reduced RBF in patients with DM2 and CKD, whereas GFR, BP and TVR were reduced in all groups. This pattern, together with a lack of reduction in RVR, suggests SGLT2i protect the glomerulus through combined pre-glomerular and post-glomerular effects.

Renal Artery Blood Flow and Surface Parenchymal Perfusion During Renal Artery Endoshunting in a Porcine Model

ObjectiveIschaemia and reperfusion can result in permanent tissue damage. During complex open abdominal aortic surgery, transient clamping of renovisceral arteries may be required to successfully complete the vascular repair. Endovascular shunting (endoshunting) presents an alternative technique for managing such temporary renovisceral ischaemia. This study aimed to investigate the performance of endoshunting to the renal circulation in a porcine model. MethodsThis study of five domestic pigs investigated arterial volume flow rates during endoshunting of a single renal artery and the associated impact on renal perfusion parameters (laser Doppler renal parenchymal perfusion, renal oxygen extraction, and selective urinary output). The study was performed in three steps: baseline registrations (30 minutes), endoshunting (120 minutes), and restitution (60 minutes). The right kidney was used as the experimental side and the left kidney as control. ResultsThe median arterial flow rate in the left control kidney remained constant throughout the experiment. On the right (endoshunted) side, the baseline median arterial flow rate was 267 (range, 160 – 404) mL/min. Following activation of the endoshunt, the median arterial volume flow dropped by 59% to 110 (range, 45 – 150) mL/min (p = .018). During endoshunting, the median kidney surface perfusion decreased to 42% of the baseline value. On the control side, a rise in the median parenchymal perfusion was observed after endoshunt activation, which was again normalised following restitution of native right renal artery flow. During endoshunting, the median regional urine production was 0.32 (range, 0.12 – 0.50) mL/hour but resumed after renal artery flow restitution. ConclusionOn average, the endoshunted kidneys showed a rapid restoration of blood flow, parenchymal perfusion, and urine production after 120 minutes of endoshunting. This suggests that endoshunting to the kidney using an endoshunt system might be a promising strategy to preserve renal function when a temporary interruption of native renal artery blood flow is needed during complex vascular surgical repairs involving the renal arteries.

Pegloticase-Induced Rapid Uric Acid Lowering and Kidney and Cardiac Health Markers in Youth-Onset Type 2 Diabetes: A Pilot Clinical Trial

Rationale & ObjectiveElevated serum uric acid (SUA) is a risk factor for incident hypertension and diabetic kidney disease in young persons with type 2 diabetes (T2D), particularly men. The acute benefit of aggressively lowering SUA on kidney and cardiovascular function in this population remains underexplored. This study was conducted to investigate the impact of a single pegloticase infusion on kidney and cardiovascular function. Study DesignAn open-label pilot trial. Setting & ParticipantsThe study involved 10 young adult males with youth-onset T2D and SUA levels ≥5 mg/dL. Intervention(s)Participants received a single infusion of pegloticase (8 mg). Evaluations were conducted using iohexol-based measured glomerular filtration rate (mGFR) and cardiac/kidney MRI before and one week after infusion. OutcomesThe primary outcomes were changes in SUA and mGFR one week after pegloticase infusion. ResultsNine participants (mean [±SD] age 22±5 years, HbA1c 8.6±3.3%, BMI 40.1±11.0 kg/m2, SUA 6.7±1.1 mg/dL) completed the pegloticase infusion and were included in the analysis. One week after the infusion, median [p25,p75] SUA concentrations dropped from 6.4 [5.6,7.6] to 0.5 [0.5,4.6] mg/dL (p=0.01). Mean mGFR increased from 113±20 to 122±19 ml/min per 1.73 m2 (p=0.004). Among responders (SUA reduction ≥3 mg/dL), an increase in mGFR correlated with an increase in renal artery blood flow (r:0.60, p=0.24) and decrease in SUA (r:-0.79, p=0.05). Mean MRI peak longitudinal cardiac strain additionally decreased from 15.4±2.2 to 13.1±2.2 % (p=0.03) in these responders. LimitationsThe pilot nature of the study and the small sample size limit the generalizability of the findings. ConclusionsIn young adult males with T2D, a single pegloticase infusion decreased SUA levels, which increased mGFR and was strongly associated with increased renal blood flow and impaired cardiac global longitudinal strain. Further research is required to assess the long-term efficacy and safety of pegloticase in patients with T2D.

Renal Blood Flow during Adenosine-Stress by Magnetic Resonance Imaging in a Large Cohort of Patients with Type 2 Diabetes

Renal Blood Flow during Adenosine-Stress by Magnetic Resonance Imaging in a Large Cohort of Patients with Type 2 Diabetes

Perirenal fat and chronic kidney disease in type 2 diabetes: The mediation role of afferent arteriolar resistance

AimPerirenal fat (PRF) is an independent predictor for chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) patients. Previous studies speculated that PRF may promote renal dysfunction through affecting renal hemodynamics. To verify this hypothesis, we studied the relationship between PRF and renal hemodynamics in T2DM. Methods91 T2DM patients were included. PRF thickness (PRFT) was measured by magnetic resonance imaging. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by renal dynamic imaging. Renal vascular resistance (RVR), glomerular hydrostatic pressure (PGLO), afferent (RA) and efferent (RE) arteriolar resistance were calculated by Gomez equations. Multiple linear regression was used to determine the relationship between PRFT and renal hemodynamics. Mediation analysis was conducted to estimate the mediation effects of renal hemodynamics on the relationship between PRF and CKD. ResultsAll patients were divided into three groups according to the tertiles of PRFT. Compared with patients in tertile 1, GFR and ERPF were significantly decreased in patients in tertile 3, while RVR and RA were significantly increased. PRFT was negatively correlated with GFR, ERPF and PGLO, and positively correlated with RVR and RA after adjustment for sex, age, visceral adipose tissue and treatments with ACE inhibitors/angiotensin receptor blockers and sodium-glucose cotransporter protein-2 inhibitors. Moreover, RVR and RA mediated the effect of PRF on GFR, with a mediated proportion of 29.1 % and 41.4 % respectively. ConclusionIn T2DM patients, PRF was negatively correlated with GFR, and positively correlated with RA. RA mediated the relationship between PRF and CKD.

Comparative Effects of Fedratinib and Upadacitinib on Renal Ischemia-Reperfusion Injury in Rat Models

Renal ischemia-reperfusion injury (RIRI) is a severe condition that frequently occurs following kidney transplantation or surgical procedures affecting renal blood flow. Inflammatory responses, oxidative stress, and apoptotic pathways significantly contribute to RIRI. This study aimed to compare the renoprotective effects of Fedratinib, a JAK2 inhibitor, and Upadacitinib, a JAK1 inhibitor, in rat models of RIRI. Both inhibitors were administered one hour prior to ischemia induction, and the effects on renal function, inflammation, and cell death pathways were assessed. The findings revealed that both Fedratinib and Upadacitinib significantly reduced serum creatinine and urea levels, inflammatory cytokines (TNF-α, IL-6), and markers of apoptosis (BCL2/BAX) by suppressing the JAK/STAT signaling pathways. Histopathological analysis showed substantial reduction in renal tissue damage in the treated groups compared to controls. The study concludes that JAK inhibition by either drug provides significant renoprotection in RIRI, though with some differences in the degree of pathway inhibition and clinical implications.

Prostaglandin E2 signaling through prostaglandin E receptor subtype 2 and Nurr1 induces fibroblast growth factor 23 production

Bone cells produce fibroblast growth factor 23 (FGF23), a hormone regulating renal phosphate and vitamin D homeostasis, and a paracrine factor produced in further tissues. Chronic kidney disease and cardiovascular disorders are associated with early elevations of plasma FGF23 levels associated with clinical outcomes. FGF23 production is dependent on many conditions including inflammation. Prostaglandin E2 (PGE2) is a major eicosanoid with a broad role in pain, inflammation, and fever. Moreover, it regulates renal blood flow, renin secretion, natriuresis as well as bone formation through prostaglandin E receptor 2 (EP2). Here, we studied the role of PGE2 and its signaling for the production of FGF23. Osteoblast-like UMR-106 cells were exposed to EP receptor agonists, antagonists or RNAi. Wild type and EP2 knockout mice were treated with stable EP2 agonist misoprostol. Fgf23 or Nurr1 gene expression was determined by quantitative real-time PCR, hormone and further blood parameters by enzyme-linked immunosorbent assay and colorimetric methods. PGE2 and EP2 agonists misoprostol and butaprost enhanced FGF23 production in UMR-106 cells, effects mediated by EP2 and transcription factor Nurr1. A single dose of misoprostol up-regulated bone Fgf23 expression and FGF23 serum levels in wild type mice with subtle effects on parameters of mineral metabolism only. Compared to wild type mice, the FGF23 effect of misoprostol was significantly lower in EP2-deficient mice. To conclude, PGE2 signaling through EP2 and Nurr1 induces FGF23 production. Given the broad physiological and pathophysiological implications of PGE2 signaling, this effect is likely of clinical relevance.