Resistive Index Research Articles

Toll-like receptor 4 mutation mitigates gut microbiota-mediated hypertensive kidney injury

Hypertension-associated dysbiosis is linked to several clinical complications, including inflammation and possible kidney dysfunction. Inflammation and TLR4 activation during hypertension result from gut dysbiosis-related impairment of intestinal integrity. However, the contribution of TLR4 in kidney dysfunction during hypertension-induced gut dysbiosis is unclear. We designed this study to address this knowledge gap by utilizing TLR4 normal (TLR4N) and TLR4 mutant (TLR4M) mice. These mice were infused with high doses of Angiotensin-II for four weeks to induce hypertension. Results suggest that Ang-II significantly increased renal arterial resistive index (RI), decreased renal vascularity, and renal function (GFR) in TLR4N mice compared to TLR4M. 16 S rRNA sequencing analysis of gut microbiome revealed that Ang-II-induced hypertension resulted in alteration of Firmicutes: Bacteroidetes ratio in the gut of both TLR4N and TLR4M mice; however, it was not comparably rather differentially. Additionally, Ang-II-hypertension decreased the expression of tight junction proteins and increased gut permeability, which were more prominent in TLR4N mice than in TLR4M mice. Concomitant with gut hyperpermeability, an increased bacterial component translocation to the kidney was observed in TLR4N mice treated with Ang-II compared to TLR4N plus saline. Interestingly, microbiota translocation was mitigated in Ang-II-hypertensive TLR4M mice. Furthermore, Ang-II altered the expression of inflammatory (IL-1β, IL-6) and anti-inflammatory IL-10) markers, and extracellular matrix proteins, including MMP-2, −9, −14, and TIMP-2 in the kidney of TLR4N mice, which were blunted in TLR4M mice. Our data demonstrate that ablation of TLR4 attenuates hypertension-induced gut dysbiosis resulting in preventing gut hyperpermeability, bacterial translocation, mitigation of renal inflammation and alleviation of kidney dysfunction.

Evaluation of infrared thermography, arterial Doppler ultrasound, and Doppler echocardiography in healthy adult dogs exposed to a single session of Whole-body vibration at different frequencies

This study aimed to evaluate the infrared thermography, arterial Doppler ultrasound, and Doppler echocardiography in healthy adult dogs exposed to a single Whole-body vibration (WBV) at different frequencies. Sixteen (16) healthy crossbreed dogs males of ages 1 to 5 years, weighing 16.3 to 24.5 kg were enrolled in the study. The dogs were exposed to a single WBV session at frequencies of 30 Hz (5 min), 40 Hz (5 min), and 50 Hz (5 min) with intervals between each frequency exposure of 10 min. The cutaneous temperature, arterial Doppler ultrasound, and Doppler echocardiography were evaluated 10 min before the WBV session, between each frequency, and 1 min after the last frequency. The cutaneous temperature of the regions of the superficial gluteal muscle and biceps femoris muscle of both hind limbs was obtained with an infrared camera. Resistive indexes of carotid and femoral arteries were determined using Doppler ultrasound, and Doppler echocardiography was used to assess the end-systolic volume and end-diastolic volume, heart rate, aortic blood flow velocity, and pulmonary artery flow velocity. Clinical parameters, complete blood count, and serum biochemical (alanine aminotransferase, creatinine, and creatine phosphokinase) were evaluated 10 min before and 60 min after the end of the WBV session. Statistically significant differences were not found in any of the variables among the time points. In conclusion, the protocol of increasing vibration frequencies (30, 40, and 50 Hz) at short-period WBV can be considered appropriate since no change occurred in the parameters evaluated.

An In Silico Modelling Approach to Predict Hemodynamic Outcomes in Diabetic and Hypertensive Kidney Disease

Early diagnosis of kidney disease remains an unmet clinical challenge, preventing timely and effective intervention. Diabetes and hypertension are two main causes of kidney disease, can often appear together, and can only be distinguished by invasive biopsy. In this study, we developed a modelling approach to simulate blood velocity, volumetric flow rate, and pressure wave propagation in arterial networks of ageing, diabetic, and hypertensive virtual populations. The model was validated by comparing our predictions for pressure, volumetric flow rate and waveform-derived indexes with in vivo data on ageing populations from the literature. The model simulated the effects of kidney disease, and was calibrated to align quantitatively with in vivo data on diabetic and hypertensive nephropathy from the literature. Our study identified some potential biomarkers extracted from renal blood flow rate and flow pulsatility. For typical patient age groups, resistive index values were 0.69 (SD 0.05) and 0.74 (SD 0.02) in the early and severe stages of diabetic nephropathy, respectively. Similar trends were observed in the same stages of hypertensive nephropathy, with a range from 0.65 (SD 0.07) to 0.73 (SD 0.05), respectively. Mean renal blood flow rate through a single diseased kidney ranged from 329 (SD 40, early) to 317 (SD 38, severe) ml/min in diabetic nephropathy and 443 (SD 54, early) to 388 (SD 47, severe) ml/min in hypertensive nephropathy, showing potential as a biomarker for early diagnosis of kidney disease. This modelling approach demonstrated its potential application in informing biomarker identification and facilitating the setup of clinical trials.

Role of Uterine Artery Doppler Study Between 11 and 14 Weeks as a Predictor of Preeclampsia.

Introduction Preeclampsia is a serious complication marked by antepartum hemorrhage, resulting in severe maternal and fetal complications. Predicting this condition using placental dysfunction assessments, such as uterine artery Doppler ultrasound, is challenging due to the placenta's evolving structural and biochemical characteristics throughout different stages of pregnancy. Objectives To determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the uterine artery Doppler Pulsatility Index (PI) and Resistive Index (RI) in predicting preeclampsia. To compare the Doppler ultrasound measurements between normal pregnancies and those that develop preeclampsia. To assess the diagnostic accuracy of uterine artery Doppler ultrasound in predicting gestational hypertension in addition to preeclampsia. Methodology Conducted as a prospective study, 116 antenatal mothers with computed gestational ages and scan gestational ages between 11 and 14 weeks, and a previous history of preeclampsia were included. Subjects with chronic hypertension or multiple gestations were excluded. Participants underwent uterine artery Doppler screening, during which the PI and RI were measured upon obtaining three consecutive similar waveforms, and the mean PI of the left and right arteries was calculated. The outcomes of patients with normal pregnancies and those who developed preeclampsia were compared. Data were entered into Microsoft Excel (Microsoft® Corp., Redmond, WA, USA) and analyzed using IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, NY, USA). Results The mean PI among participants was 1.75 (±0.38), with a range from 1 to 2.75. The mean RI was 0.58 (±0.08), ranging from 0.45 to 0.8. The cutoff for the mean PI in predicting preeclampsia was 2.27, which showed a sensitivity of 92.9%, specificity of 97.1%, PPV of 81.47%, NPV of 99.01%, and a diagnostic accuracy of 96.59% (area under the curve (AUC): 0.982). The cutoff for the mean RI for predicting preeclampsia was 0.695, with a sensitivity of 85.7%, specificity of 98%, PPV of 85.47%, NPV of 98.04%, and diagnostic accuracy of 96.52% (AUC: 0.965). In predicting gestational hypertension, the cutoff for the mean PI was 1.975, with a sensitivity of 80%, specificity of 82.9%, PPV of 17.41%, NPV of 98.92%, and diagnostic accuracy of 82.78% (AUC: 0.848). The cutoff for the mean RI in predicting gestational hypertension was 0.615, showing a sensitivity of 80%, specificity of 80.2%, PPV of 15.4%, NPV of 98.89%, and diagnostic accuracy of 80.19% (AUC: 0.767). Conclusion The research demonstrated that aberrant readings in uterine Doppler ultrasound, specifically in the PI and RI, possess strong overall validity in forecasting the occurrence of preeclampsia.

Evaluation of renal resistive index and new biomarkers in post-hepatitis C cirrhosis patients for developing kidney injury

Background In liver cirrhosis, hemodynamic changes in splanchnic and systemic circulations are involved. Indeed, no established laboratory markers for altered renal hemodynamics in cirrhosis were implicated. The duplex Doppler waveform analysis of intrarenal arteriolar vessels is considered a noninvasive estimate of renovascular impedance and renal arterial vasoconstriction. In particular, the renal resistive index (RRI) is considered as the best reliable indicator of renal blood flow in patients with different diseases. The study aimed to evaluate RRI, serum and urinary cystatin C, beta-trace protein, liver fatty acid protein, and kidney injury molecule-I as noninvasive indicators of altered renal hemodynamics in patients with cirrhosis with normal urea and creatinine. Patients and methods A case–control study included 60 patients with post-hepatitis C virus (HCV) cirrhosis and 40 healthy controls. Serum and urinary biomarkers were measured. Renal color Doppler duplex was used to evaluate RRI. Results Mean serum and urinary biomarkers in HCV patients were significantly higher than controls. Moreover, the RRI was higher in patients than in controls with P value less than 0.001. Rising levels of urea, high direct bilirubin, and hypoprothrombinemia with high serum kidney injury molecule 1 and RRI were significant independent predictors for subsequent kidney injury. Conclusion Urinary kidney injury molecule 1 is a reliable, sensitive, and specific biomarker for the prediction of kidney injury among HCV cirrhotic patients with an obvious superior test performance and specificity to e other biomarkers. An increase in serum kidney injury molecule 1 and RRI were associated with poor prognosis.

Renal Resistive Index and Estimated Glomerular Filtration Rate in Nondiabetic Chronic Kidney Disease Stage 3: A Cross-Sectional Analytical Study

Renal Resistive Index and Estimated Glomerular Filtration Rate in Nondiabetic Chronic Kidney Disease Stage 3: A Cross-Sectional Analytical Study

Impact of Norepinephrine and Dopamine Infusion on Renal Arterial Resistive Index during Pre-Emptive Living Donor Kidney Transplantation: Propensity Score Matching Analysis.

Background: Living donor kidney transplantation (LDKT) is a crucial treatment for end-stage renal disease, with pre-emptive LDKT (transplantation before dialysis initiation) offering significant benefits in graft function and patient survival. The selection of a vasopressor during LDKT, particularly between norepinephrine and dopamine, and its impact on renal arterial hemodynamics measured using the renal arterial resistive index (RARI) is poorly understood. Methods: This retrospective observational cohort study enrolled 347 eligible pre-emptive LDKT recipients from the Seoul St. Mary's Hospital between January 2019 and June 2023. Utilizing propensity score matching (PSM), the patients were categorized into dopamine and norepinephrine groups to compare the effects of these vasopressors on the intraoperative RARI, postoperative estimated glomerular filtration rate (eGFR), and hourly urine output. The RARI was measured via the Doppler ultrasonography of the renal hilum and parenchyma post-graft vascular and ureteral anastomoses. Results: The preoperative differences in the recipients' and donors' characteristics were mitigated following PSM. The dopamine group exhibited higher intraoperative RARI values at the renal hilum (0.77 ± 0.11 vs. 0.66 ± 0.13, p < 0.001) and parenchyma (0.71 ± 0.1 vs. 0.6 ± 0.1, p < 0.001) compared to those of the norepinephrine group. However, these differences were not statistically significant on postoperative day 7. The norepinephrine infusion adjusted for the propensity scores was associated with significantly lower odds of an RARI > 0.8 (hilum: OR = 0.214, 95% CI = 0.12-0.382, p < 0.001; parenchyma: OR = 0.1, 95% CI = 0.029-0.348, p < 0.001). The early postoperative outcomes showed a higher eGFR (day 1: 30.0 ± 13.3 vs. 25.1 ± 17.4 mL/min/1.73 m2, p = 0.004) and hourly urine output (day 1: 41.8 ± 16.9 vs. 36.5 ± 14.4 mL/kg/h, p = 0.002) in the norepinephrine group. Furthermore, the long-term outcomes were comparable between the groups. Conclusions: Norepinephrine infusion during pre-emptive LDKT is associated with more favorable intraoperative renal arterial hemodynamics, as evidenced by a lower RARI and improved early postoperative renal function compared to those of dopamine. These findings suggest a potential preferential role for norepinephrine in optimizing perioperative management and early graft functions in LDKT recipients. Given the retrospective nature of this study, further prospective studies are needed to confirm these observations. Additionally, the study limitations include the potential for unmeasured confounding factors and the inability to determine causality due to its observational design.

Renal resistive index measurements by ultrasound in patients with liver cirrhosis: Magnitude and associations with renal dysfunction

BACKGROUND The hemodynamic alterations seen in liver cirrhosis lead to renal vasoconstriction, ultimately causing acute kidney injury (AKI). The renal resistive index (RRI) is the most common Doppler ultrasound variable for measuring intrarenal vascular resistance. AIM To evaluate the association of the RRI with AKI in patients with liver cirrhosis and to identify risk factors for high RRI. METHODS This was a prospective observational study, where RRI was measured using Doppler ultrasound in 200 consecutive hospitalized patients with cirrhosis. The association of RRI with AKI was studied. The receiver operating characteristic (ROC) curve analysis was utilized to determine discriminatory cut-offs of RRI for various AKI phenotypes. Multivariate analysis was conducted to determine the predictors of high RRI. RESULTS The mean patient age was 49.08 ± 11.68 years, with the majority (79.5%) being male; the predominant etiology of cirrhosis was alcohol (39%). The mean RRI for the study cohort was 0.68 ± 0.09, showing a progressive increase with higher Child-Pugh class of cirrhosis. Overall, AKI was present in 129 (64.5%) patients. The mean RRI was significantly higher in patients with AKI compared to those without it (0.72 ± 0.06 vs 0.60 ± 0.08; P &lt; 0.001). A total of 82 patients (41%) had hepatorenal syndrome (HRS)-AKI, 29 (22.4%) had prerenal AKI (PRA), and 18 (13.9%) had acute tubular necrosis (ATN)-AKI. The mean RRI was significantly higher in the ATN-AKI (0.80 ± 0.02) and HRS-AKI (0.73 ± 0.03) groups than in the PRA (0.63 ± 0.07) and non-AKI (0.60 ± 0.07) groups. RRI demonstrated excellent discriminatory ability in distinguishing ATN-AKI from non-ATN-AKI (area under ROC curve: 93.9%). AKI emerged as an independent predictor of high RRI (adjusted odds ratio [OR]: 11.52), and high RRI independently predicted mortality among AKI patients (adjusted OR: 3.18). CONCLUSION In cirrhosis patients, RRI exhibited a significant association with AKI, effectively differentiated between AKI phenotypes, and predicted AKI mortality.

Relation between interleukin-13 and annexin-V levels and carotid intima-media thickness in nephrotic syndrome.

The aim of the current study is to assess the relation between carotid intima-media thickness (CIMT) measurements, renal Doppler resistive index (RI) and serum levels of interleukin-13 (IL-13) and annexin-V (An-V) in children with idiopathic nephrotic syndrome (INS). The present case-control study was conducted on 60 children with INS and 60 age- and sex-matched healthy children. All participants were subjected to evaluation of serum levels of IL-13 and An-V and ultrasound Doppler measurement of CIMT and renal RI. Patients expressed significantly higher An-V (5.9 ± 2.6 vs. 2.1 ± 0.8 ng/mL, p<0.001) and IL-13 (19.2 ± 7.6 vs. 3.4 ± 1.4 ng/L) levels when compared with healthy counterparts. Moreover, it was shown that patients had significantly higher CIMT (0.49 ± 0.06 vs. 0.35 ± 0.03, p<0.001) as compared to controls. No significant differences were noted between the studied groups regarding right or left RIs. Correlation analysis identified significant direct correlation between serum An-V levels and albumin/creatinine ratio (ACR) (r = 0.55), cholesterol (r = 0.48), triglycerides (r = 0.36), IL-13 (r = 0.92) and CIMT (r = 0.53). Similar correlations could be found between serum IL-13 levels and CIMT measurements and the corresponding parameters. The present study suggests an association between higher early atherosclerosis expressed as elevated CIMT measurements in children with INS and elevated serum levels of An-V and IL-13.

Doppler-Derived Renal Functional Reserve in the Prediction of Postoperative Acute Kidney Injury in Patients Undergoing Robotic Surgery.

Postoperative acute kidney injury (PO-AKI) is a frequent complication after surgery. Various tools have been proposed to identify patients at high risk for AKI, including preoperative serum creatinine or estimated glomerular filtration rate (eGFR), urinary cell cycle arrest, and tubular damage biomarkers; however, none of these can appropriately assess AKI risk before surgery. Renal functional reserve (RFR) screened by the Doppler-derived intraparenchymal renal resistive index variation (IRRIV) test has been proposed to identify patients at risk for AKI before a kidney insult. IRRIV test has been developed in healthy individuals and previously investigated in cardiac surgery patients. This study aims to evaluate the value of the IRRIV test in identifying PO-AKI among patients undergoing robotic abdominal surgery in the Trendelenburg position for pelvic oncological disease. We performed a prospective, double-blinded, observational study. Preoperative baseline renal function and RFR were assessed in 53 patients with baseline eGFR >60 mL/min/1.73 m2, undergoing robotic surgery in the Trendelenburg position for pelvic oncological disease. The capability of Doppler-derived RFR in predicting PO-AKI was investigated with the area under the receiver operating characteristic curve (ROC-AUC). Approximately 15.1% of patients developed AKI within the first 3 postoperative days. Thirty-one (58.5%) patients had a physiologic delta-RRI (ie, ≥0.05), while 22 (41.5%) patients did not. The ROC-AUC for PO-AKI was 0.85 (95% confidence interval [CI], 0.74-0.97; P = .007) for serum creatinine, 0.84 (95% CI, 0.71-0.96; P = .006) for eGFR, and 0.84 (95% CI, 0.78-0.91; P = .017) for delta-RRI. When combined with eGFR, the ROC-AUC for delta-RRI was 0.95 (95% CI, 0.9-1). Our findings show that the preoperative assessment of Doppler-derived RFR combined with baseline renal function improves the capability of identifying patients at high risk for PO-AKI with eGFR >60 mL/min/1.73 m2 after robotic abdominal surgery in Trendelenburg position for pelvic oncological disease.

Doppler ultrasound compared to shear wave elastography for assessment of liver cirrhosis

BackgroundThe progression of liver fibrosis to cirrhosis is a dynamic process necessitating non-invasive evaluation modalities. This study aims to evaluate the ability of Doppler ultrasound studies (DUS) in defining morphological and hemodynamic blood flow changes in the hepatic vasculature coinciding with advanced liver fibrosis.MethodsA prospective study was conducted on 100 patients with liver cirrhosis (F4). All cases underwent liver stiffness (LS) measurement by shear wave elastography (SWE), along with DUS to evaluate the liver texture, splenic size, hepatic artery resistive index (HARI), portal and splenic vein diameters, portal vein velocity (PVV), and hepatic vein waveform (HVV). All measures were assessed concurrently with a highly qualified single operator.ResultsPatients aged 55.5 ± 10.2 years with male predominance (72%). A highly significant correlation was found between LS by SWE and hepatic parenchymal texture, splenic size, portal vein width, and HVV (monophasic and biphasic) (p < 0.001). There were also high significant positive correlations (p < 0.001) between LS and PVV. However, there was no definitive correlation between LS and HARI, as well as splenic vein diameter.ConclusionThe widely available economic Doppler studies including portal vein velocity and hepatic vein waveform changes could be of substantial diagnostic value to liver cirrhosis.Study designProspective cohort study, employing descriptive and analytical statistics.

The effect of endoscopic renal and ureteral stone surgeries on renal blood flow in children: a prospective trial

Aim: To assess the impact of endoscopic stone surgeries on renal perfusion and blood flow in children. Materials and methods: Children who underwent percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), ureterorenoscopy (URS), endoscopic combined intrarenal surgery (ECIRS) were included to the study. Renal Doppler ultrasonography (RDUS) was performed one day before the operation, and on the postoperative 1st day and 1st month. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were measured, and resistive index (RI) was calculated with the (PSV-EDV)/PSV formula. RDUS parameters were compared before and after surgery and between ipsilateral and contralateral kidneys. Results: A total of 45 children with a median age was 8 (2–17) years were included (15 (33.3%) girls, 30 (66.7%) boys). PCNL was performed in 13 children (28.9%), RIRS 11 (24.4%), URS 12 (26.7%), and ECIRS 9 (20%). There was no significant difference in renal and segmental PSV, EDV and RI values of operated kidney in the preoperative, postoperative periods. There was no significant difference between RDUS parameters of the ipsilateral and contralateral kidneys in preoperative or postoperative periods. PSV and EDV values were significantly higher in the 1st postoperative month in the group without preoperative DJ stent than in the group with DJ stent (p = 0,031, p = 0,041, respectively). However, RI values were similar. The mean RI were below the threshold value of 0.7 in each period. Conclusion: RDUS parameters didn’t show a significant difference in children. Endoscopic surgeries can be safely performed in pediatric stone disease.

The resistive and pulsatility indices of the dorsal metatarsal artery for the screening of peripheral lower artery disease in patients with and without diabetes

BackgroundIn lower extremity peripheral artery disease (PAD), the ankle-brachial index (ABI) is an easily reproducible diagnostic tool for PAD, but it loses reliability when > 1.4 due to calcification of the vessel wall. Patients with diabetes are at higher risk for wall calcification. In order to overcome the limitation and reliability of ABI, particularly in patients with diabetes, we decided to assess resistive (RI) and pulsatility index (PI) by ultrasound doppler of the dorsal metatarsal artery (DMA). ResultsWe therefore analyzed 51 legs (32 patients), evaluating the correlation between PI, RI, and ABI. Patients with diabetes were 21 (65.6 %), accounting for 33 legs (64.7 %). Out of 51 legs assessed, 37 (72.5 %) cases had compressible arteries, whereas in 14 legs (27.5 %) ABI was not calculable due to wall calcification. PAD was significantly associated with lower both RI and PI of the DMA (both p < 0.000). RI, but not PI, showed a significant correlation (r = 0.535) with ABI, when ABI was less than 1.4, but not when ABI > 1.4. When analyzed separately, patients with diabetes showed a similar figure in comparison with those without diabetes (r = 0.600), RI, but not PI, showed a significant correlation with ABI. ConclusionDorsal metatarsal artery resistive index (MARI) showed a significant inverse correlation with PAD, similarly to ABI, irrespective of the presence of diabetes. MARI seems to be an effective screening tool for PAD even in patients with wall calcification. Further studies are needed for confirming the results of the present pilot study.

Early Morbidities of Hypoxia-Ischemic Encephalopathy in Term Neonates With a Resistive Index as a Prognostic Indicator.

Background Acidosis, hypoxemia, and hypercarbia are symptoms of a syndrome known as perinatal asphyxia that occurs during the first and second stages of labor and shortly after delivery due to poor gas exchange. The Doppler technique is a non-invasive way to assess the risk of neurodevelopment damage in hypoxic-ischemic encephalopathy (HIE) that may be done at the patient's bedside without disturbing them. The study aims to evaluate cranial ultrasound findings in HIEand investigate the role of resistive index (RI) values assessed by color Doppler transcranial ultrasonography in predicting early morbidities in neonates with HIE within 72 hours of life. Methodology Prospective observational research was carried out at the north Karnataka region's tertiary newborn critical care unit. The study included 54 infants with HIE in total. The male-to-female ratio was 1.7:1, with 34 (63%) male and 20 (37%) female newborns. Results About 32 instances had grade I HIE, 8 had grade II HIE, and 14 had grade III HIE. In 35 instances (64.81%), the RI was normal; in 19 cases (35.19%), it was abnormal. Increased periventricular density and cerebral parenchyma echo density were common Doppler ultrasonography findings. Roughly 93% of people survived, and 7% of people died from HIE. Seizures (12.96%) and acute renal damage (33.33%) were the most frequent consequences. Conclusion In instances of HIE, the RI was revealed to be a favorable predictive indicator for newborn prognosis. Counselingand educating parents about early morbidities, anticipated long-term consequences, and the need for follow-up will all benefit from it. Additionally, color Doppler is a practical and secure diagnostic method for determining a newborn's level of HIE.

The protective effect of bergamot polyphenolic fraction on reno-cardiac damage induced by DOCA-salt and unilateral renal artery ligation in rats

Abstract Funding Acknowledgements None. The complex pathological interactions between renal and cardiovascular systems represent a real global epidemic and renovascular hypertension remains among the most prevalent, but also potentially reversible, risk factor for numerous reno-cardiac diseases in humans and pets. Here, we investigated the anti-inflammatory and reno-cardiac protective effects of a polyphenol-rich fraction of citrus bergamot (BPF) in an experimental model of hypertension induced by unilateral renal artery ligation (RAL). Adult male Wistar rats underwent unilateral renal artery ligation and treatment with 20 mg/kg deoxycorticosterone acetate (DOCA), twice a week for a period of 4 weeks, and 1% sodium chloride water. A subgroup of hypertensive rats received 100 mg/kg/day of BPF for 28 days, by gavage. Another group of animals was treated with a sub-cutaneous injection of vehicle (CTRL). RAL DOCA-Salt rats showed a significant increase in mean arterial blood pressure (MAP; p&amp;lt;0.05 vs CTRL) which strongly increased the resistive index (RI; p&amp;lt;0.05 vs CTRL) of contralateral renal artery flow and kidney volume after 4 weeks (p&amp;lt;0.001 vs CTRL). Renal dysfunction also led to a dysfunction of cardiac tissue strain associated with overt dyssynchrony in cardiac wall motion, as shown by the increased time-to-peak (T2P; p&amp;lt;0.05) and the decreased whole peak capacity (Pk; p&amp;lt;0.01) in displacement and strain rate (p&amp;lt;0.05) in longitudinal motion. The hearts of RAL DOCA-Salt rats showed a larger time delay between the fastest and the lowest region (Maximum Opposite Wall Delay-MOWD) (p&amp;lt;0.05 in displacement and p&amp;lt;0.01 in strain rate vs CTRL). A significant increase in the levels of the circulating pro-inflammatory cytokines and chemokines (p&amp;lt;0.05 for IL-12(40), p&amp;lt;0.01 for GM-CSF, KC, IL-13, and TNF- α) and in the NGAL expression of the ligated kidney (p&amp;lt;0.001) was observed.This pathological condition was prevented by BPF treatment, by reducing the increase of blood pressure in RAL DOCA-Salt rats (p&amp;lt;0.05) and exerting a protective effect on the volume of the contralateral kidney (p&amp;lt;0.01). BPF ameliorates cardiac tissue strain dysfunction by increasing Pk in displacement (p&amp;lt;0.01) and reducing the T2P in strain rate motion (p&amp;lt;0.05). These effects significantly improve MOWD (p&amp;lt;0.05) preventing the overt dyssynchrony in cardiac wall motion. The reno-cardiac protective effect of BPF was associated with a significant reduction in serum level of the pro-inflammatory cytokines and chemokines (p&amp;lt;0.05 for KC and IL-12(40), p&amp;lt;0.01 for GM-CSF, IL-13, and TNF- α)restoring physiological levels of NGAL (p&amp;lt;0.05) protein of the tethered kidney. In conclusion, the present results show that BPF promotes an efficient renovascular protection preventing the progression of inflammation and reno-cardiac damage, suggesting the potential clinical and veterinary role of dietary supplementation with the polyphenol-rich fraction of citrus bergamot in counteracting hypertension-induced reno-cardiac syndrome.

Prophylactic Anticoagulation Reduces the Risk of Kidney Graft Venous Thrombosis in Recipients From Uncontrolled Donation After Circulatory Death Donors With High Renal Resistive Index.

Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplantation (KT) at the expense of a higher risk of primary graft nonfunction (PNF). At least half of the cases of PNF are secondary to graft venous thrombosis. The potential benefit from prophylactic anticoagulation in this scenario remains unclear. In this single-center retrospective study we compared 2 consecutive cohorts of KT from uDCD with increased (≥0.8) renal resistive index (RRI) in the Doppler ultrasound examination performed within the first 24-72 h after transplantation: 36 patients did not receive anticoagulation ("nonanticoagulation group") and 71 patients underwent prophylactic anticoagulation until normalization of RRI in follow-up Doppler examinations ("anticoagulation group"). Anticoagulation was initiated at a median of 2 d (interquartile range, 2-3) after transplantation and maintained for a median of 12 d (interquartile range, 7-18). In 4 patients (5.6%), anticoagulation had to be prematurely stopped because of the development of a hemorrhagic complication. In comparison with the nonanticoagulation group, recipients in the anticoagulation group had a lower 2-wk cumulative incidence of graft venous thrombosis (19.4% versus 0.0%; P < 0.001) and PNF (19.4% versus 2.8%; P = 0.006). The competing risk analysis with nonthrombotic causes of PNF as the competitive event confirmed the higher risk of graft thrombosis in the nonanticoagulation group (P = 0.0001). The anticoagulation group had a higher incidence of macroscopic hematuria (21.1% versus 5.6%; P = 0.049) and blood transfusion requirements (39.4% versus 19.4%; P = 0.050) compared with the nonanticoagulation group. No graft losses or deaths were attributable to complications potentially associated with anticoagulation. Early initiation of prophylactic anticoagulation in selected KT recipients from uDCD with an early Doppler ultrasound RRI of ≥0.8 within the first 24-72 h may reduce the incidence of graft venous thrombosis as a cause of PNF.

Renal Arterial and Venous Doppler in Cardiorenal Syndrome: Pathophysiological and Clinical Insights.

In recent decades, there has been considerable effort in investigating the clinical utility of renal Doppler measurements in both cardiovascular and renal disorders. In particular, a measure of renal arterial resistance, the renal resistive index (RRI), has been demonstrated to predict chronic kidney disease progression and acute kidney injury in different clinical settings. Furthermore, it is linked to a poorer prognosis in individuals suffering from chronic heart failure. Examining the renal venous flow through pulsed Doppler can offer additional insights into renal congestion and cardiovascular outcomes for these patients. This review seeks to summarize the existing data concerning the clinical significance of arterial and venous renal Doppler measurements across various cardiovascular and renal disease contexts.

#1273 Rapidly progressive glomerulonephritis with anti-neutrophil cytoplasmic antibodies, in a patient on golimumab

Abstract Background 73-year-old Chinese lady presented with fever, gross hematuria, and dysuria of 1-week duration. She has seronegative arthritis and was treated with human anti-tumor necrosis factor alpha monoclonal antibody (TNF-alpha inhibitor), golimumab injection 50 mg monthly, as she had previous adverse reaction with sulfasalazine and methotrexate. She suffered from severe osteoporosis and was treated with oral alendronic acid. At presentation, her blood pressure was 172/76 mmHg and pulse rate 100 beats per minute. The highest recorded temperature was 38.1 degrees Celsius. Clinical examination was unremarkable. She was diagnosed with rapidly progressive glomerulonephritis (RPGN). Creatinine at presentation was 252 µmol/L, estimated glomerular filtration rate (eGFR) 16 mL/min/1.73 m2. Two months ago, her creatinine was 68 µmol/L, eGFR 66 mL/min/1.73 m2. Urinalysis showed dysmorphic red blood cells of more than 2250 per high power field, few white blood cells, and no epithelial cells. Urine protein/creatine ratio (UPCR) was 2.3 g/g and serum albumin level was 30 g/L. ANA was borderline raised at 1:160 titer with homogeneous pattern. Anti-double stranded DNA (anti-dsDNA) was indeterminate at 29.34 IU. Anti-myeloperoxidase (MPO) antibody was positive at 162 RU/mL (Normal &amp;lt; 20 RU/mL). Anti-proteinase-3 (PR3) antibody was negative. Serum complement levels (C3 and C4) were normal. Screening for hepatitis B, hepatitis C, and HIV was negative. Ultrasound imaging of the kidneys showed raised renal echoes and resistive index. Percutaneous kidney biopsy was performed. On light microscopy, 19 glomeruli were seen. Some displayed segmental increase in mesangial cells and expansion of mesangial matrix. 4 glomeruli showed cellular crescents (Fig. 1). Immunofluorescence showed dominant 2+ staining for Immunoglobulin A (IgA) in the mesangium and electron microscopy revealed electron dense deposits in the mesangial and para-mesangial region. An occasional tubuloreticular structure was found. Diagnosis of IgA nephropathy was made and Oxford classification was M0 E1 S0 T0 C1. Results Our patient presented with rapidly progressive glomerulonephritis (RPGN) with positive MPO antibody, as well as ANA and anti-dsDNA at indeterminate levels. TNF-alpha inhibitors may lead to autoantibody formation and kidney biopsy was the key in clinching the diagnosis for our patient. Diagnosis of IgA nephropathy was made on the basis of dominant mesangial IgA on immunofluorescence and ultrastructural electron dense deposits within the mesangial and para-mesangial area. To our best knowledge, there has been only one case of IgA nephropathy reported with golimumab that occurred after 3 years and with mild albuminuria and no decline in renal function. Golimumab was promptly discontinued for our patient and she was inducted with pulsed methylprednisolone and high dose oral prednisolone 1 mg/kg/day. As she had history of severe osteoporosis, oral mycophenolate mofetil at 750 mg twice a day was commenced as steroid sparing agent. Prednisolone dose was then tapered to 0.5 mg/kg/day. She achieved full clinical remission after 3 months of immunosuppressive therapy. MPO antibody level decreased to normal after 5 months. Arthritis activity remained quiescent and she was maintained on low dose prednisolone. Conclusion We report a case of IgA nephropathy with crescents associated with golimumab. Treatment was successful with withdrawal of drug, oral prednisolone and mycophenolate mofetil.

#2421 Kidney injury in scleroderma: serum level of fibroblast growth factor-23, klotho and neutrophil gelatinase-associated lipocalin after iloprost infusion

Abstract Background and Aims Systemic sclerosis (SSc) is characterized by progressive derangement of the microcirculation leading to a state of chronic tissue hypoxia with release of several inflammatory cytokines such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho. Renal scleroderma associated-vasculopathy is characterized by vascular damage with normal renal function and increased intrarenal stiffness, assessed by renal resistive index (RRI) Aim of this study was to evaluate at baseline serum levels of FGF-23, Klotho and NGAL in SSc patients and healthy controls (HC) and to correlate the serum levels of these markers with microvascular damage of skin and kidney. Secondary aim was to evaluate the serum levels of FGF-23, Klotho and NGAL after Iloprost infusion. Method Twenty-one SSc patients and 20 HC were enrolled. All patients had a 2-months wash-out of Iloprost infusion before of clinical, laboratory and instrumental assessment. Peripheral venous blood was collected at three different time points for SSc patients: t0 immediately before the first Iloprost infusion (after 2-months wash-out period), t1 immediately after the first Iloprost infusion and t2 the day of the next Iloprost infusion (about 14 days from the last infusion). Results SSc patients had higher serum level of FGF-23 [18.7 pg/mL (± 6.4) vs 3.6 pg/mL (± 2.2), p &amp;lt; 0.001], Klotho [5.1 pg/mL (±0.8) vs 2.3 pg/mL (±0.6), p &amp;lt; 0.001] and NGAL [20.9 pg/mL (±2.6) vs 14.5 pg/mL (±1.7), p &amp;lt; 0.001] compared to HC. The one-way repeated-measures ANOVA showed that mean FGF-23 [F (2,40) = 71.255, p &amp;lt; 0.001], Klotho [F (1.405, 28.103) = 195.095, p &amp;lt; 0.001] and NGAL [F (2,40) = 48.024, p &amp;lt; 0.001] differed significantly between time points. Conclusion SSc patients had higher FGF-23, Klotho and NGAL than HC. Our present data demonstrate that microvascular damage is associated to chronic hypoperfusion with increased circulating markers such as FGF-23, Klotho and NGAL. For the first time, we demonstrated that Iloprost infusion reduces significantly serum level of FGF-23, Klotho and NGAL and it has showed to be a key role in renal vasculopathy in SSc patients. In literature, there are no data about the modification of these serum markers before and after vasoactive treatment, especially of Iloprost infusion.

Nimbidiol protects from renal injury by alleviating redox imbalance in diabetic mice.

Chronic hyperglycemia-induced oxidative stress plays a crucial role in the development of diabetic nephropathy (DN). Moreover, adverse extracellular matrix (ECM) accumulation elevates renal resistive index leading to progressive worsening of the pathology in DN. Nimbidiol is an alpha-glucosidase inhibitor, isolated from the medicinal plant, 'neem' (Azadirachta indica) and reported as a promising anti-diabetic compound. Previously, a myriad of studies demonstrated an anti-oxidative property of a broad-spectrum neem-extracts in various diseases including diabetes. Our recent study has shown that Nimbidiol protects diabetic mice from fibrotic renal dysfunction in part by mitigating adverse ECM accumulation. However, the precise mechanism remains poorly understood. The present study aimed to investigate whether Nimbidiol ameliorates renal injury by reducing oxidative stress in type-1 diabetes. To test the hypothesis, wild-type (C57BL/6J) and diabetic Akita (C57BL/6-Ins2Akita/J) mice aged 10-14weeks were used to treat with saline or Nimbidiol (400μgkg-1 day-1) for 8weeks. Diabetic mice showed elevated blood pressure, increased renal resistive index, and decreased renal vasculature compared to wild-type control. In diabetic kidney, reactive oxygen species and the expression levels of 4HNE, p22phox, Nox4, and ROMO1 were increased while GSH: GSSG, and the expression levels of SOD-1, SOD-2, and catalase were decreased. Further, eNOS, ACE2, Sirt1 and IL-10 were found to be downregulated while iNOS and IL-17 were upregulated in diabetic kidney. The changes were accompanied by elevated expression of the renal injury markers viz., lipocalin-2 and KIM-1 in diabetic kidney. Moreover, an upregulation of p-NF-κB and a downregulation of IkBα were observed in diabetic kidney compared to the control. Nimbidiol ameliorated these pathological changes in diabetic mice. Altogether, the data of our study suggest that oxidative stress largely contributes to the diabetic renal injury, and Nimbidiol mitigates redox imbalance and thereby protects kidney in part by inhibiting NF-κB signaling pathway in type-1 diabetes.