Alterations In Renal Hemodynamics Research Articles

Nondiagnostic 99mTc-MAG3 Diuresis Renography Studies Caused by Propofol Sedation: A Case Series.

99mTc-MAG3 diuresis renography is a noninvasive functional imaging technique used to assess clearance of radiotracer in a dilated urinary tract under high diuresis. It is commonly performed in patients to diagnose functionally significant urinary tract obstruction. In some pediatric patients, sedation is required to enable imaging. However, propofol, a commonly used IV sedative agent, is associated with altered renal hemodynamics. We report a case series of 3 pediatric patients at our institution who received propofol sedation to enable 99mTc-MAG3 diuresis renography using a F+0 protocol, outlining that some "abnormal" studies were in fact assessed to be nondiagnostic.

The New Challenge of Obesity - Obesity-Associated Nephropathy.

In recent years, obesity has become one of the major diseases that affect human health and consume human health resources, especially when it causes comorbidities such as hypertension, diabetes, cardiovascular disease and kidney disease. Many studies have demonstrated that obesity is associated with the development of chronic kidney disease and can exacerbate the progression of end-stage renal disease. This review described the mechanisms associated with the development of obesity-associated nephropathy and the current relevant therapeutic modalities, with the aim of finding new therapeutic targets for obesity-associated nephropathy. The mechanisms of obesity-induced renal injury include, in addition to the traditional alterations in renal hemodynamics, the involvement of various mechanisms such as macrophage infiltration in adipose tissue, alterations in adipokines (leptin and adiponectin), and ectopic deposition of lipids. At present, there is no "point-to-point" treatment for obesity-induced kidney injury. The renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporter 2 (SGLT-2) inhibitors and bariatric surgery described in this review can reduce urinary protein to varying degrees and delay the progression of kidney disease. In addition, recent studies on the therapeutic effects of intestinal flora on obesity may reduce the incidence of obesity-related kidney disease from the perspective of primary prevention. Both of these interventions have their own advantages and disadvantages, so the continuous search for the mechanism of obesity-induced related kidney disease will be extremely helpful for the future treatment of obesity-related kidney disease.

Crush syndrome-related acute kidney injury in earthquake victims

ABSTRACT Natural disasters are unpredictable and thousands of people are affected yearly. Currently, this risk persists, given the large population living in risk areas prone to suffering another seismic event. Generally, on-site mortality is high and occurs immediately from massive trauma or asphyxia. After surviving the first event, extricated patients are at risk of developing crush syndrome caused by direct physical trauma and compression of the human body with lesions in different tissues. This could lead to several systemic complications, including acute kidney injury (AKI), sepsis, acute respiratory distress syndrome, bleeding, hypovolemic shock, arrhythmias, electrolyte disturbances and disseminated intravascular coagulation. Hence, AKI in this scenario can occur due to many causes, such as rhabdomyolysis, direct renal trauma, hypovolemia and hemodynamic alterations. The most important measure to reduce crush syndrome mortality and prevent the development of crush syndrome-related AKI in disaster situations is the immediate start of treatment. Nevertheless, despite optimal therapy delivery, these previous efforts might not suffice the development and progression of AKI, consequently, the indication of extracorporeal blood purification techniques. This narrative review provides a focused overview of crush syndrome-related AKI, including etiology, mechanisms, diagnosis, current treatment, removal of myoglobin and their limitations.

Elevated urinary angiotensinogen excretion links central and renal hemodynamic alterations

Inappropriate activation of intrarenal renin–angiotensin system (RAS) may contribute to the pathogenesis of cardio-renal syndrome (CRS). We aimed to examine the cross-sectional associations of urinary angiotensinogen (AGT) excretion, a biomarker of intrarenal RAS activity, with central (aortic) and renal hemodynamic parameters in middle-aged and older adults, including patients with chronic kidney disease. Aortic and renal hemodynamic parameters were measured using applanation tonometry and duplex ultrasonography in 282 participants. Urinary AGT, liver-type fatty acid-binding protein (L-FABP), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured for each participant. Multiple linear regression analyses demonstrated that urinary AGT levels were associated with aortic blood pressures, pulsatile measures of renal blood flow, plasma NT-proBNP and urinary L-FABP levels after adjusting for potential covariates, including age, sex, body mass index, estimated glomerular filtration rate (GFR), and medication use. Additionally, when classified based on GFR stages and urinary AGT levels, plasma NT-proBNP and urinary L-FABP levels increased in participants with lower GFR and higher AGT groups. Our findings suggest that urinary AGT excretion is a shared determinant of central (aortic) and renal hemodynamics in middle-aged and older adults, providing clinical evidence for the potential role of intrarenal RAS activity in the development of CRS.

Ultrassonografia modo-B e Doppler dos rins de cadelas com neoplasias mamárias submetidas à quimioterapia adjuvante

ABSTRACT: Mammary neoplasia represents the most frequently diagnosed type of neoplasia in bitches. Although surgical removal is the procedure of choice for therapeutic management, chemotherapy protocols appear as important allies and adjuvants. Despite the great advances that have occurred in the field of cancer therapy, the systemic repercussions of these drugs still impose important limitations on their use. In this sense, the development of increasingly targeted therapeutic protocols and preventive monitoring of patients represent important strategies to avoid possible complications - among them, Acute Kidney Injury (AKI). Routinely, ultrasound evaluation is used to identify morphological or metastatic variations in abdominal cavity organs. Acting complementary to the B-mode evaluation, Doppler mapping proves to be efficient in recognizing alterations in vascular hemodynamics. Therefore, the objective of the present study was to evaluate the use of B-mode and Doppler ultrasound to identify renal morphological and hemodynamic alterations in bitches with mammary neoplasia submitted to adjuvant chemotherapy protocols that associate gemcitabine with carboplatin. Thirteen bitches were included, without distinction of breed and between seven and 13 years of age. The animals were evaluated ultrasonographically at two different times during three consecutive chemotherapy cycles: before (T0) and one and a half hours after each cycle (T1), for 42 days. No morphological changes were observed in B-mode throughout the chemotherapy protocol. However, the Doppler velocimetry indices demonstrated statistical differences before (T0) and after (T1) the administration of the drugs. It was concluded that Doppler ultrasound could be used as a complementary method for monitoring the renal response of patients exposed to nephrotoxic drugs and potentially causing renal injury.

Renoprotective Mechanism of Sodium-Glucose Cotransporter 2 Inhibitors: Focusing on Renal Hemodynamics

Diabetic kidney disease (DKD) is a prevalent renal complication of diabetes mellitus that ultimately develops into end-stage kidney disease (ESKD) when not managed appropriately. Substantial risk of ESKD remains even with intensive management of hyperglycemia and risk factors of DKD and timely use of renin-angiotensin-aldosterone inhibitors. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce hyperglycemia primarily by inhibiting glucose and sodium reabsorption in the renal proximal tubule. Currently, their effects expand to prevent or delay cardiovascular and renal adverse events, even in those without diabetes. In dedicated renal outcome trials, SGLT2 inhibitors significantly reduced the risk of composite renal adverse events, including the development of ESKD or renal replacement therapy, which led to the positioning of SGLT2 inhibitors as the mainstay of chronic kidney disease management. Multiple mechanisms of action of SGLT2 inhibitors, including hemodynamic, metabolic, and anti-inflammatory effects, have been proposed. Restoration of tubuloglomerular feedback is a plausible explanation for the alteration in renal hemodynamics induced by SGLT2 inhibition and for the associated renal benefit. This review discusses the clinical rationale and mechanism related to the protection SGLT2 inhibitors exert on the kidney, focusing on renal hemodynamic effects.

First Author Spotlight.

AnnouncementFirst Author SpotlightPublished Online:28 Mar 2022https://doi.org/10.1152/ajprenal.2022.322.4.AUMoreSectionsPDF (372 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations HANNAH M. COSTELLODepartment of Physiology and Functional Genomics, University of Florida, Gainesville, FloridaFigure 1.Hannah CostelloDownload figureDownload PowerPointHannah Costello is a postdoctoral fellow in Dr. Michelle Gumz’s laboratory at the University of Florida in the Department of Physiology and Functional Genomics. She completed her British Heart Foundation-funded PhD in 2021 at the University of Edinburgh. Her research interest focuses on the role of the adrenal and kidney clock in blood pressure regulation. In her spare time, she enjoys traveling, hiking, and reading [Photo: Fig. 1].https://doi.org/10.1152/ajprenal.00385.2021LAUREN G. DOUMADepartment of Physiology and Functional Genomics, University of Florida, Gainesville, FloridaFigure 2.Lauren DoumaDownload figureDownload PowerPointLauren Douma is a Research Assistant Professor at the University of Florida in the Department of Biochemistry and Molecular Biology. She completed her PhD in Genetics and Genomics at the University of Florida. In 2017, she began her postdoctoral fellowship with Dr. Michelle Gumz and since then has been studying the role of the kidney molecular circadian clock in blood pressure regulation. Additionally, she teaches undergraduate- and graduate-level biochemistry and molecular biology courses. She enjoys running, baking, and reading comic books in her free time [Photo: Fig. 2].https://doi.org/10.1152/ajprenal.00385.2021RADMILA MICANOVICDivision of Nephrology and Hypertension, Indiana University School of Medicine, Indianapolis, IndianaFigure 3.Dr. Radmila MicanovicDownload figureDownload PowerPointDr. Radmila Micanovic is an Assistant Research Professor of Medicine at the Indiana University School of Medicine in the Division of Nephrology and Hypertension. She is a researcher and laboratory manager in Dr. Tarek El-Ashkar’s laboratory, a Principal Investigator of the same Division. Prior to joining the Indiana University School of Medicine, she spent 20 yr working in the pharmaceutical industry in drug discovery. She earned her PhD in Biochemistry from the University of Wyoming and completed her postdoctoral studies at the former Roche Institute of Molecular Biology. Her BS degree in Molecular Biology and Physiology was completed in her home country, at the University of Belgrade, Republic of Serbia. Her current work with Dr. El-Achkar focuses on the role of Tamm-Horsfall protein in renal physiology and in the pathophysiology of acute kidney injury. Away from the laboratory, she enjoys great literature, movies, and European TV shows [Photo: Fig. 3].https://doi.org/10.1152/ajprenal.00322.2021SUMIT R. MONUDivision of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Hospital, Detroit, MichiganFigure 4.Sumit R. MonuDownload figureDownload PowerPointSumit R. Monu is currently an Instructor-II in the Division of Hypertension and Vascular Research (Internal Medicine) at Henry Ford Hospital and an affiliate Assistant Professor at Wayne State University. He completed his Veterinary Medicine degree (DVM) from Madras Veterinary College, India, and did his PhD at the University of Toledo School of Medicine. Currently, he is working on unraveling the role/mechanism of altered renal hemodynamics in kidney damage commonly seen in obesity, diabetes, and hypertension. Away from the laboratory, he enjoys traveling along with his wife, Mani, and playing with his son, Neil, and is fond of great food and music [Photo: Fig. 4].https://doi.org/10.1152/ajprenal.00307.2021This article has no references to display. Download PDF Back to Top Next FiguresReferencesRelatedInformation Related ArticlesKidney-specific KO of the circadian clock protein PER1 alters renal Na+ handling, aldosterone levels, and kidney/adrenal gene expression 15 Mar 2022American Journal of Physiology-Renal PhysiologyThe kidney releases a nonpolymerizing form of uromodulin in the urine and circulation that retains the external hydrophobic patch domain 15 Mar 2022American Journal of Physiology-Renal PhysiologyDecreased tubuloglomerular feedback response in high-fat diet-induced obesity 15 Mar 2022American Journal of Physiology-Renal Physiology More from this issue > Volume 322Issue 4April 2022Pages i-ii Crossmark Copyright & PermissionsCopyright © 2022 the American Physiological Society.https://doi.org/10.1152/ajprenal.2022.322.4.AUPubMed35344383History Published online 28 March 2022 Published in print 1 April 2022 Metrics

POS-459 EXAMINING THE EFFECT OF CALCULI SHAPE AND DIMENSION ON URETER OUTFLOW RATES USING AN ARTIFICIAL 3D PRINTED KIDNEY

Kidney stone disease is a urological disorder that affects about 12% of the world population. A deeper understanding of the underlying etiologies and effects which this condition generates, such as alterations in renal hemodynamics, is essential for developing models to study this disorder. Several experimental approaches have been employed, and recent developments in 3D printing offer an exciting opportunity to mimic impediments to urine flow characteristics caused by calculi. Here we present one such simplified model. A 3D artificial renal model was developed using SolidWorks 2019 software ( to provide the template (Figure 1a) for the bioprinted scaffolds (Figure 1b). Spherical and elliptical kidney stones, ranging from 0 to 6 mm, mimic calculi embedded in the artificial ureter designed with flexible plastic tubing (Figure 1C). A mechanical circulation pump was then used to induce urine flow (Figure 1D). Flow velocities were obtained using different geometries of 3D printed kidney stones. Flow magnitude and characteristics were compared to understand the effect of having different geometries on the distribution of urinary flow (Figure 1E). The minimum flow velocities for spherical and elliptical stones were 0 and 34.1 cm/sec for 5 and 4 mm stone sizes, respectively. Surprisingly, elliptical kidney stones showed an increase in the flow velocity at the maximum elliptical stone size of 6 mm (54.39 cm/sec) due to the nature of its geometry. For the case of the spherical shape, it converged to (0 cm/sec). Figure 1. The 3D artificial renal model outlining: SolidWorks 2019 organ template (a); (b) the bioprinter model; (c) spherical and elliptical artificial kidney stones embedded in the ureter; (d) mechanical circulation pump was then used to induce urine flow; and an outline of the variations in volumetric floe rate with calculi size. The results from this study provide insight on ways to create simplified artificial organ models that simulate hemodynamic observed in Kidney stone disease and can be used to develop more sophisticated reverse-engineered artificial 3D-printed kidney models.

Doppler profiles of renal and hepatic hemodynamics in patients with cirrhosis of the liver

One in five individuals with cirrhosis of the liver may experience renal impairment, a frequent consequence that is linked to increased mortality and morbidity. Even before changes in serum creatinine concentration can be detected, renal hemodynamic alterations start to occur early in the course of functional kidney failure caused by liver disease. Studying the Doppler profiles of renal and hepatic hemodynamics in people with liver cirrhosis is the goal of this review article. People with liver cirrhosis, even before clinical signs of renal impairment appear. Doppler is a quick, reliable, and noninvasive technique that makes it possible to identify renal hemodynamic changes in individuals with liver cirrhosis even before they become clinically obvious.

Renoprotective effect of direct renin inhibitor (aliskiren) during partial ureteral obstruction

Partial ureteral obstruction (PUO) is a major clinical problem in the daily urologic practice that is treatable and often reversible. Renin-angiotensin system (RAS) is implicated in the pathophysiology of PUO as angiotensin II induces alterations in renal hemodynamics, apoptosis, inflammation and fibrosis

Pharmacological Insights Into Safety and Efficacy Determinants for the Development of Adenosine Receptor Biased Agonists in the Treatment of Heart Failure.

Adenosine A1 receptors (A1R) are a potential target for cardiac injury treatment due to their cardioprotective/antihypertrophic actions, but drug development has been hampered by on-target side effects such as bradycardia and altered renal hemodynamics. Biased agonism has emerged as an attractive mechanism for A1R-mediated cardioprotection that is haemodynamically safe. Here we investigate the pre-clinical pharmacology, efficacy and side-effect profile of the A1R agonist neladenoson, shown to be safe but ineffective in phase IIb trials for the treatment of heart failure. We compare this agent with the well-characterized, pan-adenosine receptor (AR) agonist NECA, capadenoson, and the A1R biased agonist VCP746, previously shown to be safe and cardioprotective in pre-clinical models of heart failure. We show that like VCP746, neladenoson is biased away from Ca2+ influx relative to NECA and the cAMP pathway at the A1R, a profile predictive of a lack of adenosine-like side effects. Additionally, neladenoson was also biased away from the MAPK pathway at the A1R. In contrast to VCP746, which displays more ‘adenosine-like’ signaling at the A2BR, neladenoson was a highly selective A1R agonist, with biased, weak agonism at the A2BR. Together these results show that unwanted hemodynamic effects of A1R agonists can be avoided by compounds biased away from Ca2+ influx relative to cAMP, relative to NECA. The failure of neladenoson to reach primary endpoints in clinical trials suggests that A1R-mediated cAMP inhibition may be a poor indicator of effectiveness in chronic heart failure. This study provides additional information that can aid future screening and/or design of improved AR agonists that are safe and efficacious in treating heart failure in patients.

“Adenosine an old player with new possibilities in kidney diseases”: Preclinical evidences and clinical perspectives

Renal injury might originate from multiple factors like ischemia reperfusion (I/R), drug toxicity, cystic fibrosis, radio contrast agent etc. The four adenosine receptor subtypes have been identified and found to show diverse physiological and pathological roles in kidney diseases. The activation of A1 adenosine receptor (A1) protects against acute kidney injury by improving renal hemodynamic alterations, decreasing tubular necrosis and its inhibition might facilitate removal of toxin or drug metabolite in chronic kidney disease models. Furthermore, recent findings revealed that A2A receptor subtype activation regulates macrophage phenotype in experimental models of nephritis. Interestingly the emerging role of adenosine kinase inhibitors in kidney diseases has been discussed which act by increasing adenosine availability at target sites and thereby promote A2A receptor stimulation. In addition, the least explored adenosine receptor subtype A3 inhibition was observed to exert anti- oxidant, immunosuppressive and anti-fibrotic effects, but more studies are required to confirm its benefits in other renal injury models. The clinical studies targeting A1 receptor in patients with pre-existing kidney disease have yielded disappointing results, perhaps owing to the origin of unexpected neurological complications during the course of trial. Importantly, conducting well designed clinical trials and testing adenosine modulators with lesser brain penetrability could clear the way for clinical approval of these agents for patients with renal functional impairments.

Physical Training Is a Potential Modifier of Risk for Contrast-Induced Acute Kidney Injury in Diabetes Mellitus.

Background Iodinated contrast (IC) is a leading cause of hospital-based acute kidney injury (AKI). Contrast-induced acute kidney injury (CI-AKI) is a decline in renal function due to iodinated contrast administration and occurs more frequently in individuals with increasingly common risk factors, such as diabetes mellitus (DM). Physical training (PT) can have renoprotective effects on CI-AKI in diabetic nephropathy. The aim of this study was to evaluate the injury in kidneys of diabetic rats submitted to treatment with IC, evaluating the impact of PT on hemodynamics and renal function in addition to oxidative profile in diabetic rats submitted to IC-AKI. Materials and Methods Adult male Wistar rats are randomized into four groups: citrate (n = 7): control group, citrate buffer (streptozotocin-STZ vehicle), intravenous tail (iv), single dose; DM (n = 7): STZ, 60 mg/kg, iv, single dose; DM+IC (n = 7): DM rats treated with IC (sodium meglumine ioxithalamate, 6 mL/kg, intraperitoneal (ip), single dose); DM+IC+PT (n = 7): DM rats treated with IC as mentioned and submitted to physical training. Renal function parameters (inulin clearance, neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine, and urinary albumin), hemodynamics (renal blood flow and renal vascular resistance), and oxidative profile (urinary peroxides, urinary TBARS, urinary nitric oxide, and renal tissue thiols) were evaluated. Results It was possible to observe a decrease in inulin clearance, renal blood flow, and thiols in renal tissue accompanied by an increase in urinary flow, serum creatinine, urinary albumin, renal vascular resistance, urinary peroxides, urinary nitrate, and TBARS in the DM group compared to the citrate group. The DM+IC group showed a reduction in inulin clearance, and the renal dysfunction was also seen by the increased NGAL. Renal hemodynamics and oxidative profile compared were also worsened in the DM group. PT improved renal function by increasing renal blood flow and thiol levels in renal tissue and reduced renal vascular resistance, metabolites of reactive oxygen, nitrogen species, and lipid peroxidation in the DM+IC+PT group compared to DM+IC. Conclusions Our results confirmed that DM induction increases renal vulnerability to the toxicity of IC and an association between DM with IC predisposes to severe AKI with reduced renal function alongside with renal hemodynamic alterations and oxidative mechanism of injury. The PT showed a renoprotective effect in DM animals subjected to damage with IC by modulating renal hemodynamics and oxidative profile, confirming a potential to modify the risk of CI-AKI when diabetes mellitus is present.

Altered renal hemodynamics is associated with glomerular lipid accumulation in obese Dahl salt-sensitive leptin receptor mutant rats

The present study examined whether development of renal injury in the nondiabetic obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) strain is associated with elevations in glomerular filtration rate and renal lipid accumulation. Baseline mean arterial pressure at 6 wk of age was similar between Dahl salt-sensitive wild-type (SSWT) and SSLepRmutant rats. However, by 18 wk of age, the SSLepRmutant strain developed hypertension, while the elevation in mean arterial pressure was not as severe in SSWT rats (192 ± 4 and 149 ± 6 mmHg, respectively). At baseline, proteinuria was fourfold higher in SSLepRmutant than SSWT rats and remained elevated throughout the study. The early development of progressive proteinuria was associated with renal hyperfiltration followed by a decline in renal function over the course of study in the SSLepRmutant compared with SSWT rats. Kidneys from the SSLepRmutant strain displayed more glomerulosclerosis and glomerular lipid accumulation than SSWT rats. Glomeruli were isolated from the renal cortex of both strains at 6 and 18 wk of age, and RNA sequencing was performed to identify genes and pathways driving glomerular injury. We observed significant increases in expression of the influx lipid transporters, chemokine (C-X-C motif) ligand 16 (Cxcl16) and scavenger receptor and fatty acid translocase (Cd36), respectively, and a significant decrease in expression of the efflux lipid transporter, ATP-binding cassette subfamily A member 2 (Abca2; cholesterol efflux regulatory protein 2), in SSLepRmutant compared with SSWT rats at 6 and 18 wk of age, which were validated by RT-PCR analysis. These data suggest an association between glomerular hyperfiltration and glomerular lipid accumulation during the early development of proteinuria associated with obesity.

Intensity of renal replacement therapy and outcomes in critically ill patients with acute kidney injury: Critical appraisal of the dosing recommendations.

The current care of critically ill patients with severe acute kidney injury requiring dialysis (AKI-D) is limited to supportive management in which renal replacement therapy (RRT) plays a central role. Renal replacement techniques are invasive bioincompatible procedures and are therefore associated with complications that may prove harmful to fragile patients. Inexperience with the standards and lacking or misinterpreted recommendations for the delivery of the RRT dose increases the risk of serious complications. Neither the optimal doses of intermittent or continuous RRTs nor the minimal or maximal effective doses are known. The Kidney Disease Improving Global outcomes (KDIGO) AKI guidelines for RRT dosing recommendations are inflexible, based on limited research, and may be at least partially outdated. High-intensity therapy may be associated with clinically relevant alterations in systemic and renal hemodynamics, profound electrolyte imbalances, the loss of nutrients or thermal energy, and underdosing of antimicrobial agents. However, higher doses of continuous renal replacement therapy (CRRT) may confer a survival benefit for certain subgroups of intensive care patients with severe AKI. Lower CRRT doses than the recommended adequate dosage may not lead to negative health outcomes, at least in Asian patients. Future research should evaluate the demand-capacity concept, recognizing that the delivery of the RRT dose is dynamic and should be modified in response to patient-related factors. There is a need for large-scale studies evaluating whether precision RRT dose modifications may improve patient-centered outcomes in subgroups of critically ill patients.

P254 The differential impact of renal resistive index on future cardiovascular event in the hospitalised cardiovascular patients according to left ventricular ejection fraction: J-VAS study

Abstract Introduction Renal resistive index (RRI) not only reflects renal vascular hemodynamics but also correlates well with systemic arterial stiffness. RRI associated with cardiovascular events in the selected group of cardiovascular patients including heart failure (HF). However, previous study limited only in the preserved ejection fraction (EF) patients. Purpose To determine the differential impact of RRI on cardiovascular events among cardiovascular patients according to EF. Methods A retrospective analysis of the Jichi Vascular Hemodynamics in Hospitalised Cardiovascular Patients (J-VAS) cohort. EF and RRI were measured in all patients, then categorised into groups of reduced EF (rEF < 40%), mid-range EF (mrEF 41-49%), and preserved EF (pEF≥50%). The latter group was subdivided into RRI≥0.8 and <0.8 to identify the risk of the primary endpoint, which was the composite of cardiac death, HF, acute coronary syndrome (ACS), aortic disease, arterial occlusion, and stroke. Results We included 1765 patients (mean age 64.7 years, 76% men). The most common diagnoses were ACS(66%) and HF(25%). During the median follow up of 1.9 years, 252 cardiovascular events occurred, 30.7%, 17.7%, and 10.4% in the rEF, mrEF and pEF group. RRI≥0.8 associated with the primary endpoint in the patients with pEF (Hazard ratio(HR), 1.69; 95%confident interval(CI) 1.11-2.58), but the association was not found in the other EF groups. Multivariate Cox regression analysis putting the pEF with RRI < 0.8 as a reference, pEF with RRI≥0.8 had a comparable risk for the primary endpoint to the mrEF group (HR, 1.55; 95%CI, 1.04-2.30 and HR, 1.92; 95%CI, 1.31-2.80, respectively), while the risk was highest in the rEF group (HR, 3.80; 95%CI, 2.73-5.29). Conclusions The risk of cardiovascular events in cardiovascular patients with pEF related to renal vascular hemodynamic alterations justified by RRI. In the patients with pEF, those with high RRI had comparable risk to the mrEF patients. Risk of RRI≥0.8 for the primary endpoint Preserved EF HR (95%CI); P Mid-range EF HR (95%CI); P Reduced EF HR (95%CI); P Model 1 2.05 (1.39-3.02); P <0.001 1.60 (0.81-3.18); P =0.179 0.94 (0.53-1.67); P =0.838 Model 2 1.86 (1.25-2.78); P =0.002 1.33 (0.65-2.72); P =0.430 0.93 (0.52-1.66); P =0.792 Model 3 1.69 (1.11-2.58); P =0.015 1.10 (0.51-2.36); P =0.810 0.70 (0.38-1.28); P =0.242 Adjusted hazard ratio of RRI≥0.8 for the primary endpoint, RRI≥0.8 associated with a significant risk for the primary endpoint in the pEF group but not in the mrEF and rEF group. Model 1 was adjusted for age, sex and body mass index (BMI). Model 2 was adjusted for age, sex, BMI, smoking, dyslipidemia, and diabetes. Model 3 was adjusted for age, sex, BMI, smoking, dyslipidemia, diabetes, and glomerular filtration rate (GFR). Abstract P254 Figure. Survival plot of the 4 subgroups

Nitric oxide involvement in post-exercise proteinuria of sedentary young men

Summary Objectives Post-exercise proteinuria is generally characterised based on the alterations in renal hemodynamics. The present study was focused on the role of nitric oxide in post-exercise proteinuria; nitric oxide is a biomolecule involved in mechanisms that affect renal hemodynamics and is a mediator that rises during exercise bouts. Methods Healthy human subjects performed three high-intensity exercise sessions with a one-week interval; control, NO donor (isosorbide mononitrate) and vasodilator that unrelated nitric oxide (diltiazem). Urine samples obtained immediately before and 30 and 120 minutes after the exercise session were examined for proteinuria. The alterations in systemic blood pressure induced by the drugs were evaluated by performing blood pressure measurements. Results Both the agents that were administered caused a significant decrease in the systolic or diastolic blood pressure; however, the extent of reduction was not different between the two agents. Exercise session induced apparent proteinuria at 30 minutes post-exercise during all the protocols. Exercise-induced rise in urinary protein excretion was significantly reduced by isosorbide mononitrate, while a similar effect was not observed for diltiazem. Conclusion Our results revealed that exogenous nitric oxide could alter the hemodynamic changes during exercise and thus reduce post-exercise proteinuria. Further, endogenous nitric oxide may prevent excessive elevation in the post-exercise proteinuria during normal physiological conditions.

The renal resistive index as a new complementary tool to predict microvascular diabetic complications in children and adolescents: a groundbreaking finding.

The increasing prevalence of type 1 diabetes mellitus (DM) has made it necessary to have new markers for early detection of diabetic nephropathy. Renal resistive index (RI) by using renal Doppler can be a helpful tool in detecting functional alterations in renal hemodynamics. This study was conducted on 100 children and adolescents with type 1 DM. They were further subdivided into two equal subgroups: group 1 with type 1 DM and normo-albuminuria [urinary albumin excretion (UAE) <30 mg/24 hours], and group 2 with type 1 DM and hyper-albuminuria (increased UAE >30 mg/24 hours). There were 37 males (37%) and 63 females (63%); their mean ages were 13.6±2.53 (range, 10-19) years and mean disease duration was 8.867±2.260 (range, 5-13) years. Progressive increase in RI was significantly associated with increased disease duration more than 10 years, elevated serum HbA1c more than 7.5% and early pubertal stages. While not significantly related to sex, weight, height, blood pressure or serum lipid profile, diabetic micro-vascular complications (nephropathy and sensory neuropathy) were more prevalent among patients with RI more than 0.58. Renal RI could be a useful complementary test for the evaluation of functional alterations in renal hemodynamics in the early stages of diabetic nephropathy.

Contrast Induced Acute Kidney Injury and Direct Cytotoxicity of Iodinated Radiocontrast Media on Renal Proximal Tubule Cells.

The administration of intravenous iodinated radiocontrast media (RCM) to visualize internal structures during diagnostic procedures has increased exponentially since their first use in 1928. A serious side effect of RCM exposure is contrast-induced acute kidney injury (CI-AKI), which is defined as an abrupt and prolonged decline in renal function occurring 48-72 hours after injection. Multiple attempts have been made to decrease the toxicity of RCM by altering ionic strength and osmolarity, yet there is little evidence to substantiate that a specific RCM is superior in avoiding CI-AKI. RCM-associated kidney dysfunction is largely attributed to alterations in renal hemodynamics, specifically renal vasoconstriction; however, numerous studies indicate direct cytotoxicity as a source of epithelial damage. Exposure of in vitro renal proximal tubule cells to RCM has been shown to affect proximal tubule epithelium in the following manner: 1) changes to cellular morphology in the form of vacuolization; 2) increased production of reactive oxygen species, resulting in oxidative stress; 3) mitochondrial dysfunction, resulting in decreased efficiency of the electron transport chain and ATP production; 4) perturbation of the protein folding capacity of the endoplasmic reticulum (ER) (activating the unfolded protein response and inducing ER stress); and 5) decreased activity of cell survival kinases. The present review focuses on the direct cytotoxicity of RCM on proximal tubule cells in the absence of in vivo complications, such as alterations in renal hemodynamics or cytokine influence.

Pulse pressure and perioperative stroke.

Central pulse pressure (PP), a marker of vascular stiffness, is a novel indicator of risk for perioperative morbidity including ischemic stroke. Appreciation for the mechanism by which vascular stiffness leads to organ dysfunction along with understanding its clinical detection may lead to improved patient management. Vascular stiffness is associated with increased mortality and neurologic, cardiac, and renal injury in nonsurgical and surgical patients. Left ventricular hypertrophy and diastolic dysfunction along with microcirculatory changes in the low vascular resistance, high blood flow, cerebral and renal vasculature are seen in patients with vascular stiffness. Pulse wave velocity and the augmentation index have higher sensitivity for detecting of vascular stiffness than peripheral PP as the hemodynamic consequences of vascular stiffness are secondary to alterations in the central vasculature. Vascular stiffness alters cerebral autoregulation, resulting in a high likelihood of having a lower limit of autoregulation more than 65 mmHg during surgery. Vascular stiffness may predispose to cerebral hypoperfusion, increasing vulnerability to ischemic stroke, postoperative delirium, and acute kidney injury. Vascular stiffness leads to alterations in cerebral, cardiac, and renal hemodynamics increasing the risk of perioperative ischemic stroke and neurologic, cardiac, and renal dysfunction.