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Current Opinion in Nephrology and... Jul 2017Renal arteriovenous oxygen shunting has been proposed as a mechanism by which oxygen supplied to the kidney can bypass the renal parenchyma. Shunting could, therefore,... (Review)
Review
PURPOSE OF REVIEW
Renal arteriovenous oxygen shunting has been proposed as a mechanism by which oxygen supplied to the kidney can bypass the renal parenchyma. Shunting could, therefore, play a crucial role in renal hypoxia and hyperoxia. In the absence of suitable quantitative experimental methods, computational modeling has been employed in recent years to estimate the extent and potential impact of oxygen shunting.
RECENT FINDINGS
Overestimation of the separation distance between arteries and veins was suggested to be responsible for previous findings that only negligible amounts of oxygen are shunted in the preglomerular vasculature. However, models considering the correct separation distance and wrapping of artery-vein pairs still showed shunting at negligible levels of less than 1% of total renal oxygen delivery. The effect of reverse CO2 shunting on the oxygen-hemoglobin dissociation curve was found to impair, rather than promote, preglomerular oxygen shunting.
SUMMARY
Oxygen is unlikely to be shunted along the preglomerular vasculature in sufficient quantities to affect renal oxygenation. There may be substantial shunting at the level of the postglomerular vasculature, but more extensive efforts in structural imaging and computational modeling are needed to quantify it reliably.
Topics: Carbon Dioxide; Humans; Hypoxia; Kidney; Kidney Diseases; Kidney Glomerulus; Oxygen; Oxygen Consumption; Renal Artery; Renal Circulation; Renal Veins
PubMed: 28399018
DOI: 10.1097/MNH.0000000000000332 -
Physiological Reports Oct 2022The maternal cardiovascular system, led by renal volume regulatory responses, changes during pregnancy to ensure an adequate circulation for fetal development and...
The maternal cardiovascular system, led by renal volume regulatory responses, changes during pregnancy to ensure an adequate circulation for fetal development and growth. Circulatory maladjustment predisposes to hypertensive complications during pregnancy. Mathematical models can be used to gain insight in the gestational cardiovascular physiology. In this study, we developed an accurate, robust, and transparent model for renal autoregulation implemented in an existing circulatory gestational model. This renal autoregulation model aims to maintain steady glomerular pressure by the myogenic response, and glomerular filtration rate by tubuloglomerular feedback, both by inducing a change in the radius, and thus resistance, of the afferent arteriole. The modeled response of renal blood flow and the afferent arteriole following blood pressure increase were compared to published observations in rats. With solely the myogenic response, our model had a maximum deviation of 7% in change in renal blood flow and 7% in renal vascular resistance. When both the myogenic response and tubuloglomerular feedback were concurrently activated, the maximum deviation was 7% in change in renal blood flow and 5% in renal vascular resistance. These results show that our model is able to represent renal autoregulatory behavior comparable to empirical data. Further studies should focus on extending the model with other regulatory mechanisms to understand the hemodynamic changes in healthy and complicated pregnancy.
Topics: Animals; Blood Pressure; Glomerular Filtration Rate; Hemodynamics; Homeostasis; Kidney; Rats; Renal Circulation
PubMed: 36200318
DOI: 10.14814/phy2.15484 -
Nephrology (Carlton, Vic.) May 2021Diabetic kidney disease remains the leading cause of end-stage kidney disease and a major risk factor for cardiovascular disease. Large cardiovascular outcome trials and... (Review)
Review
Diabetic kidney disease remains the leading cause of end-stage kidney disease and a major risk factor for cardiovascular disease. Large cardiovascular outcome trials and dedicated kidney trials have shown that sodium-glucose cotransporter (SGLT)2 inhibitors reduce cardiovascular morbidity and mortality and attenuate hard renal outcomes in patients with type 2 diabetes (T2D). Underlying mechanisms explaining these renal benefits may be mediated by decreased glomerular hypertension, possibly by vasodilation of the post-glomerular arteriole. People with T2D often receive several different drugs, some of which could also impact the renal vasculature, and could therefore modify both renal efficacy and safety of SGLT2 inhibition. The most commonly prescribed drugs that could interact with SGLT2 inhibitors on renal haemodynamic function include renin-angiotensin system inhibitors, calcium channel blockers and diuretics. Herein, we review the effects of these drugs on renal haemodynamic function in people with T2D and focus on studies that measured glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) with gold-standard techniques. In addition, we posit, based on these observations, potential interactions with SGLT2 inhibitors with an emphasis on efficacy and safety.
Topics: Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diuretics; Drug Interactions; Hemodynamics; Humans; Renal Circulation; Renin-Angiotensin System; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33283420
DOI: 10.1111/nep.13839 -
Kidney International Jan 2017The pathogenesis of sepsis-associated acute kidney injury is complex and likely involves perfusion alterations, a dysregulated inflammatory response, and bioenergetic... (Review)
Review
The pathogenesis of sepsis-associated acute kidney injury is complex and likely involves perfusion alterations, a dysregulated inflammatory response, and bioenergetic derangements. Although global renal hypoperfusion has been the main target of therapeutic interventions, its role in the development of renal dysfunction in sepsis is controversial. The implications of renal hypoperfusion during sepsis probably extend beyond a simple decrease in glomerular filtration pressure, and targeting microvascular perfusion deficits to maintain tubular epithelial integrity and function may be equally important. In this review, we provide an overview of macro- and microcirculatory dysfunction in experimental and clinical sepsis and discuss relationships with kidney oxygenation, metabolism, inflammation, and function.
Topics: Acute Kidney Injury; Animals; Clinical Trials as Topic; Glomerular Filtration Rate; Humans; Kidney; Microcirculation; Nitric Oxide; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Reactive Oxygen Species; Renal Circulation; Sepsis
PubMed: 27692561
DOI: 10.1016/j.kint.2016.07.032 -
Journal of Magnetic Resonance Imaging :... Feb 2022Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal... (Review)
Review
BACKGROUND
Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool.
PURPOSE
To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies.
STUDY TYPE
Systematic consensus process using a modified Delphi method.
POPULATION
Not applicable.
SEQUENCE FIELD/STRENGTH
Renal fast gradient echo-based 2D PC-MRI.
ASSESSMENT
An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4-10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated.
STATISTICAL TESTS
Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60-74% agreement among the experts.
RESULTS
Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting.
DATA CONCLUSION
These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI.
LEVEL OF EVIDENCE
1 TECHNICAL EFFICACY STAGE: 1.
Topics: Consensus; Delphi Technique; Humans; Kidney; Magnetic Resonance Imaging; Multicenter Studies as Topic; Renal Circulation
PubMed: 33140551
DOI: 10.1002/jmri.27419 -
PloS One 2020Acute early vascular complications are rare, but serious complications after kidney transplantation. They often result in graft loss. For this reason, shortening the...
INTRODUCTION
Acute early vascular complications are rare, but serious complications after kidney transplantation. They often result in graft loss. For this reason, shortening the diagnostic process is crucial. Currently, it is standard procedure to monitor renal graft perfusion using Doppler ultrasound (DU). With respect to acute vascular complications, the main disadvantage of this type of examination is its periodicity. It would be of great benefit if graft blood perfusion could be monitored continuously during the early postoperative period. It appears evident that a well-designed near infrared spectroscopy (NIRS) monitoring system could prove very useful during the early post-transplantation period. Its role in the immediate diagnosis of vascular complications could result in a significant increase in graft salvage, thus improving the patient's overall quality of life and lowering morbidity and mortality for renal graft recipients. The aim of this study was to design, construct and test such a monitoring system.
MATERIALS AND METHODS
We designed a rough NIRS-based system prototype and prepared a two-stage laboratory experiment based on a laboratory pig model. In the first stage, a total of 10 animals were used to verify and optimize the technical aspects and functionality of the prototype sensor by testing it on the animal kidneys in-vivo. As a result of these tests, a more specific prototype was designed. During the second stage, we prepared a unique laboratory model of a pig kidney autotransplantation and tested the system for long-term functionality on a group of 20 animals. Overall sensitivity and specificity were calculated, and a final prototype was prepared and completed with its own analytic software and chassis.
RESULTS
We designed and constructed a NIRS-based system for kidney graft perfusion monitoring. The measurement system provided reliable performance and 100% sensitivity when detecting acute diminished blood perfusion of the transplanted kidneys in laboratory conditions.
CONCLUSION
The system appears to be a useful tool for diagnosing diminished blood perfusion of kidney transplants during the early postoperative period. However, further testing is still required. We believe that applying our method in current human transplantation medicine is feasible, and we are confident that our prototype is ready for human testing.
Topics: Animals; Early Diagnosis; Kidney; Kidney Transplantation; Models, Animal; Renal Circulation; Sensitivity and Specificity; Spectroscopy, Near-Infrared; Swine; Vascular Diseases
PubMed: 33264371
DOI: 10.1371/journal.pone.0243154 -
American Journal of Physiology. Renal... Oct 2015When introduced clinically 6 years ago, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication. The... (Review)
Review
When introduced clinically 6 years ago, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication. The initial two studies, SYMPLICITY HTN-1 and HTN-2, demonstrated great magnitudes of blood pressure reduction within 6 mo of the procedure and were based on a number of assumptions that may not have been true, including strict adherence to medication and absence of white-coat hypertension. The SYMPLICITY HTN-3 trial controlled for all possible factors believed to influence the outcome, including the addition of a sham arm, and ultimately proved the demise of the initial overly optimistic expectations. This trial yielded a much lower blood pressure reduction compared with the previous SYMPLICITY trials. Since its publication in 2014, there have been many analyses to try and understand what accounted for the differences. Of all the variables examined that could influence blood pressure outcomes, the extent of the denervation procedure was determined to be inadequate. Beyond this, the physiological mechanisms that account for the heterogeneous fall in arterial pressure following renal denervation remain unclear, and experimental studies indicate dependence on more than simply reduced renal sympathetic activity. These and other related issues are discussed in this paper. Our perspective is that renal denervation works if done properly and used in the appropriate patient population. New studies with new approaches and catheters and appropriate controls will be starting later this year to reassess the efficacy and safety of renal denervation in humans.
Topics: Denervation; Drug Resistance; Humans; Hypertension, Renal; Kidney; Renal Circulation; Sympathectomy
PubMed: 26224718
DOI: 10.1152/ajprenal.00246.2015 -
European Review For Medical and... 2016The purpose of the study is to further investigate the effects of increased intra-abdominal pressure (IAP) on renal hemodynamics and renal perfusion, and to evaluate the...
OBJECTIVE
The purpose of the study is to further investigate the effects of increased intra-abdominal pressure (IAP) on renal hemodynamics and renal perfusion, and to evaluate the renal cortical and sublingual microcirculation by sidestream dark field (SDF) imaging, both with a porcine model.
MATERIALS AND METHODS
IAP was increased stepwise to 10, 15, 20, 25 mmHg, during which hemodynamic parameters, urinary output, renal contrast-enhanced ultrasound (CEUS), sublingual and renal SDF videos were all recorded from 12 pigs.
RESULTS
Wash in time (WT) and time to peak (TTP) prolonged significantly (p<0.05), while peak intensity (PI) wash in slope (WS) and AUC (area under curve) in CEUS declined significantly (p<0.05) compared with baseline when IAP elevated to 25 mm Hg. With an increase of abdominal pressure, sublingual microvascular flow index (MFI) drop significantly, especially upon IAP was over 20 mmHg. But other parameters such as the total vascular density (TVD), De Backer Score, proportion of perfused vessels (PPV), perfused vessel density (PVD), and heterogeneity index (HI) of tongue were not significantly changed. With increasing IAP, renal vascular resistance increased and MFI decreased about 30%. RFG, instead of RFG showed a moderate correlation with AUC (R=0.47, p<0.05) and MFI (R=0.49, p<0.05).
CONCLUSIONS
CEUS is a safe, real-time dynamic, noninvasive and simple technique to evaluate renal microvascular perfusion in intra-abdominal hypertension. Descending slope, PI and AUC can be used for the diagnosis of the renal microvascular damage in a porcine model of IAP-induced renal impairment. Also, SDF on the surface of the kidney is a useful tool to evaluate the microcirculation of kidney but sublingual SDF imaging was barely useful.
Topics: Animals; Contrast Media; Disease Models, Animal; Hemodynamics; Intra-Abdominal Hypertension; Kidney; Kidney Cortex; Microcirculation; Renal Circulation; Swine; Vascular Resistance
PubMed: 26914119
DOI: No ID Found -
Current Hypertension Reports Jan 2019In this review, we summarized the current knowledge of connecting tubule-glomerular feedback (CTGF), a novel mechanism of renal microcirculation regulation that... (Review)
Review
PURPOSE OF REVIEW
In this review, we summarized the current knowledge of connecting tubule-glomerular feedback (CTGF), a novel mechanism of renal microcirculation regulation that integrates sodium handling in the connecting tubule (CNT) with kidney hemodynamics.
RECENT FINDINGS
Connecting tubule-glomerular feedback is a crosstalk communication between the CNT and the afferent arteriole (Af-Art), initiated by sodium chloride through the epithelial sodium channel (ENaC). High sodium in the CNT induces Af-Art vasodilation, increasing glomerular pressure and the glomerular filtration rate and favoring sodium excretion. CTGF antagonized and reset tubuloglomerular feedback and thus increased sodium excretion. CTGF is absent in spontaneous hypertensive rats and is overactivated in Dahl salt-sensitive rats. CTGF is also modulated by angiotensin II and aldosterone. CTGF is a feedback mechanism that integrates sodium handling in the CNT with glomerular hemodynamics. Lack of CTGF could promote hypertension, and CTGF overactivation may favor glomerular damage and proteinuria. More studies are needed to explore the alterations in renal microcirculation and the role of these alterations in the genesis of hypertension and glomerular damage in animals and humans.
KEY POINTS
• CTGF is a vasodilator mechanism that regulates afferent arteriole resistance. • CTGF is absent in spontaneous hypertensive rats and overactivated in Dahl salt-sensitive rats. • CTGF in excess may promote glomerular damage and proteinuria, while the absence may participate in sodium retention and hypertension.
Topics: Animals; Feedback; Humans; Hypertension; Kidney Glomerulus; Kidney Tubules; Microcirculation; Proteinuria; Rats; Renal Circulation; Sodium
PubMed: 30659366
DOI: 10.1007/s11906-019-0911-5 -
Nature Reviews. Drug Discovery Aug 2016Chronic kidney disease (CKD) represents a leading cause of death in the United States. There is no cure for this disease, with current treatment strategies relying on... (Review)
Review
Chronic kidney disease (CKD) represents a leading cause of death in the United States. There is no cure for this disease, with current treatment strategies relying on blood pressure control through blockade of the renin-angiotensin system. Such approaches only delay the development of end-stage kidney disease and can be associated with serious side effects. Recent identification of several novel mechanisms contributing to CKD development - including vascular changes, loss of podocytes and renal epithelial cells, matrix deposition, inflammation and metabolic dysregulation - has revealed new potential therapeutic approaches for CKD. This Review assesses emerging strategies and agents for CKD treatment, highlighting the associated challenges in their clinical development.
Topics: Animals; Fibrosis; Humans; Mice; Renal Agents; Renal Circulation; Renal Insufficiency, Chronic
PubMed: 27230798
DOI: 10.1038/nrd.2016.67