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Critical Care Clinics Apr 2021Sepsis-associated acute kidney injury (S-AKI) is a common and life-threatening complication in hospitalized and critically ill patients. It is characterized by rapid... (Review)
Review
Sepsis-associated acute kidney injury (S-AKI) is a common and life-threatening complication in hospitalized and critically ill patients. It is characterized by rapid deterioration of renal function associated with sepsis. The pathophysiology of S-AKI remains incompletely understood, so most therapies remain reactive and nonspecific. Possible pathogenic mechanisms to explain S-AKI include microcirculatory dysfunction, a dysregulated inflammatory response, and cellular metabolic reprogramming. In addition, several biomarkers have been developed in an attempt to improve diagnostic sensitivity and specificity of S-AKI. This article discusses the current understanding of S-AKI, recent advances in pathophysiology and biomarker development, and current preventive and therapeutic approaches.
Topics: Acute Kidney Injury; Biomarkers; Humans; Microcirculation; Renal Circulation; Sepsis
PubMed: 33752856
DOI: 10.1016/j.ccc.2020.11.010 -
Pflugers Archiv : European Journal of... Aug 2022Our kidneys receive about one-fifth of the cardiac output at rest and have a low oxygen extraction ratio, but may sustain, under some conditions, hypoxic injuries that... (Review)
Review
Our kidneys receive about one-fifth of the cardiac output at rest and have a low oxygen extraction ratio, but may sustain, under some conditions, hypoxic injuries that might lead to chronic kidney disease. This is due to large regional variations in renal blood flow and oxygenation, which are the prerequisite for some and the consequence of other kidney functions. The concurrent operation of these functions is reliant on a multitude of neuro-hormonal signaling cascades and feedback loops that also include the regulation of renal blood flow and tissue oxygenation. Starting with open questions on regulatory processes and disease mechanisms, we review herein the literature on renal blood flow and oxygenation. We assess the current understanding of renal blood flow regulation, reasons for disparities in oxygen delivery and consumption, and the consequences of disbalance between O delivery, consumption, and removal. We further consider methods for measuring and computing blood velocity, flow rate, oxygen partial pressure, and related parameters and point out how limitations of these methods constitute important hurdles in this area of research. We conclude that to obtain an integrated understanding of the relation between renal function and renal blood flow and oxygenation, combined experimental and computational modeling studies will be needed.
Topics: Humans; Hypoxia; Kidney; Oxygen; Oxygen Consumption; Renal Circulation
PubMed: 35438336
DOI: 10.1007/s00424-022-02690-y -
Clinical Science (London, England :... Feb 2022Renovascular disease (RVD) remains a common etiology of secondary hypertension. Recent clinical trials revealed unsatisfactory therapeutic outcomes of renal... (Review)
Review
Renovascular disease (RVD) remains a common etiology of secondary hypertension. Recent clinical trials revealed unsatisfactory therapeutic outcomes of renal revascularization, leading to extensive investigation to unravel key pathophysiological mechanisms underlying irreversible functional loss and structural damage in the chronically ischemic kidney. Research studies identified complex interactions among various players, including inflammation, fibrosis, mitochondrial injury, cellular senescence, and microvascular remodeling. This interplay resulted in a shift of our understanding of RVD from a mere hemodynamic disorder to a pro-inflammatory and pro-fibrotic pathology strongly influenced by systemic diseases like metabolic syndrome (MetS), hypertension, diabetes mellitus, and hyperlipidemia. Novel diagnostic approaches have been tested for early detection and follow-up of RVD progression, using new imaging techniques and biochemical markers of renal injury and dysfunction. Therapies targeting some of the pathological pathways governing the development of RVD have shown promising results in animal models, and a few have moved from bench to clinical research. This review summarizes evolving understanding in chronic ischemic kidney injury.
Topics: Animals; Fibrosis; Humans; Hypertension, Renovascular; Inflammation; Ischemia; Kidney; Kidney Diseases; Renal Artery Obstruction; Renal Circulation
PubMed: 35129198
DOI: 10.1042/CS20210509 -
Best Practice & Research. Clinical... Sep 2017Acute kidney injury (AKI) remains one of the main causes of morbidity and mortality in the intensive care medicine today. Its pathophysiology and progress to chronic... (Review)
Review
Acute kidney injury (AKI) remains one of the main causes of morbidity and mortality in the intensive care medicine today. Its pathophysiology and progress to chronic kidney disease is still under investigation. In addition, the lack of techniques to adequately monitor renal function and microcirculation at the bedside makes its therapeutic resolution challenging. In this article, we review current concepts related to renal hemodynamics compromise as being the event underlying AKI. In doing so, we discuss the physiology of the renal circulation and the effects of alterations in systemic hemodynamics that lead to renal injury specifically in the context of reperfusion injury and sepsis. The ultimate key culprit of AKI leading to failure is the dysfunction of the renal microcirculation. The cellular and subcellular components of the renal microcirculation are discussed and how their injury contributes to AKI is described.
Topics: Acute Kidney Injury; Animals; Critical Care; Disease Progression; Hemodynamics; Humans; Kidney; Microcirculation; Renal Circulation; Renal Insufficiency, Chronic; Sepsis
PubMed: 29248139
DOI: 10.1016/j.bpa.2017.10.002 -
Current Opinion in Critical Care Dec 2020Acute kidney injury (AKI) is a common complication in critically ill patients. Understanding the pathophysiology of AKI is essential to guide patient management. Imaging... (Review)
Review
PURPOSE OF REVIEW
Acute kidney injury (AKI) is a common complication in critically ill patients. Understanding the pathophysiology of AKI is essential to guide patient management. Imaging techniques that inform the pathogenesis of AKI in critically ill patients are urgently needed, in both research and ultimately clinical settings. Renal contrast-enhanced ultrasonography (CEUS) and multiparametric MRI appear to be the most promising imaging techniques for exploring the pathophysiological mechanisms involved in AKI.
RECENT FINDINGS
CEUS and MRI can be used to noninvasively and safely evaluate renal macrocirculation and microcirculation and oxygenation in critical ill patients. These techniques show that a decrease in renal blood flow, particularly cortical blood flow, may be observed in septic AKI and may contribute to its development. MRI may be a valuable method to quantify long-term renal damage after AKI that cannot currently be detected using standard clinical approaches.
SUMMARY
CEUS and multiparametric renal MRI are promising imaging techniques but more evidence is needed to show how they can first be more widely used in a research setting to test key hypotheses about the pathophysiology and recovery of AKI, and then ultimately be adopted in clinical practice to guide patient management.
Topics: Acute Kidney Injury; Critical Illness; Humans; Kidney; Renal Circulation; Ultrasonography
PubMed: 33074946
DOI: 10.1097/MCC.0000000000000768 -
Advances in Kidney Disease and Health Mar 2024Hepatorenal syndrome type 1 (HRS-1) is a unique form of acute kidney injury that affects individuals with decompensated cirrhosis with ascites. The primary mechanism... (Review)
Review
Hepatorenal syndrome type 1 (HRS-1) is a unique form of acute kidney injury that affects individuals with decompensated cirrhosis with ascites. The primary mechanism leading to reduction of kidney function in HRS-1 is hemodynamic in nature. Cumulative evidence points to a cascade of events that led to a profound reduction in kidney perfusion. A state of increased intrahepatic vascular resistance characteristic of advanced cirrhosis and portal hypertension is accompanied by maladaptive peripheral arterial vasodilation and reduction in systemic vascular resistance and mean arterial pressure. As a result of a fall in effective arterial blood volume, there is a compensatory activation of the sympathetic nervous system and the renin-angiotensin system, local renal vasoconstriction, loss of renal autoregulation, decrease in renal blood flow, and ultimately a fall in glomerular filtration rate. Systemic release of nitric oxide stimulated by the fibrotic liver, bacterial translocation, and inflammation constitute key components of the pathogenesis. While angiotensin II and noradrenaline remain the critical mediators of renal arterial and arteriolar vasoconstriction, other novel molecules have been recently implicated. Although the above-described mechanistic pathway remains the backbone of the pathogenesis of HRS-1, other noxious elements may be present in advanced cirrhosis and likely contribute to the renal impairment. Direct liver-kidney crosstalk via the hepatorenal sympathetic reflex can further reduce renal blood flow independently of the systemic derangements. Tense ascites may lead to intraabdominal hypertension and abdominal compartment syndrome. Cardio-hemodynamic processes have also been increasingly recognized. Porto-pulmonary hypertension, cirrhotic cardiomyopathy, and abdominal compartment syndrome may lead to renal congestion and complicate the course of HRS-1. In addition, a degree of ischemic or toxic (cholemic) tubular injury may overlap with the underlying circulatory dysfunction and further exacerbate the course of acute kidney injury. Improving our understanding of the pathogenesis of HRS-1 may lead to improvements in therapeutic options for this seriously ill population.
Topics: Humans; Hepatorenal Syndrome; Liver Cirrhosis; Renal Circulation; Hemodynamics; Renin-Angiotensin System; Kidney; Hypertension, Portal; Ascites
PubMed: 38649221
DOI: 10.1053/j.akdh.2024.01.002 -
Physiological Research Jul 2020Proper renal blood flow (RBF) and glomerular filtration rate (GFR) are critical for maintaining normal blood pressure, kidney function and water and electrolyte... (Review)
Review
Proper renal blood flow (RBF) and glomerular filtration rate (GFR) are critical for maintaining normal blood pressure, kidney function and water and electrolyte homeostasis. The renal microvasculature expresses a multitude of receptors mediating vasodilation and vasoconstriction, which can influence glomerular blood flow and capillary pressure. Despite this, RBF and GFR remain quite stable when arterial pressure fluctuates because of the autoregulatory mechanism. ATP and adenosine participate in autoregulatory control of RBF and GFR via activation of two different purinoceptor families (P1 and P2). Purinoceptors are widely expressed in renal microvasculature and tubules. Emerging data show altered purinoceptor signaling in hypertension-associated kidney injury, diabetic nephropathy, sepsis, ischemia-reperfusion induced acute kidney injury and polycystic kidney disease. In this brief review, we highlight recent studies and new insights on purinoceptors regulating renal microvascular function and renal hemodynamics. We also address the mechanisms underlying renal microvascular injury and impaired renal autoregulation, focusing on purinoceptor signaling and hypertension-induced renal microvascular dysfunction. Interested readers are directed to several excellent and comprehensive reviews that recently covered the topics of renal autoregulation, and nucleotides in kidney function under physiological and pathophysiological conditions (Inscho 2009, Navar et al. 2008, Carlstrom et al. 2015, Vallon et al. 2020).
Topics: Animals; Glomerular Filtration Rate; Homeostasis; Humans; Hypertension; Kidney; Receptors, Purinergic; Renal Circulation
PubMed: 32301620
DOI: 10.33549/physiolres.934463 -
Journal of Magnetic Resonance Imaging :... Oct 2018Renal function varies according to the nature and stage of diseases. Renal functional magnetic resonance imaging (fMRI), a technique considered superior to the most... (Review)
Review
UNLABELLED
Renal function varies according to the nature and stage of diseases. Renal functional magnetic resonance imaging (fMRI), a technique considered superior to the most common method used to estimate the glomerular filtration rate, allows for noninvasive, accurate measurements of renal structures and functions in both animals and humans. It has become increasingly prevalent in research and clinical applications. In recent years, renal fMRI has developed rapidly with progress in MRI hardware and emerging postprocessing algorithms. Function-related imaging markers can be acquired via renal fMRI, encompassing water molecular diffusion, perfusion, and oxygenation. This review focuses on the progression and challenges of the main renal fMRI methods, including dynamic contrast-enhanced MRI, blood oxygen level-dependent MRI, diffusion-weighted imaging, diffusion tensor imaging, arterial spin labeling, fat fraction imaging, and their recent clinical applications.
LEVEL OF EVIDENCE
5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:863-881.
Topics: Algorithms; Animals; Contrast Media; Diffusion Magnetic Resonance Imaging; Humans; Image Processing, Computer-Assisted; Kidney; Magnetic Resonance Imaging; Mice; Oxygen; Perfusion; Rats; Renal Circulation; Water
PubMed: 30102436
DOI: 10.1002/jmri.26180 -
Seminars in Nephrology Mar 2015Endothelin (ET) is one of the most potent renal vasoconstrictors. Endothelin plays an essential role in the regulation of renal blood flow, glomerular filtration, sodium... (Review)
Review
Endothelin (ET) is one of the most potent renal vasoconstrictors. Endothelin plays an essential role in the regulation of renal blood flow, glomerular filtration, sodium and water transport, and acid-base balance. ET-1, ET-2, and ET-3 are the three distinct endothelin isoforms comprising the endothelin family. ET-1 is the major physiologically relevant peptide and exerts its biological activity through two G-protein-coupled receptors: ET(A) and ET(B). Both ET(A) and ET(B) are expressed by the renal vasculature. Although ET(A) are expressed mainly by vascular smooth muscle cells, ET(B) are expressed by both renal endothelial and vascular smooth muscle cells. Activation of the endothelin system, or overexpression of downstream endothelin signaling pathways, has been implicated in several pathophysiological conditions including hypertension, acute kidney injury, diabetic nephropathy, and immune nephritis. In this review, we focus on the effects of endothelin on the renal microvasculature, and update recent findings on endothelin in the regulation of renal hemodynamics.
Topics: Endothelins; Glomerular Filtration Rate; Humans; Microcirculation; Renal Circulation
PubMed: 25966346
DOI: 10.1016/j.semnephrol.2015.02.004 -
American Journal of Physiology. Renal... May 2019Tubuloglomerular feedback and the myogenic mechanism form an ensemble in renal afferent arterioles that regulate single-nephron blood flow and glomerular filtration.... (Review)
Review
Tubuloglomerular feedback and the myogenic mechanism form an ensemble in renal afferent arterioles that regulate single-nephron blood flow and glomerular filtration. Each mechanism generates a self-sustained oscillation, the mechanisms interact, and the oscillations synchronize. The synchronization generates a bimodal electrical signal in the arteriolar wall that propagates retrograde to a vascular node, where it meets similar electrical signals from other nephrons. Each signal carries information about the time-dependent behavior of the regulatory ensemble. The converging signals support synchronization of the nephrons participating in the information exchange, and the synchronization can lead to formation of nephron clusters. We review the experimental evidence and the theoretical implications of these interactions and consider additional interactions that can limit the size of nephron clusters. The architecture of the arterial tree figures prominently in these interactions.
Topics: Animals; Arterioles; Blood Flow Velocity; Glomerular Filtration Rate; Homeostasis; Humans; Kidney Glomerulus; Kidney Tubules; Models, Biological; Renal Circulation; Signal Transduction
PubMed: 30759020
DOI: 10.1152/ajprenal.00484.2018