Comparative Study Review

Authors: Kirk P Conrad, John M Davison

During the first trimester of human pregnancy, the maternal systemic circulation undergoes remarkable vasodilation. The kidneys participate in this vasodilatory response resulting in marked increases in renal plasma flow (RPF) and glomerular filtration rate (GFR). Comparable circulatory adaptations are observed in conscious gravid rats. Administration of the corpus luteal hormone relaxin (RLN) to nonpregnant rats and humans elicits vasodilatory changes like those of pregnancy. Systemic and renal vasodilation are compromised in midterm pregnant rats by neutralization or elimination of circulating RLN and in women conceiving with donor eggs who lack a corpus luteum and circulating RLN. Although RLN exerts both rapid (minutes) and sustained (hours to days) vasodilatory actions through different molecular mechanisms, a final common pathway is endothelial nitric oxide. In preeclampsia (PE), maternal systemic and renal vasoconstriction leads to hypertension and modest reduction in GFR exceeding that of RPF. Elevated level of circulating soluble vascular endothelial growth factor receptor-1 arising from the placenta is implicated in the hypertension and disruption of glomerular fenestrae and barrier function, the former causing reduced Kf and the latter proteinuria. Additional pathogenic factors are discussed. Last, potential clinical ramifications include RLN replacement in women conceiving with donor eggs and its therapeutic use in PE. Another goal has been to apply knowledge gained from investigating circulatory adaptations in pregnancy toward identifying and developing novel therapeutic strategies for renal and cardiovascular disease in the nonpregnant population. So far, one candidate to emerge is RLN and its potential therapeutic use in heart failure.

Topics: Animals; Female; Glomerular Filtration Rate; Humans; Kidney; Models, Animal; Pre-Eclampsia; Pregnancy; Pregnancy, Animal; Rats; Regional Blood Flow; Relaxin; Renal Circulation; Renal Plasma Flow; Vasodilation

PubMed: 24647709
DOI: 10.1152/ajprenal.00042.2014

Authors: F Sui, Y Zheng, W-X Li...

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

Review

Authors: Aurelie Edwards, Vartan Kurtcuoglu

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

Review

Authors: Z Guan, M N Makled, E W Inscho...

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

Review

Authors: Zhengrong Guan, Justin P VanBeusecum, Edward W Inscho...

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

Review

Authors: Murray Epstein, Garabed Eknoyan

This article reviews the pioneering and visionary contributions of the Catalan surgeon Josep Trueta (1897–1977) to the changes in renal circulation that contribute to the pathogenesis of acute renal failure (ARF). An erudite scientist with eclectic interests in physiology, orthopedics, politics, and medical history, Trueta's initial involvement in wound healing as a trauma surgeon during the Spanish Civil War and the London Blitz is what prompted him to postulate that a trauma-induced “neural effect” on the renal vasculature, with resultant renal arterial constriction could cause ARF. To test his hypothesis, Trueta assembled an experienced radiologist, a renowned physiologist, and a renal pathologist to study ARF in Oxford. They investigated the renal circulation of rabbits in response to diverse traumatic conditions by injecting a radio-opaque substance, using cine-radiography to visualize the flow of blood through the renal vasculature. Trueta's suggestion of renal cortical ischemia and diversion of blood to the less resistant medullary circulation (Trueta shunt) was criticized by Homer Smith and coworkers. In contrast to Homer Smith's data, which were derived from clearance studies and renal arteriovenous oxygen, Trueta used the diametrical opposite method of “direct” observation of the renal circulation. Their differing methodologies, direct visualization of the renal circulation as opposed to inferred computations from clearance studies, accounts for some of their conflicting theories. Nevertheless, the proposal of disparate renal flow compartments focused attention on intrarenal hemodynamics. Trueta's focus on renal cortical ischemia was ultimately validated by the studies of Barger in the dog and Hollenberg and Epstein in human subjects.

Topics: Acute Kidney Injury; Animals; Biomedical Research; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Nephrology; Renal Circulation

PubMed: 25995107
DOI: 10.1152/ajprenal.00075.2015

Review

Authors: Erika Guise, Alejandro R Chade

Renovascular disease (RVD), which is prevalent in the elderly, significantly increases cardiovascular risk and can progressively deteriorate renal function. The loss of renal function in patients with RVD is associated with a progressive dysfunction, damage, and loss of renal microvessels, which can be combined with decreased renal bioavailability of vascular endothelial growth factor (VEGF) and a defective vascular repair and proliferation. This association has been the impetus for recent efforts that have focused on developing methods to stop the progression of renal injury by protecting the renal microvasculature. This mini-review focuses on recent studies supporting potential applications of VEGF therapy for the kidney and discusses underlying mechanisms of renoprotection.

Topics: Animals; Humans; Kidney; Neovascularization, Physiologic; Renal Artery Obstruction; Renal Circulation; Vascular Endothelial Growth Factor A

PubMed: 29442546
DOI: 10.1152/ajprenal.00617.2017

Review

Authors: D R Steinmuller

Cyclosporine is a potent and useful immunosuppressive agent used primarily in conjunction with solid organ transplantation. The most serious adverse reaction that limits its use is nephrotoxicity due to effects on the renal vasculature, glomeruli, and tubular function. These effects result in a variety of clinical syndromes. This review outlines the clinical syndromes and discusses way to minimize nephrotoxicity in patients receiving cyclosporine.

Topics: Cyclosporins; Drug Synergism; Glomerular Filtration Rate; Humans; Kidney Diseases; Kidney Tubules; Renal Circulation

PubMed: 2659201
DOI: 10.3949/ccjm.56.1.89

Review

Authors: Emiel Hendrik Post, Jean-Louis Vincent

The importance of personalized blood pressure management is well recognized. Because renal pressure-flow relationships may vary among patients, understanding how renal autoregulation may influence blood pressure control is essential. However, much remains uncertain regarding the determinants of renal autoregulation in circulatory shock, including the influence of comorbidities and the effects of vasopressor treatment. We review published studies on renal autoregulation relevant to the management of acutely ill patients with shock. We delineate the main signaling pathways of renal autoregulation, discuss how it can be assessed, and describe the renal autoregulatory alterations associated with chronic disease and with shock.

Topics: Animals; Blood Pressure; Disease Models, Animal; Dogs; Homeostasis; Kidney; Mice; Renal Circulation; Shock; Swine; Vasoconstrictor Agents

PubMed: 29566705
DOI: 10.1186/s13054-018-1962-8

Authors: Takako Iino, Hiroyuki Watanabe

Topics: Atherosclerosis; Humans; Kidney; Renal Circulation

PubMed: 31866627
DOI: 10.2169/internalmedicine.4145-19