Kidney ischemia

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Kidney ischemia [1] is a disease with a high morbidity and mortality rate. [2] Blood vessels shrink and undergo apoptosis which results in poor blood flow in the kidneys. More complications happen when failure of the kidney functions result in toxicity in various parts of the body which may cause septic shock, hypovolemia, and a need for surgery. [3] What causes kidney ischemia is not entirely known, but several pathophysiology relating to this disease have been elucidated. Possible causes of kidney ischemia include the activation of IL-17C and hypoxia due to surgery or transplant. Several signs and symptoms include injury to the microvascular endothelium, apoptosis of kidney cells due to overstress in the endoplasmic reticulum, dysfunctions of the mitochondria, autophagy, inflammation of the kidneys, and maladaptive repair.[ citation needed ]

Contents

Kidney ischemia can be diagnosed by checking the levels of several biomarkers such as clusterin and cystatin C. While the duration of ischemia was used as a biomarker, it was found that it has significant flaws in predicting renal function outcomes. More emerging treatments are in the clinical trials such as Bendavia in targeting mitochondrial dysfunction and using Mesenchymal Stem Cell Therapy. Several receptors agonists and antagonists have shown promise in animal studies; however, they have not been proven clinically yet.[ citation needed ]

Causes

Little is known as to what causes ischemic injury in the kidneys; however, several physical insults are stated to be activated during injury. Physical stress such as infarction, surgery and transplant may produce kidney ischemia. Dietary habits and genetics could cause ischemic injury, as well. Diseases such as sepsis can cause kidney ischemia too. [4]

Infarction or Physical Injury

Infarction is defined as the blockage of blood flow in tissues or organs, which may cause necrosis or death of a group of cells in the tissue. [5] In studies of mice models, clamping of the kidney may result in kidney ischemia. [6]

Renal Surgery and Transplant

Renal surgery and coronary artery bypass grafting can produce renal ischemia and reperfusion injury. This could lead to an acute kidney injury. Moreover, renal ischemia can cause the delay of graft function after renal transplant and can cause rejection of the transplant. [7]

Dietary Habits

In studies of mice models, a high-fat diet can induce greater injury to the kidney with renal ischemia-reperfusion as compared to mice with normal diet. [8] This is because in a high-fat diet model, accumulation of phospholipids resulted in enlarged lysosomes within proximal tubular cells. [8] This accumulation of phospholipids lead to an increase aggregation of ubiquitin in the kidney cells. When this happens, autophagy becomes exaggerated and results in malfunction of the mitochondria and inflammation of the tissue. [8]

Atherosclerosis

A common cause of ischemic renal disease is atherosclerosis. [9] Atherosclerosis is a specific type of arteriosclerosis. Arteriosclerosis is defined as the thickening or stiffening or both of the blood vessels; more specifically, atherosclerosis refers to the buildup of cholesterol and fats in the artery walls. [10] Because the blood vessels carry oxygen and nutrients throughout the body, having atherosclerosis restrict blood flow and consequently prevent necessary nutrients to reach the kidneys. [10] This accounts for 60-97% of renal arterial lesions, which could lead to the occlusion of the renal artery and ischemic atrophy of the kidneys. [9]

Genetics

Several genetic pathways that lead to apoptosis of kidney cells have been implicated in mice models and in-vitro assays. These are proapoptotic genes that can be categorized in two: extrinsic and intrinsic pathways. The extrinsic pathway are directly induced upon renal ischemic injury, while intrinsic pathways are dependent on mitochondrial signaling pathways. [11] Moreover, several genes have been implicated as risk factors in the development of ischemic injury. [12]

Extrinsic Pathway

Activation of pro-caspase 8 initiates apoptosis via signaling from cell-surface death receptors such as Fas proteins and their ligands FADD and DAXX. [11] This series of signaling cascade generally regulates programmed cell-death or apoptosis. Upregulation of Fas and FADD protein has occurred in mice models after a 24h period of ischemic injury. [11] This is also shown in cell-based assays wherein tubule cells are monitored after ischemic-like injury. This shows that the Fas-pathway may play a role in the pathogenesis of the apoptosis of tubule cells during the early ischemic-reperfusion period. The role of DAXX is still unclear; however, DAXX mediates both Fas-dependent and TGF-beta-induced apoptosis and renal induction of TGF-beta is well documented in renal ischemia studies. [11]

Intrinsic Pathway

Activation of pro-caspase 9 is dependent on mitochondrial signaling pathways which are regulated by the Bcl-2 family of proteins. Activation of Bcl-2 proteins such as Bax and Bak triggers a signaling cascade that results in the release of cytochrome c into the cytosol. This then activates pro-caspase 9 and results in apoptosis of the cells. [11]

Genetic Risk Factors

Polymorphisms in genes have been shown to increase or decrease risk of renal ischemic injury. Genes such as Apolipoprotein E (APO E), which controls cholesterol metabolism, NADPH Oxidase which regulates oxidative stress, Angiotensin-converting enzyme (ACE) for vasomotor regulation, HSP72 which helps in tolerance of ischemic injury, Interleukin cytokines which is an inflammation modulator, and VEGF which regulates angiogenesis or the formation of blood vessels have all been shown to have significant effects in acute kidney injury. [12]

Apolipoprotein E

Apolipoprotein E are proteins that metabolize fats in the body. In studies of patients undergoing coronary artery bypass grafting, carriers of APO-E e4 allele was found to have a decreased risk of acute kidney injury compared to non-carriers of the allele. [12]

NADPH Oxidase

NADPH Oxidase regulates oxidative stress by conjugating with reactive oxygen species in cells. Polymorphisms in NADPH Oxidase p22phox and with the T allele has been shown to have a greater risk of dialysis and mortality. [12]

Angiotensin-converting Enzyme

Angiotensin-converting enzyme regulates vasomotor movement by controlling blood pressure going through the kidneys. Similarly to the APO-E polymorphism, patients with the D-allele for ACE has an increased risk of acute kidney injury after coronary artery bypass grafting, as well. [12]

HSP72

In infant studies, it was shown that HSP72 gene with the G allele gave an increased risk for acute kidney injury. [12]

Interleukin

Researchers have found that IL-17C is activated in kidney injury. In hypoxia-induced studies of mice, an upregulation of the synthesis of IL-17C was evident upon oxygen loss in the kidney. Moreover, Knockout variants of the IL-17C decreased the inflammation caused by activation of IL-17C.Using antibodies and siRNA against IL-17C also provided the same results. [13] Also, studies of IL-60174GG showed that carriers of this polymorphism have a higher creatinine levels in the blood; however, carriers of the G-allele of IL-10 have a decreased risk of death after organ failure. [12]

VEGF

Unlike with HSP72 polymorphism, infant studies show that VEGF with a homozygous A allele resulted in reduced risk for acute kidney injury. [12]

Examples of Signs and Symptoms of Kidney Ischemia. On the left shows the difference in the size of the kidneys resulting from Kidney Ischemia. Kidney Ischemia may result in a shrinkage of the kidney to about 2cm or more. The top right shows the disruption of the mitochondria due to dysfunctions, This leads to a release of proapoptotic proteins such as cytochrome c and results in cell death. The lower right shows inflammation of the glomeruli of the kidneys. This schematic diagram was drawn using BioRender.com Examples of Signs and Symptoms of Kidney Ischemia.png
Examples of Signs and Symptoms of Kidney Ischemia. On the left shows the difference in the size of the kidneys resulting from Kidney Ischemia. Kidney Ischemia may result in a shrinkage of the kidney to about 2cm or more. The top right shows the disruption of the mitochondria due to dysfunctions, This leads to a release of proapoptotic proteins such as cytochrome c and results in cell death. The lower right shows inflammation of the glomeruli of the kidneys. This schematic diagram was drawn using BioRender.com

Pathophysiology

Several pathophysiological conditions that change when the kidney is undergoing ischemic injuries are listed below. This includes changes in the vasculature, endoplasmic reticulum stress, disfunction of the mitochondria, autophagy of cells, inflammation, and incorrect or maladaptive repair.[ citation needed ]

Vasculature

Normal functions of the kidney require a high amount of oxygen, as such the oxygen supply to the kidney is well regulated. Production of adenosine triphosphate and nitric oxide requires a high concentration of oxygen. These compounds, as well as some reactive oxygen species, are required for the kidney to function properly. With an injury, cellular respiration is compromised. This leads to an imbalance of the supply of oxygen and the products of cellular respiration. When that happens, the kidney undergoes oxidative stress and injury to the microvascular endothelium promotes the recruitment of leukocytes and platelets. This leads to changes in perfusion and oxygen delivery. [14]

Endoplasmic Reticulum Stress

Misfolded and unfolded proteins accumulate in the endoplasmic reticulum. This triggers the unfolded protein response (UPR). The unfolded protein response is an adaptive mechanism to restore cell and tissue homeostasis. If the stress is too severe, the maladaptive response is activated and the C/EBP Homologous Protein pathway (CHOP) is induced. This leads to apoptosis. [14]

Mitochondrial Dysfunction

In acute kidney ischemia, the proximal tubules are vulnerable to mitochondrial dysfunction because they rely on aerobic metabolism and they are in a more oxidized state as compared to the distal tubules. [14] When mitochondrial dysfunction happens, cellular respiration is disrupted. This leads to the mitochondria releasing pro-apoptotic proteins such as cytochrome c and end up in the death of kidney cells.[ citation needed ]

Autophagy

During ischemic stress, the cross-talk between the mitochondria and the UPR is activated. This results in autophagy by which proteins, organelles, and cytoplasmic components are recycled and degraded by the lysosomes. The process of autophagy helps in removing unnecessary components of the cells to maintain more important functions. In this case, autophagy is induced in kidneys in response to hypoxia to protect against further kidney injury. [14]

Inflammation

The renal inflammatory process involves events that lead to injury or death of renal cells. [15] When the kidneys undergo inflammatory responses, it produces mediators such as bradykinin, histamine, and pro-inflammatory cytokines such as interleukin-1 and tumor necrosis factor-a. In mice models, studies wherein removal of these mediators from plasma were observed and has shown beneficial to mice. [15]

Maladaptive Repair

When an injury is severe, the adaptive responses that are activated to restore normal cell and tissue homeostasis become maladaptive. This leads to cell and tissue malfunction. This could lead to chronic kidney disease progression. [14]

Physical Symptoms

Physical symptoms implicated with kidney ischemia includes kidney shrinkage or a difference in kidney sizes, renovascular hypertension, acute renal failure, progressive azotemia, diagnosed by an increase of nitrogen compounds in urine, and acute pulmonary edema which is excess fluid in the lungs. This diagram is drawn using BioRender.com Physical symptoms implicated with Kidney Ischemia.png
Physical symptoms implicated with kidney ischemia includes kidney shrinkage or a difference in kidney sizes, renovascular hypertension, acute renal failure, progressive azotemia, diagnosed by an increase of nitrogen compounds in urine, and acute pulmonary edema which is excess fluid in the lungs. This diagram is drawn using BioRender.com

Kidney features can be clinically suggestive of renal ischemia. Because renal failure can be correlated to hypertension, both of these situations have been observed. [16] In general, kidney sizes differ in patients with acute kidney ischemia. Hypertension, acute renal failure, progressive azotemia, and acute pulmonary edema are also signs of a developing ischemic injury for hypertensive patients.[ citation needed ]

Kidney size differences

In normal patients, the length of the two kidneys only differ by less than 1.5  cm; however, hypertensive patients tend to have an asymmetric kidney size. This strongly suggests ischemic renal disease. [16]

Renovascular hypertension

Renovascular hypertension or renal artery stenosis is characterized as an increase in blood pressure through the arteries to the kidneys. [17] This is due to an abnormal narrowing of the arteries. [17]

Acute Renal Failure caused by the treatment of hypertension

In patients with hypertension, treatment of the disease using Angiotensin-converting enzyme inhibitors (ACEIs) are sometimes necessary. [16] The glomerular filtration rate (GFR) in patients is regulated by vasoconstriction of the efferent arteriole. [16] When ACEI is taken by the patient, this vasoconstrictor effect of the efferent arteriole is blocked. This then leads to a decrease in GFR and leads to acute renal failure. Studies have shown that 6-38% of patients with renal vascular disease or hypertension will develop acute renal ischemia through acute renal failure. [16]

Progressive Azotemia (with Renovascular Hypertension, refractory or severe hypertension, or atherosclerotic diseases)

Azotemia is characterized as an increase of creatinine and blood urea nitrogen (BUN) in the plasma. Patients who have renovascular hypertension often get a deterioration of the renal function. [16]

Likewise above, patients who are being treated with an antihypertensive drug for renovascular, refractory or severe hypertension exhibit progressive azotemia. [16] Acute kidney ischemia may result from taking ACEIs due to the alteration of intrarenal hemodynamics. [16]

Acute pulmonary edema

Acute pulmonary edema is characterized as a fluid collection in the air sacs of the lungs. This makes it difficult for patients to breathe. [18] Patients with poorly-controlled hypertension and renal insufficiency usually also have recurrent acute pulmonary edema. [16] While patients may have other risk factors for having pulmonary edema, volume-dependent renovascular hypertension appears to be the dominant factor. [16]

Diagnosis and Screening

Screening of Biomarkers is one way to diagnose a patient if their kidney is functioning normally.

Biomarkers

Imaging Tests

Duplex Doppler Sonography

Sonography example Sonographer doing pediatric echocardiography.JPG
Sonography example

Duplex Doppler Sonography(DDS) is an imaging test for evaluating blood flow in the kidney or the renal system. B-mode ultrasonography is combined with Doppler ultrasonography, to locate and assess the renal artery and the velocity of blood flowing through it. This test is useful even in the presence of azotemia and for patients with hypertension, it is not necessary to relieve the administration of ACEIs. By assessing the velocity of blood flow, the doctors can measure whether the kidney is receiving enough blood and nutrients to function normally. [16]

Magnetic Resonance Angiography

Assessment of the kidneys magnetic resonance angiography in perfusion and diffusion

Similar to DDS, Magnetic Resonance Angiography(MRA) also images blood vessels. MRA uses magnetic resonance and unlike a traditional angiogram, this does not require inserting a catheter. [24] This test can be used to evaluate stenosis and occlusions in the kidney. This test can also be used to determine aneurysms in the brain. More clinical uses of MRA is used to check blood vessels in different parts of the body, such as the thorax, lower limbs, and the heart. [25]

Functional Tests

Plasma renin activity

Plasma renin activity is also known as renin assay. This assay measures the activity of renin, also known as angiotensinogenase, which plays a role in blood pressure regulation and urine output. [26] This is considered a non-invasive test and patients who are taking ACEIs should opt to take it. This is because it is useful in detecting renovascular hypertension, one of the symptoms of kidney ischemia, with sensitivity going to 90%. [16] However, renal failure may diminish the accuracy of this test. [16]

Renography after administration of ACEI

Renography uses radioisotopes in diagnosing renovascular disease. This test compares normal function of kidney versus stenotic kidney by measuring the amount of the radionucleotides going to the kidney and being excreted by it. [16] Two radionuclides are used in renography: Tc99m-MAG3 (mercaptoacetyltriglycine) and TC99m-DTPA (diethylenetriaminepentacetate). [27] In this test, the radionucleotides are injected intravenously to the system. The compound then progresses through the renal system and is tracked with a gamma camera. [28] The camera then takes images at intervals and a measurement of the radioactivity is taken. By performing this scan, doctors can differentiate between kidney ischemia and intrinsic renal disease by checking the amount of time for the radioactivity to peak and decline. Renovascular hypertension is very sensitive to this imaging, with a specificity of 95% and sensitivity of 96%. [16]

Treatments

Traditional Treatments

Our knowledge of renal ischemia comes from animal studies. Based on these studies, kidney transplants and retrospective partial nephrectomy series indicate the risk of renal function impairment the longer the ischemic injury persists. [29] However, based on historical studies, the use of the duration of the ischemia as a dichotomous marker has been found to have significant flaws in predicting renal function outcomes. The duration of kidney ischemia does not affect kidney function either in the short term or long term. [29]

Ischemic Preconditioning

In patients who get a kidney transplant or a coronary artery bypass, ischemic preconditioning is given. In ischemic preconditioning, the kidney is given a tolerable amount of ischemia. This preconditions the kidney to tolerate subsequent ischemia-induced injuries. This reduces cell lysis and apoptosis of kidney cells and improves the overall renal function of the kidneys post-ischemia as compared to not having the preconditioning. [4]

Furosemide to Promote Post-perfusion Diuresis [29]

A vial of furosemide taken intravenously or intramuscularly Furosemide (cropped).jpg
A vial of furosemide taken intravenously or intramuscularly

Furosemide is a common diuretic and is used for the prevention or to reverse acute kidney injury. [30] A diuretic is a substance that promotes excretion of water from the body. [31] When the kidneys undergo ischemia, it leads to reperfusion or a return of blood supply to the organs. As such, using diuretics has helped in getting rid of excess water in the kidneys after reperfusion. Taking furosemide as a tablet, as a liquid solution, or via injection is used as a preventative measure or as treatment of kidney ischemia has shown to reduce the severity of renal failure, reduce apoptosis induced by ischemia, and speed the recovery of renal function. This as also lead to the reduction of the need of surgical renal replacement in some patients. [30] [31]

Fenoldopam Mesylate

Fenoldopam is used postoperatively in treating Acute Kidney Injury, if used before kidney damage. Similar to Furosemide, this can be taken orally or intravenously; however, bioavailability, or the amount of the drug that reaches the blood circulation, is reduced if taken orally. Fenoldopam is used as a vasodilator and can increase blood flow to the kidneys, as well as renin secretion. Thus, it can be used to regulate the blood pressure in the arteries and reduce injury due to ischemia. [32]

Emerging Treatments

Bendavia

Bendavia is currently in clinical studies targeting mitochondrial dysfunction. It is protective in rat models of kidney ischemia when it was administered before the injury. Bendavia binds to cardiolipin on the inner mitochondrial membrane and this inhibits cytochrome c peroxidase activity. This protects respiration during the early reperfusion and accelerates the recovery of ATP. In the animal models, it was found that tubular cell death and dysfunction were reduced. [14]

Therapeutic Gases: CO, NO, and H2S

This figure shows how Carbon Monoxide, Nitric Oxide, and Hydrogen Sulfide help in attenuating kidney ischemia by reducing inflammation, tissue injury, hypoxia, apoptosis of cells, and vasoconstriction. This was drawn using BioRender.com Mechanism of therapeutic Gases in attenuating Kidney Ischemia.png
This figure shows how Carbon Monoxide, Nitric Oxide, and Hydrogen Sulfide help in attenuating kidney ischemia by reducing inflammation, tissue injury, hypoxia, apoptosis of cells, and vasoconstriction. This was drawn using BioRender.com

Carbon monoxide (CO) helps in stabilizing HIF, which helps in regulating autophagy and hypoxic response. Through this, inflammation and tissue injury are stabilized. Nitric Oxide (NO) is a byproduct of the metabolism of arginine to citrulline by NO synthase. This gas is available in all cells, and inhalation of NO has been found to be therapeutically active. This reduces pulmonary vasoconstriction and lessens apoptosis during renal ischemia. Hydrogen Sulfide (H2S) is also an endogenous product of metabolic activity in cells. This is a byproduct of the metabolism of cysteine by cystathionine-b-synthase. Like with NO, inhalation of H2S has been found to be therapeutic and has been shown to stabilize hypothermia and stabilize cardiovascular hemodynamics which protects from ischemic injury. [33]

Mesenchymal Stem Cell

Mesenchymal Stem Cells (MSCs) are multipotent mature stem cells that are capable of differentiating into different types of cells. This is a promising line of therapy as regenerative medicine has shown benefits in the restoration of the kidneys. MSCs have anti-inflammatory properties and has been applied in animal and human patients. Because of their regenerative capabilities, the kidney can benefit from it by transdifferentiation into kidney cells. Moreover, they can give anti-inflammatory and immuno-modulatory properties and therefore protecting the kidney as well as repairing it from ischemic injury. [34]

Outcome

Ischemic kidney injury might result in fibrosis, irreversible renal dysfunction, and a need for renal replacement therapy. Acute kidney ischemia is associated with high mortality. Chronic ischemic kidney disease (CIKD) usually involves loss of renal parenchyma or reduction of GFR caused by gradual vascular obstruction. Clinically, the term “ischemic renal disease” most often describes CIKD, which contributes to 6–27% of end-stage kidney disease, particularly among patients older than 50 years [34]

Related Research Articles

<span class="mw-page-title-main">Kidney</span> Organ that filters blood and produces urine

In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retroperitoneal space, and in adult humans are about 12 centimetres in length. They receive blood from the paired renal arteries; blood exits into the paired renal veins. Each kidney is attached to a ureter, a tube that carries excreted urine to the bladder.

<span class="mw-page-title-main">Thrombosis</span> Medical condition caused by blood clots

Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an embolus.

<span class="mw-page-title-main">Renin</span> Aspartic protease protein and enzyme

Renin, also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the renin–angiotensin–aldosterone axis—that increases the volume of extracellular fluid and causes arterial vasoconstriction. Thus, it increases the body's mean arterial blood pressure.

<span class="mw-page-title-main">Kidney failure</span> Disease where the kidneys fail to adequately filter waste products from the blood

Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as either acute kidney failure, which develops rapidly and may resolve; and chronic kidney failure, which develops slowly and can often be irreversible. Symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications of acute and chronic failure include uremia, hyperkalaemia, and volume overload. Complications of chronic failure also include heart disease, high blood pressure, and anaemia.

<span class="mw-page-title-main">Ischemia</span> Restriction in blood supply to tissues

Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism. Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue i.e. hypoxia and microvascular dysfunction. It also implies local hypoxia in a part of a body resulting from constriction. Ischemia causes not only insufficiency of oxygen, but also reduced availability of nutrients and inadequate removal of metabolic wastes. Ischemia can be partial or total blockage. The inadequate delivery of oxygenated blood to the organs must be resolved either by treating the cause of the inadequate delivery or reducing the oxygen demand of the system that needs it. For example, patients with myocardial ischemia have a decreased blood flow to the heart and are prescribed with medications that reduce chronotrophy and ionotrophy to meet the new level of blood delivery supplied by the stenosed vasculature so that it is adequate.

<span class="mw-page-title-main">Reperfusion injury</span> Tissue damage after return of blood supply following ischemia or hypoxia

Reperfusion injury, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than restoration of normal function.

<span class="mw-page-title-main">Acute kidney injury</span> Medical condition

Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both.

<span class="mw-page-title-main">Renal artery stenosis</span> Medical condition

Renal artery stenosis (RAS) is the narrowing of one or both of the renal arteries, most often caused by atherosclerosis or fibromuscular dysplasia. This narrowing of the renal artery can impede blood flow to the target kidney, resulting in renovascular hypertension – a secondary type of high blood pressure. Possible complications of renal artery stenosis are chronic kidney disease and coronary artery disease.

<span class="mw-page-title-main">Hypertensive kidney disease</span> Medical condition

Hypertensive kidney disease is a medical condition referring to damage to the kidney due to chronic high blood pressure. It manifests as hypertensive nephrosclerosis. It should be distinguished from renovascular hypertension, which is a form of secondary hypertension, and thus has opposite direction of causation.

<span class="mw-page-title-main">Hypertensive emergency</span> Profoundly elevated blood pressure resulting in symptomatic end-organ injury

A hypertensive emergency is very high blood pressure with potentially life-threatening symptoms and signs of acute damage to one or more organ systems. It is different from a hypertensive urgency by this additional evidence for impending irreversible hypertension-mediated organ damage (HMOD). Blood pressure is often above 200/120 mmHg, however there are no universally accepted cutoff values.

Secondary hypertension is a type of hypertension which by definition is caused by an identifiable underlying primary cause. It is much less common than the other type, called essential hypertension, affecting only 5-10% of hypertensive patients. It has many different causes including endocrine diseases, kidney diseases, and tumors. It also can be a side effect of many medications.

<span class="mw-page-title-main">Arteriolosclerosis</span> Medical condition

Arteriolosclerosis is a form of cardiovascular disease involving hardening and loss of elasticity of arterioles or small arteries and is most often associated with hypertension and diabetes mellitus. Types include hyaline arteriolosclerosis and hyperplastic arteriolosclerosis, both involved with vessel wall thickening and luminal narrowing that may cause downstream ischemic injury. The following two terms whilst similar, are distinct in both spelling and meaning and may easily be confused with arteriolosclerosis.

<span class="mw-page-title-main">Renovascular hypertension</span> Medical condition

Renovascular hypertension is a condition in which high blood pressure is caused by the kidneys' hormonal response to narrowing of the arteries supplying the kidneys. When functioning properly this hormonal axis regulates blood pressure. Due to low local blood flow, the kidneys mistakenly increase blood pressure of the entire circulatory system. It is a form of secondary hypertension - a form of hypertension whose cause is identifiable.

<span class="mw-page-title-main">Brain ischemia</span> Medical condition

Brain ischemia is a condition in which there is insufficient bloodflow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus leads to the death of brain tissue or cerebral infarction/ischemic stroke. It is a sub-type of stroke along with subarachnoid hemorrhage and intracerebral hemorrhage.

Ischemic preconditioning (IPC) is an experimental technique for producing resistance to the loss of blood supply, and thus oxygen, to tissues of many types. In the heart, IPC is an intrinsic process whereby repeated short episodes of ischaemia protect the myocardium against a subsequent ischaemic insult. It was first identified in 1986 by Murry et al. This group exposed anesthetised open-chest dogs to four periods of 5 minute coronary artery occlusions followed by a 5-minute period of reperfusion before the onset of a 40-minute sustained occlusion of the coronary artery. The control animals had no such period of “ischaemic preconditioning” and had much larger infarct sizes compared with the dogs that did. The exact molecular pathways behind this phenomenon have yet to be fully understood.

Renal angina is a clinical methodology to risk stratify patients for the development of persistent and severe acute kidney injury (AKI). The composite of risk factors and early signs of injury for AKI, renal angina is used as a clinical adjunct to help optimize the use of novel AKI biomarker testing. The term angina from Latin and from the Greek ankhone ("strangling") are utilized in the context of AKI to denote the development of injury and the choking off of kidney function. Unlike angina pectoris, commonly caused due to ischemia of the heart muscle secondary to coronary artery occlusion or vasospasm, renal angina carries no obvious physical symptomatology. Renal angina was derived as a conceptual framework to identify evolving AKI. Like acute coronary syndrome which precedes or is a sign of a heart attack, renal angina is used as a herald sign for a kidney attack. Detection of renal angina is performed by calculating the renal angina index.

Remote ischemic conditioning (RIC) is an experimental medical procedure that aims to reduce the severity of ischaemic injury to an organ such as the heart or the brain, most commonly in the situation of a heart attack or a stroke, or during procedures such as heart surgery when the heart may temporary suffer ischaemia during the operation, by triggering the body's natural protection against tissue injury. Although noted to have some benefits in experimental models in animals, this is still an experimental procedure in humans and initial evidence from small studies have not been replicated in larger clinical trials. Successive clinical trials have failed to identify evidence supporting a protective role in humans.

Ischemia-reperfusion (IR) tissue injury is the resultant pathology from a combination of factors, including tissue hypoxia, followed by tissue damage associated with re-oxygenation. IR injury contributes to disease and mortality in a variety of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Whether resulting from traumatic vessel disruption, tourniquet application, or shock, the extremity is exposed to an enormous flux in vascular perfusion during a critical period of tissue repair and regeneration. The contribution of this ischemia and subsequent reperfusion on post-traumatic musculoskeletal tissues is unknown; however, it is likely that similar to cardiac and kidney tissue, IR significantly contributes to tissue fibrosis.

Page kidney or Page phenomena is a potentially reversible form of secondary arterial hypertension caused by external compression of the renal parenchyma by some perirenal process. Any process that causes mass effect can be a potential cause of Page kidney. Hematomas, urinomas, tumors, cysts, lymphoceles, and aneurysms have all been reported in the literature. The compression is believed to cause activation of the renin–angiotensin–aldosterone system (RAAS) via microvascular ischemia.

Roberta Anne Gottlieb is an American oncologist, academic, and researcher. She is a Professor, and Vice-Chair of Translational Medicine in the Department of Biomedical Sciences at Cedars-Sinai Medical Center, and a Professor of Medicine at the University of California, Los Angeles.

References

  1. ↑ Sharfuddin, Asif A.; Molitoris, Bruce A. (April 16, 2011). "Pathophysiology of ischemic acute kidney injury". Nature Reviews Nephrology. 7 (4): 189–200. doi:10.1038/nrneph.2011.16. PMID   21364518. S2CID   32234965 – via www.nature.com.
  2. ↑ Sharfuddin, Asif A.; Molitoris, Bruce A. (April 2011). "Pathophysiology of ischemic acute kidney injury". Nature Reviews Nephrology. 7 (4): 189–200. doi:10.1038/nrneph.2011.16. ISSN   1759-507X. PMID   21364518. S2CID   32234965.
  3. ↑ Munshi, Raj; Hsu, Christine; Himmelfarb, Jonathan (2011-02-02). "Advances in understanding ischemic acute kidney injury". BMC Medicine. 9 (1): 11. doi: 10.1186/1741-7015-9-11 . ISSN   1741-7015. PMC   3038966 . PMID   21288330.
  4. 1 2 Malek, Maryam; Nematbakhsh, Mehdi (2015-06-01). "Renal ischemia/reperfusion injury; from pathophysiology to treatment". Journal of Renal Injury Prevention. 4 (2): 20–27. doi:10.12861/jrip.2015.06. ISSN   2345-2781. PMC   4459724 . PMID   26060833.
  5. ↑ "Definition of INFARCTION". www.merriam-webster.com. Retrieved 2020-12-09.
  6. ↑ Wei, Qingqing; Dong, Zheng (2012-12-01). "Mouse model of ischemic acute kidney injury: technical notes and tricks". American Journal of Physiology. Renal Physiology. 303 (11): F1487–F1494. doi:10.1152/ajprenal.00352.2012. ISSN   1931-857X. PMC   3532486 . PMID   22993069.
  7. ↑ Jonker, Simone J.; Menting, Theo P.; Warlé, Michiel C.; Ritskes-Hoitinga, Merel; Wever, Kimberley E. (2016-03-10). "Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis". PLOS ONE. 11 (3): e0150863. Bibcode:2016PLoSO..1150863J. doi: 10.1371/journal.pone.0150863 . ISSN   1932-6203. PMC   4786316 . PMID   26963819.
  8. 1 2 3 Yamamoto, Takeshi; Takabatake, Yoshitsugu; Takahashi, Atsushi; Kimura, Tomonori; Namba, Tomoko; Matsuda, Jun; Minami, Satoshi; Kaimori, Jun-ya; Matsui, Isao; Matsusaka, Taiji; Niimura, Fumio (2017-05-01). "High-Fat Diet–Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Lipotoxicity in the Kidney". Journal of the American Society of Nephrology. 28 (5): 1534–1551. doi: 10.1681/ASN.2016070731 . ISSN   1046-6673. PMC   5407727 . PMID   27932476.
  9. 1 2 Preston, Richard A.; Epstein, Murray (December 1997). "Ischemic renal disease: an emerging cause of chronic renal failure and end-stage renal disease". Journal of Hypertension. 15 (12): 1365–1377. doi:10.1097/00004872-199715120-00001. PMID   9431840. S2CID   25715659 . Retrieved 2020-12-10.
  10. 1 2 "Arteriosclerosis / atherosclerosis - Symptoms and causes". Mayo Clinic. Retrieved 2020-12-10.
  11. 1 2 3 4 5 Devarajan, Prasad; Mishra, Jaya; Supavekin, Suroj; Patterson, Larry T; Steven Potter, S (2003-12-01). "Gene expression in early ischemic renal injury: clues towards pathogenesis, biomarker discovery, and novel therapeutics". Molecular Genetics and Metabolism. 80 (4): 365–376. doi:10.1016/j.ymgme.2003.09.012. ISSN   1096-7192. PMID   14654349.
  12. 1 2 3 4 5 6 7 8 Lu, Jonathan C. T.; Coca, Steven G.; Patel, Uptal D.; Cantley, Lloyd; Parikh, Chirag R. (June 2009). "Searching for Genes That Matter in Acute Kidney Injury: A Systematic Review". Clinical Journal of the American Society of Nephrology. 4 (6): 1020–1031. doi:10.2215/CJN.05411008. ISSN   1555-9041. PMC   2689876 . PMID   19443624.
  13. ↑ Wang, Feng; Yin, Jianyong; Lin, Yingying; Zhang, Fangfei; Liu, Xuanchen; Zhang, Guangyuan; Kong, Yiwei; Lu, Zeyuan; Wu, Rui; Wang, Niansong; Xing, Tao (2020-06-01). "IL-17C has a pathogenic role in kidney ischemia/reperfusion injury". Kidney International. 97 (6): 1219–1229. doi: 10.1016/j.kint.2020.01.015 . ISSN   0085-2538. PMID   32331702.
  14. 1 2 3 4 5 6 Zuk, Anna; Bonventre, Joseph V. (2016-01-14). "Acute Kidney Injury". Annual Review of Medicine. 67 (1): 293–307. doi:10.1146/annurev-med-050214-013407. ISSN   0066-4219. PMC   4845743 . PMID   26768243.
  15. 1 2 Chatterjee, Prabal K. (2007-10-01). "Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: a comprehensive review". Naunyn-Schmiedeberg's Archives of Pharmacology. 376 (1): 1–43. doi:10.1007/s00210-007-0183-5. ISSN   1432-1912. PMID   18038125. S2CID   25227803.
  16. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 "Ischemic renal disease: an emerging cause of chronic renal... : Journal of Hypertension". LWW. Retrieved 2020-12-09.
  17. 1 2 "Renovascular hypertension: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2020-12-09.
  18. ↑ "Pulmonary edema - Symptoms and causes". Mayo Clinic. Retrieved 2020-12-10.
  19. ↑ Mussap, M.; Noto, A.; Fanos, V.; Van Den Anker, J. N. (2014). "Emerging biomarkers and metabolomics for assessing toxic nephropathy and acute kidney injury (AKI) in neonatology". BioMed Research International. 2014: 602526. doi: 10.1155/2014/602526 . PMC   4071811 . PMID   25013791.
  20. ↑ Tarrant, J (2017). Comprehensive Medicinal Chemistry III. Elsevier. ISBN   9780128032008.
  21. ↑ "Cystatin C". National Kidney Foundation. 2015-12-24. Retrieved 2020-12-07.
  22. 1 2 3 4 5 6 7 Shiva, Niharika; Sharma, Nisha; Kulkarni, Yogesh A.; Mulay, Shrikant R.; Gaikwad, Anil Bhanudas (2020-09-01). "Renal ischemia/reperfusion injury: An insight on in vitro and in vivo models". Life Sciences. 256: 117860. doi:10.1016/j.lfs.2020.117860. ISSN   0024-3205. PMID   32534037. S2CID   219637062.
  23. ↑ Bennett, Michael; Dent, Catherine L.; Ma, Qing; Dastrala, Sudha; Grenier, Frank; Workman, Ryan; Syed, Hina; Ali, Salman; Barasch, Jonathan; Devarajan, Prasad (May 2008). "Urine NGAL Predicts Severity of Acute Kidney Injury After Cardiac Surgery: A Prospective Study". Clinical Journal of the American Society of Nephrology. 3 (3): 665–673. doi:10.2215/CJN.04010907. ISSN   1555-9041. PMC   2386703 . PMID   18337554.
  24. ↑ "Magnetic Resonance Angiography (MRA)". www.hopkinsmedicine.org. 19 November 2019. Retrieved 2020-12-10.
  25. ↑ Hartung, Michael P; Grist, Thomas M; François, Christopher J (2011-03-09). "Magnetic resonance angiography: current status and future directions". Journal of Cardiovascular Magnetic Resonance. 13 (1): 19. doi: 10.1186/1532-429X-13-19 . ISSN   1097-6647. PMC   3060856 . PMID   21388544.
  26. ↑ "Renin Test: What is a Renin Test? Renin Test Definition, Procedure, Considerations, Results - UCLA". www.uclahealth.org. Retrieved 2020-12-10.
  27. ↑ Taylor, Andrew T. (2014-04-01). "Radionuclides in Nephrourology, Part 1: Radiopharmaceuticals, Quality Control, and Quantitative Indices". Journal of Nuclear Medicine. 55 (4): 608–615. doi: 10.2967/jnumed.113.133447 . ISSN   0161-5505. PMC   4061739 . PMID   24549283.
  28. ↑ Elgazzar, Abdelhamid H. (2011-05-10). A Concise Guide to Nuclear Medicine. Springer Science & Business Media. ISBN   978-3-642-19426-9.
  29. 1 2 3 Mir Maria C.; Pavan Nicola; Parekh Dipen J. (2016-06-01). "Current Paradigm for Ischemia in Kidney Surgery". Journal of Urology. 195 (6): 1655–1663. doi:10.1016/j.juro.2015.09.099. hdl: 11368/2968852 . PMID   26804756.
  30. 1 2 Bove, Tiziana; Belletti, Alessandro; Putzu, Alessandro; Pappacena, Simone; Denaro, Giuseppe; Landoni, Giovanni; Bagshaw, Sean M.; Zangrillo, Alberto (2018-04-24). "Intermittent furosemide administration in patients with or at risk for acute kidney injury: Meta-analysis of randomized trials". PLOS ONE. 13 (4): e0196088. Bibcode:2018PLoSO..1396088B. doi: 10.1371/journal.pone.0196088 . ISSN   1932-6203. PMC   5915682 . PMID   29689116.
  31. 1 2 "Furosemide: MedlinePlus Drug Information". medlineplus.gov. Retrieved 2020-12-11.
  32. ↑ Noce, Annalisa; Marrone, Giulia; Rovella, Valentina; Busca, Andrea; Gola, Caterina; Ferrannini, Michele; Di Daniele, Nicola (April 2019). "Fenoldopam Mesylate: A Narrative Review of Its Use in Acute Kidney Injury". Current Pharmaceutical Biotechnology. 20 (5): 366–375. doi:10.2174/1389201020666190417124711. ISSN   1389-2010. PMC   6751352 . PMID   31038062.
  33. ↑ Eltzschig, Holger K.; Eckle, Tobias (November 2011). "Ischemia and reperfusion—from mechanism to translation". Nature Medicine. 17 (11): 1391–1401. doi:10.1038/nm.2507. ISSN   1546-170X. PMC   3886192 . PMID   22064429.
  34. 1 2 Zhu, Xiang-Yang; Lerman, Amir; Lerman, Lilach O. (September 2013). "Concise review: Mesenchymal stem cell treatment for ischemic kidney disease: MSC in Ischemic Kidney Disease". Stem Cells. 31 (9): 1731–1736. doi:10.1002/stem.1449. PMC   3795813 . PMID   23766020.
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