Renal Artery Stenosis

Epidemiology and Etiology

Epidemiology

• Renal artery Renal artery A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. Glomerular Filtration stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) (RAS) accounts for < 2% of all cases of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension.
• 2 main types of RAS:
  • Atherosclerotic type: 
    • 80% of all RAS cases
    • Strong association with atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis in other parts of the body
    • Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship > 45 years of age, males > females
    • More common in Whites than in Blacks
    • Present in 10%–40% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with acute, severe, or refractory hypertension Refractory hypertension Blood pressure that cannot be controlled even with maximally tolerated doses of ≥ 5 drugs. Uncontrolled Hypertension 
    • Bilateral disease is present in 23%–54% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (rarely do both sides show the same degree of stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS)).
  • Fibromuscular dysplasia Fibromuscular dysplasia Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory, medium-sized angiopathy due to fibroplasia of the vessel wall. The condition leads to complications related to arterial stenosis, aneurysm, or dissection. Fibromuscular Dysplasia ( FMD FMD Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory, medium-sized angiopathy due to fibroplasia of the vessel wall. The condition leads to complications related to arterial stenosis, aneurysm, or dissection. Fibromuscular Dysplasia) type:
    • 20% of all RAS cases
    • 90% of adult cases are in women.
    • Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are women < 50 years but all ages can be affected.
    • May be associated with FMD FMD Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory, medium-sized angiopathy due to fibroplasia of the vessel wall. The condition leads to complications related to arterial stenosis, aneurysm, or dissection. Fibromuscular Dysplasia of the carotid and vertebral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology

Etiology

• Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis type: diffuse atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis usually present, but can be isolated
• FMD FMD Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory, medium-sized angiopathy due to fibroplasia of the vessel wall. The condition leads to complications related to arterial stenosis, aneurysm, or dissection. Fibromuscular Dysplasia type: unknown etiology but genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics believed to play an important role
• Rare causes of RAS (approximately 1% of cases):
  • Extrinsic compression Compression Blunt Chest Trauma: usually by tumor Tumor Inflammation
  • Intimal dissection: caused by trauma or endovascular intervention
  • Thromboembolism Thromboembolism Obstruction of a blood vessel (embolism) by a blood clot (thrombus) in the blood stream. Systemic Lupus Erythematosus: caused by local sources (e.g., trauma, vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus) or by distant emboli (e.g., from left atrium or fat emboli from fractures)
  • Iatrogenic Iatrogenic Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment. Anterior Cord Syndrome causes: migration and/or placement of endovascular aortic stent over the renal orifices 

Pathophysiology

• Pathogenesis of all RAS cases:
  • Significant decrease of lumen ≥ 70% (less than 30% patent) with poststenotic gradient → blood pressure is affected
  • Renal hypoperfusion → activation of the renin-angiotensin-aldosterone system Renin-angiotensin-aldosterone system A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin i; angiotensin ii; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system. Adrenal Hormones ( RAAS RAAS A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin i; angiotensin ii; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system. Adrenal Hormones) → increased renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation, angiotensin, and aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia → increased sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia (Na) retention and peripheral vascular resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
  • Renovascular (secondary) hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension (RVH) is the final result → affects both kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy and other target organs
• RAS caused by atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis:
  • Usually involves the aortic orifice or the proximal main renal artery Renal artery A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. Glomerular Filtration
  • Without treatment, 50% of cases progress, sometimes to complete obstruction.
• RAS caused by fibromuscular dysplasia Fibromuscular dysplasia Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory, medium-sized angiopathy due to fibroplasia of the vessel wall. The condition leads to complications related to arterial stenosis, aneurysm, or dissection. Fibromuscular Dysplasia:
  • Medial fibroplasia Fibroplasia Fibromuscular Dysplasia represents the most common dysplastic lesion, but intima  fibroplasia Fibroplasia Fibromuscular Dysplasia and fibrous Fibrous Fibrocystic Change hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation of the adventitia also occur.
  • Typically, involves the mid- or distal main renal artery Renal artery A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. Glomerular Filtration or the intrarenal branches 
  • Focal loss of the internal elastic Elastic Connective Tissue: Histology lamina, with intervening fibromuscular hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation, produces the typical “string of beads” appearance on an angiogram.
  • Rarely leads to complete obstruction

Clinical Presentation and Diagnosis

Clinical signs and medical history

• Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are asymptomatic, with only mild hemodynamic effects, if the lumen is < 70% occluded.
• RVH should be suspected, and investigation for RVH initiated, if there are any of the following findings:
  • Diastolic hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension develops abruptly in a patient < 30 years or > 50 years.
  • New or previously stable hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension rapidly worsens.
  • Very severe hypertension Severe hypertension A confirmed blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic. Uncontrolled Hypertension: systolic ≥ 180 and/or diastolic ≥ 120 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension with worsening renal function or refractory to drug treatment
  • Elevated serum creatinine within 1 week of starting an angiotensin-converting enzyme inhibitor ( ACEI ACEi A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Renin-Angiotensin-Aldosterone System Inhibitors), angiotensin II Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the c-terminal by angiotensin converting enzyme. The amino acid in position 5 varies in different species. To block vasoconstriction and hypertension effect of angiotensin II, patients are often treated with ace inhibitors or with angiotensin II type 1 receptor blockers. Renal Sodium and Water Regulation receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors blocker (ARB), or a direct renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation inhibitor
  • Abdominal bruit Abdominal Bruit Abdominal Examination on 1 side
  • History of trauma to the back or flank or acute pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in the back or flank region with or without hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma (suggestive of arterial injury Arterial Injury Hemothorax) 
  • Asymmetric renal size (> 1 cm difference) discovered incidentally by imaging 
  • Recurrent episodes of unexplained acute pulmonary edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema or heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) 
• Atherosclerotic-type RAS:
  • > 50 years of age
  • Strong association with other cardiovascular pathologies
  • Often presents with concurrent small-vessel disease in kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy
  • Bilateral renal arterial stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) is associated with more widespread atherosclerotic disease, higher serum creatinine levels, and higher mortality Mortality All deaths reported in a given population. Measures of Health Status than the unilateral disease.
• FMD-type RAS:
  • Mostly in premenopausal women 15–50 years of age
  • Strongly suspect if hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension occurs in a child
  • Typically, found incidentally on imaging
  • A systolic-diastolic bruit in the epigastrium Epigastrium Surgical Anatomy of the Abdomen is present in only 50% of FMD FMD Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory, medium-sized angiopathy due to fibroplasia of the vessel wall. The condition leads to complications related to arterial stenosis, aneurysm, or dissection. Fibromuscular Dysplasia cases.

Diagnostic procedures

Additional diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests can be used in the following cases:

• Once other causes of secondary hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension have been excluded
• If confirmation is needed, due to diagnostic uncertainty
• If therapeutic revascularization Revascularization Thromboangiitis Obliterans (Buerger’s Disease) procedures are indicated

However, the tests are expensive and may have serious side effects, especially if renal insufficiency is present.

• Noninvasive tests: less reliable for FMD FMD Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory, medium-sized angiopathy due to fibroplasia of the vessel wall. The condition leads to complications related to arterial stenosis, aneurysm, or dissection. Fibromuscular Dysplasia, related to distally located lesions:
  • Duplex Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography) ultrasonography
  • Computed tomographic angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery ( CTA CTA A non-invasive method that uses a ct scanner for capturing images of blood vessels and tissues. A contrast material is injected, which helps produce detailed images that aid in diagnosing vascular diseases. Pulmonary Function Tests)
  • Magnetic resonance angiography Magnetic resonance angiography Non-invasive method of vascular imaging and determination of internal anatomy without injection of contrast media or radiation exposure. The technique is used especially in cerebral angiography as well as for studies of other vascular structures. Imaging of the Urinary System ( MRA MRA Imaging of the Heart and Great Vessels)
  • Captopril Captopril A potent and specific inhibitor of peptidyl-dipeptidase a. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. Hypertension Drugs renogram: radionuclide renography using captopril Captopril A potent and specific inhibitor of peptidyl-dipeptidase a. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. Hypertension Drugs, an ACEI ACEi A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Renin-Angiotensin-Aldosterone System Inhibitors, mainly used to determine the relative function of each kidney
• Invasive testing: intra-arterial angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery:
  • Gold standard for assessing RAS
  • Perform only after non-invasive testing has been done.
  • Carries risk of atheroembolism Atheroembolism An embolus is an intravascular solid, liquid, or gaseous material that is carried by the blood to a site distant from its point of origin. Emboli of all types warrant immediate medical attention. The majority of emboli dislodge from a thrombus, forming a thromboembolus. Other less common nonthrombotic types of emboli are cholesterol, fat, air, amniotic fluid, and tumor emboli. Nonthrombotic Embolism

Laboratory testing

• Routine testing to evaluate kidney function by estimated glomerular filtration Glomerular filtration The kidneys are primarily in charge of the maintenance of water and solute homeostasis through the processes of filtration, reabsorption, secretion, and excretion. Glomerular filtration is the process of converting the systemic blood supply into a filtrate, which will ultimately become the urine. Glomerular Filtration rate ( GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests, from serum creatinine) and urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children
• Other labs:
  • Complete blood count (CBC)
  • Serum electrolyte levels ( sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia, potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia, chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes, and total carbon dioxide)
  • Blood urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle nitrogen Nitrogen An element with the atomic symbol n, atomic number 7, and atomic weight [14. 00643; 14. 00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth’s atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. Urea Cycle (BUN)
  • Lipid panel and fasting glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance 
• Findings:
  • In mild RAS, insufficient to affect blood pressure → no abnormal labs
  • If RAS is severe enough to affect blood pressure (decrease of lumen ≥ 70%, with poststenotic gradient), specific testing is of limited value (poor sensitivity or specificity):
    • Plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation activity ( PRA PRA Purine and Pyrimidine Metabolism) is elevated in only 50%–80% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with renovascular hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension.
    • Renal vein Renal vein Short thick veins which return blood from the kidneys to the vena cava. Glomerular Filtration renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation measurements have many false positives and negatives.

Management

Medical therapy

• Blockade of the renin-angiotensin system ( ACEIs ACEIs A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Heart Failure and Angina Medication, ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Angina Medication)
• Blood pressure control ( calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers, diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication, beta blockers)
• Lifestyle changes: cessation of tobacco
• Statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins in atherosclerotic RAS
• Antiplatelet therapy

Invasive procedures

• Revascularization Revascularization Thromboangiitis Obliterans (Buerger’s Disease) is usually reserved for cases in which medical therapy has failed.
• Major complications occur in 5%–9% of cases, even with experienced operators.
• Procedures include percutaneous transluminal renal angioplasty Angioplasty Reconstruction or repair of a blood vessel, which includes the widening of a pathological narrowing of an artery or vein by the removal of atheromatous plaque material and/or the endothelial lining as well, or by dilatation (balloon angioplasty) to compress an atheroma. Except for endarterectomy, usually these procedures are performed via catheterization as minimally invasive endovascular procedures. Cardiac Surgery or aortorenal bypass surgery.
• Therapeutic nephrectomy Nephrectomy Excision of kidney. Renal Cell Carcinoma is advised in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with uncontrolled hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension and unilateral renovascular occlusion, especially if the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy are poorly functioning (< 15% of total GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests).

Differential Diagnosis

Primary (“essential”) hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension

The most common type of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, with an unknown etiology. In 2017, the American College of Cardiology/ American Heart Association American Heart Association A voluntary organization concerned with the prevention and treatment of heart and vascular diseases. Congestive Heart Failure (ACC/AHA) revised their definitions, which may vary among different countries:

• Normal blood pressure: systolic < 120 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg and diastolic < 80 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg
• Elevated blood pressure: systolic 120–129 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg and diastolic < 80 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg
• Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension stage 1 Stage 1 Trypanosoma brucei/African trypanosomiasis: systolic 130–139 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg or diastolic 80–89 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg
• Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension stage 2: systolic at least 140 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg or diastolic at least 90 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg

Secondary causes of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension

Five to ten percent of all cases of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension include the following conditions:

• Primary kidney disease: suspected with elevated serum creatinine concentration and/or abnormal urinalysis. Chronic kidney disease typically has a persistent and progressive reduction in GFR, but differential diagnosis from RVH can be difficult.
• Primary aldosteronism: usually caused by an aldosterone-producing adenoma in the adrenal gland or bilateral adrenal hyperplasia. Clues include hypokalemia and increased plasma aldosterone to plasma renin activity.
• Sleep apnea syndrome: characterized by repeated apneic episodes at night due to passive collapse of the pharyngeal muscles during inspiration. Usually occurs in obese men who snore loudly while asleep. Can have hypertension, headache, cardiac arrhythmias, daytime somnolence and fatigue, confusion, personality changes, and depression.
• Oral contraceptives: normally, can elevate the blood pressure to hypertensive levels
• Pheochromocytoma: a catecholamine-secreting tumor from chromaffin cells of the adrenal medulla or the sympathetic ganglia. Paroxysmal elevations in blood pressure occur, with the classic symptom triad of pounding headache, palpitations, and sweating. 
• Cushing’s syndrome: caused by excess corticosteroid, which may be exogenous or endogenous, usually from a benign adrenal adenoma. Presents with Cushingoid facies, central obesity, proximal muscle weakness, and ecchymoses. 
• Coarctation of the aorta: a major cause of secondary hypertension in young children but may be diagnosed initially in adulthood. Causes hypertension in the upper extremities, low blood pressure in the lower extremities, and diminished or delayed femoral pulses (“brachial-femoral delay”). May auscultate a “machinery murmur” from the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy over the posterior thorax. 
• Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism: symptoms of hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism ( fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, sensitivity to cold, weight gain, constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation, depression, muscle aches, and cramps Cramps Ion Channel Myopathy) with an elevated serum thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones (TSH) level.
• Primary hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism: due to parathyroid adenoma Parathyroid Adenoma Hyperparathyroidism and associated with hypercalcemia Hypercalcemia Hypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Hypercalcemia, elevated levels of parathyroid hormone Parathyroid hormone A polypeptide hormone (84 amino acid residues) secreted by the parathyroid glands which performs the essential role of maintaining intracellular calcium levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of calcium from bone, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates. Parathyroid Glands: Anatomy
• Renal atheroemboli: also called cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism crystal emboli, usually affects older patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with diffuse erosive atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis. Renal atheroemboli occur when portions of an atherosclerotic plaque Atherosclerotic plaque Lesions formed within the walls of arteries. Atherosclerosis break off and embolize distally. Can affect kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy or other organs.
• Chemotherapeutic agents: agent-related kidney injury by a thrombotic microangiopathy pathway or by inhibiting vascular endothelial growth factor Vascular endothelial growth factor A family of angiogenic proteins that are closely-related to vascular endothelial growth factor a. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells. Wound Healing (VEGF) signaling pathways