Azotemia (), also spelled azotaemia, is a medical condition characterized by abnormally high levels of

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

-containing compounds (such as

urea Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...

creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an impor ...

, various body waste compounds, and other nitrogen-rich compounds) in the

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

. It is largely related to insufficient or dysfunctional filtering of

by the

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

s. It can lead to

uremia Uremia is the condition of having high levels of urea in the blood. Urea is one of the primary components of urine. It can be defined as an excess in the blood of amino acid and protein metabolism end products, such as urea and creatinine, which ...

and

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

(kidney failure) if not controlled.

Types

Azotemia has three classifications, depending on its causative origin: prerenal azotemia, renal azotemia, and postrenal azotemia. Measurements of

and

(Cr) in the blood are used to assess renal function. For historical reasons, the lab test measuring urea is known as " blood urea nitrogen" (BUN) in the US. The BUN:Cr ratio is a useful measure in determining the type of azotemia and will be discussed in each section below. A normal BUN:Cr is equal to 15.

Prerenal azotemia

Prerenal azotemia is caused by a decrease in blood flow (

hypoperfusion Perfusion is the passage of fluid through the circulatory system or lymphatic system to an organ or a tissue, usually referring to the delivery of blood to a capillary bed in tissue. Perfusion may also refer to fixation via perfusion, used in ...

) to the kidneys. However, there is no inherent kidney disease. It can occur following

hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, ...

shock Shock may refer to: Common uses Healthcare * Acute stress reaction, also known as psychological or mental shock ** Shell shock, soldiers' reaction to battle trauma * Circulatory shock, a medical emergency ** Cardiogenic shock, resulting from ...

volume depletion Hypovolemia, also known as volume depletion or volume contraction, is a state of abnormally low extracellular fluid in the body. This may be due to either a loss of both salt and water or a decrease in blood volume. Hypovolemia refers to the loss ...

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF typically pr ...

, adrenal insufficiency, and narrowing of the renal artery among other things. The BUN:Cr in prerenal azotemia is greater than 20. The reason for this lies in the mechanism of filtration of urea and creatinine. Renal Plasma Flow (RPF) is decreased due to hypoperfusion which results in a proportional decrease in

Glomerular Filtration Rate Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearance (medicine), clearing toxins; absorption of glucose, amino acids, and other small molecules; reg ...

(GFR). In turn, the decreased flow and pressure to the kidney will be sensed by baroreceptors in the Juxtaglomerular (JG) Cells of the afferent arteriole. If the decrease in blood pressure is systemic (rather than occlusion of the renal artery), baroreceptors in the carotid sinus and aortic arch will be stimulated. This leads to sympathetic nerve activation, resulting in

renin Renin ( etymology and pronunciation), 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 reni ...

secretion through β₁ receptors. Constriction of the afferent arterioles causes a decrease in the intraglomerular pressure, reducing GFR proportionally. Renin is the main effector of the juxtaglomerular baroreceptors. Renin is secreted from granules in the JG cells, and once in the blood stream, it acts as a protease to convert

angiotensin Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adr ...

ogen to angiotensin I, which is converted by

angiotensin converting enzyme Angiotensin-converting enzyme (), or ACE, is a central component of the renin–angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. It converts the hormone angiotensin I to the active vasocon ...

, to angiotensin II, which, in turn, stimulates aldosterone release. Increased

aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays ...

levels results in salt and water absorption in the distal collecting tubule. A decrease in volume or pressure is a non-osmotic stimulus for antidiuretic hormone production in the hypothalamus, which exerts its effect in the medullary collecting duct for water reabsorption. Through unknown mechanisms, activation of the sympathetic nervous system leads to enhanced proximal tubular reabsorption of salt and water, as well as urea (BUN), calcium, uric acid, and bicarbonate. The net result of these 4 mechanisms of salt and water retention is decreased output and decreased urinary excretion of sodium (< 20mEq/L). The increased reabsorption of Na leads to increased water and urea reabsorption from the

proximal tubule The proximal tubule is the segment of the nephron in kidneys which begins from the renal (tubular) pole of the Bowman's capsule to the beginning of loop of Henle. At this location, the glomerular parietal epithelial cells (PECs) lining bowman’s ...

s of the kidney back into the blood. In contrast, creatinine is actually secreted in the proximal tubule. This generally leads to a BUN:Cr ratio greater than 20, a fractional excretion of Na of less than 1%, and an elevated urine osmolarity.

Primary renal azotemia

Renal azotemia (acute kidney failure) typically leads to

. It is an intrinsic disease of the kidney, generally the result of kidney

parenchyma upright=1.6, Lung parenchyma showing damage due to large subpleural bullae. Parenchyma () is the bulk of functional substance in an animal organ such as the brain or lungs, or a structure such as a tumour. In zoology, it is the tissue that ...

l damage. Causes include

kidney failure Kidney failure, also known as renal failure or end-stage renal disease (ESRD), 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 fa ...

glomerulonephritis Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the ...

acute tubular necrosis Acute tubular necrosis (ATN) is a medical condition involving the death of tubular epithelial cells that form the renal tubules of the kidneys. Because necrosis is often not present, the term acute tubular injury (ATI) is preferred by pathologis ...

, or other

kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an Inflammation, inflammatory kidney disease and has several types according to the location of the inflammation. Infla ...

. The BUN:Cr in renal azotemia is less than 15. In cases of kidney disease, glomerular filtration rate decreases, so nothing gets filtered as well as it normally would. However, in addition to not being normally filtered, what urea does get filtered is not reabsorbed by the proximal tubule as it normally would be. This results in lower levels of urea in the blood and higher levels of urea in the urine as compared to creatinine. Creatinine filtration decreases, leading to a higher amount of creatinine in the blood. Third-spacing of fluids, as in

peritonitis Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and covering of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One pa ...

, osmotic diuresis, or low aldosterone states such as

Addison's disease Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adr ...

all elevate urea.

Postrenal azotemia

Blockage of urine flow in an area below the kidneys results in postrenal azotemia. It can be caused by

congenital abnormalities A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth de ...

such as

vesicoureteral reflux Vesicoureteral reflux (VUR), also known as vesicoureteric reflux, is a condition in which urine flows retrograde, or backward, from the urinary bladder, bladder into one or both ureters and then to the renal calyx or kidneys. Urine normally trave ...

, blockage of the

ureter The ureters are tubes composed of smooth muscle that transport urine from the kidneys to the urinary bladder. In an adult human, the ureters typically measure 20 to 30 centimeters in length and about 3 to 4 millimeters in diameter. They are lin ...

s by

kidney stone Kidney stone disease (known as nephrolithiasis, renal calculus disease, or urolithiasis) is a crystallopathy and occurs when there are too many minerals in the urine and not enough liquid or hydration. This imbalance causes tiny pieces of cr ...

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

, compression of the ureters by

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

, prostatic hyperplasia, or blockage of the

urethra The urethra (: urethras or urethrae) is the tube that connects the urinary bladder to the urinary meatus, through which Placentalia, placental mammals Urination, urinate and Ejaculation, ejaculate. The external urethral sphincter is a striated ...

by kidney or

bladder stone A bladder stone is a stone found in the urinary bladder. Signs and symptoms Bladder stones are small mineral deposits that can form in the bladder. In most cases bladder stones develop when the urine becomes very concentrated or when one is ...

s. Like in prerenal azotemia, there is no inherent renal disease. The increased resistance to urine flow can cause back up into the kidneys, leading to

hydronephrosis Hydronephrosis is the hydrostatic dilation of the renal pelvis and Renal calyx, calyces as a result of obstruction to urine flow downstream. Alternatively, hydroureter describes the dilation of the ureter, and hydronephroureter describes the dila ...

. The BUN:Cr in postrenal azotemia is initially >15. The increased

nephron The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structu ...

tubular pressure (due to fluid back-up) causes increased reabsorption of urea, elevating it abnormally relative to creatinine. Persistent obstruction damages the tubular epithelium over time, and renal azotemia will result with a decreased BUN:Cr ratio.

Signs and symptoms

* Oliguria or anuria (decreased or absent urine output) * Fatigue *

Asterixis Asterixis (more colloquially referred to as flapping tremor) is not actually a tremor, but rather a negative myoclonus. This movement disorder is characterized by an inability to maintain a position, which is demonstrated by jerking movements of t ...

(flapping tremor) * Decreased alertness * Confusion * Pale skin *

Tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

(rapid pulse) *

Xerostomia Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, reduced salivary flow, or have no identifiable cause. This symptom is very common and is o ...

(dry mouth) * Thirst *

Edema Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...

anasarca Anasarca is a severe and generalized form of edema, with subcutaneous tissue swelling throughout the body. Unlike typical edema, which almost everyone will experience at some time and can be relatively benign, anasarca is a pathological process r ...

(swelling) * Orthostatic blood pressure (fluctuates depending on body position) *

Uremic frost Uremia is the condition of having high levels of urea in the blood. Urea is one of the primary components of urine. It can be defined as an excess in the blood of amino acid and protein metabolism end products, such as urea and creatinine, which ...

, a condition that occurs when

and urea derivatives are secreted through the skin in sweat, which evaporates away to leave solid uric compounds, resembling a

frost Frost is a thin layer of ice on a solid surface, which forms from water vapor that deposits onto a freezing surface. Frost forms when the air contains more water vapor than it can normally hold at a specific temperature. The process is simila ...

. A

urinalysis Urinalysis, a portmanteau of the words ''urine'' and ''analysis'', is a Test panel, panel of medical tests that includes physical (macroscopic) examination of the urine, chemical evaluation using urine test strips, and #Microscopic examination, m ...

will typically show a decreased urine sodium level, a high urine

-to-serum creatinine ratio, a high urine urea-to-serum urea ratio, and concentrated urine (determined by osmolality and specific gravity). None of these is particularly useful in diagnosis. In pre-renal and post-renal azotemias, elevation of urea exceeds that of the creatinine (i.e., BUN>12*creatinine). This is because urea is readily reabsorbed by the kidneys while creatinine is not. In

(a cause of pre-renal azotemia) or any other condition that causes poor perfusion of kidneys, the sluggish flow of glomerular filtrate results in excessive absorption of urea and elevation of its value in blood. Creatinine, however, is not absorbable and therefore does not rise significantly. Stasis of urine in post-renal azotemia has the same effect.

Treatment

Prompt treatment of some causes of azotemia can result in restoration of kidney function; delayed treatment may result in permanent loss of renal function. Treatment may include

hemodialysis Hemodialysis, American and British English spelling differences#ae and oe, also spelled haemodialysis, or simply ''"'dialysis'"'', is a process of filtering the blood of a person whose kidneys are not working normally. This type of Kidney dialys ...

or peritoneal

dialysis Dialysis may refer to: * Dialysis (chemistry), a process of separating molecules in solution **Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric po ...

, medications to increase cardiac output and increase blood pressure, and the treatment of the condition that caused the azotemia.

References

{{Authority control Abnormal clinical and laboratory findings for blood