Uremia

Uremia
Specialty	Urology

Uremia or uraemia (see spelling differences) is a term used to loosely describe the illness accompanying kidney failure (also called renal failure), in particular the nitrogenous waste products associated with the failure of this organ. This is not to be confused with uricemia, or hyperuricemia, a build up of uric acid in the blood.

In kidney failure, urea and other waste products, which are normally excreted into the urine, are retained in the blood. Early symptoms include anorexia and lethargy, and late symptoms can include decreased mental acuity and coma. Other symptoms include fatigue, nausea, vomiting, cold, bone pain, itch, shortness of breath, and seizures. It is usually diagnosed in kidney dialysis patients when the glomerular filtration rate, a measure of kidney function, is below 50% of normal.

Azotemia is another word that refers to high levels of urea, but is used primarily when the abnormality can be measured chemically but is not yet so severe as to produce symptoms. Uremia can also result in uremic pericarditis. There are many dysfunctions caused by uremia affecting many systems of the body, such as blood (lower levels of erythropoietin), sex (lower levels of testosterone/estrogen), and bones (osteoporosis and metastatic calcifications). Uremia can also cause decreased peripheral conversion of T4 to T3, producing a functionally hypothyroid state.

Signs and symptoms

Uremic frost present on the forehead and scalp of a young man who presented with complaints of anorexia and fatigue with blood urea nitrogen and serum creatinine levels of approximately 100 and 50 mg/dL respectively.

Neural and muscular

• Fatigue
• Peripheral neuropathy
• Decreased mental acuity
• Seizures
• Anorexia
• Nausea
• Weakness
• Decreased taste and smell
• Cramps
• Restless legs, potentially due to decreased muscle membrane potential
• Sleep disturbance
• Coma
• Encephalopathy

Endocrine and metabolic

• Amenorrhea
• Sexual dysfunction
• Reduced body temperature
• Altered levels of amino acids
• Bone disease by hyperphosphatemia, hyperparathyroidism, and vitamin D deficiency
• Reduced basal metabolic rate
• Insulin resistance
• Increased muscle protein catabolism

Other

• Serositis, including pericarditis
• Itching
• Hiccups
• Oxidative stress
• granulocyte and lymphocyte dysfunction
• Platelet dysfunction
• Excretion of retained urea through the skin with subsequent crystallization leading to a characteristic "uremic frost"

Because uremia is mostly a consequence of kidney failure, its signs and symptoms often occur concomitantly with other signs and symptoms of kidney failure, such as hypertension due to volume overload, hypocalcemic tetany, and anemia due to erythropoietin deficiency. These, however, are not signs or symptoms of uremia. Still, it is not certain that the symptoms currently associated with uremia are actually caused by excess urea, as one study showed that uremic symptoms were relieved by initiation of dialysis, even when urea was added to the dialysate to maintain the blood urea nitrogen level at approximately 90 mg per deciliter (that is, approximately 32 mmol per liter).

Causes

Besides renal failure, the level of urea in the blood can also be increased by:

• increased production of urea in the liver, due to:
  • high protein diet
  • increased protein breakdown (surgery, infection, trauma, cancer)
  • gastrointestinal bleeding
  • drugs (e.g. tetracyclines and corticosteroids)

• decreased elimination of urea, due to:
  • decreased blood flow through kidney (e.g. hypotension, cardiac failure)
  • urinary outflow obstruction
  • bladder rupture

• dehydration
• chronic infection of the kidney such as chronic pyelonephritis

Diagnosis

Detailed and a accurate history and physical will help determine if uremia is acute or chronic. In the cases of acute uremia, causes may be identified and eliminated, leading to higher chance for recovery of normal renal function, if treated correctly.

Blood tests

Primary tests performed for the diagnosis of uremia are basic metabolic panel with serum calcium and phosphorus to evaluate the GFR, blood urea nitrogen and creatinine as well as serum potassium, phosphate, calcium and sodium levels. Principal abnormality is very low (<30) GFR. Uremia, unlike azotemia will demonstrate elevated both urea and creatinine, likely elevated potassium, high phosphate and normal or slightly high sodium, as well as likely depressed calcium levels. As a basic work up a physician will also evaluate for anemia and thyroid and parathyroid functions. Chronic anemia may be an ominous sign of established renal failure. The thyroid and parathyroid panels will help work up any symptoms of fatigue, as well as determine calcium abnormalities as they relate to uremia vs longstanding or unrelated illness of calcium metabolism.

Urine tests

A 24 hour urine collection for determination of creatinine clearance may be an alternative although not very accurate test due to collection procedure. Other laboratory that should be considered are urinalysis with microscopic examination for the presence of protein, casts, blood and and pH.

Radioisotope tests

The "gold-standard" for determining GFR is iothalamate clearance. However, it may be cost-prohibitive and time-consuming. Clinical labs generally calculate the GFR with Modification of Diet in Renal Disease (MDRD) formula or the Cockcroft-Gault formula.

Other

In addition, coagulation studies may indicate prolonged bleeding time with otherwise normal values (see below).
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