Uremia

Uremia is a raised level in the blood of urea and other nitrogenous waste compounds that are normally eliminated by the kidneys. It develops in parallel with deterioration of renal (kidney) function. Uremia is a major symptom of renal failure.

• The term uremia, which "llterally means urine in the blood, was first used by Piorry to describe the clinical condition associated with renal failure.
• Uremia more commonly develops with chronic kidney disease (CKD), especially the later stages of CKD, but it also may occur with acute kidney injury (AKI) if loss of renal function is rapid. Urea itself has both direct and indirect toxic effects on a range of tissues.
• Uremic syndrome can be defined as the terminal clinical manifestation of kidney failure (also called renal failure).
• Uremia is a clinical syndrome marked by elevated concentrations of urea in the blood and associated with fluid, electrolyte, and hormone imbalances and metabolic abnormalities, which develop in parallel with deterioration of renal function.
• Uremia more commonly develops with chronic kidney disease (CKD), especially the later stages of CKD, but it also may occur with acute kidney injury (AKI) if loss of renal function is rapid. Urea itself has both direct and indirect toxic effects on a range of tissues.
• It can happen because of a long-running health problem, like diabetes or high blood pressure, or because a severe injury or an infection damages the kidneys.
• If it’s not treated, uremia can also cause other problems, like:
  • High blood pressure
  • Anemia (when you don’t have enough red blood cells)
  • Heart disease
  • Brain damage

Causes

Uremia is caused by extreme and usually irreversible damage to your kidneys. This is usually from chronic kidney disease. The kidneys are no longer able to filter the waste from your body and send it out through your urine. Instead, that waste gets into your bloodstream, causing a potentially life-threatening condition.

• Causes of chronic kidney disease may include:
  • high blood pressure
  • polycystic kidney disease
  • diabetes (both type 1 and 2)
  • inflammation of the filtering units in the kidneys called glomeruli
  • inflammation of the kidney’s tubules and the structures around them
  • enlarged prostrate
  • some types of cancer
  • kidney stones that block the urinary tract for a prolonged period of time
  • kidney infections that recur

Diagnosis

• May include seeing a nephrologist (kidney specialist)
• Blood tests that include:
  • Basic metabolic panel, serum calcium, phosphorus, blood urea nitrogen, and creatinine.
    • Uremia will demonstrate elevation of both urea and creatinine, likely elevated potassium, high phosphate and normal or slightly high sodium, as well as likely depressed calcium levels.
  • Evaluation for anemia and thyroid and parathyroid functions may also be included.
    • 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.
• Urinalysis which may show blood cells or proteins that shouldn’t be there.
• A 24-hour urine collection will determine creatinine clearance.

Uremia results in many different compounds being retained by the body. With the failure of the kidneys, these compounds can build up to dangerous levels. There are more than 90 different compounds that have been identified. Some of these compounds can be toxic to the body.

Many regulatory functions of the body are affected. Regulation of body fluids, salt retention, acid and nitrogenous metabolite excretion are all impaired and can fluctuate widely. Body fluid regulation is impaired due to a failure to excrete fluids, or due to fluid loss from vomiting or diarrhea. Regulation of salt is impaired when salt intake is low or the vascular volume is inadequate. Acid excretion and nitrogenous metabolite excretion are impaired with the loss of kidney function

In patients with uremia, the diagnosis of renal failure is based primarily on an abnormal glomerular filtration rate (GFR) or abnormal creatinine clearance through blood tests and urinalysis.

In patients with uremia, the diagnosis of renal failure is based primarily on an abnormal glomerular filtration rate (GFR) or abnormal creatinine clearance through blood tests and urinalysis. ICD10 code = R39.2

Symptoms

• Nausea
• Vomiting
• Extreme fatigue
• Anorexia (loss of appetite or taste for some foods)
• Weight loss
• Muscle cramps (esp. in the legs or feet—caused by damage to nerves)
• Pruritus (itching)
• Mental status changes (trouble concentrating)
• Visual disturbances
• Increased thirst

Physical findings

• Skin: Uremic frost (classic finding); sallow discoloration or hyperpigmentation as uremia worsens Patients may become hyperpigmented as uremia worsens (melanosis).
• Eyes: Slightly icteric sclera, or "red eye"
• Mouth: A broad range of oral lesions (eg, gingival hyperplasia, enamel hypoplasia, petechiae, gingival bleeding)
• Cardiovascular: Pericardial rub or a pericardial effusion
• Pulmonary: Crackles in the lungs, due to pulmonary edema

Complications

• Severe complications of untreated uremia include seizure, coma, cardiac arrest, and death. Spontaneous bleeding can occur with severe uremia and may include gastrointestinal (GI) bleeding, spontaneous subdural hematomas, increased bleeding from any underlying disorder, or bleeding associated with trauma.
• Cardiac arrest may occur from severe underlying electrolyte abnormalities, such as hyperkalemia, metabolic acidosis, or hypocalcemia.
• Severe hypoglycemic reactions may occur in patients with diabetes if hyperglycemic medications are not adjusted for decreased creatinine clearance in these individuals.
• Renal failure associated bone disease (renal osteodystrophy) may lead to an increased risk of osteoporosis or bone fracture with trauma.
• Medication clearance is decreased in persons with renal failure and may lead to untoward adverse effects, such as a digoxin overdose, an increased sensitivity to narcotics, and a decreased excretion of normal medications.

Treatment

The ultimate treatment for uremia is renal replacement therapy, which can be accomplished by hemodialysis, peritoneal dialysis, or kidney transplantation.

• Initiation of dialysis is indicated, regardless of the GFR level, when signs or symptoms of uremia are present and are not treatable by other medical means. Despite dialysis, an array of signs and symptoms that have been labeled residual syndrome may develop; this is thought to result from the accumulation of toxic solutes not removed by dialysis.
• Kidney transplantation is the best renal replacement therapy and results in improved survival and quality of life.

History

• Urea was crystallized and identified between 1797 and 1808.
• Urea was hypothesized to be the source of urinary ammonia during this time and was confirmed in 1817. It was hypothesized that excess urea may lead to specific disorders. Later in 1821, it was confirmed that the body did produce urea and that it was excreted by the kidneys.
• In 1827, urea was first synthesized in the lab, confirming the composition of urea and making it the first biological substance synthesized.
• In 1856, urea was produced in vitro via oxidation of proteins.
• It was in 1850 that Thomas Dutrochet seeded the idea of dialysis with the discovery of separating smaller molecules from larger molecules through a semipermeable membrane.
• It was in 1829 and 1831 when convincing proof was obtained that in certain patients, blood urea was elevated. They also suggested that harm may be caused by this. Later research suggested that major neurological disorders like coma and convulsions did not correlate with physical findings which included generalized edema of the brain. This suggested that uremia was a form of blood poisoning.
• In 1851, E.T. Frerich described clinical uremic syndrome and suggested that a toxicity was the mechanism of its cause.
• It was in 1856 that J. Picard developed a sensitive method to reproducibly measure blood urea. He was able to detect a 40% decrease of urea concentration between the renal artery and the renal vein. This work solidified the fact that renal failure coincided with an increase in blood urea. It was J. Picard with E.T. Frerich's work that made the term uremia popular.

Outlook and long-term effects

From: MedicalNewsToday – Outlook and long-term effects (uremia)

• Kidney disease is a chronic illness that can cause many potentially fatal health problems. People who develop uremia may die from kidney failure, particularly if they do not get treatment.
• One study from 1998 followed 139 people with uremia for up to 5 years when 30 percent died.
• People who receive a kidney transplant, as a treatment for kidney failure, are more likely to survive than those who receive dialysis.
• Some people develop uremia due to a temporary and treatable condition, such as a blockage in the kidneys or an enlarged prostate. The outlook for them depends on whether the kidneys are permanently damaged, and whether their uremia damages any other organs.
• Conclusion
  • Uremia is a potentially deadly medical condition that usually signals a chronic illness.
  • A person’s long-term survival and quality of life depend on factors, such as their age, overall health, the quality of their treatment, and the cause of the uremia.
  • People can survive uremia if they have prompt treatment. However, no one should delay seeking treatment for suspected uremia and should ensure they receive treatment from a doctor specializing in kidney failure.

Notables who died from uremia

From: UKRO – Famous People Who Have Died of Kidney Disease

• Jean Harlow actress, died 1937 of kidney failure and uremic poisoning

Resources & additional reading

• Medscape – Uremia
• Healthline – What is Uremia?
• WebMD – What are Uremia and Uremic Syndrome?
• Wikipedia – Uremia
• MedicalNewsToday – All you need to know about uremia
• SlidePlayer Uremia: Effects on Body Systems. By Mary Knutson, RN (6:50 min)
• NCBI – Uremia
• Journal of the American Society of Nephrology – Approaches to Uremia. By Timothy W Meyer and Thomas H Hostetter. JASN October 2014, 25 (10) 2151-2158; DOI: https://doi.org/10.1681/ASN.2013121264