What Is Kidney Failure?

Kidney failure, also known as renal failure or renal insufficiency, is a medical condition of impaired kidney function in which the kidneys fail to adequately filter metabolic wastes from the blood. The two main forms are acute kidney injury, which is often reversible with adequate treatment, and chronic kidney disease, which is often not reversible. In both cases, there is usually an underlying cause.

Kidney failure is mainly determined by a decrease in glomerular filtration rate, which is the rate at which blood is filtered in the glomeruli of the kidney. The condition is detected by a decrease in or absence of urine production or determination of waste products (creatinine or urea) in the blood. Depending on the cause, hematuria (blood loss in the urine) and proteinuria (protein loss in the urine) may be noted.

In kidney failure, there may be problems with increased fluid in the body (leading to swelling), increased acid levels, raised levels of potassium, decreased levels of calcium, increased levels of phosphate, and in later stages anemia. Bone health may also be affected. Long-term kidney problems are associated with an increased risk of cardiovascular disease.

Kidney Failure Classification

Kidney failure can be divided into two categories: acute kidney injury or chronic kidney disease. The type of renal failure is differentiated by the trend in the serum creatinine; other factors that may help differentiate acute kidney injury from chronic kidney disease include anemia and the kidney size on sonography as chronic kidney disease generally leads to anemia and small kidney size.

Acute Kidney Injury

Acute kidney injury (AKI), previously called acute renal failure (ARF), is a rapidly progressive loss of renal function, generally characterized by oliguria (decreased urine production, quantified as less than 400 mL per day in adults, less than 0.5 mL/kg/h in children or less than 1 mL/kg/h in infants); and fluid and electrolyte imbalance.

AKI can result from a variety of causes, generally classified as prerenal, intrinsic, and postrenal. The underlying cause must be identified and treated to arrest the progress, and dialysis may be necessary to bridge the time gap required for treating these fundamental causes.

Chronic Kidney Disease

Chronic kidney disease (CKD) can also develop slowly and, initially, show few symptoms. CKD can be the long term consequence of irreversible acute disease or part of a disease progression.

Chronic kidney disease is identified by a blood test for creatinine, which is a breakdown product of muscle metabolism. Higher levels of creatinine indicate a lower glomerular filtration rate and as a result a decreased capability of the kidneys to excrete waste products. Creatinine levels may be normal in the early stages of CKD, and the condition is discovered if urinalysis (testing of a urine sample) shows the kidney is allowing the loss of protein or red blood cells into the urine. To fully investigate the underlying cause of kidney damage, various forms of medical imaging, blood tests, and sometimes a kidney biopsy (removing a small sample of kidney tissue) are employed to find out if a reversible cause for the kidney malfunction is present.

Acute-on-chronic Kidney Failure

Acute kidney injuries can be present on top of chronic kidney disease, a condition called acute-on-chronic kidney failure (AoCRF). The acute part of AoCRF may be reversible, and the goal of treatment, as with AKI, is to return the patient to baseline kidney function, typically measured by serum creatinine. Like AKI, AoCRF can be difficult to distinguish from chronic kidney disease if the patient has not been monitored by a physician and no baseline (i.e., past) blood work is available for comparison.

Signs And Symptoms Of Kidney Failure

Symptoms can vary from person to person. Someone in early stage kidney disease may not feel sick or notice symptoms as they occur. When kidneys fail to filter properly, waste accumulates in the blood and the body, a condition called azotemia. Very low levels of azotaemia may produce few, if any, symptoms. If the disease progresses, symptoms become noticeable (if the failure is of sufficient degree to cause symptoms). Kidney failure accompanied by noticeable symptoms is termed uraemia.

Symptoms of kidney failure include the following:

High levels of urea in the blood, which can result in:

  • Vomiting and/or diarrhea, which may lead to dehydration
  • Nausea
  • Weight loss
  • Nocturnal urination
  • More frequent urination, or in greater amounts than usual, with pale urine
  • Less frequent urination, or in smaller amounts than usual, with dark coloured urine
  • Blood in the urine
  • Pressure, or difficulty urinating
  • Unusual amounts of urination, usually in large quantities

A buildup of phosphates in the blood that diseased kidneys cannot filter out may cause:

  • Itching
  • Bone damage
  • Nonunion in broken bones
  • Muscle cramps (caused by low levels of calcium which can be associated with hyperphosphatemia)

A buildup of potassium in the blood that diseased kidneys cannot filter out (called hyperkalemia) may cause:

  • Abnormal heart rhythms
  • Muscle paralysis

Failure of kidneys to remove excess fluid may cause:

  • Swelling of the legs, ankles, feet, face and/or hands
  • Shortness of breath due to extra fluid on the lungs (may also be caused by anemia)
  • Polycystic kidney disease, which causes large, fluid-filled cysts on the kidneys and sometimes the liver, can cause:
  • Pain in the back or side

Healthy kidneys produce the hormone erythropoietin that stimulates the bone marrow to make oxygen-carrying red blood cells. As the kidneys fail, they produce less erythropoietin, resulting in decreased production of red blood cells to replace the natural breakdown of old red blood cells. As a result, the blood carries less hemoglobin, a condition known as anemia. This can result in:

  • Feeling tired and/or weak
  • Memory problems
  • Difficulty concentrating
  • Dizziness
  • Low blood pressure

Normally, proteins are too large to pass through the kidneys, however, they are able to pass through when the glomeruli are damaged. This does not cause symptoms until extensive kidney damage has occurred,[13] after which symptoms include:

  • Foamy or bubbly urine
  • Swelling in the hands, feet, abdomen, or face

Other symptoms include:

  • Appetite loss, a bad taste in the mouth
  • Difficulty sleeping
  • Darkening of the skin
  • Excess protein in the blood
  • With high dose penicillin, people with kidney failure may experience seizures

Causes

Acute Kidney Injury

Acute kidney injury (previously known as acute renal failure) – or AKI – usually occurs when the blood supply to the kidneys is suddenly interrupted or when the kidneys become overloaded with toxins. Causes of acute kidney injury include accidents, injuries, or complications from surgeries in which the kidneys are deprived of normal blood flow for extended periods of time. Heart-bypass surgery is an example of one such procedure.

Drug overdoses, accidental or from chemical overloads of drugs such as antibiotics or chemotherapy, may also cause the onset of acute kidney injury. Unlike chronic kidney disease, however, the kidneys can often recover from acute kidney injury, allowing the patient to resume a normal life. People suffering from acute kidney injury require supportive treatment until their kidneys recover function, and they often remain at increased risk of developing future kidney failure.

Among the accidental causes of renal failure is the crush syndrome, when large amounts of toxins are suddenly released in the blood circulation after a long compressed limb is suddenly relieved from the pressure obstructing the blood flow through its tissues, causing ischemia. The resulting overload can lead to the clogging and the destruction of the kidneys. It is a reperfusion injury that appears after the release of the crushing pressure.

The mechanism is believed to be the release into the bloodstream of muscle breakdown products – notably myoglobin, potassium, and phosphorus – that are the products of rhabdomyolysis (the breakdown of skeletal muscle damaged by ischemic conditions). The specific action on the kidneys is not fully understood, but may be due in part to nephrotoxic metabolites of myoglobin.

Chronic Kidney Disease

Chronic kidney disease (CKD) has numerous causes. The most common causes of CKD are diabetes mellitus and long-term, uncontrolled hypertension. Polycystic kidney disease is another well-known cause of CKD. The majority of people afflicted with polycystic kidney disease have a family history of the disease. Other genetic illnesses affect kidney function, as well.

Overuse of common drugs such as ibuprofen, and acetaminophen (paracetamol) can also cause chronic kidney damage.

Some infectious disease agents, such as hantavirus, can attack the kidneys, causing kidney failure.

Genetic Predisposition

The APOL1 gene has been proposed as a major genetic risk locus for a spectrum of nondiabetic renal failure in individuals of African origin, these include HIV-associated nephropathy (HIVAN), primary nonmonogenic forms of focal segmental glomerulosclerosis, and hypertension affiliated chronic kidney disease not attributed to other etiologies.

Two western African variants in APOL1 have been shown to be associated with end stage kidney disease in African Americans and Hispanic Americans.

Image: Intermountain Medical Center