Kidney Failure (formerly called Renal Insufficiency)

Renal failure or kidney failure (formerly called renal insufficiency) describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood. The two forms are acute (acute kidney injury) and chronic (chronic kidney disease); a number of other diseases or health problems may cause either form of renal failure to occur.

Renal failure is described as a decrease in the glomerular filtration rate. Biochemically, renal failure is typically detected by an elevated serum creatinine level. Problems frequently encountered in kidney malfunction include abnormal fluid levels in the body, deranged acid levels, abnormal levels of potassium, calcium, phosphate, and (in the longer term) anemia as well as delayed healing in broken bones. Depending on the cause, hematuria (blood loss in the urine) and proteinuria (protein loss in the urine) may occur. Long-term kidney problems have significant repercussions on other diseases, such as cardiovascular disease.

Classification

Renal failure can be divided into two categories: acute kidney injury or chronic kidney disease. The type of renal failure is determined by the trend in the serum creatinine. Other factors which may help differentiate acute kidney injury from chronic kidney disease include anemia and the kidney size on ultrasound. 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. An 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 develop slowly and, initially, show few symptoms. CKD can be the long term consequence of irreversible acute disease or part of a disease progression.

Acute-on-chronic renal failure

Acute kidney injuries can be present on top of chronic kidney disease, a condition called acute-on-chronic renal 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 renal 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.

Symptoms

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). Renal failure accompanied by noticeable symptoms is termed uraemia.

Symptoms of kidney failure include:

    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 build up 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 cause hypocalcaemia)

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

    Abnormal heart rhythms

    Muscle paralysis[6]

    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 which 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

 Proteins are usually too big to pass through the kidneys, but they can pass through when the glomeruli are damaged. This does not cause symptoms until extensive kidney damage has occured, 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

Causes

Acute renal failure

Acute kidney failure usually occurs when the blood supply to the kidneys is suddenly interrupted or when the kidneys become overloaded with toxins. Causes of acute failure 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, whether accidental or from chemical overloads of drugs such as antibiotics or chemotherapeutics, may also cause the onset of acute kidney failure. Unlike in chronic kidney disease, however, the kidneys can often recover from acute failure, allowing the patient to resume a normal life. People suffering from acute failure require supportive treatment until their kidneys recover function, and they often remain at increased risk of developing future kidney failure.

Amongst the accidental causes of renal failure is there also 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

CKD has numerous causes. The most common is diabetes mellitus. The second most common is long-standing, uncontrolled, hypertension, or high blood pressure. 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 aspirin, ibuprofen, and acetaminophen can also cause chronic kidney damage.

Some infectious diseases 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 Africans variants in APOL1 have been shown to associate with end stage kidney disease in African Americans and Hispanic Americans.