ESRD

What is kidney disease?

Kidney disease occurs when the kidneys are damaged and cannot function properly. Numerous conditions and diseases can result in damage to the kidneys, thus affecting their ability to filter waste from the blood while reabsorbing important substances. Generally, kidney disease may present or develop in a few different ways:

• Acute kidney injury (AKI) is the rapid loss of kidney function. It may be recognised when a person suddenly produces much less urine and/or has a significant increase in the level of waste products in the blood that the kidneys normally filter out. As such AKI is not a specific diagnosis but is the response of the kidneys to a certain bodily insult. The response of the healthcare team is to identify and treat that insult as quickly as possible. AKI is often the result of concurrent illness including sepsis, an immune attack on the kidneys such as a vasculitis or a medication that may alter the effective blood flow to the kidneys or may cause direct damage. It is common in people who present to hospital: about 15-20% of patients with an acute medical illness will have AKI as part of their overall illness. It is also common in patients who are already hospitalised, such as those who are critically ill and in the intensive care unit. If the damage caused by AKI persists, it can eventually progress to chronic kidney disease.
• Chronic kidney disease (CKD) occurs over time and is usually defined as lasting over 3 months. The most common causes in the UK are diabetes and high blood pressure (hypertension). Approximately 1 in 10 people in the UK have CKD. In some cases CKD is preventable or, if detected early enough, treatable to prevent or delay progression to kidney failure.
• Nephrotic syndrome is characterised by the loss of too much protein in the urine. It is caused by damage to the glomeruli and can be a primary disorder of the kidney or secondary to an illness or other condition, such as diabetes or cancer. Along with a high amount of protein in the urine, signs and symptoms of nephrotic syndrome include a low amount of albumin in the blood, higher than normal lipid levels in the blood, and swelling (oedema) in the legs, feet, and ankles. The condition may be acute or chronic, and the outcome can vary.
• Kidney failure, also called end-stage renal disease or ESRD, is the total or near total loss of kidney function and is permanent. Treatment with haemodialysis, peritoneal dialysis or kidney transplantation are the options at this stage of kidney disease that are necessary to sustain life.

Various factors can cause different patterns of injury to the kidneys and can affect kidney function. Some factors affect the functional units, the nephrons, or parts of the nephrons, such as the glomeruli or the tubules. Some factors affect the passage of urine from the kidney while others cause damage to the kidney(s) as a whole.

The most common causes of and main risk factors for kidney disease are:

• Diabetes: a sustained high level of blood glucose from uncontrolled diabetes can over time damage the nephrons in the kidneys. This risk can be minimised by maintaining good glucose control.
• High blood pressure (hypertension): can damage blood vessels within the kidneys,and thus can cause CKD. Conversely, having CKD can cause high blood pressure as well and a critical part of CKD management is good blood pressure control.
• Family history of kidney disease: for example, polycystic kidney disease (PKD) is an inherited disorder in which cysts grow in the kidneys, reducing kidney function over time and eventually leading to kidney failure.

Some other examples of factors affecting the kidneys or patterns of kidney disease include:

• Glomerulonephritis (The glomerulonephritides are a group of diseases that cause inflammation and damage to the blood filtering units of the kidneys (glomeruli) and are the third most common type of kidney disease. They vary in presentation: they may occur acutely and resolve rapidly; they can present acutely but evolve into a more chronic phase; or they may be chronic causing a gradual decline in renal function. In all forms as blood filtering becomes impaired, water and waste products accumulate in the blood, and blood may appear in the urine (haematuria). In some the haematuria may only be detected on testing of the urine in other forms urine often becomes brown because of broken down blood. Certain body tissues swell with the excess water (a condition called oedema). Outcomes can vary: the condition may go away in a few weeks, permanently reduce kidney function, or progress to kidney failure.
• Obstruction: the urinary tract can become blocked, or obstructed, from such things as a kidney stone or tumour and, in men, enlargement of the prostate gland. The blockage can lead to infection and injury of the kidney.
• Autoimmune disease: in autoimmune diseases, the body's immune system mistakenly attacks and damages its own tissue and organs, including the kidneys. Sometimes an autoimmune disorder such as systemic lupus erythematosus or Goodpasture's syndrome can lead to glomerular disease and affect the kidneys.
• Infections: certain bacteria and viruses can infect the kidneys and cause damage. Urinary tract infections (UTIs) that spread to the kidneys (pyelonephritis) is an example.
• Immune response: infections in other parts of the body can stimulate an immune response that has an adverse effect on the kidneys. Examples include streptococcal infection of the throat or skin, the skin infection impetigo, an infection inside the heart (endocarditis), or viral infections such as HIV, hepatitis B, or hepatitis C.
• Congenital defects: defects present at birth, such as those that impede the normal flow of urine.
• Injury: Direct trauma to the kidneys is an uncommon cause of AKI but if severe can lead to chronic kidney disease.
• Toxins: some contrast dyes used for imaging procedures and certain medications can have toxic effects on the kidneys.
• Drugs: use and/or overuse of non-steroidal anti-inflammatory drugs (NSAIDS), such as over-the-counter ibuprofen, and various prescription drugs can damage the kidneys. Use of analgesics (pain killers) has been associated with two different forms of kidney damage: AKI and a type of chronic kidney disease called analgesic nephropathy. Certain antibiotics can be directly toxic to the kidneys if their levels are too high. Some drugs may trigger an immune response by the body that subsequently causes kidney damage (interstitial nephritis see below).
• Pre-renal azotaemia: any situation in which there is reduced blood flow to the kidneys will prevent them from working properly.  This can occur with severe burns, severe dehydration, or septic shock.
• Interstitial nephritis: a kidney disorder in which the spaces between the kidney tubules become inflamed and swollen. It may be acute or chronic. Causes include side effects of certain medications, certain autoimmune disorders, and having a low blood potassium level or a high blood level of calcium or uric acid. It is associated with decreased urine output, blood in the urine, and oedema. Usually, this is a short-term condition.
• Acute tubular necrosis (ATN): ATN is the most common causes of dialysis dependent acute kidney failure and will complicate pre-renal azotaemia if the underlying cause for that condition is not managed adequately. It is caused by a lack of oxygen to the kidney tissues or from damage to the kidneys by toxic substances such as contrast dyes used for x-ray studies and certain medications. In most cases, ATN is reversible.

Chronic kidney disease (CKD) can progress silently over many years, with no signs or symptoms or with ones that are too general for a person to suspect as related to kidney function. For that reason, blood and urine tests are important to allow the detection of blood or protein in the urine and/or abnormal levels of certain waste products in the blood, such as creatinine and urea. The accumulation of these waste products in the blood is a sign of kidney dysfunction. The following problems may, however, be warning signs of kidney disease and should not be ignored. Prompt medical attention is required when any of these are present:

• Swelling or puffiness, particularly around the eyes or in the face, wrists, abdomen, thighs or ankles
• Urine that is foamy, bloody, or coffee-coloured
• A decrease in the amount of urine or the development of a need to pass far more urine especially at night
• Problems urinating, such as a burning feeling or abnormal discharge during micturition
• Mid-back pain (flank), below the ribs, near where the kidneys are located
• High blood pressure (hypertension)especially when this is resistant to treatment

As kidney disease worsens, symptoms may include:

• Urinating more or less often
• Feeling itchy
• Tiredness, loss of concentration
• Loss of appetite, nausea and/or vomiting
• Swelling and/or numbness in hands and feet
• Darkened skin
• Muscle cramps

Acute kidney injury (AKI) is a sudden loss of kidney function and can be fatal. It requires prompt treatment. Symptoms may include:

• Urinating less frequently
• Fluid retention, causing swelling in the legs, ankles or feet
• Drowsiness, fatigue
• Shortness of breath
• Nausea
• Confusion
• Seizures or coma
• Chest pain

The blood and urine tests listed below may provide the first indication of a kidney problem or may be requested if CKD is suspected due to a person's signs and symptoms. These tests reflect how well the kidneys are removing excess fluids and waste products.

A blood pressure measurement is also important since high blood pressure (hypertension) can lead to CKD. When a structural problem is suspected, a variety of imaging tests can be used to evaluate the kidneys. A sample of kidney tissue, a biopsy, is sometimes helpful in diagnosing the specific cause of a problem.

Tests commonly used for screening and diagnosis
The National Institute for Health and Care Excellence (NICE) recommend that people who are at high risk be screened for chronic kidney disease to detect it in its earliest stages. Risk factors include diabetes, high blood pressure, heart disease, or a family history of these or kidney disease. NICE recommend two laboratory tests to screen for kidney disease:

• Urine protein—a few different tests may be used to screen for protein in the urine:
  • Urine albumin—this test may be done on a 24-hour urine sample, or both urine albumin and creatinine can be measured in a random urine sample and the albumin to creatinine ratio (ACR) can be calculated. The ACR as the preferred test for screening for albumin in the urine.
  • Urinalysis—this is a routine test that can detect protein in the urine as well as red blood cells and white blood cells. These are not normally found in the urine and, if present, may indicate kidney disease.
  • Urine total protein or urine protein to creatinine ratio (UPCR)—detects not just albumin, but all types of proteins that may be present in the urine.

Urinalysis and urine total protein are not as sensitive as urine albumin for detecting kidney damage.

• The glomerular filtration rate (GFR) refers to the amount of blood that is filtered by the glomeruli per minute. As a person's kidney function declines due to damage or disease, the filtration rate decreases and waste products begin to accumulate in the blood. To estimate the GFR a blood creatinine test, or possibly a cystatin C test, is performed.

Tests to monitor kidney function
If a person has been diagnosed with a kidney disease, several laboratory tests may be requested to help monitor kidney function. Some of these include:

• Blood levels of creatinine are measured from time to time to see if the kidney disease is getting worse.
• The amount of calcium and phosphorus in the blood and the balance of serum electrolytes can also be measured as these are often affected by kidney disease.
• Haemoglobin in the blood, measured as part of a full blood count (FBC), may also be evaluated as the kidneys make a hormone, erythropoietin, that controls red blood cell production and this may be affected by kidney damage.
• Parathyroid hormone (PTH), which controls calcium levels, is often increased in kidney disease and may be checked to help determine if enough calcium and vitamin D are being taken to prevent bone damage.

Tests to help determine the cause and/or guide treatment
Other tests may be requested to help determine the cause and/or guide treatment, depending on several factors including a person's signs and symptoms, physical examination, and medical history. Some examples of these tests include:

• Urinalysis with a urine culture may be done when someone has symptoms suggesting infection to confirm the presence of a bacterial infection.
• Hepatitis B or C testing—to detect a hepatitis viral infection associated with some types of kidney disease
• Antinuclear antibody (ANA)—to help identify an autoimmune condition such as lupus that may be affecting the kidneys.
• Kidney stone risk panel—this test evaluates a person's risk of developing a kidney stone, to help guide and monitor treatment and prevention
• Kidney stone analysis—this test determines the composition of a kidney stone passed or removed from the urinary tract and may be done to help determine the cause of its formation, to guide treatment, and prevent recurrence
• Complement tests, most commonly C3 and C4—may be tested and monitored with glomerulonephritis
• Serum protein electrophoresis—may be done to determine whether there is a source of an abnormal protein in the blood that could cause kidney damage e.g. myeloma

Imaging techniques
If a structural problem or blockage is suspected, imaging of the kidneys can be helpful. Imaging techniques such as an ultrasound, CT scan (computed tomography), isotope scan, or intravenous pyelogram (IVP) may be used.

Kidney biopsy
A biopsy is sometimes used to help determine the nature and extent of structural damage to a kidney. Analysing a small piece of kidney tissue, obtained using a biopsy needle and diagnostic imaging equipment, can sometimes be useful when disease of the glomeruli (or sometimes the tubules) is suspected.

Appropriate treatment will vary, depending on the cause of the kidney disorder. In general, the earlier kidney disease is recognised, the more likely it is to be treatable, and sometimes – as may occur with acute kidney disease – the damage may be reversible. Goals of treatment are to treat underlying conditions, minimise kidney dysfunction, control symptoms, and prevent the progression of kidney disease to the extent possible.

In the case of diabetes, monitoring and controlling blood glucose levels is paramount. For people with hypertension, lowering blood pressure, often through the use of medications, can help protect the kidneys from damage.

Other medications may be used to relieve some of the symptoms of kidney disease, such as anaemia and oedema, or to lower cholesterol in order to reduce the risk of heart disease. Dietary changes may also be recommended.

Some kidney conditions, such as infections and some acute kidney injuries, can be resolved without causing permanent kidney damage. In many cases, however, the damage cannot be reversed. If the damage is severe and kidney failure has been reached, treatment involves dialysis – either using a machine several times a week to take over kidney filtration or by using peritoneal dialysis – or kidney transplantation.