Kidney Disease

What are the kidneys and how do they work?

The kidneys are a pair of bean-shaped organs located at the bottom of the ribcage to the right and left of the spine. They are part of the urinary tract and perform a few essential roles and functions within the body.

Within the kidneys are about a million tiny blood filtering units called nephrons. In each nephron, blood is continually filtered through a cluster of looping blood vessels, called a glomerulus, which allows the passage of water and small molecules but retains blood cells and larger molecules.
Attached to each glomerulus are tubes (tubules) that have a number of sections that collect the fluid and molecules that pass through the glomerulus, reabsorb what can be re-used by the body, add other molecules through a process called secretion and, finally, adjust the amount of water that is eventually eliminated along with the waste as urine.
Besides eliminating wastes and helping to regulate the amount of water in the body, these activities allow the kidneys to maintain normal chemical balance in the body. Among the important substances the kidneys help to regulate are sodium, potassium, chloride, bicarbonate, calcium, phosphorus, and magnesium. The right balance of these substances is critical. When the kidneys are not working properly, the concentrations of these substances in the blood may be abnormal, and waste products and fluid may build up to dangerous levels in the blood, creating a life-threatening situation.
Kidneys also have a number of other miscellaneous roles in maintaining a healthy body including the production of a hormone that stimulates red blood cell production (called erythropoietin), production of a hormone that helps maintain a normal blood pressure (called renin), and turning one form of vitamin D into a more active form, which enhances calcium absorption.

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What is kidney disease and what are some of the causes?

Kidney disease occurs when the kidneys cannot function properly. There is not one type of “kidney disease”. Rather, a number of different conditions can cause disease and/or a loss in kidney function, and they have different signs and symptoms depending on how they affect the kidneys. These various causes fall into one of three main groups:

Decreased blood flow to the kidney (“pre-renal”) prevents the kidneys from performing their functions and over time, can damage the kidneys.
- Decreased blood flow can happen very quickly and can be caused by conditions such as shock, severe dehydration and sepsis
- It can also develop slowly over time as a result of heart failure and liver failure, for example
Conditions can affect the kidney itself (“renal”) causing damage and/or impaired function. Some examples include:
- Diabetes
- High blood pressure (hypertension)
- Autoimmune diseases such as lupus or Goodpasture syndrome, or other abnormal immune responses
- Infection—for example, if left untreated, urinary tract infections (UTIs) can spread to the kidneys
- Injury, trauma
- Toxins-- heavy metals and ethylene glycol, for example
- Medications—examples include non-steroidal anti-inflammatory drugs (NSAIDS) and other analgesics (pain killers), certain antibiotics
- Some contrast dyes used for imaging procedures
- Severe damage to muscles (rhabdomyolysis)
- Congenital forms of renal disease (those present at birth), including failure of the kidneys to form or develop normally
- Polycystic kidney disease--a group of disorders characterized by multiple fluid-filled spaces or sacks within the kidneys
Blockage of drainage from the kidney (“post-renal”) can increase pressure within the kidneys and also prevent the kidneys from functioning. As with decreased blood flow, ongoing obstruction can also damage the kidneys. Obstruction of drainage can be due to conditions such as
- Tumors
- Kidney stones
- Enlargement of the prostate, such as benign prostatic hyperplasia (BPH)

Some of these causes can affect all functions of the kidney, and depending on the duration, occur in one of three main ways:

Acute kidney injury (AKI) is the rapid loss of kidney function. It may be recognized when a person suddenly produces urine much less frequently and/or has a dramatic increase in the level of waste products in the blood that the kidneys normally filter out. AKI is often the result of trauma, illness, or a medication that damages the kidneys. It is common in people who are already hospitalized, 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. An older name for AKI is “acute renal failure (ARF).”
Chronic kidney disease (CKD) is the loss of a significant degree of kidney function gradually over time. According to the National Kidney Foundation, 30 million American adults have CKD and millions more are at increased risk. In some cases, CKD is preventable or, if detected early enough, treatable to prevent or delay progression to end-stage renal disease.
End-stage renal disease or ESRD, is the total or near total loss of kidney function and is permanent. Treatment with dialysis or kidney transplantation is the only option at this stage of kidney disease to sustain life.

Some causes of kidney damage initially affect only one part of the kidney, particularly the glomerulus (which filters the blood to let water and small molecules pass into the urine but retains cells and large molecules such as proteins). Glomerular damage often presents in one of three main ways:

Proteinuria refers to increased amounts of protein in the urine. With mild damage, the glomeruli lose their ability to retain protein, which can be detected in the urine. If the body can compensate for the protein loss, there are few to no symptoms.
Nephrotic syndrome occurs with more severe damage to the glomeruli, although the nature of the damage (and the cause) can vary. Large amounts of protein (especially one protein called albumin) are lost in the urine, exceeding the body’s ability to compensate. Because albumin is important for maintaining the right amount of water in the blood, patients with nephrotic syndrome often have an accumulation of fluid in their bodies causing swelling (edema).
Glomerulonephritis (nephritic syndrome) can also reflect severe damage to the glomeruli. Severe inflammation and damage affects kidney function, causing high blood pressure and fluid accumulation, and decreasing urine production. Smaller amounts of protein and some blood (red blood cells) also leak into the urine.

Tumors of the kidney often do not have any effect on kidney function, but are detected as a mass in the kidney by imaging studies or felt by the patient, family, or healthcare practitioner. Blood and/or protein may be present in the urine. Three major tumors that arise in the kidney are:

Renal cell carcinoma is a cancer that develops in the kidney in adults.
Wilms tumor is a cancer that develops in the kidney in children, often between the ages of 2 and 5.
Transitional cell carcinoma is a cancer that develops most commonly in the bladder, but may develop in the lining of the ureters (the tubes between the kidney and the bladder) or rarely within the kidney itself.

About Kidney Disease

Risk Factors
The major risk factors for kidney disease are:

Diabetes: a sustained high level of blood glucose from uncontrolled diabetes can gradually damage the nephrons in the kidneys. People with diabetes can help reduce the risk of this by maintaining good glucose control.

High blood pressure (hypertension): can damage blood vessels within the kidneys. Keeping blood pressure under control can help lower the risk of kidney disease as well as other health problems.

Age: while kidney disease can develop at any age, people over age 60 are more likely to develop the disease

Family history of kidney disease: for example, polycystic kidney disease (PKD) is an inherited disorder

Having heart disease can also increase risk. Chronic kidney disease is more common in African Americans, Hispanic Americans, Asians, Pacific Islanders, and Native Americans.
Signs and Symptoms
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. Routine lab tests done during a health examination can help detect early warning signs of kidney disease such as:

Blood in the urine (hematuria) and/or protein in the urine (proteinuria)

Decreased estimated glomerular filtration rate (eGFR) and elevated creatinine and urea (blood urea nitrogen or BUN), which are early signs of kidney dysfunction.

Other signs and symptoms may include:

Swelling or puffiness, particularly around the eyes or in the face, wrists, abdomen, thighs or ankles

Urine that is foamy, bloody, or coffee-colored

A marked decrease in the amount of urine

Problems urinating, such as a burning feeling or abnormal discharge during urination, or a change in the frequency of urination, especially at night

Mid-back pain (flank), below the ribs, near where the kidneys are located

High blood pressure (hypertension)

As kidney disease worsens, additional signs and symptoms may include a combination of the following:

Feeling itchy

Tiredness, loss of concentration

Loss of appetite, nausea and/or vomiting

Numbness in hands and feet

Darkened skin

Muscle cramps

Gout

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
Tests for screening and diagnosis
The National Kidney Foundation (NKF) and the National Kidney Disease Education Program (NKEDP) recommend that people at high risk be screened for kidney disease.

The NKF recommends that everyone with diabetes between the ages of 12 and 70 be screened at least once a year.

Children with type 1 diabetes should be screened for kidney disease within 5 years of diagnosis while children with type 2 diabetes should be screened as soon as they are diagnosed. Both should then be screened for kidney disease once a year.

At this time, there is no consensus on screening people who have no risk factors or symptoms.

The NKF and NKDEP recommend two tests, in addition to blood pressure measurement, to screen for kidney disease:

Urine protein—a few different tests may be used to screen for protein in the urine:
Urine albumin and albumin/creatinine ratio (ACR)—these detect small amounts of albumin in the urine. The American Diabetes Association recommends ACR as the preferred test for screening for albumin in the urine (microalbuminuria).

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 (UP/CR)—detects not just albumin, but all types of proteins that may be present in the urine.

Estimated glomerular filtration rate (eGFR)— a calculation based on the results of a blood creatinine test or a cystatin C test, along with other variables such as age, sex, and race (e.g., African-American, non-African American), depending on the equation used. The glomerular filtration rate refers to the amount of blood that is filtered by the glomeruli per minute. As kidney function declines, the filtration rate decreases.
General tests for kidney function and disease
Renal panel—a group of tests that may be used to evaluate kidney function and/or screen for, diagnose or monitor kidney disease. While the tests included in the panel can vary by laboratory, they typically include:

Electrolytes: sodium, potassium, chloride, bicarbonate (CO2)

Urea (urea nitrogen or blood urea nitrogen, BUN)

Creatinine

Phosphorus

Calcium

Albumin

Glucose

Calculated values may include eGFR, urea (BUN)/creatinine ratio and anion gap.

Alternatively, each of the above tests may be ordered individually.

Creatinine clearance—this test measures creatinine levels in both a sample of blood and a sample of urine from a 24-hour urine collection. Decreased creatinine clearance may indicate decreased kidney function.

Parathyroid hormone (PTH), which controls calcium levels in the blood, is often increased in kidney disease

Hemoglobin (part of a complete blood count or CBC)—may be done to detect anemia. The kidneys make a hormone called erythropoietin that controls red blood cell production and this may be affected by kidney damage. Erythropoietin may also be measured directly, although this is not a routine test.

Beta 2 microglobulin (B2M) tests may be ordered along with other kidney function tests to evaluate kidney damage and disease and to distinguish between disorders that affect the glomeruli and the renal tubules.

Uric acid is eliminated from the body by the kidneys and is frequently elevated with chronic kidney disease

Vitamin D levels are often decreased; vitamin D is essential to managing calcium and phosphate metabolism in addition to playing a role in cell kidney, cardiac, and immune system functions.
Select tests
Based on an individual's medical history, physical findings, and routine laboratory test results, some select tests may be ordered. Examples include:

Urinalysis with a urine culture—to detect a urinary tract infection and guide antibiotic treatment

Blood culture—possibly may be done to help detect sepsis, which can cause kidney damage

Hepatitis B or hepatitis C testing—to detect a hepatitis viral infection associated with some types of kidney disease

Antinuclear antibody (ANA) and anti-dsDNA—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

Urine protein electrophoresis—may be done to help determine the source of a high level of protein in the urine

Myoglobin—in people who have had extensive damage to their skeletal muscles (rhabdomyolysis), a urine myoglobin test may be ordered. With severe muscle injury, blood and urine levels of myoglobin can rise very quickly.

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. For more on these see RadiologyInfo's web pages on Kidney and Bladder Stones or Kidney (Renal) Failure.

Kidney biopsy

A biopsy is sometimes used to help determine the nature and extent of structural damage to a kidney. Analyzing 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.

Tests for biomarkers of acute kidney injury

Several biomarkers are gaining attention as early indicators of acute kidney injury (AKI). Studies suggest that blood or urine tests for these biomarkers can detect acute kidney damage earlier than currently used kidney function tests, such as serum creatinine. Early detection of AKI is critical because injury occurs rapidly over a period of hours to days. AKI biomarkers are still being studied and may become more widely available in the future.

Although AKI is a serious condition and costs the U.S. healthcare system millions of dollars each year, the measurement of AKI biomarkers does not directly help in treating people with AKI because there are no specific FDA-approved therapies currently available. When AKI is diagnosed, imaging scans of the kidneys are frequently performed to rule out the presence of an obstruction in the urinary tract. General supportive treatment may be given, such as IV fluids or transfusion of blood components. Drugs used to improve blood pressure and heart function may be used if a person is in shock. If a person does not recover from AKI spontaneously, some type of dialysis is required.

Examples of promising AKI biomarkers include:

Urinary insulin-like growth factor-binding protein 7 (IGFBP7) and urinary tissue inhibitor of metalloproteinases-2 (TIMP-2)—these two markers have been combined into a point-of-care test. It is the first test approved by the U.S. Food and Drug Administration to help assess critically ill patients for risk of developing AKI within the next 12 hours.

Neutrophil gelatinase-associated lipocalin (NGAL)—this is a protein that is found in many tissues in the body, including kidney cells. Part of the reason NGAL is a good indicator of AKI is that its level rises rapidly in response to kidney injury, typically within 2-4 hours.

Other biomarkers are currently being studied. Example include kidney injury molecule 1 (KIM-1), interleukin 18 (lL-18), liver-type fatty-acid-binding protein (L-FABP), and tissue inhibitor of metalloproteinase 2 (TIMP-2)
Prevention and Treatment

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

For people with diabetes and/or hypertension, monitoring and controlling their condition, in some cases 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 anemia and edema, 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 end-stage renal disease has been reached, treatment involves dialysis or kidney transplant surgery.

For more on treatment, see the links to other resources in Related Content.

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