Kidney Disease

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.

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

• 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.

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.

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)