Kidney Disease and Related Laboratory Tests

Improperly functioning kidneys can lead to what is known as kidney disease. Kidney Disease does not fall into one particular description. Instead, there are a variety of conditions that can cause kidney disease and even the loss of kidney function.

Various symptoms and signs of kidney disease depend on how the kidneys are affected. They fall into three main categories:

  • Pre-renal

Pre-renal describes decreased blood flow to the kidney. This reduced flow stops the kidneys from operating correctly. Over time, the reduced flow can damage the kidneys.

When blood flow to the kidneys decreases, it can happen quickly. Shock, severe dehydration, and sepsis are examples of conditions that can cause reduced blood flow. Heart failure and liver failure, for example, can also, over time, contribute to reduced blood flow.

  • Renal

Some conditions can affect the actual kidney. These conditions are called “renal.” When this happens, the kidney is damaged or impaired in function.

Examples of health conditions that contribute to a “renal” condition are:

  • Diabetes
  • Hypertension, otherwise known as high blood pressure
  • Autoimmune diseases such as Goodpasture syndrome, lupus or other abnormal immune responses
  • Infection such as an untreated urinary tract infection or UTI that has spread to the kidneys
  • Injury or trauma
  • Toxins such as ethylene glycol or heavy metals
  • Medications such as non-steroidal anti-inflammatory drugs or NSAIDs, analgesics or pain killers, and particular antibiotics
  • Certain contrast dyes that are used for imaging procedures
  • Damage to muscles otherwise known as rhabdomyolysis
  • Congenital renal disease (those that appear at birth) which includes kidneys that do not develop or form normally
  • Polycystic kidney disease which are disorders that are identified as multiple fluid-filled sacks or spaces within the kidneys

Post-renal

Post-renal kidney disease occurs when the drainage of the kidney is blocked. It can increase the pressure in the kidneys and prevent the organs from functioning. When there is an ongoing obstruction within the organs and, similar to decreased blood flow, the kidneys can be damaged. When there is obstruction of drainage from the kidneys, it can be due to health conditions such as:

  • Tumors
  • Kidney stones
  • An enlarged prostate, such as BPH (benign prostatic hyperplasia)

All functions of the kidney can be affected by some of these causes. Depending on the duration, they occur in one of three primary ways:

  • Acute Kidney Injury or AKI (an older name for AKI is acute renal failure or ARF) is defined as the rapid loss of kidney function. If suddenly, a person produces urine significantly less frequently and/or has a massive increase in the amount of waste products in the blood that are typically filtered out by the kidneys, the condition may be recognized.  AKI is often caused by trauma, medication that damages the kidneys, or illness. Many people who are hospitalized, such as those in intensive care and who are critically ill, commonly exhibit AKI. If AKI-related damage continues, it can become chronic kidney disease.
  • Chronic Kidney Disease, or CKD, occurs when a significant amount of kidney function is lost over time. The National Kidney Foundation reports that 30 million adults are suffering from CKD and that there are millions more that are at an increased risk. CKD is preventable. If it is found early, it can be treated to stop or delay the progression that leads to end-stage renal disease.
  • End-stage Renal Disease, or ESRD, is described as when kidney function is at a near or total loss. It is permanent. The only options to treat ESRD are dialysis or a kidney transplant.

Glomerular Damage

There are some contributors to kidney damage that initially affect only one part of the kidney, especially the glomerulus. The glomerulus filters blood to let water and small molecules move into the urine while retaining cells and large molecules, such as proteins. The appearance of glomerular damage manifests itself in three main ways:

  • Proteinuria is an increased amount of protein found in the urine. When there is mild damage, the glomeruli lose the ability to keep protein that can be detected in the urine. However, if the body can make up for the protein loss, there will be few to no symptoms.
  • Nephrotic syndrome is when the glomeruli are more severely damaged.  The type of damage can vary. Specifically, large amounts of protein (mainly albumin, a protein that helps to maintain the proper amount of water in the blood) get lost in one’s urine, making the body unable to compensate fully. People with nephrotic syndrome often have edema, which is an accumulation of fluid that causes swelling.
  • Glomerulonephritis, known as nephritic syndrome, may also indicate severe damage to the glomeruli.  The specific result is severe inflammation and damage to the functioning of the kidneys. This causes high blood pressure, accumulation of fluid, a decrease in urine production, and small amounts of protein and blood or red blood cells leaking into the urine.

Tumors of the Kidney

When there are tumors in the kidney, there is often no effect on the function of the organs. However, when they are detected, these tumors present as a mass in the kidney detectable through imaging and/or they can be felt by the patient, family, or medical practitioner. There may also be blood and protein in the urine.

Three significant tumors can appear in the kidney:

  • Renal cell carcinoma is cancer that can develop in adult kidneys.
  • Wilms tumor is a cancer that develops in the kidneys of children mostly those that are between the ages of 2 and 5.
  • Transitional cell carcinoma is cancer that often occurs in the bladder and can also develop in the lining of the ureters (which are the tubes that exist between the bladder and the kidney). In addition, sometimes it can appear in the kidney itself.

Risk Factors

  • Diabetes is when there is a continued high level of blood glucose as a result of uncontrolled diabetes that can gradually damage the nephrons located in the kidneys. Therefore, people with diabetes need to maintain good glucose control.
  • High Blood Pressure is known as hypertension and can damage the blood vessels inside the kidneys. Therefore, it’s essential to keep your blood pressure under control to help reduce the risk of kidney disease as well as other health problems.
  • Age: People over 60 are more likely to develop kidney disease. However, the condition can occur at any age.
  • Family History: If there is a history of kidney disease in the family, a person is at risk for developing it. For example, polycystic kidney disease or PKD is an inherited medical disorder.
  • Heart Disease: If you have been diagnosed with heart disease, you are at higher risk for developing kidney disease.
  • Certain Races: It is more common for Native Americans, African Americans, Hispanic Americans, Asians, and Pacific Islanders to get chronic kidney disease.

Signs and Symptoms

The condition of chronic kidney disease or CKD can creep up silently over the years. There may be no signs or symptoms, or the signs and symptoms can be so general that a person doesn’t know it’s related to kidney function. Regular health examinations with routine lab tests can help to detect the early warning signs of kidney disease.

Early warning signs of kidney disease include:

  • Blood in the urine (hematuria)
  • Protein in the urine (proteinuria)
  • Decreased estimated glomerular filtration rate, or eGFR
  • Elevated creatinine
  • Urea (blood urea nitrogen, or BUN)

Some other early warning signs:

  • Puffiness or swelling on the face, around the eyes, on the wrists, abdomen, thighs, ankles, etc.
  • Urine that is bloody, coffee-colored or foamy
  • Decreased quantity of urine that is out-of-the-ordinary
  • Issues with urinating, such as abnormal discharge, a burning feeling, or a change in the number of times you urinate, particularly at night
  • Flank or mid-back pain, pain below the ribs, close to where the kidneys are located
  • High blood pressure or hypertension

The worse the kidney disease gets, additional signs and symptoms may occur and are likely to occur in combination:

  • Itchy feeling
  • Tiredness
  • Loss of concentration
  • Loss of appetite
  • Nausea
  • Vomiting
  • Hands and feet numbness
  • Darkened skin
  • Muscle cramps
  • Gout

Acute Kidney Injury

Acute kidney injury, or AKI, is the sudden loss of kidney functioning. This is a condition that can be fatal and requires immediate treatment.

The symptoms include:

  • Reduced number of urinations
  • Fluid retention that causes swelling in the feet, ankles, and legs
  • Drowsiness
  • Fatigue
  • Shortness of breath
  • Nausea
  • Confusion
  • Seizures
  • Coma
  • Chest pain

Tests for Screening and Diagnosis

The National Kidney Disease Education Program (NKDEP) and The National Kidney Foundation (NKF) both recommend that if you are a person of high risk, you should be screened for kidney disease. The NKF recommends explicitly that if you have diabetes and are between the ages of 12 and 70, you should get tested at least once per year.

A child with type 1 diabetes should get a kidney disease screening within five years of the diagnosis. A child with type 2 diabetes should get a kidney disease screening as soon as the diagnosis. After the initial screening, such children should be screened for kidney disease once per year.

Currently, no consensus exists on screening people who have no risk symptoms or factors.  However, both the NKF and the NKDEP recommend two tests, in addition to testing for blood pressure, to screen for kidney disease:

1. Urine Protein

Urine albumin as well as albumin/creatinine ratio (ACR): These tests will look for tiny amounts of albumin in the urine. According to the American Diabetes Association, ACR is the recommended test for screening for albumin in the urine, also known as microalbuminuria.

Urinalysis: This routine test can find protein, red blood cells, and white blood cells in the urine. These are not typically found in the urine and, therefore, can indicate if there may be kidney disease.

Urine total protein and urine protein to creatinine ratio (UP/CR): This test detects not only albumin but also any other proteins that may be in the urine.

2. Estimated glomerular filtration rate (eGFR) is a calculation that is based on a blood creatinine or cystatin C test. Also, other variables, such as sex, age, race (for example, if you are African-American or non-African-American) are taken into consideration depending on the equation used.  The eGFR rate means the amount of blood filtered by the glomeruli per minute. When kidney function declines, the filtration rate also drops.

General Tests for Kidney Function and Disease: https://www.ultalabtests.com/Shop/Items/Item/Comprehensive-Metabolic-Panel-CMP

A renal panel is a group of tests that can be used to evaluate how the kidneys are functioning. They can also screen for, monitor, or diagnose kidney disease. The test panels vary by laboratory, but generally include:

  • Electrolytes, specifically potassium, sodium, chloride, and carbon dioxide (CO2)
  • Urea (urea nitrogen or blood urea nitrogen, BUN)

There may be calculated values that include eGFR, urea (BUN) to creatinine ratio, and anion gap.

Each of the tests above can be ordered individually.

Further Tests:

  • Creatinine clearance: The patient produces a 24-hour collection. A blood sample is tested as well. Both of these tests will measure creatinine levels. If the level of creatinine clearance is decreased, it may signal a decrease in kidney function.
  • Parathyroid hormone (PTH) controls calcium levels in the blood. PTH levels are often increased in the presence of kidney disease.
  • Hemoglobin, which is part of a complete blood count or CBC, may be performed to detect anemia. Kidneys typically create the erythropoietin hormone that controls red blood cell production. It can be negatively affected by kidney damage. A medical laboratory can also measure erythropoietin directly, but it 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, as well as to distinguish between disorders affecting the renal tubules and the glomeruli.
  • Uric acid, which is eliminated from the body by the kidneys, is often elevated when there is chronic kidney disease.
  • Vitamin D is necessary for managing calcium and phosphate metabolism. It also plays a part in cell kidney, immune system, and cardiac functions.

After considering a person’s physical condition, medical history, and routine lab test results, additional tests may be ordered, such as:

  • A blood culture may be used to identify sepsis, which can cause kidney damage.
  • Hepatitis B and C tests detect a hepatitis viral infection that is associated with some kinds of kidney disease.

Kidney stone risk panel assesses the risks of developing a kidney stone. It is also used to suggest and monitor treatment and prevention.

Kidney stone analysis reveals the composition of a kidney stone that has passed or that is removed from the urinary tract. The test may also be done to determine how the kidney stone was formed, how other stones can be treated, and how to prevent another occurrence.

  • Myoglobin is another test that may be ordered for patients who have had severe damage to their skeletal muscles (rhabdomyolysis).  When there is rhabdomyolysis, both urine and blood levels of myoglobin can quickly rise.

Structural problems or blockage can occur in the kidneys and, if suspected, a medical professional is likely to order an image. The techniques used for imaging include ultrasound, CT scan (or computed tomography), intravenous pyelogram (or IVP), and isotope scan.

Kidney Biopsy

If there is structural damage to the kidney suspected, a kidney biopsy can help establish the nature and extent of the damage. A medical professional analyzes a small piece of kidney tissue that is obtained with the use of a biopsy needle and diagnostic imaging equipment. This can be useful when disease of the glomeruli or tubules is suspected.

Tests for Biomarkers of Acute Kidney Injury

There are a few biomarkers that are becoming popular as early indicators of acute kidney injury (or AKI). Traditional tests, such as serum creatinine, a kidney function test, may not detect AKI as early as some other tests highlighted below. Early detection of AKI is critical. This is because injury to the kidneys can occur rapidly over hours to days. These AKI biomarkers are still under study but may become more widely available in the future.

AKI is a severe condition that creates millions of dollars in cost to the American healthcare system every year. However, AKI biomarkers do not directly help in the treatment of AKI as there are no particular FDA-approved therapies that are currently available. When a diagnosis of AKI is produced, imaging scans of the kidneys are frequently performed to rule out the possibility of an obstruction in the urinary tract. Supportive treatment, such as an introduction of IV fluids or a transfusion of blood components. If a person is in shock, drugs to improve blood pressure and heart function may be provided. Dialysis may be dictated if a person does not spontaneously recover from AKI.

Examples of New AKI Tests that Look Promising

Urinary insulin-like growth factor-binding protein 7 (IGFBP7), as well as urinary tissue inhibitor of metalloproteinases-2 (TIMP-2), are two markers that have been combined into a point-of-care test, and it is the first test that has been approved by the U.S. Food and Drug Administration to determine what the risk is for a critically ill patient to develop AKI within 12 hours.

Neutrophil gelatinase-associated lipocalin (NGAL) is a protein found in many tissues in the body, including kidney cells.  The level of NGAL rises rapidly when there is AKI (within 2 to 4 hours), making it a good indicator.  Other factors are also under study.  These include biomarkers like metalloproteinase 2 (a tissue inhibitor known as TIMP-2). They also include liver-type fatty-acid-binding protein (or L-FABP). Two other biomarkers under study include interleukin 18 (or IL-18) as well as kidney injury molecule 1 (or KIM-1).