Clinical Biochemistry Fall Semester
Kidney (Renal) Function Tests
The kidneys are vital organs.
Functions :
Urine formation
Fluid and electrolyte balance
Excretion of the metabolic waste products
Excretion of drugs and toxins
Secretion of hormones (erythropoietin, 1,25 dihydroxy vitamin D3, prostaglandins)
RENAL PHYSIOLOGY
1. Glomerular filtration: water, electrolytes, amino acids, glucose, low molecular weight proteins (< 66.000 Da), urea, creatinine pass freely thorough the basement membrane and enter the proximal tubule. Other blood constituents, such as albümin, many plasma proteins, cellular elements, protein-bound substances, such as lipids and bilurubin are too large to be filtered. 1200- 1500 mL of blood that the kidneys receive each minute , the glomerulus filters out 125-130 mL glomerular filtrate. The volume of blood filtered per minute is the glomerular filtration rate (GFR) , and its determination is essential in evaluating renal function.
2. Tubular reabsorption and 3. Tubular secretion: One function of the proximal tubule, is to return the bulk of each valuable substance back to the blood circulation. Thus 75% of the water, sodium and chloride, 100% of the glucose, almost all the amino acids, vitamins, varying amounts of urea* (%50), uric acid** and ions are reabsorbed. A second function of the is to secrete products of kidney tubular cell metabolism such as H ions and drugs (tubular secretion). Loop of Henle’s main function is to reabsorb water and sodium chloride from the filtrate. This conserves water for the organism, producing highly concentrated urine. The countercurrent multiplier system, which is responsible for maintaining an osmotic medullary gradient in the outer medullary tissue. Distal tubule: The filtrate entering this section of the nephron, is close to the its final composition . About %95 of the sodium and chloride and %90 of water have already been reabsorbed from the original glomerular filtrate. The function of the distal tubule is to effect small adjustments to achieve electrolyte and acid-base homeostasis.These adjustments ocur under the hormonal control of aldosterone and ADH. Collecting ducts are the final site for either concentrating or diluting urine.
*About 50 g of urea are filtered per day, of which approximately 25–40 g are excreted in the urine. The reabsorption of urea (proximal tubule, collecting ducts) and active secretion of urea (Henle loop) leads to a urea circulation between the lumen of the nephron and renal medulla, which is an important element of the renal urine concentration.
**Uric acid is filtered completely and is partially absorbed in the proximal tubule. In addition, uric acid is also secreted in the proximal tubule.
Renal Clearance
All lab methods used for the evaluation of renal function rely on the measurement of waste products in blood,usually urea and creatinine, which accumulate when the kidneys begin to fail.
The rate at which creatinine and urea are removed or cleared from the blood into the urine is termed clearence. Clearence is defined as that volume of plasma from which a measured amount of substance can be completely eliminate into the urine per unit of time expressed mL/min.
CALCULATION
Calculation of creatinine clearance has become the standart lab method for determine the GFR. Glomerular filtration rate (GFR) is a test used to check how well the kidneys are working. Specifically, it estimates how much blood passes through the glomeruli each minute. The normal serum creatinine reference
interval does not necessarily reflect a normal GFR for a patient. Because mild and moderate kidney injury is poorly inferred from serum creatinine alone. Assessment of kidney function through GFR is essential once albuminuria is discovered.
Creatinine clearance, is derived by mathematically relating the serum creatinine concentration to the urine creatinine concentration excreted during a period of time, usually 24 hours.
Ucr (mg/dL)xVur (mL/24hrs)/Pcr (mg/dL) = Ccr( mL/min)
Elimination of Nonprotein Nitrogen Compounds (NPN)
NPN are waste products (urea, creatinine and uric acid) formed in the body as a result of the degradative metabolism of nucleic acids, amino acids and proteins. Excretion of these compounds is an important funtion of kidneys.
Urea (MW 60 Da) , makes up the majority (> 75) of the NPN waste excreted daily as a result of protein catabolism. Readily filtered by the glomerulus and, in tubulules %40-60 of urea is reabsorbed.
Creatinine (MW 113 Da): every day up to %20 of total muscle creatine spontaneously dehydrates and cycles to form the creatinine (waste product) . Therefore, creatinine levels are a function of muscle mass and remain approximately the same in an individual from day to day unless muscle mass or renal funtion changes. Readily filtered by the glomerulus , unlike urea is not absorbed by the tubules.However, a small amount of creatinine is
secreted by the kidney tubules at high serum concentrations.
Uric acid (MW 168 Da), readily filtered by the glomerulus and, then undergoes a complex cycle of reabsorbtion and secretion as it cources through the nephron . Only 6-12% of the original filtered uric acid is finally excreted.
The National Kidney Foundation (NKF)recommends that estimated GFR, be calculated each time a
serum creatinine level is reported.
The equation is used to predict GFR and is based on serum creatinin age, body size, gender and race without the need of urine creatinine.
There are a number of formulas used to eGFR on the basis of serum creatinine levels.
Purpose of the Renal Function Tests
To evaluate kidney function and aid in the diagnosis of kidney disease.
To monitor the progression of renal insufficiency.
The BUN-to-creatinine ratio may aid in the evaluation of a person’s state of hydration.
Analysis of blood and urine samples can be essential for the evaluation of kidney (renal) function.
Blood urea nitrogen (BUN) provides a rough measurement of the glomerular filtration rate, the rate at which blood is filtered in the kidneys. Urea is formed in the liver as an end product of protein metabolism and is carried to the kidneys for excretion. Nearly all kidney diseases cause inadequate excretion of urea, elevating BUN levels in the blood.
Creatinine is a breakdown product of creatine, an important component of muscle. The
production of creatinine depends on muscle mass, which varies very little. Creatinine is excreted exclusively by the kidneys, and its level in the blood is proportional to the glomerular filtration rate. The serum creatinine level (serum is the clear liquid that remains after whole blood has clotted) provides a more sensitive test of kidney function than BUN because kidney impairment is almost the only cause of elevated creatinine. It can also be measured with a urine test.
Creatinine clearance rate determines how efficiently the kidneys are clearing creatinine from the blood and serves as an estimate of kidney function. For renal function test, urine and serum levels of creatinine are measured, as well as the volume of urine excreted over a 24-hour period.
The creatinine clearance rate is then calculated and expressed as the volume of blood, in
militers, that can be cleared of creatinine in 1 minute. A low creatinine clearance value indicates abnormal kidney function. It requires both a urine and blood sample.
Symptoms of Kidney Problems
Symptoms that may indicate a problem with your kidneys include:
high blood pressure
blood in the urine
frequent urges to urinate
difficulty beginning urination
painful urination
swelling of the hands and feet due to a buildup of fluids in the body
A single symptom may not mean something serious. However, when
occurring simultaneously, these symptoms suggest that your kidneys aren’t working properly. Kidney function tests can help determine the reason.
Prerenal causes causes are due to decreased blood supply to the kidney. Examples of prerenal causes of kidney failure are:
Hypovolemia
Dehydration from loss of body fluid (for example, vomiting, diarrhea, sweating, fever)
Poor intake of fluids
Medication, for example, diuretics may cause excessive water loss
Abnormal blood flow to and from the kidney due to obstruction of the renal artery or vein.
Renal causes of kidney failure (damage directly
to the kidney itself) include:
Sepsis: The body's immune system is overwhelmed from infection and causes inflammation and shutdown of the kidneys.
This usually does not occur with simple urinary tract infections.
Medications: Some medications are toxic to the kidney including:
Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Advil, Motrin, and others), and naproxen (Aleve, Naprosyn)
Antibiotics like aminoglycosidesgentamicin (Garamycin), tobramycin
lithium (Eskalith, Lithobid)
Iodine-containing medications such as those injected for radiology dye studies
Rhabdomyolysis: This is a situation in which there is significant muscle breakdown in the body, and the damaged muscle fibers clog the filtering system of the kidneys. Massive muscle injury may occur because of trauma, crush injuries, and burns.
Some medications used to treat highcholesterol may causerhabdomyolysis. Multiple myeloma
Acute glomerulonephritis or inflammation of the glomeruli, the filtering system of the kidneys. Many diseases can cause this inflammation including:
Systemic lupus erythematosus
Wegener's granulomatosis
Goodpasture syndrome.
Hemolytic uremic syndrome: This condition results from abnormal destruction of red blood cells. It most often occurs in children after certain infections, but also may be caused by medications, pregnancy, or can occur for unknown reasons.
Postrenal causes of kidney failure.
Examples are:
a kidney stone may cause the remaining kidney to fail.
Chronic renal failure develops over months and years. The most common causes of chronic renal failure are related to:
poorly controlled diabetes,
poorly controlled high blood pressure, and
chronic glomerulonephritis.
tumors
Types of Kidney Function Tests
Urinalysis
Serum Creatinine Test
This blood test examines whether creatinine is building up in your blood. The kidneys usually completely filter creatinine from the blood. A high level of creatinine suggests a kidney problem.
According to the National Kidney Foundation (NKF), a creatinine level higher than 1.2 for women and 1.4 for men is a sign of a kidney problem.
Blood Urea Nitrogen (BUN)
BUN test also checks for waste products in te body. BUN tests measure the amount of nitrogen in the blood. Urea nitrogen is a breakdown product of protein. However, not all elevated BUN tests are due to kidney damage. Common medications, including large
doses of aspirin and some types of antibiotics, can also increase BUN. A normal BUN level is between 7 and 20. A higher value could suggest several different health problems.
Estimated Glomerular Filtration Rate (GFR)
This test estimates kidneys filtering capacity of waste products. The test determines the rate by looking at factors, such as:
test results, specifically creatinine levels
age
gender
race
height
weight
Any result lower than 60 may be a warning sign of kidney disease.
