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 high
cholesterol 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.