2. RENAL FUNCTION TEST - LAB Flashcards
What are the standard tests used to measure the filtering capacity of the glomeruli called?
Clearance tests.
What does a clearance test measure?
The rate in milliliters per minute at which the kidneys remove (clear) a filterable substance from the blood.
What is an important requirement for the substance used in a clearance test?
The substance must not be reabsorbed or secreted by the tubules.
What OTHER factors should be considered when selecting a substance for a clearance test?
Stability of the substance in urine
consistency of plasma levels
availability to the body
availability of tests to analyze the substance.
Why is it important that the substance used in a clearance test is not reabsorbed or secreted by the tubules?
To ensure accurate measurement of glomerular filtration.
How should the substance in a clearance test behave during a 24-hour collection period?
It should remain stable in the urine.
What must be consistent for an accurate clearance test?
The plasma level of the substance being tested.
What must be available for the substance used in a clearance test?
Tests to analyze the substance.
What is used to measure the glomerular filtration rate (GFR)?
A variety of substances, including creatinine, beta2-microglobulin (B2M), cystatin C, and possibly radioisotopes.
What are the primary substances currently used in clearance tests?
Creatinine, beta2-microglobulin (B2M), cystatin C, and possibly radioisotopes.
What is a common substance used in clearance tests that measures GFR?
Creatinine.
What is another substance used for measuring GFR, aside from creatinine?
Beta2-microglobulin (B2M).
Which substance used in GFR measurement is known for being a protein in blood plasma?
Cystatin C
What method might be used for GFR measurement that involves radioactive substances?
Radioisotopes.
What was the earliest substance measured to assess glomerular filtration?
Urea.
Why was urea used in early glomerular filtration tests?
Urea is present in all urine specimens and there were established methods for its chemical analysis.
What percentage of filtered urea is reabsorbed in the body?
Approximately 40%.
How were normal values for urea clearance adjusted to account for reabsorption?
Normal values were adjusted to reflect the 40% reabsorption of filtered urea.
What practice was used to ensure that no more than 40% of the urea was reabsorbed during measurement?
Patients were hydrated to produce a urine flow rate of 2 mL/min
What was the purpose of producing a urine flow rate of 2 mL/min in urea clearance tests?
To ensure that reabsorption of urea did not exceed 40%, providing accurate measurement.
What substance was originally used as the reference method for clearance tests?
Inulin.
What is inulin and why is it used in clearance tests?
Inulin is a polymer of fructose that is extremely stable, not reabsorbed or secreted by the tubules, making it ideal for measuring GFR.
How is inulin administered for clearance tests?
Inulin must be infused intravenously at a constant rate throughout the testing period.
Why is inulin not used as commonly today for clearance tests?
There are newer methods available that use endogenous substances and can provide accurate GFR results.
What are the advantages of using inulin in clearance tests?
Its stability and the fact that it is neither reabsorbed nor secreted by the tubules make it an accurate measure of GFR.
What is a key disadvantage of using inulin for clearance tests?
Inulin is not a normal body constituent and requires intravenous infusion, making it less convenient compared to endogenous substances.
What is a test that requires an infused substance called?
An exogenous procedure.
Why are exogenous procedures seldom the method of choice for clearance tests?
Because suitable test substances that are already present in the body (endogenous procedures) are preferred if available.
What is the main advantage of using endogenous substances in clearance tests?
They are already present in the body, eliminating the need for infusion and making the procedure simpler.
What differentiates an endogenous procedure from an exogenous procedure in clearance tests?
Endogenous procedures use substances naturally present in the body, while exogenous procedures require the infusion of external substances.
a waste product of muscle metabolism produced by creatine phosphokinase from creatine, which interacts with ATP to produce ADP and energy
Creatinine
What is creatinine and how is it produced?
Creatinine is a waste product of muscle metabolism produced by creatine phosphokinase from creatine, which interacts with ATP to produce ADP and energy.
Why is creatinine used in evaluating glomerular function?
Because it is normally found at a relatively constant level in the blood, making it an endogenous procedure for assessing kidney function.
What is one disadvantage of using creatinine for clearance tests?
Some creatinine is secreted by the tubules, and this secretion increases as blood levels rise.
How can chromogens in plasma affect creatinine clearance results?
Chromogens can react in chemical analysis, potentially counteracting falsely elevated rates caused by tubular secretion.
How can certain medications affect creatinine clearance measurements?
Medications inhibit tubular secretion of creatinine, resulting in falsely low serum levels.
Name examples of medications that inhibit tubular secretion of creatinine.
Gentamicin, cephalosporins, and cimetidine (Tagamet).
What issue can arise if urinary creatinine specimens are kept at room temperature for extended periods?
Bacteria can break down urinary creatinine, affecting the results.
How can a diet high in meat affect creatinine clearance results?
A high meat intake can increase creatinine levels in urine and plasma, affecting results if plasma specimens are drawn before the 24-hour collection period.
Why might creatinine clearance measurements be unreliable in certain patients?
In patients with muscle-wasting diseases, those engaged in heavy exercise, or athletes supplementing with creatine, creatinine clearance may not be reliable.
What factor must be corrected for when measuring creatinine clearance?
Creatinine clearance values must be corrected for body surface area and adjusted for children.
What newer methods are available for assessing glomerular filtration rate (GFR)?
Newer methods use serum creatinine, cystatin C, or beta2-microglobulin (B2M) values to estimate GFR (eGFR) without needing timed urine collections.
Why is the traditional procedure for creatinine clearance still important despite newer methods?
The traditional procedure is still performed and its principles apply to other clearance procedures using urine.
What is the main purpose of eGFR formulas?
To estimate glomerular filtration rates for screening patients, monitoring renal disease, and aiding in medication prescriptions requiring renal clearance.
What is the most frequently used eGFR formula?
The Modification of Diet in Renal Disease (MDRD) study formula.
What is the recommended eGFR formula by the National Kidney Disease Education Program (NKDEP)?
The MDRD-IDMS-traceable formula.
Why were previous eGFR formulas revised?
Discrepancies arose from the methods used to measure serum creatinine.
What makes eGFR superior to serum creatinine alone?
eGFR includes variables for race, age, and gender, making it more accurate.
What creatinine assay methods are primarily used in laboratories now?
Enzyme assays that align more closely with the isotope dilution mass spectrophotometry (IDMS) reference method.
For what GFR values is the MDRD-IDMS formula most accurate?
For GFR values lower than 60 mL/min.
How are eGFR results higher than 60 mL/min typically reported?
As “≥60 mL/min.”
What is the GFR range for Stage 1 chronic kidney disease (CKD) according to KDIGO?
Greater than 90 mL/min/1.73 m².
What is the GFR range for Stage 2 CKD according to KDIGO?
Between 60 and 89 mL/min/1.73 m².
What is the GFR range for Stage 3 CKD according to KDIGO?
Between 45 and 59 mL/min/1.73 m².
What is the GFR range for Stage 4 CKD according to KDIGO?
Between 15 and 29 mL/min/1.73 m².
What GFR value defines Stage 5 CKD (end-stage renal disease) according to KDIGO?
Less than 15 mL/min/1.73 m².
a small protein produced by all nucleated cells at a constant rate, used to screen and monitor GFR.
Cystatin C
Why is cystatin C a reliable marker for GFR?
It is filtered by the glomerulus, reabsorbed, and broken down by the renal tubular cells, with no secretion by the tubules.
What is the advantage of cystatin C measurement over creatinine clearance?
Cystatin C is independent of muscle mass, making it more accurate for patients with varying muscle conditions.
For which patients is monitoring cystatin C levels recommended?
Pediatric patients, people with diabetes, the elderly, and critically ill patients.
What is the advantage of measuring both cystatin C and creatinine levels?
Combining both measurements provides more accurate information on a patient’s GFR
How is cystatin C measured?
immunoassay procedures.
What is the molecular weight of cystatin C?
13,359
meaning of B2M
Beta2-Microglobulin (B2M)
What is the molecular weight of B2M?
11,800
From where does B2M dissociate?
Human leukocyte antigens
How is B2M removed from plasma?
Glomerular filtration
What does increased B2M in urine indicate?
Tubular damage
What does increased B2M in blood and low urine levels indicate?
Glomerular disorders
What disease and condition is B2M used to identify?
End-stage renal disease and early kidney transplant rejection
Which test is more sensitive than creatinine clearance for decreased GFR?
Plasma B2M
What patients may not have reliable B2M results?
Patients with immunologic disorders or malignancy
What method is used to measure B2M?
Enzyme immunoassay
What radionucleotide is used for glomerular filtration testing?
125I-iothalamate
Iodine-125 with iothalamate
What does the use of I-iothalamate allow?
Visualization of filtration in one or both kidneys
Which exogenous marker is used to assess a transplanted kidney’s viability?
125I-iothalamate
Iodine-125 with iothalamate
What are other exogenous markers used in renal filtration tests?
51 Cr-EDTA and 99-Tc-DTPA
Chromium-51 Ethylenediaminetetraacetic acid
Technetium-99m Diethylenetriaminepentaacetate
What nonradioactive contrast agent is used for children in filtration testing?
Iohexol
What determines the GFR besides the number of functioning nephrons?
The functional capacity of the remaining nephrons
Why does GFR not change if half of the nephrons are nonfunctional?
The remaining nephrons double their filtering capacity
What is the primary clinical significance of GFR testing?
To monitor nephron damage in known renal disease
Why is GFR testing not effective for detecting early renal disease?
Functional nephrons can compensate for nonfunctional ones
Why is GFR important for medication administration?
To prevent dangerous blood levels of medications when GFR is reduced
What are tests that determine the kidney’s ability to reabsorb essential salts and water called?
Concentration tests
What is the specific gravity of ultrafiltrate as it enters the tubules?
1.010
Why might a urine specimen have a specific gravity of 1.010 without indicating renal disease?
Because urine concentration is largely determined by the body’s state of hydration.
A concentration test where patients were deprived of fluids for 24 hours before measuring specific gravity.
Fishberg test
A test comparing the volume and specific gravity of urine collected during the day and at night to evaluate concentrating ability.
Mosenthal test
What is the current method for testing renal concentrating ability?
Osmometry after periods of fluid deprivation.
What urine osmolality reading indicates normal tubular reabsorption?
800 mOsm or higher
What does a urine-to-serum osmolality ratio of 3:1 or greater indicate?
Normal tubular reabsorption.
What condition is indicated by the kidney’s failure to produce ADH?
Neurogenic diabetes insipidus
What condition is indicated if the renal tubules do not respond to ADH?
Nephrogenic diabetes insipidus
What does osmolality measure?
Number of particles in a solution
How does osmolality differ from specific gravity?
Osmolality measures the number of particles, while specific gravity is influenced by both the number and density of particles.
What type of particles does renal concentration primarily concern?
Small particles, primarily sodium and chloride molecules
Do large-molecular-weight molecules like glucose and urea contribute to the evaluation of renal concentration?
No
Why is osmolality preferred over specific gravity for evaluating renal concentrating ability?
Because osmolality provides a more accurate evaluation of renal concentration by focusing on small particles.
What principle do freezing-point osmometers use to measure osmolality?
Freezing-point depression
How is the freezing point of a solution determined in freezing-point osmometers?
By supercooling the sample and measuring the temperature increase caused by crystallization.
What does the heat of fusion from crystallizing water temporarily raise?
The temperature of the solution to its freezing point
What is used to measure the temperature increase in freezing-point osmometers?
A thermistor
How is osmolarity calculated using freezing-point depression?
By comparing the freezing-point depression of an unknown solution with a known molal solution.
What is the known freezing-point depression value for 1 mol (1000 mOsm) of a nonionizing substance dissolved in 1 kg of water?
1.86°C
What type of solutions are used as reference standards in clinical osmometers?
Solutions of known NaCl concentration
Why are NaCl solutions used as reference standards in clinical osmometers?
Because they are more representative of urine and plasma composition.
At what temperature is the sample supercooled in freezing-point osmometers?
Approximately 27°C
What does a vapor pressure osmometer measure?
Dew point temperature
How does the depression of the dew point temperature relate to the measurement?
It parallels the decrease in vapor pressure, providing a measure of the colligative property.
What type of paper is used to absorb the sample in a vapor pressure osmometer?
Small-filter paper disks
What happens to the sample after absorption into the filter paper disks?
The sample evaporates in a sealed chamber, forming a vapor.
What role does the temperature-sensitive thermocoupler play in a vapor pressure osmometer?
It measures the temperature increase caused by the heat of condensation when the dew point temperature is reached.
How is the dew point temperature related to vapor pressure in a vapor pressure osmometer?
The dew point temperature is proportional to the vapor pressure from the evaporating sample.
How are the temperatures measured by the vapor pressure osmometer converted?
They are compared with NaCl standards and converted into milliosmoles.
Why must care be taken to prevent evaporation before testing in a vapor pressure osmometer?
Because the instrument uses microsamples, and evaporation can affect the accuracy of the measurement.
What is the typical volume of samples used in vapor pressure osmometers?
Less than 0.01 mL
What has correlation studies revealed about the accuracy of vapor pressure osmometers?
There is more variation compared to other methods, highlighting the need for careful technique.
What factor can cause erroneous results in both vapor pressure and freezing-point osmometers?
lipemic serum,
lactic acid,
and volatile substances, such as ethanol, in the specimen.
What are the major clinical uses of osmolarity?
Evaluating renal concentrating ability, monitoring renal disease, fluid and electrolyte therapy, diagnosing hypernatremia and hyponatremia, evaluating ADH secretion and response
What is the reference range for serum osmolality?
275 to 300 mOsm
Why are reference values for urine osmolality difficult to establish?
Factors like fluid intake and exercise greatly influence urine concentration.
What is the normal range for urine osmolality?
50 to 1400 mOsm
What ratio of urine to serum osmolality is considered normal under random conditions?
At least 1:1
What should the urine-to-serum osmolality ratio reach after controlled fluid intake?
3:1
What type of samples are vapor pressure osmometers primarily used to analyze?
Serum and sweat microsamples
What disorders are vapor pressure osmometers primarily used to analyze for?
Disorders not related to renal function, such as cystic fibrosis
In which department are vapor pressure osmometers primarily used?
Chemistry department
What is used in conjunction with the urine-to-serum osmolality ratio to differentiate the type of diabetes insipidus?
Controlled fluid intake and injection of ADH
What does a failure to achieve a urine-to-serum osmolality ratio of 3:1 after injecting ADH indicate?
The collecting duct does not have functional ADH receptors
What does it indicate if concentration occurs after ADH injection?
An inability to produce adequate ADH
What tests are available for difficult diagnostic cases of diabetes insipidus?
Tests to measure ADH concentration in plasma and urine
What is calculated first when determining free water clearance?
Osmolar clearance (Cosm)
What does a negative free water clearance value indicate?
Less than the necessary amount of water is being excreted (possible state of dehydration)
What does a free water clearance value of 0 indicate?
No renal concentration or dilution is taking place
What does a positive free water clearance value indicate?
Excess water is being excreted
How is osmolar clearance related to urine volume?
t indicates how much water must be cleared each minute to produce urine with the same osmolality as the plasma
What must be measured to evaluate tubular secretion and renal blood flow?
A substance that is secreted rather than filtered through the glomerulus
What test is most commonly associated with measuring tubular secretion and renal blood flow?
p-aminohippuric acid (PAH) test
What could cause an abnormal result in tubular secretion and renal blood flow tests?
Impaired tubular secretory ability or decreased renal blood flow
Why is it important to understand the principles and limitations of tests for tubular secretion and renal blood flow?
To correctly interpret the test results in correlation with other clinical data
What principle does the PAH test use to measure blood flow through the kidney?
measuring the amount of PAH completely removed from the blood by renal tissue.
Why must the PAH test substance be removed primarily in the peritubular capillaries?
To ensure measurement of blood flow through the entire nephron, not just when the blood reaches the glomerulus.
What is the range for reference values of effective renal plasma flow?
600 to 700 mL/min
Why is the term “effective” used in “effective renal plasma flow”?
Because approximately 8% of the renal blood flow does not come into contact with functional renal tissue.
What is the average renal blood flow based on normal hematocrit readings?
About 1200 mL/min
What additional method can nuclear medicine procedures use to determine renal blood flow?
Measuring the plasma disappearance of a radioactive hippurate injection and visualizing blood flow through the kidneys.
What determines the kidney’s ability to produce an acid urine?
Tubular secretion of hydrogen ions and production
Secretion of ammonia by the distal convoluted tubule.
Approximately how much acid is excreted daily by a typical person?
70 mEq/day
When does diurnal variation in urine acidity occur in typical people?
Shortly after arising, postprandially at about 2 p.m. and 8 p.m., with the lowest pH found at night.
What condition results from the inability to produce an acid urine in the presence of metabolic acidosis?
Renal tubular acidosis
What may cause renal tubular acidosis?
Impaired tubular secretion of hydrogen ions (proximal convoluted tubule) or defects in ammonia secretion (distal convoluted tubule).
How can urine pH, titratable acidity, and urinary ammonia be used in diagnosing renal function issues?
They help determine defective function by measuring and comparing the acidity and ammonia levels.
What method is used to collect specimens for titratable acidity and urinary ammonia tests?
Fresh urine specimens or those preserved with toluene, collected at 2-hour intervals after priming with an acid load (oral ammonium chloride).
How is ammonium concentration calculated in these tests?
By subtracting the titratable acidity from the total acidity of the urine specimen.
What dye was historically used to evaluate renal functions in the Phenolsulfonphthalein (PSP) test?
Phenolsulfonphthalein (PSP)
Why is standardization and interpretation of the PSP test challenging?
Due to interference by medications, elevated waste products, need for accurately timed specimens, and risk of anaphylactic shock.
What risk is associated with the PSP test that can affect its safety?
The risk of producing anaphylactic shock.
