Renal Function Tests

Question 1

Functions of the kidney?

Answer 1

-Excretion of waste products e.g creatinine, urea, metabolites of xenobiotics
-Maintaining water balance
-Maintenance of blood pressure (water and sodium excretion/retention)
-Maintenance of cardiac function (POTASSIUM EXCRETION)
-Maintenance of pH (excretion of hydrogen ions)

Question 2

What do the adrenal glands do?

Answer 2

Endocrine glands
-Bone func via synthesis of vit D (required for calcium absorption)
-Regulating bodys stress response via synthesis of cortisol (glucocorticoid) and adrenaline (corticosteroid)

Question 3

How much does the kidney filter and reabsorb everyday?

Answer 3

Filtration: 180L/day of water (sodium, chloride, sugar, amino acids)

Reabsorption: 178.5L reabsorbed (all glucose and amino acids reabsorbed, most of sodium and chloride reabsorbed)

Question 4

What is the nephron?

Answer 4

Microscopic structural and functional unit of the kidney
-Composed of renal corpuscle (glomerulus and bowmans capsule) and renal tubule (epithelial cells w a lumen)
-1 to 1.5 million nephrons in each kidney

Question 5

What are the 2 branches of renal function tests?

Answer 5

1. Glomerular function tests
2. Tubular function tests

Question 6

How does filtration of blood in the glomerulus take place?

Answer 6

-The diameter of the afferent arteriole is much greater than the diameter of the efferent arteriole, this induces a pressure within the capillaries which forces molecules with a molecular weight less than 68,000g/mol out.

Question 7

What does low levels of albumin in the urine indicate?

Answer 7

Since albumin has a molecular weight of 68,000 g/mol, measurement of low conc of albumin in urine may be one of the first indications of glomerular damage.

Question 8

What is the glomerular filtrate?

Answer 8

-An ultrafiltrate of plasma and has similar composition to plasma wo most of the proteins
-Plasma is filtered by the glomeruli at a rate of approx 140mL/min

Question 9

What is the purpose of carrying out clearance test and what does abnormalities mean?

Answer 9

Measures how effectively the kidneys filter and excrete substances from the blood
-Higher the renal clearance, the more plasma that is cleared of the substance

Question 10

What is the purpose of carrying out serum creatinine tests? Abnormality meaning?

Answer 10

Assessing waste product clearance
High in kidney dysfunction

Question 11

What is the purpose of carrying out serum urea tests? Abnormality meaning?

Answer 11

Assessing wast product clearance
High in kidney dysfunction

Question 12

What is the purpose of carrying out GFR tests? Abnormality?

Answer 12

Glomerular Filtration Rate
Estimates filtration rate of kidneys
Less than 60 suggests kidney disease

Question 13

Purpose of carrying out Urinalysis (proteinuria- often albuminuria, haematuria)

Answer 13

Detects blood, protein leakage due to glomerular damage
Presemce suggests glomerular disease

Question 14

What are the most commonly used clearance tests?

Answer 14

Creatinine clearance (CrCl) test and insulin clearance test (gold standard for GFR measurement)

Clearance - the no. of mL of blood cleared of a substance X per unit time, usually expressed in units mL/min

Question 15

What formula is used for clearance tests?

Answer 15

U.V/P
U: conc of subsnatce in urine mmol/L
P: conc of substance in plasma mmol/L
V: vol of urine per unit time mL/min

Question 16

What are the steps in clearance test?

Answer 16

1. Patient preparation - accurate urine collection over 24 hours, avoid high protein meals, hydration, stop some medications
2. 24hr Urine collection - begin collection in morning- first discarded as accumulated waste overnight - keep urine samples refridgerated
3. Blood sample collection - drawn on same day as urine collection - comparison of creatinine in blood vs urine to calc clearance
4. Lab analysis - urine vol measrement in mL, creatinine conc in urine and blood in mmol/L

Question 17

How to calculate mL/min of creatinine clearance value?

Answer 17

Divide by 24hr and by 60 min (1440)

Question 18

Creatine clearnace range?

Answer 18

-Greater than 90mL/min is normal-healthy kidney func
-60-89 mL/min is mild reduction - early kidney disease
-30-59 mL/min is moderate reduction - stage 3 CKD
-15-29 mL/min is severe reduction - stage 4 CKD
- Less than 15 mL/min - kidney failure - dialysis required

Question 19

What is eGFR and what are the 2 formulas used called?

Answer 19

Describes the flow of rate pof filtered fluid through the kidney

1)Cockcroft-Gault uses serum creatinine (sCr), age, weight and sex
2) Modification of Diet in Renal Disease eqn (MDRD) in its simplest form uses sCr, age sex and race

Question 20

Cockcroft-Gault formula and additions

Answer 20

Look at formula on slides
Applies to males and shoud be modified for women by multiplying by 0.85

1.3 factor is not part of original equation but may be used as an adjustment factor for specific populations e.g elderly, overweight, altered muscle mass

Question 21

Varialble Modification of Diet in Renal Disease equation

Answer 21

equation on slides
-X1.21 if black
-X0.742 if female

Question 22

What are normal serum creatinine values?

Answer 22

Males - 62-155µmol/L
Females - 53-97µmol/L

Question 23

How is Creatinine formed?

Answer 23

-Creatine is formed in the liver and pancreas-enters blood stream and is distributed to many cells (muscle cells)
-Creatine kinase phosphorylates creatine to form creatine phosphate (energy source for muscles)
-Creatinine is a breakdown product of creatine phosphate (muscle and protein metabolism)- formed at a constant rate based on muscle mass

Question 24

When does sCr conc in blood increase?

Answer 24

If kidney filtration is insufficient - indicates glomerular damage

Question 25

Why is CrCl slightly higher than true GFR?

Answer 25

CrCl- creatinine clearance Because creatinine is secreted by the proximal tubule - low creatine could mean tubular damage

Question 26

What is the most common methodology to determine creatinine?

Answer 26

Jaffe assay principle

Question 27

What happens in the Jaffe reaction?

Answer 27

Creatinine is reacted with alkaline picrate solution to form an alkaline creatinine picrate complex which is RED in colour

Question 28

What can produce false positives in the Jaffe rxn?

Answer 28

The presence of noncreatinine chromagens or Jaffe positive substances can produce falsely elevated creatinine values E.g acetoacetic acid, pyruvic acid and hydantoin (some samples require deproteinisation of sample prior to jaffe rxn bc protein is reactive w alkaline picrate and will form coloured complexes)

Question 29

How does the Modified Jaffe procedure work?

Answer 29

-Measures the absorbance of the rxn mixture at 2 diff pHs (colourimetric procedure) 1. The absorbance of the rxn mixture is recorded , acetic acid is then added to the rxn vessel 2. The acidification eliminates the colour produced by creatinine while the colour resulting from interfering substances such as proteins is not eliminated 3. The absorbance due to creatinine is then calculated by subtracting the absorbance of the acidified tube from the initial absorbance

Question 30

What is the clinical significance of sCr and what may elevate creatinine levels?

Answer 30

-Serum creatinine is most commonly used indicator but not direct measure of renal function -Elevates creatinine is not always representative of true reduction in GFR -Creatine may be elevated due to high intake of cooked meat, excessive intake of protein or creatinine supplements, intense exercise, dehydration

Question 31

What is the Urea : Creatinine ratio usually and what could high or low values mean?

Answer 31

Normal ration between 10:1 and 20:1 -Increased ratio - low muscle mass, GIT bleeds, fever, burns -Decreased ratio: severe liver disease, decreased protein intake

Question 32

Whta is urea?

Answer 32

Urea is the principal nitrogenous end-product of protein and amino acid catabolism -Small molecule that is water-soluble and readily excreted in urine -As amino acids are deaminated in the liver, ammonia NH3 is liberated, converted to urea by specific enzymes found in liver -Urea is freely filtered by the glomerulus but a portion is passively reabsorbed w water and returned to the blood

Question 33

What is serum urea reference range?

Answer 33

1.7- 8.3 mmol/L

Question 34

What do urea assay methods usually measure?

Answer 34

Dont measure urea directly but measure the nitrogen content of urea (blood urea nitrogen BUN)

Question 35

What is the enzyme used in serum urea tests?

Answer 35

The enzyme urease is used in hydrolysis Upon alkalinisation, ammonia is formed The ammonia is then used in assay procedures

Question 36

What are 2 kinds of urease assays?

Answer 36

Nesselers reaction and Berthelot reaction

Question 37

What happens in Nesselers reaction? What is Nesselers reagent?

Answer 37

-Ammonia formed in the urease rxn is reacted with Nesselers reagent to form a coloured end-product (brown) that can be measured spectrophotometrically Nesselers reagent is an iodine salt of mercury and potassium

Question 38

What happens in Berthelot reaction? What is the catalyst?

Answer 38

Ammonia formed in the urease rxn reacts with phenol and sodium hypochlorite to form a blue indophenol that can be measured spectrophotometrically Sodium nitroprusside serves as a catalyst

Question 39

Write out Urease GLDH assay principle

Question 40

Pros of Urease GLDH assay principle?

Answer 40

Highly quanitative so v accurate Good adaptability and allows for real time monitoring -Energy diff between NADH and NAD+ is indirectly proportional to amount of urea present

Question 41

Pre-renal causes of Azotaemia/Uraemia?

Answer 41

Azotaemia (increased nitrogen) Uraemia (increased urea) -Nitrogen narcosis/depth intoxication/rapture of the deep -> a change in consciousness and neuromuscular function caused by breathing inert gas -Low bp (shock, haemorrhage, dehydration) -Decreased blood flow to kidneys (heart failure, atherosclerosis) -Increased dietary protein or protein catabolism

Question 42

Renal causes of Uraemia?

Answer 42

-Kidney disease (nephropathy)- decreased glomerular filtration (nephritis, nephrosis) -Kidney failure (chronic kidney disease)

Question 43

Post-renal causes

Answer 43

Urinary outflow obstruction such as by calculi..................

Question 44

What are pre-renal causes of decreased urea?

Answer 44

-Live disease (impaired urea synthesis in urea cycle) -High fluid intake (dilution effect) -Malnutrition or decreased protein intake (excessive IV fluids, congestive geart failure) -Analbolic states (pregnancy, growth, post surgery, recovery) - increased protein synthesis, reducing urea formation

Question 45

Microalbuminaemia ranges in i)24-hour urine collection and ii)Spot urine reference range

Answer 45

i) 24 Hour urine collection is defined as excretion of 30-300mg/24h ii) Spot urine reference range : 20-200mg/L

Question 46

What are examples of tubular function tests?

Answer 46

-Specific proteinuria -Osmolarity measurements in plasma and urine -The water deprivation test -The acid load test To ensure important constituents are not lost unnecessarily from blood

Question 47

Specific proteinuria - beta-2 microglobulin?

Answer 47

Beta-2 microglobulin (11,800g/mol) is part of the histocompatability complex (MHC) -Filtered by the kidneys and reabsorbed by the tubules -The presence of large amounts of ß-2 microglobulin in the urine is indicative of kidney tubular dysfunction -Sensitive immunological techniques have been developed to measure the conc of this in urine samples