2.2 Clearance

Question 1

GFR changes

Answer 1

Decreased GFR
• Kidney function has worsened *
• Decline in number of nephrons OR decline in GFR of individual nephrons

Increased GFR
• Kidney function has recovered

• When kidney function declines slowly, nephrons may hypertrophy so worsened kidney function may not be seen until significant kidney damage has taken place

Question 2

Renal clearance

Answer 2

• Clearance (C) is the volume of plasma that is cleared of a specific substance in a unit of time (ml/min)

Cₓ = ( [U]ₓ + V ) / [P]ₓ

• Cₓ = Renal clearance (ml/min)
• [U]ₓ = Urine concentration (mg/ml)
• V = Urine flow rate (ml/min)
• [P]ₓ = Plasma concentration (mg/ml)

Question 3

When can clearance be used to measure GFR

Answer 3

• Substance is not actively secreted
• Substance is not reabsorbed
• Substance is not metabolised
• Substance is produced at a steady state
• Substance freely filtered across the glomerulus

If these are all true - excretion rate (clearance) = GFR

Question 4

Inulin

Answer 4

• Inulin clearance is a very accurate estimate of GFR as it is not reabsorbed, metabolised, secreted or synthesised by the kidney
• It is not however produced endogenously - needs continuous IV to maintain steady state
• Also requires catheter and timed urine collections

Question 5

Filtration rate

Answer 5

Filtration Rate = [P]ₓ x GFR

Question 6

What does GFR depend on

Answer 6

• Age
• Gender
• Size of individual
• Size of kidneys
• Pregnancy
• Premature/LBW infants usually have lower nephron numbers
• Fetal excretion is mostly via the placenta
• At birth GFR = 20 ml/min
• Normal GFR by 18 months

Question 7

Kidney in old age

Answer 7

• GFR starts declining after 30 years due to loss of functioning nephrons and some compensatory nephrons
• Rate of decline is 6/7 ml/min per decade
• Cortex specifically declines
• Medulla size increases due to compensatory hypertrophy

Question 8

Kidney in pregnancy

Answer 8

• GFR increases (by about 50%)
• Kidney size increases (1 cm) due to increased fluid volume
• Nephron number stays the same
• Back to pre-pregnancy levels 6 months post partum

Question 9

51 CR-EDTA

Answer 9

• Radio-active labelled marker
• Cleared exclusively by renal filtration - not secreted
• Timed injections with blood samples taken in regular intervals
• Approx 10% lower clearance (underestimate) than inulin - maybe reabsorbed?
• Used in children and donor kidneys to measure kidney function

Question 10

Creatinine

Answer 10

• Endogenous substance
• End product of muscle breakdown
• Measured by urine creatinine (over 24hrs) or serum creatinine
• Freely filtered across glomerulus and not reabsorbed
• Overestimates GFR by 10-20% as creatinine is also slightly secreted into renal tubules
• Normal serum creatinine: 70-150 μmol/L

Question 11

Serum creatinine levels

Answer 11

Increased serum creatinine
• Increased meat intake
• Increased muscle mass 
• Certain drugs (trimethoprim)
• Young
• Male
• Black
• Creatinine supplements

Decreased serum creatinine
• Reduced muscle mass
• Old 
• Female
• Hispanic / Indo-asian
• Vegetarian (lower meat intake)

Question 12

Creatinine vs GFR

Answer 12

• Serum creatinine is stable in steady state in an individual
• Can reflect very different GFR in different individuals based on body mass - larger men would have a higher GFR compared to shorter women
• Also affected by gender/age etc.
• eGFR can be used to better estimate GFR from sCr

Question 13

eGFR

Answer 13

• eGFR used to estimate GFR
• MDRD eGFR used in UHL - calculation used to estimate GFR
• Dependent on:
  
  • sCR
  • Age
  • Sex
  • Caucasian or black

Question 14

When is eGFR inaccurate?

Answer 14

• People without kidney disease
• Children
• Pregnancy
• Old age
• Other ethnicities
• Amputees - muscle mass reduced
• High level of kidney function
• Mild kidney disease (nephrons hypertrophy so GFR initially not affected)