S2) Measurement of Kidney Function, GFR and Clearance

Question 1

How is kidney function measured?

Answer 1

Kidney function is measured in terms of glomerular filtration rate (GFR)

Question 2

What is GFR?

Answer 2

GFR is the amount of filtrate that is produced from the blood flow per unit time

Question 3

How is GFR determined?

Answer 3

GFR is determined by the product of the average filtration of each nephron in each kidney

Question 4

Approximately how many nephrons are there in each kidney?

Answer 4

Approx. 2 million nephrons in each kidney

Question 5

What is the normal GFR value?

How does this differ across sexes?

Answer 5

• Normal GFR is 90 – 120 ml/min /1.73m²
• Males fall on the higher side and females on the lower side of the spectrum

Question 6

What is the normal total glomerular filtrate per day?

How does this differ across the sexes?

Answer 6

• The normal total glomerular filtrate per day is 140 – 180 L /day
• Males fall on the higher side and females fall on the lower side of the spectrum

Question 7

GFR varies across individuals.

Identify some factors which affect it?

Answer 7

• Gender
• Age
• Size of individual
• Size of kidneys
• Pregnancy

Question 8

When in foetal development is the nephron finished?

When is normal GFR function reached in babies?

Answer 8

• 35th – 36th week of foetal development
• 18 months after birth

Question 9

When does the GFR start to decline?

How quickly does it decline?

Answer 9

• GFR starts declining after 30 years of age
• Rate of decline ~ 6-7 mls/min per decade
• cortex starts to reduce in size

Question 10

How does a decline in GFR manifest?

Answer 10

• Loss of functioning nephrons
• Some compensatory hypertrophy

Question 11

Explain the relationship between GFR and size

Answer 11

• Bigger people tend to have bigger kidneys
• Bigger kidneys generally means more nephrons
• Hence, higher GFR in bigger people

Question 12

Why does compensatory hypertrophy happen in the kidneys?

Answer 12

• Reduced nephron number
• Existing nephrons get bigger
• Healthy kidney gets bigger

Question 13

Explain how GFR changes in pregnancy

Answer 13

• GFR increases but nephron number doesn’t change
• Kidney size increases due to increased fluid volume (vascular & interstitial)

Question 14

GFR is relatively constant in an individual unless kidney function changes.

Why does GFR decline then?

Answer 14

• Decline in number of nephrons
• Decline of GFR within individual nephrons

Question 15

Describe the relationship between GFR and disease

Answer 15

• A fall in GFR = kidney function has worsened
• A rise in GFR = kidney function has recovered

Question 16

Define clearance

Answer 16

Clearance (C) is the volume of plasma cleared of a substance per unit of time where the substance is denoted as ‘x’ aka. the rate at which you produce clear plasma

• this formula is for the whole body not just kidneys

Question 17

How is renal clearance calculated?

Answer 17

Renal Clearance of a substrate = excretion rate / plasma concentration

Question 18

What features should a substance have if it is used to measure renal clearance?

Answer 18

• Produced at a constant rate
• Freely filtered across the glomerulus
• Not be reabsorbed in the nephron
• Not be secreted into the nephron

Then, excretion rate = GFR

Question 19

Inulin is a surrogate marker for GFR.

Why isn’t used though?

Answer 19

• Requires continuous ivi to maintain steady state
• Requires catheter and timed urine collections

Question 20

51 Cr-EDTA is used clinically in children to measure GFR.

Describe its use

Answer 20

• Radio-active labelled marker that can be used because its secreted
• Cleared exclusively by renal filtration
• Approx. 10% lower clearance than inulin

Question 21

What is creatinine?

Answer 21

• Endogenous substance
• End product of muscle breakdown

Question 22

Why is creatinine not a perfect surrogate measure of GFR?

Answer 22

• Creatinine clearance overestimates GFR by 10 – 20% due to creatinine secretion
• Increases with severe renal impairment

Question 23

How is creatinine clearance measured?

Answer 23

• Collecting urine over 24 hours (can be a disadvantage)
• Measurement of serum Creatinine

Question 24

Which factors leads to increased serum creatinine in an individual?

Answer 24

• Large muscle bulk
• Male
• African heritage
• Creatine supplements / certain drugs e.g. trimethoprim
• High meat intake

Question 25

Which factors lead to decreased serum creatinine levels in the individual?

Answer 25

• Reduced muscle mass
• Old age
• Hispanic / Indo-Asian heritage
• Female
• Vegetarian diet

Question 26

Explain the variation in GFR seen with serum creatinine measurements

Answer 26

• sCr is stable in an individual (in steady state)
• But, it can reflect very different GFRs in different individuals

Question 27

Describe the modifications seen in eGFR (estimated GRF) to account for variability in individuals

Answer 27

• Adjusted for: serum creatinine, age, sex, Caucasian or Black
• Standardised to body surface area of 1.73 m² therefore don’t need patient height and weight

Question 28

eGFR is inaccurate in certain groups of people.

Identify 5 of these groups

Answer 28

• Children
• Pregnant women
• Old age
• Other ethnicities (besides Black and Caucasian)
• Amputees

– mild kidney disease

Question 29

What are the two main issues with eGFR?

Answer 29

• Underestimates true GFR when serum creatinine close/within normal range (> 60 mls/min)
• Risk of patients being labelled as having chronic kidney disease

Question 30

Why is eGFR less accurate with mild kidney disease?

Answer 30

• Reduction in GFR causes increased blood flow
• Reduced nephron number leads to nephron hypertrophy (no change in GFR)
• Reduced filtration of creatinine results in raised sCr

Question 31

what can affects creatinine levels in an individual

Answer 31

• protein intake
• muscle mass
• renal excretion

Question 32

why is a change in serum creatinine significant

Answer 32

it indicates a change in kidney function