Gfr And Clearance

Question 1

What is GFR

Answer 1

• Kidney function is measured in terms of glomerular filtration rate
(GFR).
• GFR is the amount of filtrate that is produced from the blood flow per
unit time.
• The amount of filtrate is determined by the product of the average filtration of each nephron in each kidney (i.e. normal is about 2 million nephrons)

Question 2

What is the normal GFR

Answer 2

Normal GFR is 90 – 120 mL/min /1.73m2
The normal total glomerular filtrate per day is 140 – 180 L /day
Lower for women higher for men generally

Question 3

What does GFR depend on

Answer 3

• Depends on

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

Question 4

Describe nephrons and GFR in babes

Answer 4

• Nephron development finished by 35th – 36th
week of foetal development • Premature & LBW infants often have lower
nephron numbers • Foetal excretion predominantly via placenta
• At birth GFR ~ 20 mls/min/1.73 m2 • Normal GFR by ~ 18 months

Question 5

Describe nephron change in advancing age

Answer 5

• GFR starts declining after 30 years of age • Rate of decline ~ 6-7 mls/min per decade
• Loss of functioning nephrons • Some compensatory hypertrophy

Medulla is exactly the same but cortex volume decreases

Question 6

Describe teh relationship between GFR and size

Answer 6

• Bigger people tend to have bigger kidneys
• Bigger kidneys generally means more nephrons
• Small kidneys in big person worse than small kidney in a small person

Question 7

What is compensatory hypertrophy

Answer 7

Once you have been born. Cant make more nephrons.
• Reduced nephron number
• Compensatory hypertrophy 
• Existing nephrons get bigger 
• Healthy kidney can also get bigger
• Occurs to much greater extent in
childhood
• Nephron loss in old age not associated with compensatory hypertrophy

Question 8

What is the result of compensatory hypertrophy

Answer 8

Nephrons work harder..
…And are at greater risk of wearing out
Cortical scars

Question 9

Dcesribe gfr in pregnancy

Answer 9

• GFR increases (~ 50%)
– 130 – 180 mL / minute
• Kidney size increases (~ 1 cm)
– Increased fluid volume (vascular & interstitial )
• Nephron number the same - just fluid etc
• Back to pre-pregnancy levels ~ 6
months post-partum
Pregnancy is transient so no long term effect

Question 10

Describe the GFR in a person and between individuals

Answer 10

• Big variability between individuals (even allowing for variables on previous slides)
• GFR relatively constant in an individual unless kidney function
changes
• If GFR declines it may therefore be due to:
– Decline in number of nephrons
– Decline of GFR within individual nephrons

Question 11

Describe gfr and disease

Answer 11

• A fall in GFR in an individual means that kidney function has worsened
• A rise in GFR means that kidney function has recovered
• When kidney function declines slowly, individual nephrons may hypertrophy so actual GFR may not fall until significant kidney damage has occurred.

Question 12

What is clearance

Answer 12

Clearance (C) is the volume of plasma cleared of a substance per unit of time where the substance is denoted as ‘x’

Cx=Ax/Px

C  =  clearance 
A  =  amount of substance eliminated from plasma 
P  =  plasma concentration of substrate

• This formula is clearance from the body, not just the kidneys
• Clearance is an imaginary concept – describes a volume of plasma
completely cleared of solute

Question 13

What is renal clearance

Answer 13

Renal Clearance of a substrate = excretion rate / plasma concentration

Excretion rate = U (amount in urine) x V (urine flow rate)

Question 14

What is the best substance to measure GFR

Answer 14

If used to measure kidney clearance a substance should:
• Be produced at a constant rate
• Be freely filtered across the glomerulus
• Not be reabsorbed in the nephron
• Not be secreted into the nephron
If all these are true then excretion rate = GFR

Inulin is the perfect substance for this

Question 15

Why is inulin not used to measure GFR

Answer 15

1. Requires continuous ivi to maintain steady state

2. Requires catheter and timed urine collections

Question 16

What is used clinically to measure GFR

Answer 16

• Radio-active labelled marker
• Cleared exclusively by renal filtration
• Timed injection with blood samples taken 2,3,4 hours afterward
• Approx. 10% lower clearance than inulin (reabsorption?)
• Used clinically
– In children
– Where indication of renal function required e.g. kidney transplant or
work up to donate kidney for transplant

Question 17

Is creatinine a goo measure of gfr?

Answer 17

• Endogenous substance 
• End product of muscle breakdown
 …Is it a good surrogate measure of GFR?
Produced at a constant rate -?
Freely filtered across the membrane - yes 
Not reabsorbed along nephron - yes
Not secreted into the nephron - no

Question 18

What affects creatinine love in an individual

Answer 18

See slide

Question 19

How can serum creatinine replefct differences in gfr in different individuals

Answer 19

• Serum creatinine (sCr) stable in an individual (in steady state) • But serum creatinine can reflect very different glomerular filtration
rates in different individuals

Question 20

Describe serum creatinine in early childhood

Answer 20

See slide

Question 21

Describe the relationship between true GR and serum creatinine

Answer 21

See graph

Question 22

How is GFR estimates from serum creatinine

Answer 22

• Creatinine is easy to measure but varies greatly between individuals
• Variety of models developed to try and better estimate GFR fromserum creatinine levels
• eGFR is not the same as GFR – it is a ‘best guess’

Question 23

What is mdrd egfr

Answer 23

• 4-variable equation (based on ~1600 patients with CKD)
– Serum creatinine
– Age
– Sex
– Caucasian or Black
• Standardised to body surface area of 1.73 m2 therefore don’t need
patient height and weight • Original study in non-diabetic Caucasian Americans • Subsequently validated in DM type 2, Black Americans

Question 24

Who is mdrd egfr inaccurate in

Answer 24

Inaccurate in…… • People without kidney disease (e.g. transplant donors) • Children • Pregnancy • Old age • Other ethnicities • Amputees / significantly reduced muscle mass • Patients with higher levels of kidney function (GFR > 60 mls/min)

Question 25

How is mdrd egfr in diagnosing cod

Answer 25

• Underestimates true GFR when serum creatinine close or within
normal range (> 60 mls/min)
• Risk of patients being labelled as having chronic kidney disease
(CKD)
• In an individual patient two things are important • GFR • Change in GFR • But remember: eGFR taken from serum creatinine and not all
changes in serum creatinine are due to a change in GFR

Question 26

What is ckd epi

Answer 26

• Uses same variables as MDRD calculation but calculation is slightly
different (~ 8300 patients much more diverse background)
– Serum creatinine – Age – Sex – Caucasian / Black
• As accurate as MDRD when eGFR < 60 mls/min • More accurate when eGFR > 60 mls/min but still not perfect

Question 27

Why is egfr less accurate with mild kidney disease

Answer 27

Why is eGFR less accurate with mild kidney disease?
• 3 contributing factors
1. Reduction in GFR (e.g. if glomerular surface area reduced) causes increases in blood flow) …see lecture next week
2. reduced nephron number leads to nephron hypertrophy so no change in GFR
3. reduced filtration of creatinine (due to reduced GFR) results in increased serum creatinine and increased secretion into the tubule (maintain relatively steady state of serum creatinine)