Measurement Of Kidney Function

Question 1

What is glomerular filtration rate?

Answer 1

A measure needed to kidney filtration function

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 (about 2million nephrons)

Normal: 90-120 ml/min Or 140-180 L/day

Question 2

When is nephron development finished by?

Answer 2

35th-36th week of foetal development

No nephrogenesis once born - premature/ babies with LBW often have less nephrons

At birth GFR- 20mls/ min by 18months normal

Question 3

When and why does GFR start to decline? At what rate?

Answer 3

GFR starts declining after 30 years, rate of decline: 6-7 mls/min per decade

Cortex atrophy, Some compensatory hypertrophy of renal medulla but overall atrophy of kidneys

Question 4

What happens to GFR in pregnancy and why?

Answer 4

Increase up to 50%

Kidney size increases and increases ECF

Back to pre-pregnancy levels 6 months post-partum

Question 5

What happens to GFR in disease and what could explain it? Why might this not be the case immediately?

Answer 5

Decrease in GFR means kidney function has worsened:

• Decline in number of nephrons (nephrotoxic drugs like gentamicin or anti-cancer meds/ diseases)
• Decline of GFR within individual nephrons (glomerulonephritis or high BP/ diabetics -> fibrosis of nephrons)

If kidney function declines slowly individual nephrons may hypertrophy so GFR may not fall until significant kidney damage has occurred

Question 6

What equation is used to measure kidney function?

Answer 6

Can’t measure actual GFR so need a surrogate marker

Clearance is the volume of plasma cleared of a substance per unit of time where the substance is denoted as X

Body clearance: Cx = Ax (amount of substance mls eliminated from plasma) / Px (plasma concentration of substance)

Renal clearance: excretion rate (amount in urine X urine flow rate) / plasma concentration

Cx (mls/min) = Ux X V / Pxa

Question 7

What should a substance have if used to measure kidney clearance?

Answer 7

Produced at a constant rate,
be freely filtered across the glomerulus,
not be reabsorbed in the nephron,
Not be secreted into the nephron

So that excretion rate = GFR

Question 8

What substance is mostly used to measure GFR? What are the benefits and drawbacks of using this?

Answer 8

Inulin
Freely filtered, not reabsorbed or secreted into the nephron but dietary fibre so not produced at a constant rate

Requires continuous IV to maintain steady state (45mins to achieve) and requires catheter and timed urine collections

Question 9

What marker is used to monitor kidney function of paediatric cancer patients and kidney transplant donors? How is it done?

Answer 9

51 Cr-EDTA radio-active labelled marker

Cleared exclusively by renal filtration

Timed injection with blood samples taken 2/3/4 hrs after

But radioactive so patients need to go to nuclear ward until worn off

Question 10

What are 4 markers for eGFR?

Answer 10

Exogenous markers: inulin, 51 Cr-EDTA, Iohexol (contrast agent in CT scans)

Endogenous: creatinine

Question 11

What marker is used for eGFR in pregnant women? What are the benefits and drawbacks of using this? What’s the normal serum level?

Answer 11

Creatinine (end product of muscle breakdown)
✅ freely filtered across the glomerulus and not reabsorbed in the nephron, not radioactive
❌not produced at a constant rate and about 10% secreted into the nephron, have to carry a bottle of urine, frequently inaccurate, overs estimates eGFR by 10-20% due to creatinine secretion

measure urine creatinine over 24hrs or serum creatinine (normal: 70-150 micromols/ L)

Question 12

What changes the concentration of serum creatinine?

Answer 12

Intake of protein,
Muscle mass,
Age (higher older ppl but prenatal have mums + own so high),
Ethnicity (black higher, Hispanic/ indo- Asian lower),
Gender (higher males),
Supplements,
Certain drugs like trimethoprim

Question 13

What model is used in UHL to estimate GFR from serum creatinine?

Answer 13

MDRD eGFR

4-variable equation (based on patients with CkD)

• serum creatinine
• age
• sex
• Caucasian or black

Standardised to body surface area of 1.73 m2

Inaccurate in:

• Ppl without CkD
• Children
• Pregnant ladies
• Old age
• Other ethnicities
• Amputees/ significantly reduced muscle mass
• when true GFR changes quickly (e.g. AKI)

Question 14

Why is eGFR less accurate with mild kidney disease?

Answer 14

Reduction of GFR causes increase in blood flow

Reduced nephron number leads to nephron hypertrophy so no change in GFR

Reduced filtration of creatinine results in increased serum creatinine and increased secretion into tubule