Lecture 3 - Kidney Clearance & Function

Question 1

What is the equation for urinary excretion (considering all the processes that occur within the nephron)

Answer 1

Excretion = (Filtration - Reabsorption) + Secretion

Question 2

What does a decrease in GFR and an increase in GFR mean clinically for a patient?
What are the reasons for why a decrease in GFR may occur?
Why may kidney function not fall signiciantly until significant damage has already occured?

Answer 2

• Decrease in GFR means kidney function has worsened.
• Increase in GFR means kidney function has improved
• 1) Decline in number of nephrons 2) Decline in GFR within individual nephrons
• When kidney function starts to decline, nephrons may hypertrophy so kidney function may not fall significantly until serious damage has occurred.

Question 3

What is “renal clearance”? (C)

What is the equation to calculate renal clearance?

Answer 3

• Renal clearance is the ability of the kidney to remove a substance from plasma and excrete it, and replace with cleared plasma (in mL/min)
• Cx = ([U]x x V)/[P]x.
• C is also GFR providing substance follows filtrate without being altered by kidney (i.e.: it is not reabsorbed, secreted etc)

Question 4

What is used as a marker of RBF and why?

Answer 4

• PAH (para-aminohippurate)
• It is completely 100% filtered by the glomerulus, and completely 100% removed from kidneys via tubular secretion. Therefore the rate at which the kidneys clear PAH reflects RBF

Question 5

Go over questions on slide 11 + slides 17-19 to make sure you have understanding of renal clearance calculations.

Answer 5

You’re the boss bro

Question 6

How does age affect GFR? (in young vs elderly)

Answer 6

• Nephron finishes development in 35th-36th week of development, premature and LBW infants often have lower nephron numbers.
• By Birth GFR = 20ml/min, normal GFR by roughly 18 months
• GFR starts declining after 30 Y.O, by 6-7ml/min per decade. Compensatory hypertrophy occurs for loss of functioning nephrons.
• Thinning of cortex + decline in cortex volume resulting in decreased GFR past age of 40.

Question 7

How does pregnancy affect GFR & kidney size?

Answer 7

• GFR increases roughly 50% (to 130-180mL/min)
• Kidney size increases roughly 1cm
• Nephron number the same

Question 8

What should a substance be in order to measure GFR?

Why is inulin (which is all of these) not used?

Answer 8

1) Produced at a constant rate
2) Freely filtered across the glomerulus
3) Not reabsorbed in the nephron
4) Not secreted into the nephron

Inulin requires continous I.V administration to maintain a steady state, and requires catheter and timed urine collections

Question 9

If Inulin is not used to measure GFR, what other substances can be used?
What are the limitations of these markers?

Answer 9

1) 51 Chromium-EDTA - timed injection w/blood samples 2,3 & 4 hours afterwards. However, 10% lower clearance than inulin (possibly reabsorbed). Used in children or where indication of renal function is required.
2) Creatinine - endogenous substance, end product of muscle breakdown, measured in urine and serum over 24 hours. However, overestimates GFR by 10-20% as it is secreted into the nephron and is cumbersome (have to carry a bottle of urine).

Question 10

What factors affect serum creatinine in an individual, and therefore the estimation of GFR using it as a marker?

Answer 10

• High muscle mass = high serum creatinine
• High meat intake = high serum creatinine
• Young, black, male = higher serum creatinine
• Creatinine supplement use = high serum creatinine
• Reduced muscle mass (i.e.: due to age) = low serum creatinine
• Old, female, hispanic = low serum creatinine
• Vegetarian = low serum creatinine

Although, serum creatinine is relatively stable in most individuals