Renal Clearance: Physiological Determinants and Calculations

Question 1

CLr

Answer 1

renal clearance (vol/time)

Question 2

CLf

Answer 2

filtration clearance (vol/time)

Question 3

GFR

Answer 3

glomerular filtration (vol/time)

Question 4

Ar

Answer 4

total amount excreted unchanged in urine (amt)

Question 5

dAr/dt

Answer 5

renal excretion rate (amt/time)

Question 6

tmid

Answer 6

the mid-time of a urine collection interval (time)

Question 7

Kr

Answer 7

first-order urinary excretion rate constant (time^-1)

Question 8

change Ar/Change time

Answer 8

average renal excretion rate (amt/time)

Question 9

CL =

Answer 9

CLr + CLnr

Question 10

What is the only organ clearance that can be readily determined in human subjects?

Answer 10

renal clearance

Question 11

What does systemic clearance represent?

Answer 11

the efficiency of drug removal from the body

Question 12

Systemic (or total) clearance is defined as a proportionality constant relating rate of elimination to drug conc. in plasma.

Answer 12

True

Question 13

glomerular filtration

Answer 13

output

Question 14

active tubular secretion

Answer 14

output

Question 15

tubular reabsorption

Answer 15

input

Question 16

mass balance principle

Answer 16

renal excretion rate = filtration rate + secretion rate - reabsorption rate

Question 17

What can affect glomerular filtration?

Answer 17

-PRESSURE difference at glomerulus (the driving force)
-integrity of glomerulus
-renal blood flow
-drug to plasma protein binding (unbound drug <20kDa can be filtered)

Question 18

For a substance that is not bound to plasma proteins and is only eliminated by filtration, its renal clearance should not be equal to GFR. (ex. insulin and creatinine)

Answer 18

F-it should be equal

Question 19

What can affect active tubular secretion (ATS)?

Answer 19

changes in the activity of active transporter proteins (due to saturation at high drug conc., the presence of inhibitors or inducers, etc.). Plasma protein binding should NOT affect active secretion bc active transporters often have a greater affinity to their substrates than plasma proteins.

Question 20

What can affect tubular reabsorption?

Answer 20

-urine pH
-urine flow rate (increase in flow rate decreases reabsorption due to decreased “contact time”)
-charge and lipophilicity of the drug

Question 21

Change in urine pH will have no affect renal clearance if tubular reabsorption is one of the dominant renal excretion mechanisms for a given drug (CLf>CLr)

Answer 21

false - it will have an affect

Question 22

Change in urine pH has LITTLE impact on the tubular reabsorption of drugs that are polar (or hydrophylic) in their un-ionized form or are non-polar (lipophilic) in their ionized form.

Answer 22

True

Question 23

Thought process for possible CLr manipulation

Answer 23

1. calculate CLr (if not given) and CLf (CLf=fu*GFR) - make sure CLf have the same units
2. Compare CLr and CLf to pinpoint the mechanisms involved in renal excretion of the drug
3. (scenario 1)- If CLr>CLf, filtration and secretion should be the main renal excretion mechanism and active transporter activity should be considered for CLr manipulation
4. (scenario 2)- If CLr<CLf, filtration and reabsorption should be the main renal excretion mechanism and urine pH modulation MAY BE possible for CLr manipulation
5. if reabsorption is one of the main mechanisms, check the following two requirements for a drug to be subject to urine pH modulation: (1) if the drug in its ionized form is hydrophilic/polar or its unionized form is lipophilic/nonpolar (2) if pKa ranges between 3 and 7.5 for a weak acid or between 6 and 12 for a weak base.