Renal Clearance Flashcards
Clearance renal
elimination of drugs via the kidneys
In the kidney, drugs are eliminated through:
- filtration
- secretion
- reabsorption
we estimate kidney function through the:
creatinine clearance as a biomarker
Scr means
serum creatinine
fe means
fraction eliminated
clearance
irreversible elimination of a drug from the systemic circulation
it’s not considered clearance if it’s not
made it past systemic circulation
rate of elimination
rate of elimination renal + rate of elimination hepatic
C midpoint
midpoint plasma concentration (where the drug is coming from)
ClR =
rate of urinary excretion / C midpoint
Two methods to determine renal clearance
- Urinary excretion
- fraction of total clearance
Urinary excretion
- over any time interval
- Post-dose: collect urine; collect midpoint concentration
- ClR = C urine * V urine/time all divided by C midpoint
Fraction of total clearance
provides information about the extent of renal elimination
high fe means
ClR»ClH
low fe means
ClR«ClH
fe large or small depends on
ClR relative to Cl
value for the fraction of total renal clearance
0 to 1
Components of Renal Clearance
- glomerular filtration
- secretion via transporters
- reabsorption
glomerular filtration
- movement from glomerular capillary (blood) to renal tubule at Bowman’s capsule
- directly proportional to fu
- depends on fu, GFR, and molecule size (small drug molecules)
- contributes to renal elimination
GFR
- volume of plasma filtered/min
- a measure of kidney function
20 y.o female = 110 ml/min
20 y.o male = 120 ml/min
fu formula
fu = Cu/C
fu: 0 to 1
Cu: concentration unbound
C: total concentration
Renal Secretion via transporters
- active or facilitated transport from blood to the lumen of nephron
- depends on membrane transporters
- highly subjected to drug-drug interactions
- contributes to renal elimination
- blood –> tubules
- depends on substrate
- some drug
renal tubules
network of tiny, tube-like structures in the kidneys responsible for filtering blood and reabsorbing essential substances while eliminating waste products to regulate the body’s fluid and electrolyte balance.
Proximal tubules
responsible for the initial filtration of blood, where they reabsorb essential substances like glucose, amino acids, and ions while also secreting certain waste products into the urine
intrinsic clearance
relates to the kidney’s ability to clear a substance from the blood based on filtration, reabsorption, and secretion within the renal tubules.
Cl int T = Vmax / Km
Reabsorption
- passive movement from the lumen of the nephron to the blood
- sensitive to changes in urine pH and flow
- important for unionized, lipophilic drugs
- limits renal elimination
- tubule –> blood
- some drugs
- diuretics disrupt the normal reabsorption processes in the kidneys, leading to an increase in urine production.
cardiac output
the amount of blood pumped by the heart in one minute, reflecting how effectively the heart circulates blood through the body.
Delivery of blood and concentration of filtrate in kidney
cardiac output - renal blood flow - renal plasma flow - plasma filtered - plasma not reabsorbed - urine
three factors affecting reabsorption
- lipophilicity of drug (⬆️ FR, ⬆️ reabsorption, ⬇️ clearance renal)
- unionized form of a lipophilic drug can be reabsorbed (⬆️ FR; pH < pKa more acidic; pH> pKa more alkaline)
- urine flow (⬇️ FR –> ⬆️ clearance renal) Faster flow favors CL
no secretion or reabsorption
Clr = Clrf
there is net secretion of the drug
Clr > ClRF
there is net reabsorption of the drug
sensitive to changes in urine pH and flow
Clr < ClRF
diuretic
a medication that promotes increased urine production and helps to reduce excess fluid and salt in the body, often used to treat conditions like high blood pressure and edema.
increase in urine flow leads to increase in Clr
nephron
functional unit of the kidney
creatinine clearance
a measure of kidney function that estimates the rate at which the kidneys filter and remove creatinine, a waste product, from the blood, typically used to assess renal health.
- drugs largerly excreted unchanged into urine
- fe=1; fu=1
metabolic by-product of muscle which is higher when the body weight is higher and more muscle you have
rate of creatinine elimination
Clcr * Scr
Cockcroft-Gault equation
estimates creatinine clearance in adults aged 18 or older and is often used to assess kidney function for drug dosing purposes.
Typical patient
- 55 years old
- 70 kg
- Scr = 0.8 mg/dL
Clcr males
100 ml/min
Clcr females
85 ml/min
Should the dose be adjusted in this patient?
- BW (kg) and height (in)
- IBW
- Determine which weight to use in the C-G equation (TDBW; IBW, or BWadj)
- C-G equation
- Deteremine RFI CrCl (value from the C-G equation / normal value based on gender) ~ in %
- Dose adjusted if fe > 0.25 & RFI reduced more than 0.30 (or RFI equal or smaller than 0.70) ~ depending on the question
RFI (Renal Function Index): index related to renal (kidney) function.
fe > 0.5
drug is primarily renally cleared
fe < 0.5
drug is primarily hepatically cleared
high fu
drug is highly protein unbound and is more available to be filtered/secreted and goes to filtrate
low fu
drug is highly protein bound and thus less able to be filtered/secreted and stays in the blood
1 kg
2.2 lbs
1 inch
2.54 cm
12 inches
1 foot
Why is ideal body weight (IBW) used in
the Cockroft and Gault Equations to
calculate CrCl rather than total body weight
(TBW)?
We use the IBW instead of the TBW because creatinine is a metabolic by-product of muscle metabolism.
What could happen if we used TBW to calculate CrCl in a patient with a ratio of TDBW/IBW > 1.3? Would we overestimate or underestimate the CrCl?
If we use TBW, we would overestimate the creatinine clearance in normal weight patients and underestimate in overweight patients. Since we rely on CrCl to determine drug dosage, using TBW in the calculation for an obese patient might lead to overdosing. Thus, for overweight patients, we can use adjusted body weight.
If a patient has a ratio of TDBW/IBW < 1, what weight should be used in the Cockroft and Gault Equation to calculate the patient’s creatinine clearance?
For patients with TDBW/IBW ratio < 1, the
patient is considered underweight. When the patient is underweight, TDBW is used to calculate creatinine clearance in the Cockroft and Gault Equation. TDBW is
the best estimate of muscle mass in an underweight individual. TDBW is the TBW-3rd space fluid
