Determination of Renal Function and Basics of TDM

Question 1

Describe excretion and how to calculate it.

Answer 1

Things that are eliminated from the kidney into the urine.

Rate of elimination = rate of filtration + (rate of secretion - rate of absorption)

Question 2

Describe filtration.

Answer 2

Mass movement of water and solutes from plasma to the renal tubule that occurs in the renal corpuscle
* driven by hydraulic pressure (blood pressure) in the capillaries of the glomerulus
* majority of proteins are too large or too charged to be filtered through the kidney
* Molecules bound to protein cannot cross

Question 3

Describe secretion.

Answer 3

After filtration, the tubules continue to secrete additional substances into the tubular fluid
* via active transport
* enhances the kidney’s ability to eliminate certain wastes and toxins
* occurs in the proximal tubule

Question 4

Describe reabsorption.

Answer 4

Movement of water and solutes from the tubule back into the plasma
* distal tubule and collecting duct
* non-ionizing drugs are reabsorbed
* ionizing drugs are excreted

Question 5

Explain glomerular filtration rate (GFR)

Answer 5

Marks renal function
The volume of plasma filtered across the glomerulus per unit time
* Represents the total sum of filtration rates of all nephrons in both kidneys
* best index of overall renal function
* cannot be measured directly –> must use creatinine clearance
* normal GFR = 100-140 ml/min

Question 6

Describe creatine.

Answer 6

• Derived from meat or supplements
• produced in the liver, pancreas, and kidney
• transported to muscle tissue

Question 7

Describe creatinine.

Answer 7

Waste product of creatine from muscle metabolism.
* released into serum at a constant rate proportional to muscle mass
* more muscle = more creatinine eliminated

Question 8

Explain serum creatinine.

Answer 8

Scr - amount of creatinine in the blood
* normal range in younger people - 0.5-1.1 mg/dL

Question 9

What are some things to consider when estimating GFR in patients?

Answer 9

• Creatinine clearance (CrCl) is roughly proportional to GFR
• however, creatinine undergoes active renal tubular secretion
• 10-40% (lower end with good kidneys, higher end with bad kidneys)
• total % creatinine secreted (rather than filtered by glomeruli)

Question 10

How do you calculate CrCl?

Answer 10

CrCl = Crfilt + crsec
* GFR is the same as CrCl - Crsec but Crsec is very small –> therefore, GFR is equated to CrCl
* equation is less accurate for those with worse kidneys

Question 11

What is the relationship between src and GFR?

Answer 11

Large Scr changes = less significant decline in GFR over lower GFR ranges

Smaller Scr changes = more significant decline in GFR over higher GFR ranges

A fall in GFR decreases creatinine filtration and produces a proportionate rise in the serum creatinine concentration

Question 12

Name factors that can impact production and secretion of Src.

Answer 12

Production:
* diet
* muscle mass
* acute muscle damage

secretion:
* secretion % can cause Scr to appear “normal” even with significant real GFR declines
* secretion of creatinine gets close to saturated once Scr 1.5-2.0 mg/dL is reached

Question 13

Describe Src caveats.

Answer 13

• Scr doesn’t immediately reflect acute changes in kidney function (lag)
• type of lab assay used may impact result
• some medications directly impact creatinine secretion (transport proteins)

Question 14

Name the types of drugs that can inhibit tubular secretion of creatinine.

Answer 14

• diuretics - increase kidney water excretion
• antibiotics/anti-infectives
• cimetidine - potent inhibitor of creatinine
• anti-HIV medications
• pharmacokinetic boosters - pair with other drugs to increase therapeutic effect of other drugs
• anticancer drugs