Drugs and the Kidney

Question 1

How does an increase in tubular flow rate affect potassium secretion?

Answer 1

Increased flow rate washes away potassium in the tubular lumen, maintaining a high concentration for potassium to move out of the cells into the lumen to be excreted in urine.

Question 2

In which part of the nephron are the following transporters found?

Sodium/Chloride co-transporters

Sodium, potassium, 2-chloride co-transporters

Answer 2

Sodium/Chloride co-transporters are found in the early distal tubule

Sodium, potassium, 2-chloride co-transporters are found in the thick ascending loop of Henle.

Question 3

What should be considered when prescribing for patients with renal disease?

Answer 3

The effect of the renal impairment on the handling and effectiveness of the drug.

The potential of the drug to worsen renal impairment (avoid nephrotoxics)

Question 4

What effects can reduced renal function have on drugs?

Answer 4

Reduced renal excretion of a drug or its metabolites.

Reduced ability to tolerate side effects (e.g. increased potassium as they will have a smaller reserve to cope with this increase)

Increased sensitivity to some drugs

Reduced effectiveness of some drugs (e.g. diuretics) as they depend on filtration or secretion to enter the lumen and access the transporter they act on.

Question 5

What are dose adjustments based on consideration of?

Answer 5

Severity of renal impairment

Proportion of drug eliminated by renal excretion

Drug toxicity/ safety margin

Question 6

In what circumstances is eGFR limited as a guide to prescribing in patients with renal disease?

Answer 6

Patients at extremes of weight

Toxic drugs

Elderly patients (>75 years)

Question 7

Give an example of drugs that may be directly toxic to kidney cells

Answer 7

Aminoglycosides (e.g. gentamicin)

Question 8

What is pre-renal AKI?

What drugs can cause this?

Answer 8

An insult predominantly affecting blood flow to the kidneys affecting perfusion.

Antihypertensives can cause this by reducing blood pressure too far to the point where renal perfusion is reduced affecting the GFR.

NSAIDs and ACE-inhibitors can also cause a fall in GFR.

Question 9

What is renal AKI?

What drugs can cause this?

Answer 9

Direct damage to the tubular cells of the kidney

Aminoglycosides (e.g. gentamicin) can be directly toxic to kidney cells

Question 10

What is post-renal AKI?

Answer 10

Predominantly caused by obstruction in the urinary tract below the kidneys causes build up of waste in the kidneys causing damage.

Question 11

Name two classes of drugs that may cause a fall in GFR

Answer 11

NSAIDs

ACE-inhibitors

Question 12

How can renal complications secondary to medications be avoided?

Answer 12

Reduced dose/ frequency

Alternative medicines (less nephrotoxic)

Question 13

What should be considered when prescribing for the elderly in terms of renal function?

Answer 13

Renal function naturally declines with age, the elderly are likely to have a reduced GFR in normal circumstances.

Question 14

How does the pH of urine alter the excretion of drugs?

Answer 14

Acidic drugs are more readily excreted in alkaline urine:

• Alkaline urine will encourage more formation of the ionised form of the acidic drug (higher concentration of H⁺)
  
  • HA ⇔ H⁺ A^- (A^- = ionised form)

Alkaline drugs are more readily excreted in acidic urine:

• Acidic urine will encourage more formation of the ionised form of the alkaline drug
  
  • B + H⁺ ⇔ BH⁺

(Most drugs are weak acids or weak bases)

Question 15

Where do carbonic anhydrase inhibitors mainly work?

Answer 15

Proximal convoluted tubule

Question 16

Where do osmotic diuretics most commonly work?

Answer 16

Proximal convoluted tubule and descending loop of Henle.

Question 17

Where do loop diuretics most commonly work?

Answer 17

Thick ascending loop of Henle

Question 18

Where do thiazide diuretics act?

Answer 18

Early distal convoluted tubule

Question 19

Where do potassium sparing diuretics act?

Answer 19

Late distal convoluted tubule and cortical collecting tubule

Question 20

Why does glucose act as an osmotic diuretic in disease states?

Answer 20

In disease states such as uncontrolled diabetes mellitus, high blood glucose causes glucose transporters in the renal tubular lumen to reach their transport maximum, where no more glucose can be absorbed.

Glucose remains in the tubular lumen and its osmotic force causes water to remain in the lumen with it and they are both excreted. This causes polyuria.