Drugs & the Kidney

Question 1

Drugs and kidney impairment….What’s the fuss?

Answer 1

• Reduced renal excretion of a drug and its metabolites may cause toxicity
• Sensitivity to some drugs is increased even if elimination is unimpaired
• Increased risk of ADRs
• Some drugs are not effective when renal function is reduced
• CKD increases risk of drug-induced kidney disorders

Question 2

Considerations before prescribing….

Answer 2

• degree of renal impairment?
• Whether acute or chronic kidney disease
• proportion of drug renally excreted
• Does drug have a narrow or wide therapeutic window?
• Is drug potentially nephrotoxic?
• Is this patient established on renal replacement therapy?

Question 3

Creatinine Clearance (CrCl) using Cockroft and Gault (C&G)

Answer 3

Need to know age, weight and serum creatinine

Question 4

Pros and cons of estimating Creatinine Clearance from C&G

Answer 4

• Good validated formulae
• Advised for narrow therapeutic index drugs
• Inaccurate for rapidly changing creatinine levels and in severe renal disease
• Need to use IBW at extremes of body weight
• Adults only

Question 5

Estimated Glomerular Filtration Rate (eGFR) factors that vary

Answer 5

creatinine, age, sex, ethnicity and has only been validated in caucasian and African Caribbean origin

Question 6

pros of using eGFR

Answer 6

• Easy reporting allows early detection of CKD
• BNF offers a broad range for guidance on dosage based on eGFR
• eGFR increasingly being used to alter drug dosing and evidence growly regarding accuracy
• Good for majority of patients and drugs

Question 7

cons of using eGFR

Answer 7

• Not validated in some patient groups e.g. acute renal failure, pregnancy, oedematous states and malnourished, extremes of weight.
• as not validated for drug dose calculations – risk of drug toxicity or therapeutic failure.

Question 8

In a hurry to get therapeutic?

Answer 8

• Renal disease = prolongs half-lives of some drugs • Can take longer to get to steady state
So….use normal loading dose as per normal renal function to reach target therapeutic serum drug concentrations then reduce maintenance dose

Question 9

Examples of potentially nephrotoxic drugs

Answer 9

• ACE inhibitors, Angiotensin II blockers • NSAIDs e.g. ibuprofen
• Diuretics
• Lithium (for bipolar disorders)
• Digoxin
• Aminoglycosides (Gentamicin) • Vancomycin
• Metformin (for T2DM)
• Iodinated contrast media
• Opioids (e.g. Morphine)

Question 10

AKI – it’s not just about the drugs….

Answer 10

• Low BP – sepsis, D&V, poor oral intake
• Low cardiac output – MI, heart Failure, arrythmia
• Reduced blood volume - GI bleed, burns, intra-op losses
• Post-renal obstruction – prostate, constipation, blocked catheter, blood clot • Intra-renal – e.g. rhabdomyolysis, myeloma, vasculitis

Question 11

What happens if dosing is wrong?

Answer 11

• too high a dose may have worse outcomes with respect to bleeding risk.
• Too low a dose may result in an increase in embolic events and result in potentially preventable strokes.

Question 12

Principles of prescribing in renal impairment….

Answer 12

• Check U’s and E’s, including eGFR and creatinine
• Look at baseline and trends in renal function
• Consider stopping or with-holding nephrotoxic drugs
• Check resources
• Choose non-nephrotoxic drug if possible
• reduce size of dose or increase dosing interval or stop or with- hold
• Use therapeutic drug monitoring to guide dose / frequency if appropriate
• Continue to monitor U&E’s, BP, AND clinical response