Renal Drug Dosing

Question 1

CKD + Nondialysis

Answer 1

• Estimate kidney function: which equation to use is debatable
• CrCl is the best to estimate for drug clearance correlations
• Historically Cockcroft Gault was used the most, but MDRD is said to be more accurate and usable when assigning patients to renal impairment groups

Question 2

Un-normalized

Answer 2

• Adjusting estimates by multiplying the normalized eGFR by the patient’s BSA/1.73
• Should be done with patients with extreme body weights (low or high)

Question 3

Comparing Renal Dosing Recommendations

Answer 3

• Substantial variation between drug dosing resources

- References also define renal disease differently

Question 4

Renal Disease + PK

Answer 4

• Main aspects that are affected are distribution and excretion
• Distribution: protein/tissue binding increases, Vd increases from fluid retention
• Excretion: consider amount normally excreted unchanged in urine, the degree of impairment, and metabolite accumulation which could be a concern from a toxic or therapeutic standpoint

Question 5

Stepwise Approach to Renal Dosing

Answer 5

1. Obtain history and relevant demographic and clinical information
2. Estimate renal function
3. Review current medications
4. Dose adjust (multiple sources, assess clinical scenario)
5. Monitor (efficacy, safety)
6. Reassess regimen and revise as needed

Question 6

Dosing with HD/PD

Answer 6

• Consult dosing guidelines
• Need to ensure HD/PD prescription is similar to the reference examples in terms of filter and freqeuncy
• Consider if a lot of drug is removed during dialysis

Question 7

Dosing Guides + HD/PD

Answer 7

• Recommendations for HD/PD specifically

- If there are no specific dialysis recommendations, consider renal function to be <10-15 mL/min

Question 8

Take Home Messages

Answer 8

• Use kidney function equations and drug dosing references as a starting point
• Consider each situation individually
• Consider drug factors
• Consider patient factors
• Consider renal replacement therapy factors
• Consult multiple reference sources
• Continually re-evaluate response to therapy
• For AKI, generally assume <10-15 mL/min renal function since equations give incorrect estimations; also, increase the dosing appropriately as kidneys recover