Table 3.
AKI, CKD, and kidney replacement therapy have differing effects on drug dosing
| Dosage Component | AKIa | CKDa | Kidney Replacement Therapy |
|---|---|---|---|
| Initial dose and need for a loading dose, see Equation 1 | Potential changes to oral bioavailability are bypassed with intravenous administration. | Potential changes to oral bioavailability are bypassed with intravenous administration. | Rarely required in addition to those for AKI or CKD, which are the indications for KRT. |
| A loading dose may be required in patients with sepsis and marked fluid overload, particularly for hydrophilic drugs that require a rapid onset of effect, such as antibiotics. | A loading dose may be required in some patients, but clinical indicators are poorly defined. Consider for hydrophilic drugs that require a rapid onset of effect, such as antibiotics. | ||
| Decreased clearance prolongs the time to achieve steady-state concentrations, which may prompt a loading dose. | Decreased clearance prolongs the time to achieve steady-state concentrations, which may prompt a loading dose. | ||
| Maintenance dosage, see Equations 2 and 3 | Kidney excretion decreases by ≥50%b: decrease amount or frequency of dose proportionally. Dose-adjustments are required frequently in response to changes in GFR. | Kidney excretion decreases by ≥50%b: decrease amount or frequency of dose proportionally. | Intermittent hemodialysis is efficient but usually of short duration. It has a minimal effect when the drug is administered after the treatment. |
| Kidney excretion decreases by <50%b: no change. | Kidney excretion decreases by <50%b: no change. | Continuous KRT often requires an increase in maintenance dosing. However, the extent of change varies markedly depending on the drug, KRT regimen, and endogenous clearance. | |
| Limited data regarding dose-adjustment for drugs with predominantly nonkidney excretion. | Reductions may be required for drugs predominantly secreted in the proximal tubule in patients with kidney tubulointerstitial disease, regardless of GFR. | Peritoneal dialysis has minimal additional effects on chronic drug therapy. | |
| Therapeutic drug monitoring can assist dosage adjustment. | Dosage reductions may be required for drugs that undergo predominantly nonkidney clearance when GFR<60 ml/min, but data are limited or contradictory. | Therapeutic drug monitoring can assist dosage adjustment. | |
| Therapeutic drug monitoring can assist dosage adjustment. |
a
A 50% decrease in GFR is chosen because this decrease has the potential to be clinically significant in most instances.
b
To estimate the decrease in kidney excretion for a drug at a point in time, multiply the decrease in GFR by the proportion that is eliminated by the kidney. For example, for a drug that is 50% eliminated by the kidney, GFR would need to be around 1 ml/min for there to be a 50% net decrease in kidney drug clearance.