Fig 1.
Kinetic eGFR equation as formulated by Chen et al.
(Equation A) SSPCr denotes steady state plasma creatinine (in this analysis, serum creatinine at enrollment. CrCl is the estimated glomerular filtration rate calculated using the Cockcroft-Gault or CKD-EPI (unadjusted for body surface area) estimating equation with the SSPCr. Mean PCr is the mean of SCr from that day and SCr from 24 hours prior. ΔPCr denotes the difference between the SCr from that day and SCr from 24 hours prior. Max ΔPCr indicates maximum change in creatinine per day as estimated by equation B. (Equation B) Max ΔPCr is calculated from the rate of creatinine generation divided by the volume of distribution. The total body water was defined as 0.6*baseline weight in kilograms.
Table 1.
Baseline characteristics of all FACTT subjects included in the analysis of kinetic GFR, and then divided by the presence and absence of AKI.
Fig 2.
Sample application of kinetic estimate.
Panel A illustrates the creatinine trajectory of one participant with AKI within the first 7 study days; Panel B illustrates the corresponding calculated CG CrCl and CKD-EPI eGFRs and their corresponding kinetic estimates. Horizontal lines in the figure demarcate FDA dosing categories (e.g., 15, 30, and 60mL/min). After the rapid creatinine rise during the development of severe AKI, the kinetic CG CrCl fell to within the 15–30mL/min dosing category on Day 1, while the CG CrCl dosing category was 30–60mL/min. This subject would be considered to have discordant drug dosing categories on this day. Conversely, on Day 7, the kinetic estimate is higher than the CG CrCl because of the lag in SCr decline during renal recovery. Using the CKD-EPI equation, discordant drug dosing categories only occurred on Day 1. On other study days, drug dosing categories were concordant.
Table 2.
Dosing recategorization using kinetic estimates of CrCl and eGFR.
The percentage of patients who required recategorization with use of kinetic estimates of each formula is shown, stratified by AKI status. The number of drug dosing categories crossed (>60, 30–60, 15–29, < 15ml/min) refers to the initial study day that redosing was required.
Table 3.
Dosing recategorization by study days.
Comparison of dosing categories for all study days using the kinetic versus standard Cockcroft Gault CrCl in all subjects and then divided by AKI status. Subjects along the diagonal have concordant drug dosing using the two estimates, whereas those in the off-diagonal cells have discordant drug dosing using the two estimates. The majority of drug redosing occurs in subjects who experienced AKI.