Creatinine kinetics and the definition of acute kidney injury

Abstract

Acute kidney injury (AKI) is a common and devastating medical condition, but no widely accepted definition exists. A recent classification system by the Acute Dialysis Quality Initiative (RIFLE) defines AKI largely by percentage increases in serum creatinine (SCr) over baseline. The Acute Kidney Injury Network defines the first stage by either an absolute or a percentage increase in SCr. To examine the implications of various definitions, we solved differential equations on the basis of mass balance principles. We simulated creatinine kinetics after AKI in the setting of normal baseline kidney function and stages 2, 3, and 4 chronic kidney disease (CKD). The percentage changes in SCr after severe AKI are highly dependent on baseline kidney function. Twenty-four hours after a 90% reduction in creatinine clearance, the rise in SCr was 246% with normal baseline kidney function, 174% in stage 2 CKD, 92% in stage 3 CKD, and only 47% in stage 4 CKD. By contrast, the absolute increase was nearly identical (1.8 to 2.0 mg/dl) across the spectrum of baseline kidney function. Time to reach a 50% increase in SCr was directly related to baseline kidney function: From 4 h (normal baseline) up to 27 h for stage 4 CKD. By contrast, the time to reach a 0.5-mg/dl increase in SCr was virtually identical after moderate to severe AKI (>50% reduction in creatinine clearance). We propose an alternative definition of AKI that incorporates absolute changes in SCr over a 24- to 48-h time period.

Figure 1.

(A) One-compartment model of creatinine kinetics. (B) Two-compartment model of creatinine kinetics.

Figure 2.

The rise and fall of SCr after severe AKI and recovery. In this simulation, creatinine clearance dropped acutely by 90% at 8 h and then recovered acutely to baseline levels 7 d later. Results from one- and two-compartment models of creatinine kinetics are shown.

Figure 3.

SCr concentrations after an abrupt 90% reduction in CrCl, superimposed on four different levels of baseline kidney function (no CKD and stages 2 through 4 CKD). Solid squares show the point at which a 100% increase in SCr has occurred; open triangles show the point at which a 1.0-mg/dl increase in SCr has occurred.

Figure 4.

SCr concentrations after an abrupt 50% reduction in CrCl, superimposed on four different levels of baseline kidney function (no CKD and stages 2 through 4 CKD). Solid squares show the point at which a 100% increase in SCr has occurred; open triangles show the point at which a 1.0-mg/dl increase in SCr has occurred.

Figure 5.

Time to reach a 50% increase in SCr after a given percentage reduction in CrCl, according to the absence or presence of stages 2 through 4 CKD 4.

Figure 6.

Time to reach a 0.5-mg/dl increase in SCr after a given percentage reduction in CrCl, according to the absence or presence of stages 2 through 4 CKD.