Estimating the dynamic GFR when creatinine concentrations are changing rapidly
Have you ever wondered how to calculate GFR from plasma creatinine in the non-steady state? I did from time to time. So I was kind of shocked to learn from Chen (1) and Winter (2) how easy it actually is:
You basically treat creatinine as a drug:
- Your dosing rate is estimated by the creatinine generation rate, using for example the Cockcroft-Gault equation.
- The difference between two creatinine concentrations times the distribution volume of creatinine gives you the amount of creatinine that is retained in the body.
- Subtracting this from the generation rate you get the amount of creatinine excretion over the corresponding time period.
- Divide that by the mean creatinine concentration in the blood and -voila- you end up with the creatinine clearance.
Crea-Clearance versus GFR
Most clinicians are using some form of GFR estimation (MDRD, CKD-EPI) in their daily clinical practice and not creatinine clearance estimates. The formulas used by Winter and Chen essentially calculate an absolute creatinine clearance, not a GFR. The term "kinetic GFR" coined by Chen is thus a misnomer.
To overcome this problem I have taken the result of the non-steady state Crea-Clearance (= Chen's kinetic GFR) and the creatinine generation rate to "back"calculate a corresponding -virtual- steady state plasma creatinine concentration. That value is then used to get a GFR estimate by CKD-EPI. I have termed this the "dynamic GFR".
Generation rate and distribution volume of creatinine
Contrary to Chen, I have chosen the Cockcroft-Gault formula as the default for estimating the creatinine generation rate, and not MDRD. First, because the calculation is based on creatinine clearance. Second because with MDRD your estimated creatinine generation rate changes with different levels of baseline kidney function. Also, I prefer using the distribution volume over the maxDeltaCrea suggested by Chen. (As a reference to Chen, I have included a calculator that allows conversion of maxDeltaCrea to Vd/kg BW, though).
Using the formulas freehand in daily clinical practice is quite a challenge. So I put them together in an Excel sheet, which
A) gives you the graphical trend of dynamic versus steady state GFR.
B) presents a tabular view of these values and the corresponding dynamic and steady state Crea-clearances.
C) works in SI and conventional units of creatinine concentration.
D) allows you to manually adjust the daily creatine generation rate, the distribution volume of creatinine and other parameters.
A simple instruction on how to use the calculator can be found here.
Use and limitations
Practical use and limitations of the method are nicely discussed by Chen. The limits obviously relate to problems with estimating generation rate, distribution volume and mean plasma concentration of creatinine. Although these problems can be profound, one should not forget, that they are not exclusive to this approach. In fact they are at work whenever we are using plasma creatinine concentrations to monitor rapidly changing renal function.
Any corrections, feedback, questions, or suggestions are highly welcomed!
- Chen S. Retooling the Creatinine clearance equation to estimate kinetic GFR when the plasma Creatinine is changing acutely. Journal of the American Society of Nephrology. 2013;24(6):877–888. doi:10.1681/asn.2012070653.
- Winter ME. Basic clinical pharmacokinetics. 5th ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health; October 1, 2009.