Retooling the Creatinine Clearance Equation to Estimate Kinetic GFR when the Plasma Creatinine Is Changing Acutely

Abstract

It is often desirable to estimate the GFR (eGFR) at the bedside to assess AKI or renal recovery. Current eGFR equations estimate kidney function when the plasma creatinine is stable, but do not work if the plasma creatinine is changing rapidly. To analyze kidney function in the acute setting, a simple formula is proposed that requires only a modest number of inputs that are readily obtainable from clinical laboratory data. The so-called kinetic eGFR (KeGFR) formula is derived from the initial creatinine content, volume of distribution, creatinine production rate, and the quantitative difference between consecutive plasma creatinines over a given time. For that period, the deciphered creatinine excretion then yields the creatinine clearance rate. The additional formula variables needed are any steady-state plasma creatinine, the corresponding eGFR by an empirical formula, and the maximum increase in creatinine per day if anuric. The kinetic formula complements clinical intuition but also adds a quantitative and visual dimension to the assessment of kidney function, demonstrated by its analysis of GFRs underlying the plasma creatinine fluctuations in several scenarios of AKI or renal recovery. Deduced from first principles regarding the physiology of creatinine balance, the KeGFR formula enhances the fundamental clearance equation with the power and versatility to estimate the kidney function when the plasma creatinine is varying acutely.

Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

“…Alternative or complementary measures of kidney function, including other filtration markers such as cystatin C and timed urine clearance measurements, could hold promise for improved phenotyping of functional recovery from AKD but require further validation before recommending their routine adoption into clinical practice 35,[63][64][65][66] . Methods to assess glomerular functional reserve (for example, by assessing the effect of a protein load on GFR) or tubular functional reserve (for example, through furosemide stress testing or the administration of intravenous creatinine) have also been developed in the CKD setting but have yet to be applied to patients with AKD 67,68 .…”

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“…In anuric AKI, it is presumed that plasma creatinine can rise by ≤ 1.0-1.5 mg/dL/day, but it is preferable that the numerical choice for MaxΔP Cr/Day be chosen using actual patient data. 1 For classifying different stages of AKI in donors, we used the risk, injury, failure, loss, and end-stage (RIFLE) classification system 5 For evaluating kidney function after living kidney donation, we measured the serum creatinine, cystatin C, and NGAL of 42 living donors before uninephrectomy and in the 3 days immediately after. Glomerular filtration rate was calculated before uninephrectomy and in each of the 3 days using CG, MDRD, and kinetic GFR equations.…”

“…Serum creatinine, in contrast, does not reflect GFR changes in real time if it is changing rapidly. 1,3 In addition, the measurement of GFR is essential in the selection of potential kidney donors. 3 In the early stages of acute kidney injury (AKI), serum creatinine levels overestimate actual GFR when the latter is markedly reduced, because there may not have been enough time for creatinine to accumulate; conversely, estimated GFR will underestimate true GFR during recovery from AKI, when serum creatinine is rapidly declining.…”

“…3,4 Also, owing to the nonlinear relation between creatinine/cystatin C and GFR, relatively small changes in these markers can represent significant alterations in GFR. 1,4 Nephrologists are always searching for comprehensive answers to questions such as: What are GFR changes over time? Are the changes gradual or precipitous?…”

“…Proponents of so-called "kinetic estimation of GFR" believe that all these answers are hidden in data on serum creatinine changes over time and can be revealed by kinetic GFR estimation. 1 By translating all creatinine measurements into kinetic GFR, they believe, these questions are answerable.…”