Fractional excretion and reabsorption in chronic kidney disease

The concepts of fractional excretion and reabsorption are often employed to elucidate the contribution of tubular transport to plasma concentrations. Fractional excretion of substance x, FEx, is the ratio of the urinary excretion rate to the filtration rate of x, or Ex/Fx. Fractional tubular reabsorption of x, FTRx, is the ratio of the reabsorption rate to the filtration rate of x, or TRx/Fx. When plasma is in equilibrium with respect to x, net influx (Ix) from gut and tissue determines Ex, and [x]p = Ex/GFR + TRx/GFR. In chronic kidney disease (CKD), Ex/GFR rises as GFR falls if Ix does not fall commensurately; at the same time, TRx/GFR may fall, remain unchanged, or rise. If TRx/GFR rises, a simultaneous, proportionately greater increment in Ex/GFR causes FEx to rise also and FTRx to fall secondarily. In this circumstance, FTRx is lower than normal even though reabsorption of x is increased per volume of filtrate. This paper reviews pertinent homeostatic principles, illustrates the potential for divergence of TRx/GFR and FTRx as GFR falls, and summarizes the conditions required for the divergence. Clinical examples show reduced FTRx despite increased TRx/GFR for phosphorus and urate, and analyses suggest that such discrepancies are often inevitable. Methods are described and arguments are advanced for using TRx/GFR to quantify tubular function in CKD.