Tsuda A, Ishimura E, Machiba Y, Uedono H, Nakatani S, Mori K, Uchida J, Emoto M: Increased Glomerular Hydrostatic Pressure is Associated with Tubular Creatinine Reabsorption in Healthy Subjects. Kidney and Blood Pressure Research DOI 10.1159/000510838
It is generally observed that creatinine is secreted by the proximal tubule (via an organic anion transporter) in subjects with normal or even modestly impaired function leading to an overestimation of the true glomerular filtration rate (GFR) when endogenous creatinine clearances (Ccr) are used to estimate kidney function. This secretion accounts for about 15–20% of the excreted creatinine. Net tubular reabsorption of creatinine has been described in special situations (e.g., newborns and very elderly), but it is the exception rather than the rule.
Tsuda and coworkers have extended these observations by performing 24-h endogenous true Ccr and GFR measurements (by urinary clearance of inulin; Cin), along with measurements of renal plasma flow by the clearance of para-aminohippurate (Cpah) in 80 apparently healthy transplant donors (age 54 ± 13 years), with pre-unilateral nephrectomy and remeasurement of these parameters in 20 of the original subjects 1 year after uninephrectomy. The glomerular hemodynamics were estimated by the Gomez equations, developed in 1951 as a way of approximation of mean glomerular capillary hydraulic pressure (Pgc) and the resistances of the afferent (Ra) and efferent (Re) glomerular arterioles.
The mean pre-nephrectomy Ccr was 102 ± 28mL/min and the Cin was 88 ± 18 mL/min (Ccr/Cin = 1.15). The mean filtration fraction (Cin/Cpah) was 0.20 ± 0.03. Thus, overall, the Ccr/Cin indicate tubular secretion of creatinine; however, 25/80 (31%) of the subjects had a Ccr/Cin value of <1.0, indicating tubular reabsorption of creatinine. It is not clear whether the Ccr and Cin determinations were performed at exactly the same time, so diurnal variation in Ccr/Cin might have contributed to this finding. Interestingly, when the Gomez equations were applied to the GFR and RPF data, apparently using the common assumption that 10% of the total renal resistance is accounted for by Ra, the Ccr/Cin ratio (a measure of tubular secretion of creatinine) was inversely correlated with Pgc and Re. The FF was equal in both subjects with values for Ccr/Cin of <1 or >1. The average Pgc was 56 and 58 mm Hg in those with a Ccr/Cin of >1 or <1, respectively (p = 0.053). These values of Pgc are about 11–13 mm Hg higher than the values believed to prevail in the human glomerulus (approx. 45 mm Hg), and it is difficult to explain the data when the FF is equal between those with a high (>1) versus a low (<1) value for Ccr/Cin. This raises questions about the merits of the Gomez equation, which tends to give unreasonably high values for Pgc. As expected, the Ccr and Cin were highly correlated with each other, but the regression analysis suggested a higher value of Ccr/Cin when GFR is 60–90 mL/min than when it is 90–120 mL/min.
In the post-uninephrectomy subjects, both the Ccr and Cin fell to about 63 and 59% of baseline 1 year after uninephrectomy and the extent of decrease in GFR was correlated with the degree of increase in the Ccr/Cin ratio. Unfortunately, a change in Pgc post-uninephrectomy was not calculated. It should have increased following uninephrectomy, which would predict a decline in Ccr/Cin (more creatinine reabsorption) in the post-nephrectomy period, whereas the opposite was observed. These are all very interesting observations, but in my opinion further work is needed to verify the validity of the hypothesis that tubular creatinine reabsorption is common in healthy adults and that it might have something to do with glomerulus hydraulic pressure.