Pseudouridine is unsuitable as an endogenous renal clearance marker

We assessed the clearance of endogenous pseudouridine in humans to evaluate the potential use of this modified nucleoside as a marker of glomerular filtration rate. Pseudouridine concentrations in serum ultrafiltrates and in the corresponding 24-h urine specimens from 19 healthy men were determined by high-performance liquid chromatography. Mean (and SD) pseudouridine concentrations in serum and urine from this group averaged 2.77 (0.34) mumol/L and 203.2 (64.8) mumol/L, respectively. The calculated clearances of the nucleoside [87.3 (24.9) mL/min, n = 19], however, averaged approximately one-third lower than the corresponding creatinine clearances in the same individuals [131.8 (28.4) mL/min]. Measurement of simultaneous clearances of [3H]pseudouridine and [14C]inulin in rats also yielded a lower pseudouridine clearance, 0.78 relative to inulin. Our results are thus consistent with a partial net reabsorption of pseudouridine in both experimental animals and in humans, indicating that this compound would not be a suitable endogenous marker for routine estimation of the glomerular filtration rate.