Renal handling of 2′-deoxyadenosine and adenosine in humans and mice

Summary

In a child lacking adenosine deaminase and in patients treated with deoxycoformycin (a potent inhibitor of the enzyme), apparent renal secretion of 2′-deoxyadenosine (dAdo) and reabsorption of adenosine (Ado) were observed. The renal clearance of dAdo in humans was approximately five-fold that of creatinine, whereas the renal clearance of Ado was only one-fifth that of creatinine. In mice treated with deoxycoformycin, a similar paradigm was observed. Specifically, plasma levels of Ado and dAdo were elevated to detectable levels and apparent renal secretion and reabsorption of these purine nucleosides became manifest. Thus, the mouse may serve as a suitable model to study the renal handling of these two compounds. The active renal secretion of dAdo may occur because the compound has not been appreciably synthesized by mouse kidney in situ, and ‘ion-trapping’ of dAdo in acid urine could not explain the net secretion. The differential transport of these similar purine nucleosides suggests a very selective transport system in mammalian kidney. Although carrier-mediated, facilitated diffusion of purine nucleosides across cell membranes is a well-known phenomenon, the present data indicate the existence of (an) active transport sysem(s) for the transepithelial secretion of dAdo, and possibly for the reabsorption of Ado.