Ischemic acute renal failure (iARF) is known to reduce renal extraction of the organic anion para-aminohippurate (PAH) in humans. The rate limiting step of renal organic anion secretion is mediated by OAT1 and OAT3 (OAT1/3), which both have a broad spectrum of substrates including a variety of pharmaceu- tics and toxins. Inulin- and PAH clearance were determined from 6 hours up to 336 hours after ischemia/reperfusion (I/R)-injury. Net secretion of PAH was calculated and expression of OAT1/3 was analysed by RT-PCR and western blot. Inulin- and PAH- clearance, along with PAH net secretion were diminished in the initial phase after I/R-injury with a gradual recovery during follow-up. Functional impairment was re-flected by decreased mRNA- and protein-levels of OAT1 and OAT3. In correlation to the improvement of kidney function both mRNA and protein levels of OAT1/3 were up regulated during the follow-up. Thus, decreased expression of OAT1/3 is sufficient to explain the decline of PAH-secretion after iARF. As a result, this may have substantial impact on excretion kinetics and half-life of organic anions. As a consequence, the biological effects of a variety of organic anions may be affected after iARF.

(supported by the IZKF Würzburg)