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1 Clinic of Internal Medicine I, Division of Nephrology, University Wuerzburg, Wuerzburg, Germany
2 Physiologisches Institut, University Wuerzburg, Wuerzburg, Germany
* To whom correspondence should be addressed. E-mail: christoph.sauvant{at}mail.uni-wuerzburg.de.
Ischemic acute renal failure (iARF) was described to reduce renal extraction of the organic anion para-aminohippurate (PAH) in humans. The rate limiting step of renal organic anion secretion is its basolateral uptake into proximal tubular cells. This process is mediated by the organic anion transporters OAT1 and OAT3, which both have a broad spectrum of substrates including a variety of pharmaceutics and toxins. Using a rat model of iARF, we investigated whether impairing the secretion of the organic anion PAH might be associated with down regulation of OAT1 or OAT3. Inulin- and PAH clearance was determined starting from 6 hours up to 336 hours after ischemia/reperfusion (I/R)-injury. Net secretion of PAH was calculated and OAT1- as well as OAT3-expression was analysed by RT-PCR and western blotting. Inulin- and PAH clearance, along with PAH net secretion were initially diminished after I/R-injury with a gradual recovery during follow-up. This initial impairment after iARF was accompanied by decreased mRNA- and protein-levels of OAT1 and OAT3 in clamped animals as compared to sham operated controls. In correlation to the improvement of kidney function both mRNA and protein levels of OAT1 and OAT3 were up regulated during the follow-up. Thus, decreased expression of OAT1 and OAT3 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.
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