Bischoff Ariane, Bucher Michael, Gekle Michael, Sauvant Christoph
Klinik für Anästhesie und Operative Intensivmedizin, Universitätsklinikum Halle, Halle (Saale), Germany.
Julius-Bernstein-Institut für Physiologie, Universität Halle-Wittenberg, Halle (Saale), Germany.
Physiol Rep. 2014 Feb 19;2(2):e00243. doi: 10.1002/phy2.243. eCollection 2014 Feb 1.
Determination of renal plasma flow (RPF) by para-aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigated this phenomenon in a rat model of renal ischemia and reperfusion by determining PAH clearance, PAH extraction, PAH net secretion, and the expression of rOat1 and rOat3. PAH extraction was seriously impaired after ischemia and reperfusion which led to a threefold underestimation of RPF when PAH extraction ratio was not considered. PAH extraction directly correlated with the expression of basolateral Oat1 and Oat3. Tubular PAH secretion directly correlated with PAH extraction. Consequently, our data offer an explanation for impaired renal PAH extraction by reduced expression of the rate limiting basolateral organic anion transporters Oat1 and Oat3. Moreover, we show that determination of PAH net secretion is suitable to correct PAH clearance for impaired extraction after ischemia and reperfusion in order to get valid results for RPF.
通过对氨基马尿酸（PAH）清除率来测定肾血浆流量（RPF）会导致对该参数的严重低估，这是因为肾缺血再灌注损伤后肾脏对PAH的摄取受损。然而，目前尚无对这一现象的机理解释。基于我们之前的研究，我们推测这可能是由于基底外侧限速有机阴离子转运体Oat1和Oat3的表达受损所致。因此，我们通过测定PAH清除率、PAH摄取、PAH净分泌以及rOat1和rOat3的表达，在肾缺血再灌注大鼠模型中研究了这一现象。缺血再灌注后PAH摄取严重受损，当不考虑PAH摄取率时，这导致RPF被低估了三倍。PAH摄取与基底外侧Oat1和Oat3的表达直接相关。肾小管PAH分泌与PAH摄取直接相关。因此，我们的数据为限速基底外侧有机阴离子转运体Oat1和Oat3表达降低导致肾脏PAH摄取受损提供了解释。此外，我们表明，测定PAH净分泌适合校正缺血再灌注后摄取受损的PAH清除率，以便获得RPF的有效结果。
