PAH is an organic anion and its clearance is used as a measure of renal plasma flow. Proximal tubular extraction of PAH is mediated by the organic anion transport proteins OAT1 and OAT3 which are rate limiting for renal organic anion secretion. Expression of OAT1/3 is down regulated after renal ischemia and reperfusion (I/R). Therefore, renal hypoperfusion after I/R may be overestimated due to the fact that PAH clearance is a function of renal extraction rather than of renal perfusion.

iAKI was induced in rats by bilateral clamping of renal arteries for 45 min. Parameters were determined after a 24 h reperfusion period. PAH clearance was corrected for renal exctraction of PAH resulting in the corrected PAH clearance representing an exact measure of renal plasma flow.

PAH clearance after ischemia and 24 h reperfusion is highly influenced by reduced renal extraction ratio of PAH. This correlates with an impaired expression of the rate limiting transporters for organic anions rOat1/3.

The widely described renal hypoperfusion after experimentally induced renal ischemia and reperfusion is overestimated (if renal extraction of PAH is not considered when determining renal plasma flow after I/R) due to down regulation of rOat 1/3. As a consequence the attempts to attenuate renal damage after acute ischemia were highly focused on renal blood flow. This may be the cause why the efforts to establish a causal strategy against renal ischemia reperfusion damage did not succeed.

Supported by DFG Grant SA 948/3-1 and Roux 22/23.