Two routes for 99mTc-DMSA uptake into the renal cortical tubular cell

Critical factors determining the renal handling of ^99mTc-dimercaptosuccinic acid (DMSA) are protein binding in plasma and the renal ^99mTc-DMSA extraction efficiency. Comparison of the count rate over soft tissue with that over the cardiac blood pool about 1 h after injection demonstrated that ^99mTc-DMSA is not exclusively an intravascular label. ^99mTc-DMSA was 76% protein bound in plasma as demonstrated by HPLC and gel filtration. Assuming that the 24% that is not protein bound is filtered at the glomerulus, the renal extraction efficiency of ^99mTc-DMSA by glomerular filtration is about 5%. Since the total renal extraction efficiency was also found to be about 5%, the majority of the activity that becomes fixed in the renal cortex arrives there as a result of filtration followed by tubular reabsorption rather than by direct extraction from peritubular blood. However, discordant changes in DMSA and DTPA uptake induced by captopril in renovascular hypertension (RVH) suggested that a minority of uptake was by direct peritubular extraction.This kinetic model was supported by indirect measurement of protein binding and extraction efficiency based on the kinetics of ^99mTc-DMSA disappearance from plasma and kinetics of uptake in the kidneys. Furthermore, differential functional studies based on ^99mTc-DMSA and ^99mTc-DTPA before and after captopril in patients with RVH due to unilateral renal artery stenosis confirmed filtration followed by tubular reabsorption as the predominant route for DMSA uptake by the kidney.