Renal localization of Tamm-horsfall protein in unilateral obstructive uropathy in rats

The distribution of Tamm-horsfall protein (THP) within nephrons and in the renal interstitium of the kidney was examined in rats after unilateral ureteral ligation. Urinary casts containing THP were detected not only distal to the site of THP synthesis in cells of the ascending limbs of the loop of Henle, but also in more proximal portions of the nephron, suggesting retrograde intratubular movement of urine. THP-positive casts within Bowman's space of glomeruli were found by 6 hours and were maximal at 2 weeks after obstruction. At this time, THP was present in 25 per cent of all glomeruli, predominantly in central zones of the outer cortex. No morphologic evidence suggesting passage of THP across Bowman's capsule of these glomeruli was found. By contrast, interstitial THP aggregates resulting from urinary extravasation from tubules were detected throughout the study. These occurred earlier and were more numerous, albeit smaller, in the cortex where they were concentrated in periarterial and periglomerular sites. Multiple pathways for escape of urinary THP from tubules were demonstrated and included tubular ruptures and necrosis, forniceal tears, and venous polyps. Although occasional masses of THP in the interstitium were surrounded by inflammatory cells, the overall time course and distribution of interstitial THP deposits did not correlate closely with the development of widespread interstitial hypercellularity and scarring after obstruction. Although not directly linked to the pathogenesis of tissue injury in obstructive uropathy, THP provides an excellent marker of urinary extravasation and of the pathways of urine flow within the kidney under pathologic conditions.