Atrophic tubules in end-stage renal disease (ESRD) may have various morphologic appearances:
some show microscopic features of "classic" atrophic tubules (thick, wrinkled tubular
basement membrane and simplified epithelium), others show "thyroidization" (round
tubules with simplified epithelium and casts), and many have the appearance of "endocrine"
tubules (small tubules with narrow lumina, clear cells, and relatively thin basement
membranes). Other tubules in ESRD may be enlarged and dilated with hypertrophic cells
("super" tubules). The exact segment of the nephron from which these tubules arise
in ESRD has not been well studied. We examined paraffin sections of 28 end-stage kidneys
with a panel of nephron-segment-specific renal epithelial markers (proximal nephron
markers: Tetragonolobus purpureas and Phaseolus vulgaris erythroagglutinin lectins;
distal nephron markers: antibodies to epithelial membrane antigen, low molecular weight
cytokeratin [AE1/AE3], the lectin Arachis hypogaea, and an antibody to Tamm-Horsfall
protein labeling the thick ascending limb of Henle). In addition, an antibody to proliferating
cell nuclear antigen was applied to determine the proliferation index (proliferating
cell nuclear antigen-positive nuclei/all counted nuclei x 100, ie, the percentage
of proliferating cell nuclear antigen-positive nuclei) of the various atrophic and
"super" tubules in ESRD. Classic atrophic tubules and the "super" tubules showed primarily
a proximal phenotype. Tubules showing thyroidization were consistently positive with
markers of the distal tubular epithelium. "Endocrine" tubules stained primarily with
distal tubular markers; however, some proximal staining also was noted. The widened
renal interstitium contained single cells or loosely organized small cell clusters
positive with both the AE1/AE3 and the epithelial membrane antigen antibodies. Serial
sectioning showed that the majority of these single cells were not forming tubules.
The proliferation index of the "classic" atrophic tubules was the highest (3.08%),
followed by the "super" tubules (2.39%), the "endocrine" tubules (1.58%), and the
"thyroid" tubules (1.09%). These indexes are all considerably higher than the proliferation
index of the normal renal tubular epithelium. Our findings suggest that different
types of tubular atrophy may arise from different segments of the nephron, and that
the renal interstitium in ESRD may harbor isolated cells with epithelial characteristics.
Furthermore, the end-stage kidney is not a resting organ; on the contrary, it shows
a high proliferative activity, particularly in the epithelium of the "classic" atrophic
and the "super" tubules.