CELL-PROLIFERATION IN THE DEVELOPING HUMAN KIDNEY

In a previous study, utilizing antibodies to proliferating cell nuclea r antigen (PCNA), we determined the proliferation index (PI) (percenta ge of PCNA-positive cells) of intrinsic renal cell populations in the normal adult and pediatric kidney. We have found that the PI in both a dult and pediatric kidneys was very low (below 0.5 in all examined cel l populations). In our present study, we investigated cell proliferati on in the developing human kidney with an antibody to PCNA. Histologic ally normal kidneys were collected from 25 fetuses (spontaneous aborti ons and stillborns) ranging from 10 wk of gestation to term. Immature mesenchyme (blastema), immature early tubules, ampulla of ureteric bud , proximal tubules, Tamm-Horsfall protein (THP)-positive tubules, dist al tubules, collecting ducts, and glomeruli were evaluated separately. The PI for each cell population was calculated. The PI of immature ea rly tubules remains high (33-43) throughout embryonic life. The PI of blastemal cells is initially similarly high, but gradually decreases s tarting from the second trimester. The PI of THP-positive tubules, dis tal tubules, collecting ducts, and glomeruli starts out relatively hig h (5.9, 8.6, 6.0, and 12.4, respectively) and decreases gradually as t erm approaches (1.8, 1.3, 1.2, and 1.4, respectively). Interestingly, as soon as proximal tubules become differentiated (appearance of light microscopic features of proximal tubular epithelium with TP lectin po sitive brush border), their PI becomes very low (below 1) irrespective of the age of the kidney. This is the first quantitative study to sho w changes of the PI in Various renal cell populations during human nep hrogenesis. These changes in the PI relate to the stage of differentia tion of the developing nephron segments.