Cell Proliferation in the Developing Human Kidney

In a previous study, utilizing antibodies to proliferating cell nuclear antigen (PCNA), we determined the proliferation index (PI) (percentage of PCNA-positive cells) of intrinsic renal cell populations in the normal adult and pediatric kidney. We have found that the PI in both adult and pediatric kidneys was very low (below 0.5 in all examined cell populations). In our present study, we investigated cell proliferation in the developing human kidney with an antibody to PCNA. Histologically normal kidneys were collected from 25 fetuses (spontaneous abortions 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, distal tubules, collecting ducts, and glomeruli were evaluated separately. The PI for each cell population was calculated. The PI of immature early tubules remains high (33–43) throughout embryonic life. The PI of blastemal cells is initially similarly high, but gradually decreases starting from the second trimester. The PI of THP-positive tubules, distal tubules, collecting ducts, and glomeruli starts out relatively high (5.9, 8.6, 6.0, and 12.4, respectively) and decreases gradually as term 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 positive brush border), their PI becomes very low (below 1) irrespective of the age of the kidney. This is the first quantitative study to show changes of the PI in various renal cell populations during human nephrogenesis. These changes in the PI relate to the stage of differentiation of the developing nephron segments.