Compensatory Renal Hypertrophy: Tubular Cell Growth and Transport Studied in Primary Culture

Abstract

In order to define the growth and transport characteristics of renal epithelia during hypertrophy, primary culture of proximal tubular cells was established from kidneys of normal rats and those with compensatory renal hypertrophy (CRH) induced by unilateral nephrectomy. At confluence, enhanced growth potential was preserved in the cells derived from the animals with CRH (CRH cells) as compared with cells derived from normal animals (N cells), as evidenced by an increased cellular protein content (250 ± 12 vs. 151 ± 11 pg protein/cell; p < 0.001) and a somewhat lesser increase in cellular thymidine incorporation (6,820 ± 52 vs. 5,151 ± 308 cpm/10⁶ cells; p < 0.02). The cellular Na transport (measured as ²²Na uptake) was increased in the CRH cells, being 733 ± 47, 886 ± Ill, and 1,026 ± 147 cpm/1,000 cells at 1,3, and 120 min, respectively, versus 353 ± 36,469 ± 31, and 549 ± 41 cpm/1,000 cells in N cells (p < 0.05 for each time point), i.e., an increase in Na transport in CRH cells of 107, 88, and 87%, respectively. Addition of Amiloride inhibited Na uptake in N cells by approximately 50% and completely suppressed the excess Na uptake in CRH cells to values observed in normal animals, i.e, 147 ± 33,224 ± 91, and 174 ± 86 cpm/1,000 cells in CRH cells at 1,3, and 120 min respectively, versus 181 ± 71,164 ± 57, and 238 ± 85 cpm/1,000 cells in N cells (p = NS at each time point). The results suggest that enhanced tubular cell growth in CRH is maintained from the in vivo setting to the in vitro cell culture system. Increased cellular Na transport in CRH is demonstrated to be via Na-H exchange by virtue of its reversion to normal in the presence of Amiloride. The results support the view that alterations in epithelial transport may be an important mechanism in the initiation or maintenance of cell growth.