Cellular Events in Renal Hypertrophy

Growth in the size of the kidney is loosely referred to as renal hypertrophy. At a cellular level the term hypertrophy is entirely appropriate since kidney mass increases predominantly by a process of cell enlargement rather than by cell proliferation (32, 33). This is reflected by an increase in protein per cell, protein per DNA, and cell size. Since the bulk of the kidney mass consists of the proximal tubule, this part of the nephron contributes most to hypertrophy. However, all parts of the nephron increase in size in response to renal ablation, including glomeruli (2, 50) and proximal (4, 18,44, 57) and distal tubular elements (4, 36). Given the unique structure of the renal tubule, in which a single layer of epithelium encloses a narrow lumen, growth by hypertrophy is a feasible way to increase tubular mass; a proliferative re­ sponse, i.e. hyperplasia (such as occurs following partial ablation of the liver), would lead to piling up of cells and tubular obstruction, and would only be economical if it followed loss of cells with denudation of the basement membrane. The causes of renal hypertrophy are numerous (see Table 1). The pattern of cell growth described above is not uniform for all forms of renal hypertrophy. Even the ablation model yields different growth patterns depending upon the specific experimental conditions. Thus, in the neonatal animal, compensatory renal growth following uninephrectomy occurs predominantly by hyperplasia whereas in the adult, total DNA content increases only marginally (11). In the adult, the extent of renal ablation appears to influence the cellular growth response: the more extensive the ablation, the greater the increase in DNA content per nephron (37). While it is usually assumed that this increase in DNA content reflects hyperplasia in a tubule that is increasing in length, the