Relationship of glomerular hypertrophy and sclerosis: studies in SV40 transgenic mice

We previously described the development of glomerulosclerosis in mice transgenic for large T-antigen, a gene whose in vitro expression markedly increases proliferation of cultured cells. In the current study we sought to determine the effect of unilateral nephrectomy on these sclerosis-prone animals which have a genetically defined potential for increased renal growth. In comparison with sham nephrectomy animals, nephrectomized transgenic female mice had significantly larger kidneys, larger glomeruli (5886 mu2 npx vs. 3796 mu2 sham), more cells per glomerulus and more severe glomerulosclerosis. Nephrectomized transgenic male animals had variable increases in kidney size, no significant increase in glomerular size (4750 mu2 npx vs. 4502 mu2 sham) or cellularity, and no worsening of glomerulosclerosis. In non-transgenic female animals nephrectomy induced an increase in kidney size but not in glomerular size (2640 mu2 npx vs. 2625 mu2 sham) and failed to induce glomerular lesions. A close correlation (r = 0.91) was found between glomerular size and severity of glomerulosclerosis in these animals. This finding supports the hypothesis that a pathophysiologic link exists between glomerular enlargement and glomerulosclerosis. We also found that increases in total kidney size and glomerular size did not consistently parallel each other, that is, renal hypertrophy may occur without an increase in glomerular size. This finding suggests that total kidney growth and glomerular growth may be independently regulated or may have different thresholds for activation following unilateral nephrectomy.