Three-Dimensional Morphometric Analysis of Segmental Glomerulosclerosis in the Rat Remnant Kidney Model

Kim, Kee Hyuck; Sim, Jay G; O, Myung Ho; Kim, Kyo Sun; Yang, Sang Kuk

Abstract

In the previous study, serial section analysis in the Adriamycin animal model of progressive glomerulosclerosis, diffuse, rather than focal glomerulosclerosis were reported. However, the study in patients with nephrotic syndrome and idiopathic focal segmental glomerulosclerosis by three-dimensional analysis demonstrated a focal pattern of sclerosis. The distribution of lesions, whether focal or diffuse, has important implications, not only for pathogenesis and potential therapeutic response, but also for relevance of animal studies to human disease. We therefore evaluated the distribution of segmental glomerulosclerosis in the rat remnant kidney model. We used male M nich-Wistar rats weighing 250 grams at the start of the experiments. Ten rats had 1-1/2 nephrectomy. At the 24th week after the surgical procedure, GFR and arterial BP were measured. Renal tissues were then perfused with 1% glutaraldehyde at physiologic pressures. Sixty serial sections(4 micrometer thick) per a rat were stained with PAS. An average of 19.2+2.4 glomeruli was examined. Sclerosis assessed on a single section involved 32.6+11.4%. After the serial section analysis, the percent of glomeruli involved by sclerosis increased to 57.6+15.0%. Our results show that single section examination of kidney tissue underestimates glomerulosclerosis in the renal ablation model. However, much more intact glomeruli were present in the renal ablation model compared to Adriamycin rat model after serial section analysis. This finding may reflect the different pathogenic mechanism between the two animal models.