Adaptation and distortion of podocytes in rat remnant kidney.

A sequence of alterations of podocytes as well as the development of glomerulosclerosis was analyzed in a five-sixths nephrectomy rat model. Morphometric measurements showed a gradual enlargement in glomerular size without any increase in the number of podocytes in the glomerulus. Structural changes of podocytes appeared as early as 4 weeks after operation, and increased their degree and extent with time. In electron microscopic studies, changes of podocytes in the early stage consisted of foot process stretching and thinning, and cell body attenuation accompanied by pseudocyst formation. As weeks passed, these changes became prominent and were occasionally associated with podocyte detachment from the glomerular basement membrane followed by tuft adhesion and the development of segmental sclerosis. In parallel to the structural changes, immunohistochemical staining demonstrated a marked increase of desmin expression in the glomerulus with intense staining in podocytes. Podocyte alterations were identified as an adaptation to the enlargement of the glomerulus and, consequently, the podocytes seemed to fall to adapt to the structural changes of the glomerulus. The present study supports the hypothesis that podocyte defects are responsible for both the initiation and progression of glomerular damage. Furthermore, the findings may provide the hypothesis that the native disposition of podocytes in the glomerulus participates in the development of glomerular lesions in a focal and segmental fashion.