Analysis of renal structural and functional features in two rat strains with a different susceptibility to glomerular sclerosis

Abstract

Individual differences in susceptibility to the development of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) after loss of renal mass were studied in two rat strains. Male Wistar rats, and most other rat strains, were found to develop FSGHS associated with proteinuria with ageing, a process which could be accelerated by unilateral nephrectomy (UN). In male PVG/c rats, however, a complete resistance to the development of FSGHS was found even at 1 year after UN. The Wistar rat was found to have a lower number of nephrons per kidney and to differ from the PVG/c rat in its response to UN: Wistar rats showed an increase of whole kidney glomerular filtration rate and renal plasma flow in the remaining kidney with expansion of glomerular volume and with increased mesangial deposition of circulating macromolecules. In the PVG/c rat, UN led to a comparable proportional increase in glomerular filtration rate and renal plasma flow in the remaining kidney. However, in contrast to the Wistar rat neither glomerular hypertrophy nor enhanced mesangial macromolecular accumulation were observed after UN. Although the precise mechanisms underlying these effects are not identified, the current data support the "mesangial overloading" concept of FSGHS in which a local enhanced mesangial accumulation of circulating macromolecular material is thought to initiate the development of the sclerotic glomerular lesions. Moreover, to our knowledge this is the first description of a rat strain showing complete resistance to the development of FSGHS after UN. This PVG/c strain therefore seems to be a useful laboratory animal in comparison to other rat strains to further study the renal adaptation process after kidney ablation.