Different types of segmental sclerosing glomerular lesions in six experimental models of proteinuria

Abstract

From 133 to 615 glomeruli were examined in sections of kidneys from each of 60 animals, representing six rodent models of proteinuria. Particular attention was paid to the position of segmental lesions. Lewis rats given sheep anti-rat glomerular basement membrane antibodies had lesions almost exclusively at the glomerulo-tubular junction. Wistar rats on a diet of 24 per cent casein or with subtotal nephrectomy and a diet of 24 per cent soya had lesions mainly at the hilum. Wistar rats given bovine serum albumin had global lesions but virtually no segmental lesions. Wistar rats given puromycin aminonucleoside had lesions at the glomerulo-tubular junction and global mesangial abnormalities shortly after the treatment but later developed segmental lesions at all parts of the glomerulus. Untreated BUF/Mna rats had lesions at the glomerulo-tubular junction early in life but later had lesions at all parts of the glomerulus. Untreated NZB/NZW hybrid mice had various types of glomerulonephritis and also had lesions at the glomerulo-tubular junction. These findings showed that (1) segmental lesions at the glomerulo-tubular junction, or glomerular tip, occur in experimental animals, a fact not previously reported, and these tip changes are a common feature in several different models of proteinuria; (2) hilar segmental lesions are seen in conditions with hyperfiltration of protein; and (3) segmental lesions at various parts of the glomerulus are seen in some models of proteinuria and probably indicate late effects of random toxic damage to the glomerulus. Thus, there are at least three different types of segmental glomerular lesions in experimental animals--tip, hilar, and random--with different morphology and pathogenesis. It is likely that these findings can be extended to human renal diseases with segmental glomerular lesions. This will help to clarify the controversial and unsatisfactory term focal segmental glomerulosclerosis.

Wild-type p53 transgenic mice exhibit altered differentiation of the ureteric bud and possess small kidneys.

“…Conditions that reduce total glomerular filtration surface are associated with progressive renal disease characterized by focal segmental glomerulosclerosis (Hostetter et al 1981) as observed in p53 transgenic mice. In addition, such changes have been seen in kidneys of adult rats subjected to reduction of renal mass (Howie et al 1989). Second, those nephrons that do develop in p53 transgenic kidneys may not be normal.…”

Comparison of a Vegetable-Based (Soya) and an Animal-Based Low-Protein Diet in Predialysis Chronic Renal Failure Patients

“…Since progression of CRF is at least partially related to glomerular hyperfiltration [4], vegetable protein might, therefore, be more advantageous in the prevention of progression of CRF than animal protein. This is indeed suggested by several animal studies where, as compared with animal-based low-protein diets (APD), soya-based vegetable low-protein diets (VPD) are more effective in slowing the progression of CRF in normal [5] and in partially nephrectomised Wistar rats [5, 6, 7] and in normal Fischer rats [8, 9, 10]. …”

Involvement of Transglutaminase-2 in Pathological Changes in Renal Disease

“…Glomerular sclerosis has been reported to be remarkable in the vicinity of vascular poles in some animal models [14, 15] and human pathology including hypertension [16, 17], diabetic nephropathy [18], and hyperfiltration [19]. Collagen III, originally extraglomerular component and known as substrate of Tg-2 [20], has been expressed in vascular poles in human diabetic nephropathy [21] and mesangial proliferative glomerulonephritis [22].…”