Glomerular hyalinosis and its relation to hyperfiltration

Reduction in renal mass in rats results in hyperfiltration of the remnant nephrons, accompanied by injury to the glomeruli and their eventual sclerosis. This study was undertaken in a rat model with 5/6 reduction of renal mass to follow the evolution of glomerular damage, over an 11-week period, with particular emphasis on the widely prevalent, although seldom discussed, lesion of hyalinosis. Light, electron, and immunofluorescence microscopic studies were performed and blood pressure, excretion of urinary albumin, and serum creatinine levels determined. Systolic blood pressure, urinary albumin excretion, and serum creatinine levels were all increased by the third week following operation. Blood pressure and serum creatinine continued to increase throughout the period of study. Glomerular damage was focal and segmental, and glomeruli were equally affected in both the juxtamedullary and outer zones of the cortex. Endothelial injury was noted to be the first indicator of glomerular damage, followed closely by alterations in the epithelial cells. The early hyalinosis lesion was characterized by an accumulation of homogeneous electron-dense material beneath damaged endothelial cells with later encroachment on the capillary lumen resulting in the easily recognizable eosinophilic, periodic acid-Schiff-positive lesion by light microscopy. These alterations were accompanied by complex changes within the mesangium, including both mesangiosclerosis and mesangiolysis. Glomerular hyalinosis, glomerular sclerosis, vascular damage, blood pressure, and albuminuria were ranked in order of severity and the rankings subjected to multiple regression analysis. Significant correlations were present between glomerular sclerosis and hyalinosis, arterial damage and blood pressure, and hyalinosis and urinary albumin excretion. The hyalinosis lesion accompanying the progressive glomerular sclerosis in this model resembles that seen in a number of human conditions. In addition, the correlations of hyalinosis with glomerular sclerosis and albuminuria reflect its association with glomerular injury; it is likely that it will prove to be a reliable marker of hyperfiltration injury.