Intraglomerular fibronectin and laminin turn-over in chronically rejected kidney allografts in humans.

Chronic rejection is primarily responsible for the late loss of allografted organs and remains an important clinical problem. Chronic rejection in the kidney is characterised by arteriolosclerosis and nephrosclerosis, glomerulonephritis and interstitial fibrosis. Recently, a large number of studies have indicated that proteolytic enzymes play important roles as mediators of glomerular injury. The aim of the study was to assess intraglomerular fibronectin and laminin contents as well as cysteine proteinases in activity chronically rejected human kidneys. We investigated kidney tissue from graftectomy specimens obtained from 11 patients with end-stage renal disease following chronic rejection. A group of 9 patients undergoing nephrectomy because of cancer served as a control group, but only not involved parts of the kidneys were used. When intraglomerular laminin contents were related to DNA content, significant accumulation in chronically rejected allografts was found in comparison to controls (382 +/- 171 micrograms per microgram DNA and 190 +/- 82 micrograms per microgram DNA, respectively, p < 0.01. The accumulation of fibronectin was higher than in controls, however the difference was not significant. When proteinase activity was related to intraglomerular DNA content, significantly enhanced cathepsin B and L activity was found in rejected kidney allografts (57 +/- 16 nmol AMC/min per mg DNA) in comparison to controls (15 +/- 2 nmol AMC/min per mg DNA). Summarizing, we observed accumulation of fibronectin and laminin in glomeruli and simultaneously an excess of proteolytic activity in human chronically rejected kidneys. The above phenomenon indicates that a very active metabolic process takes place in glomeruli during rejection.