Mast cells: the forgotten cells of renal fibrosis

Background/Aims-Mast cells, when activated, secrete a large number of fibro genic factors and have been implicated in the development of fibrotic condi tions of the Liver, lung, and skin. There is evidence that renal fibrosis i s closely linked with a chronic inflammatory cell infiltrate within the int erstitium, but a potential role for mast cells in this process has yet to b e defined. Therefore, the numbers of mast cells in normal and fibrotic kidn eys with various pathologies were investigated. Methods-Mast cells were quantified in renal transplants showing acute and c hronic rejection and cyclosporin toxicity, kidneys removed for chronic pyel onephritis, and renal biopsies from patients with IgA nephropathy, membrano us nephropathy, and diabetic nephropathy. Mast cells were stained using two methods: acid toluidine blue detected less than 30% of the mast cells reve aled by immunohistochemistry for mast cell tryptase. Results-Mast cells were scarce or absent in normal kidney (median, 1.6 mast cells/mm(2)) but numerous throughout the cortex and medulla in all specime ns that showed fibrosis. They were almost entirely confined to the renal in terstitium. Mast cells were present in large numbers in biopsies from patie nts with membranous nephropathy (median, 21.7 mast cells/mm(2)) and diabeti c nephropathy (median, 29.2 mast cells/mm(2)), which were selected an the b asis of showing chronic injury. In 24 unselected IgA nephropathy biopsies t here was a close correlation between numbers of mast cells and the extent o f interstitial fibrosis (r = 0.771; p < 0.0001). In renal transplant biopsi es, mast cells were associated with allograft fibrosis in chronic rejection (median, 27.1 mast cells/mm(2)) and chronic cyclosporin toxicity (median, 10.6 mast cells/mm(2)) but not acute rejection (median, 2.7 mast cells/mm(2 )) or acute cyclosporin toxicity (median, 2.0 mast cells/mm(2)). There was no detectable increase in mast cell numbers during acute rejection in those transplants that subsequently progressed to chronic rejection. In some bio psies the mast cells were largely intact, but in most cases some or all wer e degranulated. Conclusions-An increased number of mast cells is a consistent feature of re nal fibrosis, whatever the underlying pathology, and the number of mast cel ls correlates with the extent of interstitial fibrosis. This suggests that mast cells might play a pathogenetic role in the fibrotic process.