Increased chymase-positive mast cells in children with crescentic glomerulonephritis

Abstract

Mast cell-derived chymase is an angiotensin II-forming enzyme that appears to be involved in tubulointerstitial fibrosis in the kidneys. Previous studies have shown that the level of chymase increases in grafted kidneys after rejection and in adult patients with diabetic nephropathy. However, the significance of chymase in children with renal diseases has not been investigated. Using immunohistochemistry, we have investigated chymase expression in biopsy samples of renal tissue from 104 children with kidney diseases, including rapidly progressive crescentic glomerulonephritis (n = 3), diabetic nephropathy (n = 2), allografted kidney (n = 3), membranoproliferative glomerulonephritis (n = 6), immunoglobulin A nephropathy (n = 33) and Henoch-Schönlein purpura nephritis (n = 23). Increased numbers of chymase-positive mast cells were observed in the renal cortex of all three patients with crescentic glomerulonephritis (mean 26.0/mm(2); range 19.3-36.8/mm(2)). Chymase-positive cells were also observed in the renal biopsy of an allografted kidney and in those from children with diabetic nephropathy. The mean number of chymase-positive cells in renal tissue samples characterized by each renal disease was significantly correlated with the mean intensity of the interstitial fibrosis in that same tissue sample (Spearman's rank correlation test p = 0.0013; rank correlation coefficient 0.84). These findings suggest that mast cell-derived chymase plays an important role in juvenile crescentic glomerulonephritis.

Original paper Renal interstitial mast cell count is significantly higher in membranoproliferative glomerulonephritis than in class IV lupus nephritis

“…The study showed that the number of chymase-positive mast cells correlates with the mean intensity of the interstitial fibrosis, which is similar to the results obtained in our study [12].…”

“…Mast cells can be divided into two classes, chymase-positive and chymase-negative, due to the fact that only a portion of mast cells are positive for chymase [9][10][11]. Chymase has the ability to convert angiotensin I to angiotensin II, which regulates intrarenal blood flow, and also participates in renal interstitial fibrosis [11,12]. It is involved in renal remodeling by increasing the expression of transforming growth factor β (TGF-β) [13].…”

Mast Cell Infiltration Is Involved in Renal Interstitial Fibrosis in a Rat Model of Protein-Overload Nephropathy

“…MCs as a kind of inflammatory cells have been ignored or forgotten by nephrologists for a long time because they are not easily detected by routine histochemical staining. The associations between MC infiltration and the degree of tubulointerstitial damage in some renal diseases such as diabetic nephropathy, hypertensive nephropathy, IgA nephropathy and crescentic glomerulonephritis, support the idea that MCs are likely to be key players in the pathogenesis of interstitial fibrosis [17][18][19][20] . To our knowledge, there are no reports in the current literature that have de- scribed whether MCs participate in renal interstitial fibrosis induced by proteinuria.…”

Impact of Mast Cell Chymase on Renal Disease Progression

“…The number of mast cells closely correlates with the severity of tubulointerstitial disease in renal diseases, including IgA nephropathy [31, 32], primary and secondary glomerulonephritis [18, 19, 33, 34], diabetic nephropathy [35,36], hypertensive nephropathy [26] and allograft rejection [16, 20, 37, 38]. Mast cell accumulation is also inversely correlated with a decline in glomerular filtration rate and disease progression [31, 34, 39-41].…”