title: Evidence for abundant presence of chymase-positive mast cells in the kidneys of patients with immunoglobulin A nephropathy: effect of combination therapy with prednisolone and angiotensin II receptor blocker valsartan.
abstract: Several investigators have reported chymase-positive mast cells in tubulointerstitial damage. However, the significance of the presence of chymase in the pathophysiology of renal diseases is unclear. We investigated relationships among chymase, renal damage, and intra-renal circulation. The participant pool consisted of 52 patients with immunoglobulin A (IgA) nephropathy who underwent renal biopsy. Of these, 18 were examined before and 2 months after the initiation of treatment with prednisolone alone (n=9) or combined with the angiotensin II receptor blocker valsartan (n=9). Biopsied renal specimens were evaluated, and the degree of renal circulation (resistive index; RI) was calculated by measuring flow velocity using Doppler sonography. The number of chymase-positive mast cells as visualized by immunohistochemical staining correlated significantly with both tubulointerstitial damage (rho=0.69, p<0.001) and RI (r=0.52, p<0.001). Treatment with prednisolone combined with valsartan effectively decreased both chymase-positive mast cells and RI, displaying a significant correlation between these biomarkers (rho=0.85, p=0.016). However, no such effect was observed with prednisolone alone. The severity of tubulointerstitial damage and the degree of proteinuria were similar in both treatment groups throughout the study term. We concluded that the presence of chymase-positive mast cells and the associated decrease in renal circulation corresponded to disease progression in IgA nephropathy. Combination therapy using prednisolone and valsartan may lead to improvements in intra-renal circulation and to interference in the recruitment of chymase-positive mast cells.
authors.affiliation: Department of Internal Medicine, Osaka City General Hospital, and Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Konishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Morikawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Okada
authors.forename: Isseki
authors.initials: I
authors.lastname: Maeda
authors.forename: Chizuko
authors.initials: C
authors.lastname: Kitabayashi
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Michiaki
authors.initials: M
authors.lastname: Okumura
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Makiko
authors.initials: M
authors.lastname: Ueda
authors.forename: Shinji
authors.initials: S
authors.lastname: Takai
authors.forename: Mizuo
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Masahito
authors.initials: M
authors.lastname: Imanishi
mesh_terms: D000293:Adolescent; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001706:Biopsy; D053818:Chymases / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology; D016014:Linear Models; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D011239:Prednisolone / Q000008:administration & dosage*; D012079:Renal Circulation / Q000187:drug effects*; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000008:administration & dosage*; D018608:Ultrasonography, Doppler; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; D013777:Tetrazoles; D000068756:Valsartan; D011239:Prednisolone; D053818:Chymases; D014633:Valine