title: Tubulointerstitial fibrosis in patients with IgG4-related kidney disease: pathological findings on repeat renal biopsy.
abstract: Renal parenchymal lesions in patients with IgG4-related kidney disease (IgG4-RKD) are characterized by tubulointerstitial nephritis with storiform fibrosis and infiltration by high numbers of IgG4-positive plasma cells. The aim of this study was to evaluate the clinical and pathological effects of corticosteroid therapy in patients with IgG4-RKD. Of six patients who were diagnosed with IgG4-RKD, four patients underwent re-biopsy at approximately 30-50 days after corticosteroid therapy was initiated. Based on the classification of Yamaguchi et al., the degree of tubulointerstitial fibrosis was classified before and after therapy. In addition, tubulointerstitial expression patterns of α-smooth muscle actin (α-SMA), collagen I, III, and IV protein, and connective tissue growth factor (CTGF) mRNA were examined. Histopathological findings before treatment showed α-SMA-positive myofibroblasts in the lesion, and CTGF mRNA-positive cells were found in the cellular infiltrate. Although corticosteroid therapy improved serum creatinine clinically, the stage of fibrosis advanced pathologically as evidenced by increased staining for collagen I and III. However, the number of IgG4-positive plasma cells decreased, and CTGF mRNA expression reduced. In other words, fibrosis had advanced from the time of extensive cell infiltration in patients with IgG4-RKD and inflammation was relieved by corticosteroid. A reduced number of positive CTGF mRNA expression cells in repeat biopsies indicated that the fibrosis process was terminated by corticosteroid therapy. We propose that corticosteroid therapy could terminate the pathway of active fibrosis, thereby inhibiting progression to renal dysfunction.
authors.affiliation: Department of Nephrology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Arai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Koide
authors.forename: Waichi
authors.initials: W
authors.lastname: Sato
authors.forename: Midori
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Jan
authors.initials: J
authors.lastname: Aten
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ito
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yuzawa
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; C526317:CCN2 protein, human; D007074:Immunoglobulin G; D055513:Connective Tissue Growth Factor; D003094:Collagen