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Activation of nuclear factor‐kappa B and macrophage invasion in cyclosporin A‐ and tacrolimus‐treated renal transplants
Author(s) -
Mizuiri Sonoo,
Iwamoto Masateru,
Miyagi Moriatsu,
Kawamura Takeshi,
Sakai Ken,
Arai Kenji,
Aikawa Atsushi,
Ohara Takehiro,
Hemmi Hiromichi,
Hasegawa Akira
Publication year - 2004
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1046/j.0902-0063.2003.00104.x
Subject(s) - medicine , cd68 , tacrolimus , immunostaining , biopsy , creatinine , gastroenterology , urology , transplantation , pathology , immunohistochemistry
This retrospective study was designed to compare the efficacy of cyclosporin A (CyA) and tacrolimus (FK506) on chronic rejection (CR) associated with nuclear factor‐kappa B (NF‐ κ B) activation and macrophage invasion. Non‐episodic day 50 protocol renal biopsy was performed in 63 consecutive patients with renal transplants from living donors, treated with either CyA or FK506. Southwestern histochemistry for NF‐ κ B, immunostaining for CD68, and Banff classification were performed, and these findings were compared with outcome over 34 ± 13 months. Compared with specimens from FK506‐treated patients (n = 20), specimens from CyA‐treated patients (n = 43) showed a significant increase in tubulointerstitial CD68‐positive cells (1.5 ± 0.9 vs. 0.9 ± 0.8, p < 0.01), although no significant differences were observed in NF‐ κ B activation. Specimens with Banff acute rejection (AR) grade ≥ 1A (n = 20) showed increased macrophages (p < 0.01) compared with specimens with AR < 1A (n = 43). Specimens from patients with clinical AR prior to day 50 biopsy (n = 23) also showed increased macrophage invasion (p < 0.01) compared with specimens from patients without prior clinical AR (n = 40). The cumulative well‐functioning (serum creatinine <1.5 mg/dL) graft survival rate was significantly lower in patients with increased tubulointerstitial CD68‐positive cells (n = 63, p < 0.05). Our findings suggest that tacrolimus is more effective than CyA against CR with respect to macrophage invasion and AR.