title: Acute graft-versus-host disease of the kidney in allogeneic rat bone marrow transplantation.
abstract: Allogeneic hematopoietic cell or bone marrow transplantation (BMT) causes graft-versus-host-disease (GVHD). However, the involvement of the kidney in acute GVHD is not well-understood. Acute GVHD was induced in Lewis rats (RT1l) by transplantation of Dark Agouti (DA) rat (RT1(a)) bone marrow cells (6.0 × 10(7) cells) without immunosuppression after lethal irradiation (10 Gy). We examined the impact of acute GVHD on the kidney in allogeneic BMT rats and compared them with those in Lewis-to-Lewis syngeneic BMT control and non-BMT control rats. In syngeneic BMT and non-BMT control rats, acute GVHD did not develop by day 28. In allogeneic BMT rats, severe acute GVHD developed at 21-28 days after BMT in the skin, intestine, and liver with decreased body weight (>20%), skin rush, diarrhea, and liver dysfunction. In the kidney, infiltration of donor-type leukocytes was by day 28. Mild inflammation characterized by infiltration of CD3(+) T-cells, including CD8(+) T-cells and CD4(+) T-cells, and CD68(+) macrophages to the interstitium around the small arteries was noted. During moderate to severe inflammation, these infiltrating cells expanded into the peritubular interstitium with peritubular capillaritis, tubulitis, acute glomerulitis, and endarteritis. Renal dysfunction also developed, and the serum blood urea nitrogen (33.9 ± 4.7 mg/dL) and urinary N-acetyl-β-D-glucosaminidase (NAG: 31.5 ± 15.5 U/L) levels increased. No immunoglobulin and complement deposition was detected in the kidney. In conclusion, the kidney was a primary target organ of acute GVHD after BMT. Acute GVHD of the kidney was characterized by increased levels of urinary NAG and cell-mediated injury to the renal microvasculature and renal tubules.
authors.affiliation: Department of Nephrology, Nippon Medical School, Tokyo, Japan; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Higo
authors.affiliation: Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Masuda
authors.affiliation: Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Nagasaka
authors.affiliation: Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kajimoto
authors.affiliation: Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Kanzaki
authors.affiliation: Department of Nephrology, Nippon Medical School, Tokyo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Fukui
authors.affiliation: Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nagahama
authors.affiliation: Department of Nephrology, Nippon Medical School, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Mii
authors.affiliation: Department of Nephrology, Nippon Medical School, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kaneko
authors.affiliation: Department of Nephrology, Nippon Medical School, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsuruoka
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine*; D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000379:methods; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000097:blood / Q000473:pathology / Q000652:urine*; D007674:Kidney Diseases / Q000097:blood / Q000209:etiology / Q000473:pathology* / Q000652:urine; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D051381:Rats; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods
chemical_list: D000118:Acetylglucosaminidase