title: Transforming growth factor-beta1 expression in early biopsy specimen predicts long-term graft function following pediatric renal transplantation.
abstract: The main cause of late graft loss or declining long-term graft function is chronic allograft nephropathy (CAN), characterized by progressive interstitial fibrosis. Transforming growth factor (TGF)-beta1 plays a key role in fibrogenesis. We immunohistochemically investigated whether the degree of TGF-beta1 expression in early biopsy specimens routinely obtained from stable allografts at 100 d could predict fibrosis and graft dysfunction in the late phase. Patients were children with grafts from related donors. We immunohistochemically determined intracellular and extracellular expression of TGF-beta1 in the graft using LC antibody (LC) for intracellular TGF-beta1 and CC antibody (CC) for extracellular TGF-beta1. The change in creatinine clearance between 100 d and 3 yr after transplantation (DeltaCcr) was used as an index of long-term graft function. We also used image analysis to calculate the relative area involved by interstitial fibrosis in the trichrome-stained section of graft biopsy specimens at 100 d and 3 yr, designating the change as DeltaFI. DeltaCcr was -4.2+/-9.4 mL/min in subjects with minimal early immunoreactivity for CC and -20.5+/-15.9 mL/min in subjects with strong reactivity (p<0.05). DeltaCcr was -14.5+/-18.6 mL/min in subjects with minimal early immunoreactivity for LC and -11.7+/-12.8 mL/min in those with strong reactivity. DeltaFI in subjects with minimal CC reactivity (1.28+/-4.11%) tended to be lower than that in subjects with strong reactivity (8.45+/-15.47%). Neither fibrosis at 100 d nor DeltaFI differed between subjects with minimal and strong LC reactivity. Thus, strong extracellular TGF-beta1 expression in grafts at 100 d after transplantation is associated with a long-term decline in graft function and tends to be associated with increased graft fibrosis at 3 yr.
authors.affiliation: Department of Urology, Kobe University School of Medicine, Kobe, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ishimura
authors.forename: M
authors.initials: M
authors.lastname: Fujisawa
authors.forename: S
authors.initials: S
authors.lastname: Isotani
authors.forename: A
authors.initials: A
authors.lastname: Higuchi
authors.forename: K
authors.initials: K
authors.lastname: Iijima
authors.forename: S
authors.initials: S
authors.lastname: Arakawa
authors.forename: K
authors.initials: K
authors.lastname: Hohenfellner
authors.forename: K C
authors.initials: KC
authors.lastname: Flanders
authors.forename: N
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: S
authors.initials: S
authors.lastname: Kamidono
mesh_terms: D000293:Adolescent; D001706:Biopsy; D002648:Child; D005260:Female; D005355:Fibrosis; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology; D008297:Male; D011379:Prognosis; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta