Transforming growth factor‐β 1 expression in early biopsy specimen predicts long‐term graft function following pediatric renal transplantation

• Published in: Clinical transplantation Vol. 15; no. 3; pp. 185 - 191
• Main Authors: Ishimura, Takeshi, Fujisawa, Masato, Isotani, Shuji, Higuchi, Akihiro, Iijima, Kazumoto, Arakawa, Soichi, Hohenfellner, Katharina, Flanders, Kathleen C, Yoshikawa, Norishige, Kamidono, Sadao
• Format: Journal Article
• Language: English
• Published: 01.06.2001
• ISSN: 0902-0063; 1399-0012
• DOI: 10.1034/j.1399-0012.2001.150307.x

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)‐β 1 plays a key role in fibrogenesis. We immunohistochemically investigated whether the degree of TGF‐β 1 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‐β 1 in the graft using LC antibody (LC) for intracellular TGF‐β 1 and CC antibody (CC) for extracellular TGF‐β 1 . The change in creatinine clearance between 100 d and 3 yr after transplantation (ΔCcr) 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 ΔFI. ΔCcr 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). ΔCcr 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. ΔFI 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 ΔFI differed between subjects with minimal and strong LC reactivity. Thus, strong extracellular TGF‐β 1 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.