Transforming growth factor-beta(1) expression in early biopsy specimen predicts long-term graft function following pediatric renal transplantation

The main cause of late graft loss or declining long-term graft function is chronic allograft nephropathy (CAN), characterized by progressive interstit ial fibrosis. Transforming growth factor (TGF)-beta (1), plays a key role i n fibrogenesis. We immunohistochemically investigated whether the degree of TGF-beta (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-beta (1) in the graft using LC antibody (LC) for intracellular TGF- beta (1) and CC antibody (CC) for extracellular TGF-beta (1). The change in creatinine clearance between 100 d and 3 yr after transplantation (Delta C cr) was used as an index of longterm graft function. We also used image ana lysis to calculate the relative area involved by interstitial fibrosis in t he trichrome-stained section of graft biopsy specimens at 100 d and 3 yr, d esignating the change as Delta FI. Delta Ccr was - 4.2 +/- 9.4 mL/min in su bjects with minimal early immunoreactivity for CC and - 20.5 +/- 15.9 mL/mi n in subjects with strong reactivity (p < 0.05). Delta Ccr was - 14.5 +/- 1 8.6 mL/min in subjects with minimal early immunoreactivity for LC and - 11. 7 +/- 12.8 mL/min in those with strong reactivity. Delta FI in subjects wit h minimal CC reactivity (1.28 +/- 4.11%) tended to be lower than that in su bjects with strong reactivity (8.45 +/- 15.47%). Neither fibrosis at 100 d nor Delta FI differed between subjects with minimal and strong LC reactivit y. Thus, strong extracellular TGF-beta (1) expression in grafts at 100 d af ter transplantation is associated with a long-term decline in graft functio n and tends to be associated with increased graft fibrosis at 3 yr.