Transforming growth factor-β₁ 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 interstitial fibrosis. Transforming growth factor (TGF)-β₁ plays a key role in fibrogenesis. We immunohistochemically investigated whether the degree of TGF-β₁ 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-β₁ in the graft using LC antibody (LC) for intracellular TGF-β₁ and CC antibody (CC) for extracellular TGF-β₁. 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-β₁ 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.